Salmonella typhimurium

Environ Mutagen, 1984, 6(4), 497 - 515
Microbial mutagenicity of isomeric two-, three-, and four-ring amino polycyclic aromatic hydrocarbons; Later DW et al.; The isomers of various two-, three-, and four-ring amino polycyclic aromatic hydrocarbons were tested for mutagenic activity using a microbial plate incorporation test with four Salmonella typhimurium strains (TA98, TA100, TA1535, and TA1537) . All compounds were assayed with an S9 metabolic activating enzyme system . The two-ring compounds were tested only with TA98 . All were weakly mutagenic (1-10 rev/micrograms) except 2-aminobiphenyl, which was not mutagenic under these test conditions . All except two of the 13 fused three-ring compounds (aminofluorenes, aminoanthracenes, and aminophenanthrenes) were active frame shift mutagens; only the aminophenanthrenes were active base-pair mutagens . The potency of this group of isomeric compounds ranged from moderately (approximately 20 rev/microgram) to strongly (greater than 5,000 rev/microgram) mutagenic . As a group, the pericondensed four-ring amino compounds were the most mutagenic of the three groups tested . All of the aminofluoranthene and aminopyrene isomers showed significant mutagenic activity with TA98, TA100, and TA1537 . In general, the mutagenic potency of the amino polycyclic aromatic compounds tested was highly dependent on the structural position of the amino group.

J Cancer Res Clin Oncol, 1984, 108(1), 76 - 80
Alcoholdehydrogenase as an activating enzyme for N-nitrosodiethanolamine (NDELA): in vitro activation of NDELA to a potent mutagen in Salmonella typhimurium; Eisenbrand G et al.; N-Nitrosodiethanolamine (NDELA), a potent carcinogen, has not so far been found to be mutagenic in a wide range of test systems . In particular, mutagenicity testing in Salmonella typhimurium with rat liver S-9 mix or microsomal fraction used for activation has failed to indicate mutagenicity . However, when incubated with alcohol dehydrogenase (ADH) in the presence of NAD, NDELA is converted to a potent mutagen . A possible mechanism of activation comprises the generation of an aldehyde as a primary metabolite formed by NAD/ADH and its subsequent rearrangement into cyclic intermediates . The latter might either be further metabolized or spontaneously decompose into various alkylating agents and glycolaldehyde . Standard test conditions used for the Ames test will not favor the detection of mutagens to be activated by NAD/ADH because they require the presence of NADPH, whereas ADH needs NAD to become an activating enzyme, as shown for NDELA.

Environ Mutagen, 1984, 6(3), 343 - 54
Mutagenicity screening of foods . II . Results with fruits and vegetables; Stoltz DR et al.; A survey of the mutagenic potential of a wide variety of food products has been initiated with results for 28 different beverages reported previously {Stoltz et al, 1982b} . Here, results for samples of 46 widely consumed fruits and vegetables from six general categories are given . Each sample was concentrated and fractionated by polarity and solubility to give five fractions, each of which was assayed for mutagenic potential with Salmonella typhimurium TA98 and TA100 . Although statistical analysis of the data resulted in positive findings for 22 fruit and vegetable samples, only six products (grapes, onions, peaches, raisins, raspberries, strawberries) demonstrated potent mutagenic activity.

Environ Mutagen, 1984, 6(3), 311 - 20
Chromium (VI) potentiates mutagenesis by sodium azide but not ethyl methanesulfonate; LaVelle JM et al.; A fluctuation test using Salmonella typhimurium strain 1535 has been used in an experimental protocol to assess biological effects of interactions between chromium (VI), such as K2CrO4, and two DNA-damaging agents, ethyl methanesulfonate (EMS), and sodium azide . Mutagenicity, expressed as the average number of mutations induced over a parallel control, was determined for the compounds alone and in combination . The significance of the differences between the "expected" response, calculated by simple addition of the responses from the individual tests, and the observed response when the combination was tested, were estimated by chi square . For the combination of K2CrO4 and NaN3, the response was significantly greater than expected suggesting a possible potentiation of mutagenesis . The opposite (a less-than-additive response) was found for the K2CrO4/EMS combination . Both effects were found to be dose related to the concentration of potassium chromate used . Toxicity of the compounds or their combinations to the bacteria could not explain the results.

Drug Chem Toxicol, 1984, 7(3), 243 - 57
Evaluation of the mutagenic potential of corn (Zea mays L.) grown in untreated and atrazine (AAtrex) treated soil in the field; Sumner DD et al.; Bacterial assays using extracts from field corn plants (harvested at one month, silage and mature stages) do not indicate that soil treatment with atrazine, at its maximum use rate, alters the endogenous mutagens present in these extracts, nor that atrazine itself is degraded to mutagenic products . Extracts of corn grown in soil treated with AAtrex were equally mutagenic with those of corn grown in untreated soil when tested in Salmonella typhimurium TA-100 by a reversion assay or in Salmonella typhimurium TM-677 in a forward mutation assay . Higher concentrations of histidine in corn grown in AAtrex treated soil may interfere with the reversion assay, but do not affect the forward mutation assay . The nature of the agent(s) responsible for the positive response was not determined . The mutagenicity may be due to natural plant constituents, an artifact of the sample preparation, or mycotoxins from some unrecognized plant infection . The experimental results in these field studies do not show that atrazine is degraded or metabolized by corn plants to mutagens in this sensitive bacterial assay.

Mol Gen Genet, 1984, 194(1-2), 219 - 26
Methionine and glutamine transport systems in D-methionine utilising revertants of Salmonella typhimurium; Poland J et al.; In Salmonella typhimurium, methionine auxotrophs such as metB can use D-methionine as a methionine source . MetP mutations prevent this growth since D-methionine can enter only via the metP high-affinity methionine transport system . D-methionine utilising revertants ( Dmu +) were selected from metB23 metP760 ( HU76 ) following nitrosoguanidine mutagenesis . The properties of two such revertants, HU206 and HU415 , indicated that reversion was not due to backmutation of the metP760 mutation . Genetic analysis indicated that each strain possessed two mutations, designated dmu and gln, in addition to the original metB23 and metP760 mutations . The dmu mutation restores ability to grow on D-methionine, partly restores D- and L-methionine transport activity, and makes the cells particularly sensitive to inhibition by L-glutamine while growing on D but not L-methionine . The growth inhibition by L-glutamine was shown to be caused by competition by L-glutamine for D-methionine transport by the high-affinity methionine system . The gln mutation greatly reduces activity of the high-affinity glutamine transport system . The Dmu + strains are also partly defective in the glutamine low-affinity transport system, possibly because the partially-restored methionine high-affinity system, or a component of tis system, functions in the transport of glutamine by its low-affinity system.

Gann, 1984 Jan, 75(1), 8 - 16
Comparison of mutagenicities of N-nitrosamines on Salmonella typhimurium TA100 and Escherichia coli WP2 uvrA/pKM101 using rat and hamster liver s9; Araki A et al.; The mutagenicities of twelve N-nitrosamines were tested on Salmonella typhimurium TA100 and Escherichia coli WP2 uvrA/pKM101 in the presence of rat liver S9 or hamster liver S9 by "preincubation" and "pour-plate" assays . The following eleven N-nitrosamines were mutagenic: N-nitroso-N-dimethylamine; N-nitroso-N-diethylamine; N-nitroso-N-di-n-propylamine; N-nitroso-N-di-n-butylamine; N-nitroso-N-methyl-n- amylamine ; N-nitroso-piperidine; N-nitrosomorpholine; N-nitroso-N-methyl-piperazine; N-nitroso-N-methyl-benzylamine; N-nitroso-N-methyl- phenylamine and N-nitroso-N-phenyl-benzylamine . N-Nitroso-N-diphenylamine was not mutagenic . E . coli WP2 uvrA/pKM101 was more sensitive than S . typhimurium TA100 to the mutagenic actions of N-nitroso-dialkyl amines, N-nitroso- aklyl -aryl amines and N-nitroso- diaryl amines, but S . typhimurium TA100 was more sensitive to those of N-nitroso-cyclic amines . Hamster liver S9 was better than rat liver S9 for metabolic activation of N-nitrosamines, and the preincubation step enhanced the mutagenicities of N-nitrosamines.

Gann, 1984 Jan, 75(1), 1 - 3
Tyramine is a major mutagen precursor in soy sauce, being convertible to a mutagen by nitrite; Ochiai M et al.; Tyramine was identified as a new mutagen precursor in Japanese soy sauce, becoming mutagenic after treatment with nitrite under acidic conditions . The mutagenic compound was identified as 4-(2-aminoethyl)-6-diazo-2,4- cyclohexadienone , and its specific mutagenic activity was 112 revertants/micrograms towards Salmonella typhimurium TA100 without S9 mix.

Int Arch Occup Environ Health, 1984, 53(4), 359 - 64
Lack of mutagenic activity of white spirit; Gochet B et al.; The mutagenic potential of white spirit, a typical mixture of primarily aliphatic hydrocarbons used as a solvent, was investigated using a battery of test systems . The ability of this compound to induce gene mutations was assayed by the Ames' test with different strains of Salmonella typhimurium; its potential clastogenicity was tested in vivo on mouse bone marrow cells; in vitro induction of sister chromatid exchanges was studied in human lymphocytes . Negative results were obtained in all test systems . It is concluded that, in spite of its evident toxicity, white spirit does not display mutagenic properties.

Arch Microbiol, 1984 Jan, 137(1), 70 - 3
Transport and metabolism of trehalose in Escherichia coli and Salmonella typhimurium; Marechal LR; The metabolism of trehalose in wild type cells of Escherichia coli and Salmonella typhimurium has been investigated . Intact cells of Escherichia coli (grown on trehalose) accumulated {14C}-trehalose as {14C}-trehalose 6-phosphate . Toluene-treated cells catalyzed the synthesis of the {14C}-sugar phosphate from {14C}-trehalose and phosphoenolpyruvate; ATP did not serve as phosphoryl donor . Trehalose 6-phosphate could subsequently be hydrolyzed by trehalose 6-phosphate hydrolase, an enzyme which catalyzes the hydrolysis of the disaccharide phosphate into glucose and glucose 6-phosphate . Both Escherichia coli and Salmonella typhimurium induced this enzyme when they grew on trehalose . These findings suggest that trehalose is transported in these bacteria by an inducible phosphoenolpyruvate:trehalose phosphotransferase system . The presence of a constitutive trehalase was also detected.

Environ Mutagen, 1984, 6(2), 145 - 51
Mutagenicity of some benzidine congeners and their N-acetylated and N,N'-diacetylated derivatives in different strains of Salmonella typhimurium; Reid TM et al.; The Ames Salmonella/microsome test was used to compare the mutagenic response of Salmonella typhimurium TA100, TA98, TA1538, and TA1535 to 12 benzidine derivatives, ie, benzidine, 3,3'-dimethoxybenzidine, 3,3'-dimethylbenzidine, 3,3'-dichlorobenzidine, and the corresponding N- and N,N'-diacetylated derivatives . With a few exceptions, the mutagenic response to this series of compounds varied in the order TA98 greater than TA1538 greater than TA100 greater than TA1535 = 0, and the N-monoacetylated derivatives were more mutagenic than either the parent diamines or the N,N'-diacetyl derivatives . The relative mutagenicities of the parent amines for TA98 were 3,3'-dichlorobenzidine much greater than 3,3'-dimethoxybenzidine greater than benzidine greater than 3,3'-dimethylbenzidine.

Environ Mutagen, 1984, 6(2), 131 - 44
Contribution of nitropyrene to the mutagenic activity of coal fly ash; Harris WR et al.; Stack-collected coal fly ash from western low-sulfur coal was extracted with 60:40 benzene/methanol . This extract was fractionated by preparative-scale high performance liquid chromatography (HPLC) and the mutagenic activity of 14 fractions was evaluated by microbial assay with Salmonella typhimurium TA1538 . A widespread distribution of direct-acting mutagens, which probably includes both mono- and dinitroaromatics, was detected . HPLC methods were also used to isolate 1-nitropyrene from the total benzene/methanol extract . The identification of 1-nitropyrene was based on gas chromatographic and HPLC retention measurements and mass spectral data . The concentration of 1-nitropyrene in the ash extract was determined by quantitative HPLC analyses . Mutagenicity assays of the total extract and an authentic 1-nitropyrene standard with Salmonella strains TA1538, TA100, and TA98 indicated that the 1-nitropyrene accounts for approximately 0.03-0.16% of the total mutagenic activity of the extract.

Am J Vet Res, 1984 Jan, 45(1), 59 - 66
Aromatic-dependent Salmonella typhimurium as modified live vaccines for calves; Smith BP et al.; Strains of Salmonella sp with complete nonreverting aromatic biosynthesis (aro) defects are expected to be nonvirulent, in respect to invasive infection, because they need the aromatic metabolites paraaminobenzoate (for making folate) and dihydroxybenzoate (for making enterochelin) which are not available in host tissues . Derivatives with transposon-generated complete nonreverting aro-defects were prepared from 3 mouse-virulent strains of S typhimurium, namely, FIRN, WRAY, and UCD . The latter 2 parent strains originally were isolated from calves and are known to be calf-virulent . The resultant aromatic-dependent (aro-) strains were used to vaccinate 27 calves (2 to 3 weeks old), usually giving 2 doses by the IM route (10(9) bacteria) or orally (1.5 X 10(11)) . Vaccination did not cause severe ill effects in any calf . Thus aro- defects cause loss of virulence for calves, as previously shown for mice . Vaccinated and control calves were challenge exposed, usually at 5 weeks of age, by feeding 1.5 X 10(11) cells of 1 of 2 calf-virulent S typhimurium strains, either UCD 108-11 or SL1323 . Of the 16 challenge-exposed control calves, all became anorectic and depressed (CNS), and 15 had diarrhea . Fourteen of the 16 died; all tested tissues were bacteriologically culture-positive for Salmonella at necropsy . Vaccination with the live UCD aro- vaccine strain, SL1479 by either of 2 schedules (IM or orally) appeared effective.(ABSTRACT TRUNCATED AT 250 WORDS)

Toxicology, 1984 Jan, 29(3), 261 - 70
Quantitative correlation between the metabolism and the mutagenic activity of N-nitrosopyrrolidine; Gilbert PJ et al.; The metabolism of N-nitrosopyrrolidine (NPyrr) via alpha-hydroxylation is modified by pretreatments of the animals with compounds which affect the microsomal level of cytochrome P-450 and by addition, in vitro, of 2-diethylaminoethyl-2,2-diphenyl valerate hydrochloride (SKF 525-A), an inhibitor of cytochrome P-450 . This phenomenon is due exclusively to the induction or the inhibition of the enzymatic activity involved in the microsomal metabolism . After preincubation in liquid medium, the mutagenic activity of NPyrr towards the Salmonella typhimurium strain TA 1530 is similarly modified by these effectors . A similar effect is not observed when using the plate incorporation method . The mutagenic intermediate is formed by the microsomal fraction . The presence of the S . typhimurium strain TA 1530 decrease the transformation of NPyrr into its ultimate metabolite (1,4-butanediol); there is a relationship between the formation of 1,4-butanediol and the mutagenic activity of NPyrr . The S . typhimurium strain TA 1530 is able to partially transform 4-hydroxybutanal, the first identifiable microsomal metabolite of NPyrr, into its ultimate metabolite (1,4-butanediol).

Mutat Res, 1984 Jan, 135(1), 31 - 47
The hair-dye reagent 2-(2',4'-diaminophenoxy)ethanol is mutagenic to Salmonella typhimurium; Venitt S et al.; A new hair-dye ingredient, 2-(2',4'-diaminophenoxy)ethanol (2,4-DAPE), was described as being devoid of any genotoxic activity on the basis of a multi-laboratory study . Since 2,4-DAPE is a close analogue of 2,4-diaminoanisole (2,4-DAA), which is mutagenic and carcinogenic, we tested this claim by assaying 2,4-DAPE for bacterial mutagenicity . Two samples of 2,4-DAPE X 2HCl were synthesized by reduction of the corresponding dinitrophenoxyethanol and identity and purity were established by elemental analysis, NMR spectrometry, mass-spectrometry, UV-spectrophotometry, TLC and HPLC . Fresh aqueous solutions of 2,4-DAPE X 2HCl were assayed in several separate plate tests using S . typhimurium TA1538, TA97, TA98 and TA100, and E . coli WP2uvrA (pKM101), 3 plates per dose and 0%, 4%, 10% and 30% Aroclor 1254-induced rat-liver S9 in S9 mixes . We obtained negative results in TA100 and E . coli . Reproducible, statistically significant dose-related increases in revertants (up to 14 times the background) were obtained in frame-shift mutants of S . typhimurium in the dose range 10-80 micrograms per plate . Mutagenicity was S9-dependent, significant increases in revertants being obtained only with 50 microliter per plate or more of S9 . 2,4-DAPE induced significant mutagenic effects at doses of less than 1 micrograms per ml in TA1538 and TA98 in fluctuation tests using 2% S9 in the S9 mix . In plate tests, 2,4-DAPE was less mutagenic (by a factor of about 8) than 2,4-DAA, which gave the highest mutant yields with 20 microliter S9 per plate (4% S9 in the S9 mix) . 2,4-DAPE obtained commercially was about 8 times more mutagenic than our sample of 2,4-DAPE . After purification, the commercial product, now chromatographically identical with our own sample, gave plate-test results close to those obtained for our samples of 2,4-DAPE . A review of the published reports (in which 2,4-DAPE was claimed to be inactive in a variety of short-term tests) revealed: (a) the use of protocols for bacterial mutagenicity testing which, in the light of our own results, were probably too limited in scope, especially in the choice of conditions for metabolic activation; (b) insufficient information on the identification and purity of the samples of 2,4-DAPE tested in the published collaborative study.

Mutat Res, 1984 Jan, 135(1), 21 - 9
Some chloro derivatives of polynuclear aromatic hydrocarbons are potent mutagens in Salmonella typhimurium; Colmsjo A et al.; A series of chlorinations of some polynuclear aromatic hydrocarbons (PAH) were carried out and the products were tested for mutagenicity on Salmonella typhimurium TA98 and TA100 . We conclude that the chlorination of certain PAHs with low mutagenicity, such as pyrene and benzo{e}pyrene, resulted in the formation of two types of product . The chlorination of pyrene was studied in some detail . The major products of this chlorination were chloro-substituted pyrenes . These compounds showed an S9-dependent mutagenicity and were identified as 1-chloro-, 1,6-dichloro-, 1,8-dichloro- and 1,3-dichloropyrene . On tester strain TA100 the mutagenic effect ranged from 1.4 to 14 revertants/nmol, 1,3-dichloropyrene being the most potent of the isomers . Minor products eluting from a chromatograph in a more polar fraction than the major products were also formed . These compounds were less stable than the major products and were identified as pyrene with chloro additions in the 4- and 5-positions, with various chloro substituents at other positions . These minor products showed a high mutagenic effect on Salmonella in the absence of S9 . The mutagenic effect on strain TA100 ranged from 10 to 15 revertants per ng which is at least 40 and 4000 times higher than for 1-nitropyrene and pyrenequinones, respectively . These unstable chloro derivatives of pyrene are difficult to analyse chemically because they are easily degraded and give rise to the more stable 4-chloropyrene.

Mol Gen Genet, 1984, 193(2), 332 - 9
Bifunctionality and polarized infidelity at the hisB locus of Aspergillus nidulans; Millington Ward AM et al.; The histidine (hisB) locus of Aspergillus nidulans is unusual in two ways . Firstly, it is bifunctional; besides coding for imidazole glycerol phosphate (IGP) dehydrase, it is required for the production of ascospores (fertility) . It appears, therefore, to be partly homologous to the hisB locus of Salmonella typhimurium, which codes for IGP dehydrase and histidinol phosphate phosphatase . Secondly, during meiosis it is often inaccurately transmitted to the progeny (infidelity) . This phenomenon may be akin to the aberrant recombination events which cause Bar reversion in Drosophila, "selfing" in Salmonella and Neurospora, and gene fusions of the haemoglobin lepore type . A molecular model is proposed to account for the results.

Arch Oral Biol, 1984, 29(1), 59 - 63
The bone-resorbing activities in tissue culture of lipopolysaccharides from the bacteria Actinobacillus actinomycetemcomitans, Bacteroides gingivalis and Capnocytophaga ochracea isolated from human mouths; Iino Y et al.; The activities of lipopolysaccharides (LPS) were assessed by measuring the calcium release from mouse calvaria in vitro and compared to that of LPS from Salmonella typhimurium . Stimulation of bone resorption was maximal at an LPS concentration of 10 micrograms/ml and at this dose all oral LPS preparations showed similar levels of activity and less than that of LPS from S . typhimurium . Only S . typhimurium LPS and B . gingivalis LPS retained bone-resorbing activity at 0.1 microgram/ml . No bone-resorbing activity was observed against killed bone and histochemical observations of stable acid phosphatase activity indicated both mononuclear and multinuclear cells participating in bone removal . Addition of indomethacin to the culture medium did not inhibit calcium release from the bones by any of the LPS preparations except for that from A . actinomycetemcomitans . Fetal calf serum completely blocked the activities of all the LPS preparations whereas human serum did not inhibit the action of B . gingivalis LPS . Thus this particular LPS could be important in mediating bone loss in chronic periodontitis.

Mutat Res, 1984 Jan, 125(1), 95 - 104
Comparison of the frequency of diphtheria toxin and thioguanine resistance induced by a series of carcinogens to analyze their mutational specificities in diploid human fibroblasts; Aust AE et al.; The mutagenic specificities of ethylnitrosourea (ENU), X-rays (+/-)7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7, 8,9,10-tetrahydrobenzo{a}pyrene (BPDE), ICR-191, and N-acetoxy-2-acetylaminofluorene (N-AcO-AAF) were analyzed and compared in diploid human fibroblasts and Salmonella typhimurium . In the human fibroblasts, we compared the frequency of diphtheria toxin (DT)-resistant mutants, presumably induced in the gene coding for elongation factor-2, with the frequency of 6-thioguanine (TG) resistance induced by mutations in the gene coding for hypoxanthine(guanine)phosphoribosyltransferase (HPRT) . Recovery of DT-resistant (DTr) cells requires that the mutant EF-2 retain the ability to carry on protein synthesis since the normal EF-2 will be inactivated by DT selection . Therefore, the DTr mutation cannot involve major changes in the gene . In contrast, cells can acquire TG resistance by any mechanism which eliminates HPRT activity, e.g., base substitution, frameshift, deletion, loss of chromosomes . Each agent was assessed by calculating the ratio of the slopes of the dose-response plots (induced variant frequency as a function of dose of the agent used) for the two markers (DTr/TGr variants.) . In S . typhimurium we examined the reversion frequency in four histidine-requiring strains bearing forward mutations of the frameshift (TA1538, TA98) or missense (TA1535, TA100) type . ENU, which was predominantly a base substitution mutagen in the bacteria, gave a ratio of DTr to TGr variants of 1.5 . As expected of an agent inducing gross chromosomal changes, X-rays induced no revertants in bacteria and in human cells gave a ratio of 0.1 . ICR-191 which was predominantly a frameshift mutagen in bacteria gave a ratio of 0.15 . In the set of bacterial strains containing the plasmid pKM101, BPDE reverted both frameshift and base substitution mutations . It did not cause reversions in the other set of strains . In human cells BPDE gave a response similar to ENU, i.e., a ratio of DTr/TGr variants of 1.5 . As reported by others, N-AcO-AAF was predominantly a frameshift mutagen in bacteria . However, in the human cells it gave a ratio of DTr/TGr variants of 1.5, similar to ENU and BPDE . These results suggest that in human cells, BPDE and N-AcO-AAF, like ENU, yield predominantly base substitutions, while ICR-191 and X-rays largely produce mutations by mechanisms which result in more extensive alterations in the gene.

Mutat Res, 1984 Jan, 125(1), 23 - 31
Liver, kidney and small-intestine microsomal-mediated mutagenicity of carcinogenic aromatic amines; Fouarge M et al.; The mutagenicity of 2-aminofluorene, 4-aminobiphenyl and 3,2'-dimethylaminobiphenyl towards Salmonella typhimurium was studied in the presence of microsomes from liver, kidney and small intestine of untreated and pretreated rats . The aim was to study a possible correlation between the organotropism of these amines and their activation into mutagenic intermediates by these three tissues . Pretreatment of the rats with phenobarbital, Aroclor 1254 and 3-methylcholanthrene injected intraperitoneally increased the liver microsomal-mediated mutagenic activity of the three amines but remained without effect on the activating capacity of microsomes from the kidney and small intestine . However, pretreatment with 3-methylcholanthrene administered intragastrically increased the small-intestine microsomal-mediated mutagenicity of 2-aminofluorene almost 3-fold but remained without effect on the mutagenicity of 4-aminobiphenyl and 3,2'-dimethylaminobiphenyl . No mutagenic effect was observed with 4-aminobiphenyl in the presence of kidney microsomes or with 4-aminobiphenyl and 3,2'-dimethylaminobiphenyl in the presence of small-intestine microsomes, obtained from either untreated or pretreated animals . It is concluded that no relationship exists between the mutagenic activities of the three amines, as detected in the Ames test, and their carcinogenic organotropisms.

J Immunol, 1984 Jan, 132(1), 347 - 53
In vitro stimulation of C3H/HeJ spleen cells and macrophages by a lipid A precursor molecule derived from Salmonella typhimurium; Vogel SN et al.; C3H/HeJ mice possess a genetic lesion that renders them significantly less responsive to the biologic effects of protein-free lipopolysaccharide (LPS) preparations, and more specifically, to the lipid A region of the LPS molecule . The in vivo manifestations of this mutation are also reflected in vitro in that cells derived from this mouse strain fail to respond to LPS when compared with cells derived from fully endotoxin-responsive mouse strains . The precise nature of this gene defect has not yet been established . In this study, we have examined in vitro the biologic activities of a structurally less complex "lipid A precursor" molecule, produced by a conditionally lethal, temperature-sensitive mutant of Salmonella typhimurium . In contrast to the intact LPS or wild-type lipid A extracted from the parental strain of Salmonella typhimurium, the lipid A precursor induced a highly significant, polymyxin B-inhibitable mitogenic response in splenic cultures derived from LPS-hyporesponsive C3H/HeJ and C57BL/10ScN (nu/nu) mice . In addition, the lipid A precursor was found to stimulate cultures of C3H/HeJ macrophages to produce significant levels of both interleukin 1 (IL 1, previously referred to as "lymphocyte activating factor" or "LAF") and prostaglandins of the E series (PGE) . These findings suggest the possibility that the defect in endotoxin responsiveness exhibited by C3H/HeJ mice may be related to a defect in the processing of wild-type lipid A or LPS to a suitably stimulatory form that is structurally related to the lipid A precursor molecule.

J Bacteriol, 1984 Jan, 157(1), 171 - 8
Cloning and characterization of gdhA, the structural gene for glutamate dehydrogenase of Salmonella typhimurium; Miller ES et al.; Glutamic acid is synthesized in enteric bacteria by either glutamate dehydrogenase or by the coupled activities of glutamate synthase and glutamine synthetase . A hybrid plasmid containing a fragment of the Salmonella typhimurium chromosome cloned into pBR328 restores growth of glutamate auxotrophs of S . typhimurium and Escherichia coli strains which have mutations in the genes for glutamate dehydrogenase and glutamate synthase . A 2.2-kilobase pair region was shown by complementation analysis, enzyme activity measurements, and the maxicell protein synthesizing system to carry the entire glutamate dehydrogenase structural gene, gdhA . Glutamate dehydrogenase encoded by gdhA carried on recombinant plasmids was elevated 5- to over 100-fold in S . typhimurium or E . coli cells and was regulated in both organisms . The gdhA promoter was located by recombination studies and by the in vitro fusion to, and activation of, a promoter-deficient galK gene . Additionally, S . typhimurium gdhA DNA was shown to hybridize to single restriction fragments of chromosomes from other enteric bacteria and from Saccharomyces cerevisiae.

J Bacteriol, 1984 Jan, 157(1), 100 - 8
Hook-associated proteins essential for flagellar filament formation in Salmonella typhimurium; Homma M et al.; The hooks of the flagella of Salmonella typhimurium were purified by a newly developed method, using a flaL mutant without a filament, and the hook components were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis . As a result, we detected three protein species in addition to hook protein . We call these three proteins hook-associated proteins (HAPs) . Their molecular weights were 59,000 for HAP1, 53,000 for HAP2, and 31,000 for HAP3 . The HAP1/hook protein/HAP3/HAP2 molar ratio, calculated from their relative amounts and their molecular weights, was 1:10:1.1:0.53 . The compositions of HAPs were analyzed in the hooks from the other filamentless mutants which were defective in H1 H2, flaV, flaU, or flaW . Hooks from the H1 H2 mutant had the same HAP composition as hooks from the flaL mutant . Hooks from the flaV mutants contained HAP1 and HAP3 . Hooks from the flaU mutants contained HAP1 . Hooks from the flaW mutants contained a very small amount of HAP3 . From these results, the process of hook morphogenesis and the genes responsible for each step were postulated . Electron micrographs of hooks from the filamentless mutants showed that hooks which contained all three HAPs had a sharp clawlike tip, whereas hooks lacking any HAP had a flat tip . Electron micrographs of hooks treated with antibody against the hook protein showed that each claw-shaped end was not covered with antibody . These results strongly suggest that all three HAPs or at least some of them are located at the claw-shaped end and play an essential role in filament formation.

Gene, 1984 Jan, 27(1), 47 - 54
Cloning and characterization of the gene for Salmonella typhimurium serine hydroxymethyltransferase; Urbanowski ML et al.; A plasmid containing the glyA gene of Salmonella typhimurium LT2 was constructed in vitro using plasmid pACYC184 as the cloning vector and a lambda gt7-glyA transducing phage as the source of glyA DNA . The recombinant plasmid (pGS30) contains a 10-kb EcoRI insert fragment . Genetic and biochemical experiments established that the fragment contains a functional glyA gene . From plasmid pGS30 we subcloned a 4.4-kb SalI-EcoRI fragment containing the glyA gene and its neighboring regions (plasmid pGS38) . The location and orientation of the glyA gene within the 4.4-kb insert fragment was determined in four ways: (1) comparison of the physical map of the 4.4-kb SalI-EcoRI fragment with the physical map of a 2.6-kb SalI-PvuII fragment that carries the Escherichia coli glyA gene; (2) deletion analysis; (3) transposon Tn5 insertional inactivation experiments; (4) deoxyribonucleic acid sequencing and comparison of the S . typhimurium DNA sequence with the E . coli DNA sequence . A presumptive glyA-encoded polypeptide of Mr 47000 was detected using plasmid pGS38 as template in a minicell system, but not when the glyA gene was inactivated by insertion of a Tn5 element.

Scand J Infect Dis, 1984, 16(1), 111 - 9
Effects of Streptococcus pneumoniae, Salmonella typhimurium and Francisella tularensis infections on oxidative, glycolytic and lysosomal enzyme activity in red and white skeletal muscle in the rat; Friman G et al.; Since opinions differ as to whether the oxidative and glycolytic capabilities of skeletal muscle are altered in acute infection, enzyme activities in oxidative, glycolytic and degradative (acid hydrolases) pathways and total protein and DNA were determined in skeletal muscle of rats infected with Streptococcus pneumoniae, Salmonella typhimurium or Francisella tularensis . Studies were performed separately in red (slow twitch) and white (fast twitch) muscle tissue because these fibers function during different types of exercise . In the salmonella- and tularemia-infected rats, the intramitochondrially located oxidative enzymes of muscle were decreased to 56-83% of controls whereas the glycolytic enzyme situated in the cytosol showed an earlier and more pronounced loss of activity, 30-75% of controls . In the pneumococcal infection, only reduced glycolytic activity was significant . DNA concentrations were unchanged in any infection . Reductions during tularemia were statistically correlated with whole-cell protein degradation, while that of the glycolytic enzyme was parallelled by activation of lysosomal enzymes . Red and white muscle tissues responded similarly, in contrast to several other pathologic states that involve a catabolic component of muscle with a predominant response (or damage) in one or the other fiber type.

J Bacteriol, 1984 Jan, 157(1), 158 - 64
Isolation and characterization of the Salmonella typhimurium LT2 xylose regulon; Ghangas GS et al.; Salmonella DNA was partially digested with EcoRI, and the digest was fractionated to obtain fragments larger than 8 kilobases (kb) . These were ligated into EcoRI-cut pBR322, and the mixture was used to transform Salmonella Xyl- cells selecting for ampR xyl+ transformants . A 21- and a 27-kb plasmid were isolated, both of which contained the entire xylose regulon . The xylose regulon was localized to a 6.3-kb segment of a 13.5-kb EcoRI fragment . Subclones were constructed which contained either the genes for D-xylose isomerase and D-xylulokinase or the genes for the D-xylose transport and the D-xylose regulatory factors . The gene order determined by the subcloning experiments is consistent with that determined by genetic mapping . The spots corresponding to D-xylose isomerase and D-xylulokinase subunits were identified in two-dimensional gels of several xylose-induced strains . Each of them had a molecular weight of 45,000 and an isoelectric point of 6.2 +/- 0.1.

Mol Gen Genet, 1984, 195(1-2), 256 - 9
Application of phage lambda technology to Salmonella typhimurium . Construction of a lambda-sensitive Salmonella strain; Harkki A et al.; We have previously constructed a novel strain of S . typhimurium carrying the E . coli lamB gene and shown that this strain adsorbs phage lambda and, for example, can be used for transposon mutagenesis with lambda vectors . In this study, we show that this strain can support the lytic growth of phage lambda nin derivatives, but not growth of wild-type lambda . However, lysogenization with lambda nin does not occur . Using this strain as starting material we took the construction one step further by introducing the E . coli nusA gene in a multicopy plasmid to this strain . We could show that this new Salmonella derivative can support both the lytic and lysogenic mode of growth of several different lambda derivatives . Using the same approach it should be possible to construct lambda-sensitive derivatives of other enteric bacteria thus rendering them more amenable to in vivo genetic manipulation.

Environ Mutagen, 1984, 6(5), 757 - 62
Mutagenicity of lichen constituents; Shibamoto T et al.; Usnic acid (the most abundant lichen constituents), physodic, and physodalic acids isolated from Hypogymnia enteromorph (Ach.) Nyl . were tested for mutagenicity in the Ames Salmonella/microsome assay . Physodalic acid exhibited clear dose-related mutagenicity against Salmonella typhimurium strain TA 100 with or without S9 mix in both plate-incorporation and preincubation assays . The addition of S9 mix increased the number of revertants approximately threefold and fourfold in preincubation and plate-incorporation assays, respectively.

Teratog Carcinog Mutagen, 1984, 4(3), 273 - 83
Mutagenic, cytotoxic, and teratogenic effects of 2-acetylaminofluorene and reactive metabolites in vitro; Faustman-Watts EM et al.; The embryotoxic, mutagenic, and cytotoxic properties of 2-acetylaminofluorene (AAF) and two of its reactive metabolites, N-acetoxy-2-acetylaminofluorene (AAAF) and 2-nitrosofluorene (NF) were assessed in vitro . A combined embryo culture/biotransformation system was used to determine the ability of these compounds to produce embryonic malformations, growth retardation, and/or embryolethality . Salmonella typhimurium auxotrophs (his-) were utilized to measure the mutagenic and cytotoxic potentials of these compounds . The parent compound, AAF, did not produce embryonic malformations or mutagenicity in the absence of an added cytochrome P-450-dependent monooxygenase system . Both metabolites produced each of the measured toxic effects without supplementation of a bioactivation system . However, the three chemicals each elicited a different spectrum of malformations . Bioactivated AAF produced neural tube abnormalities, whereas embryos treated with AAAF primarily exhibited prosencephalic malformations, and NF produced abnormalities of axial rotation or flexure . NF was approximately ten times more potent than AAAF as a direct-acting mutagen but only slightly more active in producing embryonic malformations in vitro . The results indicated that differential effects on the various measured parameters could be produced by these chemicals . The results indicated further that neither NF nor AAAF appeared to be individually responsible for the neural tube abnormalities generated by biotransformed AAF.

Mol Gen Genet, 1984, 193(1), 135 - 42
Evidence that nitrogen regulatory gene ntrC of Salmonella typhimurium is transcribed from the glnA promoter as well as from a separate ntr promoter; Krajewska-Grynkiewicz K et al.; Previous work has indicated that nitrogen regulatory genes ntrB and ntrC of Salmonella typhimurium are closely linked to glnA, the structural gene encoding glutamine synthetase; proceeding clockwise the order of genes in the 86 U region of the map is polA...ntrC ntrB glnA glnA promoter...rha . To study ntrC transcription we have constructed operon fusions of ntrC to lacZ using the Casadaban Mu d1 (Apr lac) phage so that we can measure beta-galactosidase activity as a reflection of ntrC transcription and we have introduced into fusion strains promoter constitutive mutations at glnA {glnAp(Con)} . The glnAp(Con) mutations, which elevate glnA expression in fusion strains, also elevate beta-galactosidase activity, indicating that ntrC is cotranscribed with glnA . Consistent with this interpretation, polar insertion mutations in glnA decrease beta-galactosidase activity of fusion strains carrying glnAp(Con) mutations . However, glnA insertions do not eliminate beta-galactosidase activity of glnAp(Con) ntrC::Mu d1 strains and they have little effect on beta-galactosidase activity of the original ntrC::Mu d1 fusion strains . The latter results confirm that ntrC can also be transcribed from an ntr promoter downstream of glnA . Polar insertion mutations in ntrB eliminate beta-galactosidase activity of both the original fusion strains and fusion strains carrying glnA(Con) mutations, indicating that the ntr promoter lies between glnA and ntrB.

IARC Sci Publ, 1984, (63), 59 - 88
Liver carcinogenesis in tropical Africa; Uwaifo AO et al.; The geographical pathology of hepatocellular carcinoma (HCC) was essentially anecdotal until systematic cancer registration was introduced, but it is now clear that sub-Saharan Africa is a high-incidence area . The disease is multifactorial in etiology, the possible etiological agents including hepatitis B virus and a number of chemical carcinogens, among which the most important appear to be the aflatoxins and N-nitroso compounds . Medicinal plants and herbal teas used in the tropics also contain compounds such as furocoumarins that are mutagenic and/or carcinogenic . A modified form of the Ames Salmonella typhimurium assay was used to study the mutagenicity of aflatoxins B1 and M1 and palmotoxin B0, a co-metabolite of aflatoxin B1, and also of chamuvaritin and chamuvarin, two benzyldihydrochalcones derived from the roots of Uvaria chamae, which are used for medicinal purposes in West Africa . The mutagenicity of a number of furocoumarins isolated from Nigerian medicinal plants was studied by means of the same assay as well as with Chinese hamster V79 cells and C3H 10T1/2 cells; in the last two systems the studies were carried out both with and without photoactivation . The same compounds, and 8-methoxypsoralen, were also investigated by means of cell transformation studies.

Mol Gen Genet, 1984, 195(1-2), 219 - 27
Isolation and characterization of lac fusions to two nitrogen-regulated promoters; Stern MJ et al.; Mud1 (Ap, lac, cts)-mediated fusions to argTr and dhuA, two transport operon promoters in Salmonella typhimurium, were isolated and characterized in order to investigate the regulation of these promoters . Using these fusions we showed that these promoters are under nitrogen regulation and that this effect, as well as the response to a promoter-up mutation in dhuA, is at the transcriptional level . We utilized the fusions to determine that the histidine transport operon does not contain any internal promoters . The fusions were also used to screen the promoters for additional modes of regulation: argTr was found to respond to carbon regulation in addition to nitrogen regulation, while dhuA does not . The argTr promoter contains a sequence with good homology to the consensus sequence determined for the cAMP receptor protein binding site . Neither promoter responds to sulfur or phosphate regulation.

Biochemistry, 1983 Dec 20, 22(26), 6130 - 4
Phosphorus-31 nuclear magnetic resonance investigation of membrane vesicles from Escherichia coli; Hunt AG et al.; Phosphorus-31 nuclear magnetic resonance studies of isolated membrane vesicles prepared from Escherichia coli PSM116 as described by Hunt and Hong {Hunt, A . G., & Hong, J.-S . (1981) J . Biol . Chem . 256, 11988-11991; Hunt, A . G., & Hong, J.-S . (1983) Biochemistry 22, 844-850} are detailed here . This strain harbored a recombinant plasmid containing the phosphoglycerate transport system from Salmonella typhimurium (pJH7) . Evidence indicating a surprising metabolic diversity, such as the presence of the enzymes enolase and phosphoglycerate mutase, is presented . The nature of the energization of these membrane vesicles for transport as described by Hugenholtz et al . {Hugenholtz, J., Hong, J.-S., & Kaback, H . R . (1981) Proc . Natl . Acad . Sci . U.S.A . 78, 3446-3449} is also discussed . Membrane vesicles prepared from the PSM116 strain do not form a transmembrane pH gradient when phosphoenolpyruvate is added . The present results show that phosphorus-31 nuclear magnetic resonance spectroscopy is an excellent tool to investigate the metabolism of membrane vesicles.

Pharm Weekbl Sci, 1983 Dec 16, 5(6), 302 - 7
Correlations between phototoxicity of some 7-chloro-1,4-benzodiazepines and their (photo)chemical properties; De Vries H et al.; In relation to the phototoxicity of 7-chloro-I,4-benzodiazepine-N-oxides the photostability of some of these N-oxides and the thermostability of their photoproducts, the oxaziridines, were studied . Rather than a consequence of a direct phototoxic effect by the N-oxides the ultimate toxic effect in the test system Salmonella typhimurium appeared to be caused by products formed during and after the irradiation . For chlordiazepoxide (CDZ) and its main metabolites in man desmethylchlordiazepoxide (DES) and demoxepam (DEM) the formation of an oxaziridine is indeed a crucial factor for the onset of the toxic effect . However, DEM oxaziridine (DEM OX.) being very thermolabile in protic medium forms non-toxic conjugates with the solvent . CDZ OX . and DES OX . are thermally converted into their N-oxide, although DES OX . partly decomposes into 6-chloro-4-phenylquinazoline-2-carboxaldehyde as well . This compound proved to be an important factor in the toxic action of DES after irradiation.

Biochem Pharmacol, 1983 Dec 15, 32(24), 3791 - 5
Relative mutagenicity and teratogenicity of cyclophosphamide and two of its structural analogs; Hales BF; In this report, cyclophosphamide was compared to two of its structural analogs, 5,5-dimethylcyclophosphamide and diethylcyclophosphamide, with respect to mutagenic and teratogenic activities . Mutagenicity was assessed using Salmonella typhimurium TA 1535; teratogenicity was assessed in Sprague-Dawley rats on day 20 of gestation after intra-amniotic drug administration on day 13 . After metabolic activation, cyclophosphamide caused base substitution mutations in S . typhimurium TA 1535 and major structural defects in both intra-amniotically injected and contralateral uninjected fetuses . 5,5-Dimethylcyclophosphamide was neither mutagenic nor teratogenic . Diethylcyclophosphamide was not mutagenic but was teratogenic . However, diethylcyclophosphamide was less potent as a teratogen than cyclophosphamide and, unlike cyclophosphamide, caused malformations only in the intra-amniotically injected fetuses . Diethylcyclophosphamide does liberate acrolein after metabolic activation . If acrolein is responsible for the teratogenic effects of diethylcyclophosphamide, the other major cytotoxic metabolite of cyclophosphamide, phosphoramide mustard, may account for the difference in teratogenic potency between cyclophosphamide and diethylcyclophosphamide . These results would suggest that acrolein, although apparently not mutagenic, mediates the teratogenicity of diethylcyclophosphamide and a significant proportion of the teratogenicity of cyclophosphamide.

Biochem Pharmacol, 1983 Dec 15, 32(24), 3755 - 63
Genetic expression of aflatoxin metabolism . Effects of 3-methylcholanthrene and beta-naphthoflavone on hepatic microsomal metabolism and mutagenic activation of aflatoxins; Raina V et al.; The effects of pretreatment with 3-methylcholanthrene (MC) and beta-naphthoflavone (beta NF) on the hepatic microsome-mediated mutagenesis of aflatoxin B1 (AFB1) and benzo{a}pyrene, and on the metabolism of aflatoxins B1 and B2, were investigated in inbred mouse strains . The inbred strains of mice studied included Ah nonresponsive strains (DBA/2Ha, AKR/Sn and RF/J), which were also nonresponsive to the induction of the metabolism of AFB1 to AFM1 (AFB1-4-hydroxylase activity), and Ah responsive strains (C57BL/6Ha, ICR/Ha, C3H/St, A/St, Balb/cCr, C57e/Ha and CBA/Pi), which were also responsive to the induction of AFB1-4-hydroxylase activity . The hepatic microsome-mediated enzyme activities studied included: mutagenic activation of AFB1 and benzo{a}pyrene in the Ames Salmonella typhimurium TA-98 system; metabolism of AFB1 and AFB2 to AFM1 and AFM2, respectively; and benzo{a}pyrene metabolism measured as the formation of fluorescent phenolic metabolites, i.e . aryl hydrocarbon hydroxylase (AHH) activity . Time-course and dose-response studies in C57BL/6Ha mice revealed that the metabolism of aflatoxin B1/B2 to aflatoxin M1/M2 (AFB1/B2-4-hydroxylase activity) was induced by both MC and beta NF . In the nonresponsive strains studied, pretreatment with MC or beta NF produced essentially little alteration of AFB1-4-hydroxylase activity or AHH activity or the mutagenic activation of AFB1 and benzo{a}pyrene . On the other hand, AFB1-4-hydroxylase activity in the responsive strains was induced 4- to 10-fold by MC (60 mg/kg) and 2.5- to 7-fold by beta NF (150 mg/kg) . Also in the responsive strains, induction of AFB1-4-hydroxylase activity was strongly associated with (a) the depression of the mutagenic activation of AFB1, and (b) with the induction of both AHH and the mutagenic activation of benzo{a}pyrene . In summary, the results described in this report suggest that: (a) induction of AFB1-4-hydroxylase activity by MC (or beta NF) is associated with the depression of AFB1 mutagenesis and with the induction of benzo{a}pyrene mutagenesis; and (b) induction by MC (or beta NF) of AHH activity, AFB1-4-hydroxylase activity and AFB2-4-hydroxylase activity is controlled by either the same or closely linked genetic factors.

Food Chem Toxicol, 1983 Dec, 21(6), 815 - 23
Safety evaluation of thaumatin (Talin protein); Higginbotham JD et al.; Thaumatin, the sweet proteinaceous extract of the arils of Thaumatococcus daniellii (Benth.) has been studied for its subacute toxicity in rats and dogs and its ability to produce anaphylactic antibodies following oral administration to rats and normal human subjects . Thaumatin was readily digested prior to absorption in rats and no adverse effects resulted from its continuous administration to rats and dogs at dietary concentrations of 0, 0.3, 1.0 and 3.0% for 13 wk . It was not teratogenic when administered orally to rats at 0, 200, 600 and 2000 mg/kg body weight/day from day 6 to 15 of gestation and was without effect on the incidence of dominant lethal mutations when administered on five consecutive days to male mice at 200 and 2000 mg/kg/day . The lack of mutagenic potential was confirmed in bacterial mutagenic assays with Salmonella typhimurium (strains TA1535, TA1537, TA1538, TA98 and TA100) and Escherichia coli WP2, at levels of addition of 0.05-50 mg/plate . In rats, thaumatin was found to be a weak sensitizer, comparable with egg albumen, when administered systemically but to be inactive when administered orally . Prick testing of laboratory personnel who had been intermittently exposed by inhalation to thaumatin for periods up to 7 yr showed that 9.3% (13/140) responded positively to commercial thaumatin, while 30.7% were positive to Dermatophagoides pteronyssinus (house dust mite) . None of the subjects who gave a positive skin reaction to commercial thaumatin responded to the plant components remaining after removal of the specific sweet Thaumatin proteins . Challenge tests in man did not demonstrate any oral sensitization . The results indicate that thaumatin when used as a flavour modifier and extender, and partial sweetener, is unlikely to be hazardous at the anticipated level of consumption.

Mutat Res, 1983 Dec, 124(3-4), 213 - 24
Comparative genotoxicity studies of the flame retardant tris(2,3-dibromopropyl)phosphate and possible metabolites; Holme JA et al.; Tris(2,3-dibromopropyl)phosphate (Tris-BP) was activated to mutagens in the Salmonella/microsome quantitative test system . Liver microsomes from rats pretreated with phenobarbital (PB) increased the mutagenicity of 0.05 mM Tris-BP to 186% of the activity obtained with liver microsomes from untreated rats . The addition of 0.02 mM Tris-BP to V79 Chinese hamster cells co-incubated with liver microsomes from PB-pretreated rats increased the number of mutants by a factor of 9.7 . Tris-BP also caused genotoxic and cytotoxic responses in primary monolayers of rat hepatocytes . The relative increase in unscheduled DNA synthesis after treatment with 0.05 mM Tris-BP was 2.3-fold as measured by scintillation counting of radiolabelled thymidine incorporated into DNA of isolated nuclei . The use of hepatocytes isolated from PB-pretreated rats reduced the increases in DNA repair synthesis relatively to that in control cells . Monolayers of hepatocytes from untreated rats co-cultured with Salmonella typhimurium TA100 activated Tris-BP to mutagenic intermediates which were released into the culture medium . The studies with the V79 and liver-cell systems indicate that the reactive intermediates formed from Tris-BP are sufficiently stable and lipophilic to traverse the various membranes from the site of generation to the respective cellular targets . The relative degree of genotoxic responses of bis(2,3-dibromopropyl)phosphate, 2,3-dibromopropylphosphate, tris(2,3-bromopropyl)phosphate, tris(2-bromopropyl)phosphate and 2,3-dibromopropanol in the systems studied did not indicate that these compounds were proximate or ultimate reactive metabolites of Tris-BP in liver-derived activation systems.

J Med Chem, 1983 Dec, 26(12), 1715 - 9
Heterocyclic Quinones . 4 . A new highly cytotoxic drug: 6,7-bis(1-aziridinyl)-5,8-quinazolinedione; Renault J et al.; With the aim of obtaining new antitumoral agents, a series of 5,8-quinazolinediones was prepared . 5-Amino-6-methoxyquinazoline was oxidized by Fremy's salt to give 6-methoxy-5,8-quinazolinedione . Nucleophilic substitution reaction at C6, electrophilic substitution at C7, and synthesis of 7-amino-6-methoxy-5,8-quinazolinedione, the parent compound of streptonigrin, were studied . These compounds were tested for cytotoxic properties on L1210 leukemia cells in vitro . One of them, 6,7-bis(1-aziridinyl)-5,8-quinazolinedione, which exhibits a high cytotoxic activity (ID50 = 0.08 microM), was further screened in standard antitumor systems, including L1210 leukemia, P388 lymphocytic leukemia, sarcoma 180, and B16 melanocarcinoma . This drug gives a significant antitumoral effect on P388 leukemia but is inactive on other experimental models . Moreover, this compound was found to be highly mutagenic for Salmonella typhimurium TA98 and TA100 strains (Ames test), suggesting that DNA damage could be responsible for its cytotoxicity.

Cancer Res, 1983 Dec, 43(12 Pt 1), 5768 - 74
Microsomal activation of 2-amino-3-methylimidazo{4,5-f}quinoline, a pyrolysate of sardine and beef extracts, to a mutagenic intermediate; Yamazoe Y et al.; The mechanism involved in the metabolic activation of 2-amino-3-methylimidazo{4,5-f}quinoline, which is a pyrolysate isolated from broiled foods, to a mutagenic intermediate was studied in vitro . In a system containing hepatic microsomes and reduced nicotinamide adenine dinucleotide phosphate, 2-amino-3-methylimidazo{4,5-f}quinoline was converted to a product which was directly mutagenic to Salmonella typhimurium . The structure of the mutagenic metabolite was determined as the 2-N-hydroxy derivative on the basis of the chemical properties and the mass spectral evidence of the azoxy adduct with o-nitrosotoluene . The activation reaction was mediated by microsomal enzymes and was inhibited by carbon monoxide, 7,8-benzoflavone, and other chemicals which were known to inhibit the cytochrome P-450-dependent reaction . With the use of four forms of purified cytochrome P-450, the N-hydroxylation of 2-amino-3-methylimidazo{4,5-f}quinoline and the induction of the reverse mutation of the bacteria were clearly demonstrated to be catalyzed mainly by a high-spin form of cytochrome P-450, P-448 II-a.

J Appl Toxicol, 1983 Dec, 3(6), 317 - 20
The genetic activity of anthramycin, tomaymycin and sibiromycin in bacterial forward- and reverse-mutation assays and in the mouse bone-marrow micronucleus test; Gairola C et al.; The genetic activity of the structurally similar antitumor antibiotics anthramycin, tomaymycin and sibiromycin was evaluated in the standard Ames Salmonella/microsome mutagenicity assay, a Salmonella typhimurium forward-mutation assay and the micronucleus test . None of the test drugs showed any significant genetic activity in forward or reverse Salmonella mutation assays . The ability of mouse-liver enzymes to produce mutagens from the drugs was examined in the Salmonella reverse-mutation assay and was generally negative . As the concentrations of sibiromycin increased, some activity was detected in the presence of liver S-9 fractions from Aroclor-induced mice . This observation could not be verified at higher concentrations in the reverse-mutation assay due to cytotoxicity, and in the forward-mutation assay due to interference with the selection process by S-9 . Cytogenetic evaluation of anthramycin and tomaymycin in the micronucleus test also gave negative results . However, significant increases in the frequency of micronucleated polychromatic erythrocytes were observed in the bone marrow of sibiromycin-treated mice . The results suggest that, except for some possible activity of sibiromycin, these drugs are generally devoid of any marked genetic activity in the test systems employed.

Bangladesh Med Res Counc Bull, 1983 Dec, 9(2), 37 - 42
Effect of vitamin-A deficiency on plaque forming response of antibody producing spleen cells against Salmonella typhimurium in rats; Faruque SM et al.; Plaque forming response of antibody producing spleen cells against Salmonella typhimurium was studied in vitamin-A deficient and normal rats after 3, 6, 9 and 12 days of injecting the antigen . Vitamin-A deficient rats were found to have significantly decreased (P less than 0.001) number of antibody plaque forming cells in the spleen as compared to normal rats in all cases . Serum total protein and serum Vitamin-A levels were significantly (P less than 0.001) lower in the vitamin-A deficient rats as compared to the controls and immunization caused no significant change in these parameters . The average spleen weights were increased in both the groups on immunization but this increase was comparatively more in case of the control rats.

Proc Natl Acad Sci U S A, 1983 Dec, 80(24), 7496 - 500
AppppA, heat-shock stress, and cell oxidation; Lee PC et al.; Salmonella typhimurium LT2 induces a set of heat-shock proteins analogous to those found previously in Escherichia coli . These are virtually the only proteins synthesized after a temperature shift from 28 degrees C to 50 degrees C . Using a two-dimensional thin-layer chromatographic system developed to resolve adenylylated nucleotides, we have found that S . typhimurium and E . coli accumulate P1,P4-diadenosine-5'-tetraphosphate (AppppA), P1-(adenosine-5')-P3-(guanosine-3'-diphosphate-5')-triphosphate (ApppGpp), P1-(adenosine-5')-P4-(guanosine-5')-tetraphosphate (AppppG), P1-(adenosine-5')-P3-(guanosine-5')-triphosphate (ApppG), and P1,P3-diadenosine-5'-triphosphate (ApppA) after heat shock . These same adenylylated nucleotides accumulate after exposure to ethanol, an agent also known to induce the heat-shock response in a variety of cells . AppppA, ApppGpp, AppppG, ApppG, and ApppA were previously shown to accumulate under conditions of oxidation stress . We proposed that these adenylylated nucleotides may be alarmones--i.e., regulatory molecules, alerting cells to the onset of oxidation stress . The finding that these dinucleotides accumulate in response to heat shock suggests that oxidation and heat shock have a common physiological effect on cells . We hypothesize that these dinucleotides signal the onset of these stresses and trigger the "heat-shock response."

Diagn Microbiol Infect Dis, 1983 Dec, 1(4), 335 - 7
A pseudoepidemic due to Salmonella typhimurium; Harris AA et al.; A pseudoepidemic due to Salmonella typhimurium occurred in the clinical microbiology laboratory of a university hospital and involved 10 patients . One patient received "unnecessary" antibiotics . Investigation of the events implicated a contaminated rubber pipette bulb . Such bulbs should be considered as a possible source of false-positive cultures.

Clin Physiol, 1983 Dec, 3(6), 551 - 63
Biochemical responses of the myocardium and red skeletal muscle to Salmonella typhimurium infection in the rat; Ilback NG et al.; Previous studies with bacterial infections have demonstrated a reduced exercise capacity and equally pronounced catabolic responses in red and white skeletal muscle . In the present study, red skeletal muscle and heart ventricular muscle were compared in a S . typhimurium model in rats . Two days before median lethality was achieved, the activities of one oxidative (cytochrome c oxidase), one glycolytic (glyceraldehyde-3-phosphate dehydrogenase) and one lysosomal (beta-glucuronidase) enzyme were determined in the two tissues . The contents of protein, RNA and DNA were also determined . The oxidative and glycolytic capacity decreased 24-29% in red skeletal muscle but only 7-20% in the myocardium . However, the decrease in oxidative capacity in skeletal muscle and myocardium was statistically correlated . The protein synthetic capacity (RNA) also decreased and was correlated to the protein concentration in both tissues . This metabolic impairment of both skeletal and heart muscle probably contributes to the deterioration of the physical performance capacity previously observed to follow acute infectious diseases . This study emphasizes the importance of the choice of reference, such as 'wet' weight, DNA or the entire organ, when evaluating metabolic results in biologic tissues and that biochemical alterations in skeletal muscle biopsies in bacterial infections do not reflect alterations in myocardium reliably.

Food Chem Toxicol, 1983 Dec, 21(6), 745 - 7
Possible mutagenic constituents in nitrite-treated soy sauce; Shibamoto T; Soy sauce was heated with 100, 500, 1000 or 2000 ppm sodium nitrite for 30 min at 80 degrees C and pH 3 . The reaction mixtures were extracted with dichloromethane followed by ethyl acetate . After removal of the solvents, the extracts were subjected to analysis (gas chromatograph-thermal energy analyser and gas chromatograph-mass spectrometer) and Ames mutagenicity tests . N-Nitrosodimethylamine and N-nitrosodiethylamine were found in the dichloromethane extract of the soy sauce treated with 2000 ppm nitrite at levels of 10 and 120 micrograms/ml, respectively . N-Nitrosoproline was identified in the ethyl acetate extract of the same sample at a level of 0.5 microgram/ml . Both extracts exhibited dose-related mutagenicity in Salmonella typhimurium strain TA100 with S-9 mix . The dichloromethane extract showed much higher mutagenicity than did the ethyl acetate extract . The samples obtained from soy sauce treated with 100, 500 and 1000 ppm nitrite were not mutagenic, but N-nitrosodiethylamine was detected by thermal energy analysis in the soy sauce treated with 1000 ppm nitrite . The addition of 10,000 ppm L-ascorbic acid, along with 2000 ppm nitrite, to soy sauce prevented the formation of mutagenic materials or detectable nitrosamines.

Mutat Res, 1983 Dec, 124(3-4), 315 - 24
Bioactivation and biotransformation of 1-nitropyrene in liver, lung and nasal tissue of rats; Bond JA; 1-Nitropyrene (NP) is a known direct-acting bacterial mutagen and has been detected in the environment from such sources as diesel-exhaust emissions and coal-combustion fly ash . The purpose of this study was to investigate the mutagenic potential of NP in Salmonella typhimurium using rat liver, lung and nasal tissue as the enzyme-activating systems and to measure the rates of NP metabolism in these same tissues . Rat liver, lung and nasal tissue bioactivated NP to mutagens that were detected in the Ames bacterial test system . At all doses of NP and all protein concentrations of tissue S9, mutagenic responses were larger than that observed in the absence of any tissue . In both strains TA98 and TA100, about 1.0 mg/ml liver and nasal tissue S9 appeared to be the optimal concentration which resulted in the largest mutagenic response to NP, whereas 2.0 mg/ml of lung S9 was necessary to yield optimal responses . When NP was incubated with liver, lung or nasal tissue S9 and strain TA98 NR, mutagenic responses were significantly decreased when compared to the response seen in TA98 . NP was metabolized to several oxidized metabolites (3-, 6- and 8-hydroxynitropyrene) in all tissues examined . Total rates of formation of NP metabolites for nasal tissue, liver and lung S9 were 650, 300 and 60 pmoles/mg protein/min, respectively . These results suggest that the respiratory tract, in particular the nasal tissue, may be an important site for in vivo bioactivation of inhaled NP.

Mutat Res, 1983 Dec, 122(3-4), 279 - 86
Formation of mutagens by amino-carbonyl reactions; Shinohara K et al.; The formation of mutagens by amino-carbonyl reactions of 20 kinds of amino acid and sugars after heating at 100 degrees C for 10 h was examined by the Ames test . The browned solutions of Gly, Ala, Val, Leu, Ile, Ser, Thr, Gln, Lys X HCl, Arg, Phe, Cys, Met and Pro with Glc caused mutation of Salmonella typhimurium TA100 and/or TA98 with or without S9 mix . The presence of S9 mix increased the mutagenic activity of the browned solutions of Cys and Phe with Glc on TA100 and of those of Gly, Ala, Val, Ile and Cys on TA98, but decreased the activity of other solutions . No revertants of Salmonella were induced by the browned solutions of Trp, Tyr, Asp, Asn, Glu and (Cys)2 with Glc . Among positive browned solutions, Cys, Lys, Arg and Phe had the stronger activity, but their activity was weak compared with that of pyrolysates or chemical mutagens such as Trp-P-1, Trp-P-2 and 4-nitroquinoline-N-oxide . The mutagenic activity of the browned solutions increased with prolongation of heating time and varied with the pH of the reaction mixture . Fru, Gal, Ara, Xyl, Man, Lac and Suc also had the ability to form mutagens in the browning reactions with amino acids.

Mutat Res, 1983 Dec, 122(3-4), 273 - 8
Mutagenicity of coal-pyrolyzed products and their photochemical reaction products with nitrogen oxides in Salmonella typhimurium TA98 and TA100; Hirayama T et al.; The chemical class separation of coal-pyrolyzed products and the photochemical reaction of these fractions with nitrogen oxides in the experimental chamber, and the application of a short-term mutagenicity test were investigated . The altered products from the fraction hydroxy polycyclic aromatic compounds in a simulated atmosphere containing a small volume of nitrogen oxides under irradiation with a xenon lamp were the most potent mutagenic fraction among all the fractions tested against Salmonella typhimurium, both TA98 and TA100, with or without S9.

Mutat Res, 1983 Dec, 122(3-4), 267 - 72
Genetic damage in Salmonella typhimurium by near-ultraviolet radiation . Lack of repair by plasmid pKM101; Eisenstark A; Plasmid pKM101, whose mucA and B genes endow cells with enhanced mutation frequency and enhanced resistance to far-ultraviolet radiation (FUV) (254 nm), had no influence on these properties when cells were damaged by near-ultraviolet radiation (NUV) (300-400 nm) . Thus, NUV lesions did not lead to induction of SOS repair and subsequent expression of mucA and B genes on plasmid pKM101 . Further, when cells were pre-irradiated with NUV and subsequently irradiated with FUV, there was a blockage of SOS repair, including the repair normally controlled by genes on pKM101.

Mutat Res, 1983 Dec, 122(3-4), 257 - 66
Isolation of a mutant of Salmonella typhimurium strain TA1535 with decreased levels of glutathione (GSH-) . Primary characterization and chemical mutagenesis studies; Kerklaan P et al.; A mutant of Salmonella typhimurium strain TA1535 with decreased glutathione (GSH) levels was isolated after treatment with UV and selection for N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) resistance; this GSH- mutant also exhibited increased resistance to MNNG, the methyl analog of ENNG . Estimation of the cellular GSH content showed that the GSH- derivative contained about 20% of the GSH levels found in TA1535 . In mutagenicity tests (hisG46 leads to His+), the GSH- strain required the presence of GSH or L-cysteine in the medium for an optimal phenotypic expression and/or growth of spontaneous and induced His+ revertants, and may, therefore, be allelic to cys mutants of Salmonella described earlier . The mutagenic activity of MNNG, ENNG and 1,2-dibromoethane (DBE), but not that of N-ethylnitrosourea (ENU), was strongly reduced in TA1535/GSH-; pretreatment of the strain with GSH restored the mutagenicity of the first 3 chemicals to levels normally found in TA1535 . The results support the current view that MNNG, ENNG and DBE, but not ENU, can be activated via reaction with GSH to species of higher reactivity and mutagenicity . It is concluded that the present GSH- strain can be used to study more systematically the role of GSH in the bioactivation and -deactivation of xenobiotics to mutagenic factors.

Carcinogenesis, 1983 Dec, 4(12), 1615 - 8
The synthesis and mutagenicity of the N-formyl analog of N-hydroxyphenacetin; Corbett MD et al.; The synthesis and purification of N-hydroxy-N-formyl-p-phenetidine (N-OH-FP) is described . This new compound was subjected to mutagenicity testing using Salmonella typhimurium strains TA98, TA100, TA1535, TA1537 and TA1538 both in the presence and absence of the post-mitochondrial fraction of rat liver homogenate . Simultaneous mutagenicity testing of the known phenacetin metabolite, N-hydroxyphenacetin (N-OH-AP), was conducted with the same tester strains . The N-formyl derived hydroxamic acid (N-OH-FP) was found to be a much stronger mutagen than N-hydroxy-phenacetin (N-OH-AP) . Furthermore, N-OH-FP also behaved as a direct-acting mutagen unlike N-OH-AP . The chemical stabilities of N-OH-AP and N-OH-FP were studied in phosphate buffer in the pH range of 3-8; and both the hydroxamic acids were found to be stable to the conditions employed . The results of this study support the hypothesis that enzymatic deacylation is an activation process for the expression of mutagenicity by hydroxamic acids.

Carcinogenesis, 1983 Dec, 4(12), 1551 - 7
Activation and detoxication of N-hydroxy-Trp-P-2 by glutathione and glutathione transferases; Saito K et al.; The roles of non-enzymatic and enzymatic glutathione (GSH) conjugation in the activation and detoxication of 3-hydroxy-amino-1-methyl-5H-pyrido{4,3-b}indole (N-OH-Trp-P-2) were studied in vitro . N-OH-Trp-P-2 is an active metabolite of 3-amino-1-methyl-5H-pyrido{4,3-d}indole (Trp-P-2), a mutagenic and carcinogenic heterocyclic amine . 3-Nitroso-1-methyl-5H-pyrido{4,3-b}indole (NO-Trp-P-2) reacted rapidly and non-enzymatically with GSH to form N-OH-Trp-P-2 and a small amount of two GSH conjugates (CN-1 and CN-2) . On the other hand, non-enzymatic reaction of GSH with N-OH-Trp-P-2 was very slow, but the GSH conjugation with N-OH-Trp-P-2 was catalyzed by rat liver GSH transferase and a rat liver cytosol fraction to form three conjugates (CH-1, CH-2 and CH-3) . The enzymatic conjugation was effectively inhibited by organic tin compounds which are known as powerful GSH transferase inhibitors . The conjugates were unstable enough to yield Trp-P-2 (from CN-1, CN-2 and CH-2) or N-OH-Trp-P-2 (from CH-3) on incubation at 37 degrees C for 30-60 min . Only CH-1 was stable under similar conditions . The mutagenicities of the GSH conjugates and the effects of GSH and GSH transferase were studied by using Salmonella typhimurium TA98 as the tester strain . The GSH conjugates except for CH-3 were completely detoxicated products, but CH-3 was found to be a more potent mutagen than N-OH-Trp-P-2 . The mutagenicity of CH-3 seemed to be due to the direct action of the conjugate, and not to N-OH-Trp-P-2 formed from it.

Carcinogenesis, 1983 Dec, 4(12), 1547 - 50
Syntheses of hydroxyamino, nitroso and nitro derivatives of Trp-P-2 and Glu-P-1, amino acid pyrolysate mutagens, and their direct mutagenicities towards Salmonella typhimurium TA98 and TA98NR; Saito K et al.; Hydroxyamino, nitroso and nitro derivatives of 3-amino-1-methyl-5H-pyrido{4,3-b}indole (Trp-P-2) and 2-amino-6-methyldipyrido{1,2-a:3',2'-d}imidazole (Glu-P-1), mutagens-carcinogens produced on pyrolysis of amino acids, were synthesized from Trp-P-2 and Glu-P-1 . 3-Hydroxyamino-1-methyl-5H-pyrido{4,3-b}indole (N-OH-Trp-P-2) and 2-hydroxyamino-6-methyldipyrido{1,2-a:3',2'-d}imidazole (N-OH-Glu-P-1) were obtained with good yields by controlled catalytic reduction of 3-nitro-1-methyl-5H-pyrido{4,3-b}indole and 2-nitro-6-methyldipyrido{1,2-a:3',2'-d}imidazole . Subsequent oxidation of N-OH-Trp-P-2 and N-OH-Glu-P-1 with gamma-manganese dioxide yielded 3-nitroso-1-methyl-5H-pyrido{4,3-b}indole and 2-nitroso-6-methyldipyrido{1,2-a:3',2'-d}imidazole . All six synthesized compounds were mutagenic to Salmonella typhimurium TA98 without mammalian activation systems . The mutagenic activities of hydroxyamino and nitroso derivatives were identical for both S . typhimurium TA98 and TA98NR, the nitroreductase deficient strain . However, nitro derivatives were essentially mutagenic only towards S . typhimurium TA98.

Proc Natl Acad Sci U S A, 1983 Dec, 80(23), 7142 - 5
Kinetic characterization and regulation of phosphoenolpyruvate-dependent methyl alpha-D-glucopyranoside transport by Salmonella typhimurium membrane vesicles; Liu KD et al.; Membrane vesicles from Salmonella typhimurium SB3507 were used to study the kinetics of methyl alpha-D-glucopyranoside (MeGlc) transport by the phosphoenolpyruvate: glycose phosphotransferase system (PTS) . During the first minute of phosphoenolpyruvate-dependent MeGlc transport, two distinct rates were observed; an initial rapid rate, V1 (Vmax, 7.4-8.4 nmol X mg-1 X min-1; Km, 8.2-11.2 X 10(-6)M), followed by a second slower rate, V2 (Vmax, 4-4.6 nmol X mg-1 X min-1; Km, 3.4-6.4 X 10(-6) M) . The change in rate occurred when the intravesicular MeGlc phosphate concentration was 0.2 mM or less, depending on the external MeGlc concentration . The rate-limiting component in MeGlc transport was found to be enzyme II-BGlc, not phosphoenolpyruvate uptake or the PTS proteins enzyme I, HPr, and IIIGlc . The change from V1 to V2 thus suggests that the PTS is regulated in intact vesicles . However, this regulation was completely relieved by permeabilizing the vesicles with toluene . That is, the toluene-treated vesicles showed only V1 for MeGlc phosphorylation . Evidence was obtained to show that pyruvate and its metabolic products generated by the vesicles exerted no effect on the rate of MeGlc transport . Furthermore, the result from a dual-label experiment excluded exchange transphosphorylation as the mechanism for regulating MeGlc transport by the vesicles . Possible mechanisms for regulation of the PTS are discussed.

J Immunol, 1983 Dec, 131(6), 3006 - 13
Genetic control of the innate resistance of mice to Salmonella typhimurium: expression of the Ity gene in peritoneal and splenic macrophages isolated in vitro; Lissner CR et al.; The mouse Chromosome 1 locus Ity regulates the extent to which Salmonella typhimurium replicates within the reticuloendothelial cell system (RES) during the first days of infection . If animals are homozygous for the Itys susceptibility allele, the Gram-negative bacterium undergoes rapid net multiplication, and mice die of a typhoid fever-like disease by day 10 of infection . Animals that are homozygous or heterozygous for the resistance allele, Ityr, control net bacterial replication and survive the first phase of salmonellosis . Indirect studies have implicated the resident macrophage as the effector cell for regulation of early in vivo salmonellae growth . To verify this supposition and to evaluate the phenotypic expression of Ity, we developed an in vitro assay to compare kinetics of S . typhimurium growth within Ityr and Itys macrophages . Resident peritoneal and splenic macrophages were used from inbred Ityr and Itys mice and from Ity congeneic mice . With these mice and through the use of radiolabeled S . typhimurium and an avirulent temperature-sensitive mutant of the bacterium, we found that: phagocytosis of S . typhimurium by Ityr and by Itys macrophages was the same; S . typhimurium grew to a greater extent in Itys peritoneal and splenic macrophages than in Ityr cells; Ityr macrophages killed intracellular salmonellae more efficiently than did Itys macrophages . Thus, we have demonstrated directly that Ity is expressed by the macrophage and have shown for the first time with Ity congeneic mice that the basis for differential net growth of virulent S . typhimurium in Ityr and Itys macrophages is a variation in the degree of bacterial kill.

Infect Immun, 1983 Dec, 42(3), 1198 - 202
Effect of human leukocyte interferon on invasiveness of Salmonella species in HEp-2 cell cultures; Bukholm G et al.; The effect of human leukocyte interferon on the invasiveness of Salmonella and Shigella species in HEp-2 cell cultures was examined . The intracellular and extracellular bacteria were identified by a combination of Nomarski differential interference contrast microscopy and UV incident light microscopy applied on the same microscope . Pretreatment of HEp-2 cells with human leukocyte interferon reduced the number of Salmonella typhimurium and Salmonella paratyphi-B bacteria per cell and the proportion of cells containing bacteria in a dose-dependent manner . Maximum inhibitory effect was observed with ca . 100 U of interferon per ml . The inhibitory effect was neutralized with anti-human interferon globulin . Murine fibroblast interferon did not influence the invasiveness of Salmonella species . Invasiveness of Shigella flexneri was not influenced by treatment of cells with human interferon.

Cancer Res, 1983 Dec, 43(12 Pt 1), 5821 - 5
Mutagenicity of the enantiomers of the diastereomeric bay-region benz(a)anthracene 3,4-diol-1,2-epoxides in bacterial and mammalian cells; Wood AW et al.; Enantiomers of the diastereomeric pair of bay-region benz(a)anthracene 3,4-diol-1,2-epoxides in which the benzylic 4-hydroxyl group and epoxide oxygen are either cis (isomer 1) or trans (isomer 2) were evaluated for mutagenic activity in two histidine-dependent strains of Salmonella typhimurium, as well as in an 8-azaguanine-sensitive Chinese hamster cell line . In strain TA 98 of S . typhimurium, the diol-epoxide with (1S,2R,3R,4S) absolute configuration {(-)-diol-epoxide 2} was the most active isomer, although there was less than a 3-fold difference in the mutagenicity of the four diol-epoxides . However, in strain TA 100 of S . typhimurium, the enantiomeric diol-epoxide with (1R,2S,3S,4R) absolute configuration {(+)-diol-epoxide 2} was the most active diol-epoxide, and the two isomers with (3S,4R) absolute configuration {(-)-diol-epoxide 1 and (+)-diol-epoxide 2} were three to eight times more active than were the two isomers with (3R,4S) configuration . The highest degree of sensitivity to absolute configuration was observed in Chinese hamster V79 cells, in which the (1R,2S,3S,4R) isomer {(+)-diol-epoxide 2} was from three to 20 times more mutagenic than were the other three isomers . This metabolically predominant (+)-diol-epoxide 2 isomer, which has high activity in strain TA 100 of S . typhimurium and the Chinese hamster V79 cells, has the same absolute configuration as do the bay-region diol-epoxide isomers of benzo(a)pyrene and chrysene that have been shown previously to be exceptionally mutagenic to mammalian cells and highly tumorigenic in mice . Analysis of the mutagenic activity of the (+)- and (-)-isomers of the 1,2- and 3,4-tetrahydroepoxides of benz(a)anthracene revealed only small enantiomeric differences in strain TA 98 of S . typhimurium (2.5 fold) and little, if any, differences (less than 1.5-fold) in the other two mutagenicity systems . However, the extent to which the four tetrahydroepoxides were converted to nonmutagenic products by homogeneous microsomal epoxide hydrolase (EC 3.3.2.3) indicated marked differences in the stereoselectivity of the enzyme . (-)-(3R,4S)-Epoxy-1,2,3,4-tetrahydrobenz(a)anthracene appears to be an exceptionally good substrate for epoxide hydrolase.

Cancer Res, 1983 Dec, 43(12 Pt 1), 5713 - 7
Inactivation of a diol-epoxide and a K-region epoxide with high efficiency by glutathione transferase X; Glatt H et al.; Four glutathione transferases (EC 2.5.1.18), glutathione transferases A, B, and C and a hitherto unknown form, termed X, were purified to apparent homogeneity from rat liver cytosol . They were investigated for their abilities to inactivate two mutagenic epoxides derived from the polycyclic aromatic hydrocarbon benz(a)anthracene, the K-region epoxide benz(a)anthracene 5,6-oxide and the diol-epoxide r-8,t-9-dihydroxy-t-10,11-oxy-8,9,10, 11-tetrahydrobenz(a)anthracene . Mutagenic activity was determined using Salmonella typhimurium his- strain TA100 . Glutathione alone had little if any influence on the mutagenicity of the diol-epoxide but significantly decreased the mutagenic effect of the K-region epoxide . This inactivation was enhanced by the addition of glutathione transferases . Both epoxides were inactivated by glutathione in the presence of each of the four enzymes, but with varying efficiencies . Inactivation of the K-region epoxide (in terms of its mutagenicity in the presence of glutathione) required extremely little enzyme, about 1000 times less than for the diol-epoxide . On a molar basis, glutathione transferase X (followed by C greater than A greater than or equal to B) was clearly the most efficient enzyme in inactivating both substrates and also more efficient than were three other purified enzymes (microsomal epoxide hydrolase, cytosolic epoxide hydrolase, and dihydrodiol dehydrogenase) previously investigated in this test system . Taking into account the amounts of enzyme present in rat liver, the glutathione transferases C and X were most effective in inactivating the epoxides examined . Thus, the newly discovered glutathione transferase X appears to be of substantial significance in the inactivation of two structural prototypes of epoxides derived from polycyclic aromatic hydrocarbons, a K-region epoxide and a non-bay-region vicinal diol-epoxide.

Gene, 1983 Dec, 26(2-3), 147 - 58
Use of M13mp phages to study gene regulation, structure and function: cloning and recombinational analysis of genes of the Salmonella typhimurium histidine operon; Artz S et al.; A restriction map was determined for a phi 80 lambda dhis transducing phage DNA carrying the Salmonella typhimurium histidine operon . DNA fragments containing the promoter/regulatory region and the first two structural genes of the histidine operon (hisOGD) were identified by their ability to direct regulated synthesis of histidinol dehydrogenase (product of hisD) in a coupled in vitro protein synthesizing system . A 3.1-kb SalI-EcoRI restriction fragment containing the hisOGD region, was subcloned into phage M13mp8 and M13mp9 RF DNAs . Methods are described for shuttling mutant and wild-type bacterial DNA sequences between the M13mp::his phage and host bacterial genomes . Of novel importance is the use of the phage M13 gene II amber mutation to obtain integration of the M13mp::his phage genome into the homologous his region of the bacterial chromosome following transduction of recipients lacking an amber suppressor . This method can be used to facilitate allele replacement with genes carried on M13 transducing phages.

Cancer Lett, 1983 Dec, 21(2), 211 - 7
Microsomal P-450 induction by some secondary products from thermal oxidation of dietary lipids: epidermal hyperplasia, mutagenicity and cytochrome P-450 activities; Crawford L et al.; Distillable secondary products from roasted fowl were found to be cytotoxic but not mutagenic when assayed with Salmonella typhimurium strains TA98, TA100 and TA1537 . A crudely separated fraction of the volatiles produced focal hyperplasia and damage to the epidermis of the backs of mice . The volatiles also caused an apparent synthesis of non-constitutive forms of rat hepatic cytochromes P-450 which metabolize benzo{a}pyrene B {a}P differently from the constitutive P-450.

J Immunol, 1983 Dec, 131(6), 3014 - 20
Genetic control of the innate resistance of mice to Salmonella typhimurium: Ity gene is expressed in vivo by 24 hours after infection; Swanson RN et al.; The early response of inbred mice to infection with S . typhimurium is controlled by the mouse Chromosome 1 locus, Ity . To better understand the expression of this gene, the initial interactions between the reticuloendothelial system (RES) and i.v . injected salmonellae were compared in resistant (Ityr) and susceptible (Itys) mice . In both mouse strains 99% of the bacteria was cleared from the blood within 2 hr, and uptake of S . typhimurium by splenic and hepatic macrophages was similar regardless of Ity genotype . In vivo phagocytosis of bacteria was followed by a 30 to 60% decline in viable bacteria, which was attributed to the bactericidal activity of RES macrophages . Experiments with radiolabeled S . typhimurium strains TML and TML/TS27 (a temperature-sensitive mutant) confirmed that the efficiency of this early phase killing was not under Ity control . Despite the equivalent uptake and initial bactericidal activity by resident macrophages, bacterial numbers in the RES organs of Itys mice were significantly greater than in Ityr mice by approximately 24 hr after infection . These data suggest that Ity regulates the level of surviving intracellular bacteria that accumulate within resident macrophages of the liver and spleen.

J Bacteriol, 1983 Dec, 156(3), 1249 - 62
Genetic analysis of the proBA genes of Salmonella typhimurium: physical and genetic analyses of the cloned proB+ A+ genes of Escherichia coli and of a mutant allele that confers proline overproduction and enhanced osmotolerance; Mahan MJ et al.; Because of the fact that proline overproduction relieves the inhibitory effects of high external osmotic strength in a number of procaryotes, we wished to clone a mutant allele, pro-74, that confers proline overproduction and enhanced osmotolerance on Salmonella typhimurium and Escherichia coli . Therefore, the pro-74 allele, originally located on an E . coli episome F'128, was cloned into pBR322 . In a parallel experiment, the wild type proB+ A+ genes of E . coli were also cloned from F'128 into pBR322 . Both the pro-74 and the proB+ A+ alleles were obtained on a 10.4-kilobase-pair fragment that also contained the unrelated phoE gene . Strains carrying either the wild-type proB+ A+ or the pro-74 alleles on pBR322 grew more slowly, both in minimal medium and media of elevated osmotic strength, than strains carrying the same alleles on the low-copy plasmid, F'128, indicating that some gene in the cloned region is deleterious in high copy . We constructed Tn5 insertion mutations in the proB and the proA genes of E . coli, carried on F'128 in S . typhimurium . Using P22 transduction in S . typhimurium, we transferred these proB and proA::Tn5 insertions from F'128 into the cloned proBA genes on pBR322 . From the restriction maps of the plasmids thus generated, we determined the approximate locations of the proB and the proA genes . We also performed complementation tests of S . typhimurium and E . coli proB and proA mutants by using the F'128 proB and proA::Tn5 insertions . These tests revealed that the proBA genes of S . typhimurium form an operon, whose direction of transcription is from proB to proA . They also indicated that in S . typhimurium, as in E . coli, the proB+ gene encodes gamma-glutamyl kinase, and the proA+ gene encodes gamma-glutamyl phosphate reductase . Complementation tests also indicated that the pro-74 mutation is either in the proB structural gene, or its promoter-operator.

Genetics, 1983 Dec, 105(4), 801 - 11
Genetic mapping of IS200 copies in Salmonella typhimurim strain LT2; Lam S et al.; The wild-type Salmonella typhimurium strain LT2 contains six copies of the insertion sequence element IS200 which is unique to Salmonella . We have determined the chromosomal locations of all six copies of IS200 in strain LT2 . This was done by mapping the positions of Tn10 elements inserted near each copy of IS200 . Such Tn10 insertions were detected by Southern hybridization as IS200-containing restriction fragments with altered electrophoretic mobility . The copies are located at quite evenly spaced sites in the chromosome . Some are found in regions with many known genes; others are in regions with few known functions . There is no indication of a possible function for IS200 . The method described here should be applicable to the mapping of IS elements in general.

Mutat Res, 1983 Dec, 124(3-4), 191 - 200
Mutagenicity of diesel-exhaust particle extract, 1-nitropyrene, and 2,7-dinitrofluorenone in Salmonella typhimurium under various metabolic activation conditions; Kohan M et al.; The mutagenic activities of 1-nitropyrene (1-NP), 2,7-dinitrofluorenone (2,7-DNF), and a diesel-exhaust extract were compared using the Salmonella typhimurium plate-incorporation assay . Each sample was tested with and without a 9000 X g liver homogenate (S9), both with and without an NADPH-generating system . The samples were also treated with the microsome fraction of S9, cytosol fraction of S9, boiled S9, bovine serum albumin (BSA), and boiled BSA . Salmonella tester strains TA98 and TA98FR1 were used in all treatments; TA98/1,8DNP6 was used to test mutagenic activity without activation . Without the NADPH-generating system, the samples generally had less mutagenic activity than samples treated with the NADPH-generating system . The addition of the NADPH-generating system resulted in marked increases in mutagenic activity of 1-NP in the microsome and S9 treatments, and of all 3 samples in the cytosol fraction treatment . These results indicate that although protein binding reduced the mutagenic activity of diesel-exhaust extract and 1-NP, microsomal activation increased the mutagenic activity of 1-NP . Because 1-NP and 2,7-DNF contributed less than 1.5% of the mutagenic activity of the diesel-exhaust extract, the response to diesel exhaust was not typified by these compounds.

J Bacteriol, 1983 Dec, 156(3), 1344 - 8
recA-dependent recombination between rRNA operons generates type II F' plasmids; Blazey DL et al.; The formation of type II F' ilv cya metE plasmids from the Salmonella typhimurium Hfr strain SA722 occurs by general recombination between repeated rrn.

Can J Microbiol, 1983 Dec, 29(12), 1731 - 5
Attachment of Salmonella to mammalian cells in vitro; Mintz CS et al.; The attachment of Salmonella typhimurium strain PHL67342 to several mammalian tissue culture cell lines was investigated . Strain PHL67342 failed to attach in significant numbers to the Buffalo green monkey (BGM), swine testicular (ST), and HeLa cell lines . Significant attachment was observed with the Henle intestinal cell line . Log-phase cells of strain PHL67342 attached in greatest numbers to the Henle cells after 45 min of incubation at 37 degrees C . Attachment to the Henle cells was not affected by D-mannose or D-galactose, but was markedly inhibited by high concentrations of alpha-methyl-D-mannoside . Also, Salmonella lipopolysaccharide had no effect on the attachment of strain PHL67342 to the Henle cells . Fimbriae were not detected on the bacterial cells used in the adherence experiments . These results suggest that some bacterial factor(s) other than fimbriae and lipopolysaccharide mediate the attachment of strain PHL67342 to the Henle cells.

Mol Biol Evol, 1983 Dec, 1(1), 57 - 66
Evolution of antibiotic resistance genes: the DNA sequence of a kanamycin resistance gene from Staphylococcus aureus; Gray GS et al.; The kanamycin resistance gene from Staphylococcus aureus has been sequenced and its structure compared with similar genes isolated from Streptomyces fradiae and from two transposons, Tn5 and Tn903, originally isolated from Klebsiella pneumoniae and Salmonella typhimurium, respectively . The genes are all homologous but, since their common ancestor, have undergone extensive divergence, with more than 43% divergence between the closest pair . The phylogeny of the genes cannot be made congruent to the phylogeny of the taxa from which they were isolated without requiring rather improbable differences in rates . One is therefore led to conclude that there have been multiple occurrences of gene transfer between these species . Thus, although they are homologous, they are neither orthologous nor paralogous . It is suggested that homologous genes of this type be called xenologous.

J Biol Chem, 1983 Nov 25, 258(22), 13665 - 72
Rates of ligand binding to periplasmic proteins involved in bacterial transport and chemotaxis; Miller DM 3rd et al.; The ligand reactions of three binding proteins involved in bacterial transport and chemotaxis have been examined by stopped flow, rapid mixing techniques . The processes measured were: L-arabinose, D-galactose, and D-fucose binding to the Escherichia coli L-arabinose-binding protein; L-histidine binding to the Salmonella typhimurium L-histidine-binding protein; and D-maltose, maltotriose, cyclic maltohexaose, and cyclic maltoheptaose binding to the E . coli D-maltose-binding protein . Changes in tryptophan fluorescence were monitored, and the resultant time courses were analyzed quantitatively in terms of a simple one-step binding process . The fitted association rate constants for sugar binding are all about 1-3 X 10(7) M-1 s-1; variation in the affinity constants is expressed primarily by changes in the dissociation rate constants, 1-100 s-1 . The sugar-binding proteins react at equal rates with the alpha and beta anomeric forms of their substrates . The ligand dissociation rates measured in vitro are consistent with the corresponding Vmax values observed for in vivo active transport . The association rate constant for the L-histidine-binding protein is 5-10 times greater than the corresponding rate constants for the sugar-binding proteins . A similar, large bimolecular rate, approximately 1 X 10(8) M-1 s-1, has been observed for the E . coli L-glutamine-binding protein (Weiner, J . H., and Heppel, L . A . (1971) J . Biol . Chem . 246, 6933-6941) and appears to reflect favorable electrostatic interactions between the charged amino acid and the surface of the protein molecule.

Biochim Biophys Acta, 1983 Nov 23, 735(3), 337 - 40
Transport of 2-methyl-4-amino-5-hydroxymethylpyrimidine by Salmonella typhimurium; Bellion E et al.; The transport of 2-methyl-4-amino-5-hydroxymethylpyrimidine (MAHMP) by Salmonella typhimurium was studied using synthetic {methyl-3H3}MAHMP . It was found that an active transport system existed for MAHMP, having Km of 0.07 microM and Vmax 45 nmol.min-1.(g dry wt . cells)-1, that required glucose as a source of energy and was pH and temperature dependent . Uptake was inhibited by cyanide, azide, N-ethylmaleimide, 2,4-dinitrophenol and carbonyl cyanide m-chlorophenylhydrazone . Uptake was also weakly inhibited by oxythiamine, but not by thiamine, 2-methyl-4-amino-5-aminomethylpyrimidine, or 4-amino-5-hydroxymethylpyrimidine, indicating that the transport system is specific for MAHMP.

Biochim Biophys Acta, 1983 Nov 23, 735(3), 331 - 6
Transport of thiamine and 4-methyl-5-hydroxyethylthiazole by Salmonella typhimurium; Bellion E et al.; The transport of thiamine and 4-methyl-5-hydroxyethylthiazole (MHET), its thiazole moiety, was studied using whole cells of Salmonella typhimurium . It was found that the bacteria possessed an active transport system for thiamine that had Km 0.21 microM and Vmax 33 nmol.min-1.(mg dry wt . cells)-1 . Transport of thiamine was glucose dependent, whereas MHET uptake was dependent on both glucose and 2-methyl-4-amino-5-hydroxymethylpyrimidine (MAHMP), the pyrimidine moiety of thiamine . Uptake of both thiamine and MHET was severely curtailed by cyanide, azide, N-ethylmaleimide and carbonyl cyanide m-chlorophenylhydrazone . Oxythiamine inhibited thiamine, but not MHET, uptake and thiamine slightly inhibited MHET uptake . 2-Methyl-4-amino-5-methoxymethylpyrimidine and 4-amino-5-hydroxymethylpyrimidine were unable to replace MAHMP as stimulators of MHET uptake, but 2-methyl-4-amino-5-aminomethylpyrimidine was marginally effective in this regard . Similar results were obtained with attempts to replace MAHMP as a growth requirement for a purD mutant of Salmonella typhimurium . MHET uptake showed saturation kinetics only in the presence of MAHMP, and is not otherwise actively transported.

Biochim Biophys Acta, 1983 Nov 17, 741(2), 180 - 96
Sequence specificity of tRNA-modifying enzymes . An analysis of 258 tRNA sequences; Tsang TH et al.; The specificity and recognition of tRNA-modifying enzymes may be accounted for in part by nucleotide sequences which are localized next to the modifiable nucleoside . In order to determine the sequence specificity of tRNA-modifying enzymes, we have surveyed 55 published tRNA sequences from Escherichia coli, Salmonella typhimurium and T4 phage . For each modified nucleoside, the nucleotide sequence surrounding the modification site was determined for all tRNAs known to contain the modified nucleoside . Subsequently all tRNAs not containing the modified nucleoside were examined for the absence of the putative recognition site . We present the detailed analysis of 12 modified nucleosides for which we found a strong correlation between the modified nucleoside and the local nucleotide sequence . This suggests that these sequences may be recognition sites for tRNA-modifying enzymes . For each of the 12 modified nucleosides we have identified a recognition sequence present in the tRNA set containing the modification and not in the set without it . All 203 other published tRNA sequences were then examined to see if the sequence specificity rules apply to other organisms, including both prokaryotes and eukaryotes . In several cases a good adherence was found, indicating conservation of the putative recognition sequences.

Klin Wochenschr, 1983 Nov 15, 61(22), 1153 - 7
{Myocarditis caused by Salmonella typhimurium}; Gotz M et al.; A 53-year-old man died on the eight day of an acute enteritis caused by Salmonella typhimurium . Clinical signs of shock were pronounced; the electrocardiogram, initially not pathological, showed a peripheral low voltage with decreased R-amplitudes and distinct disturbances in repolarization . Laboratory findings demonstrating Salmonella typhimurium in blood cultures and stools and 45% band forms in the differential count were remarkable . The autopsy showed deep, fibrin-covered ulcera in the colon area and a dense submucous lympho-histiocyte cell infiltration . Histologically, a granulomatous myocarditis of the left ventricle with lymphocyte and histiocyte infiltration and a focal myolysis was observed . In the right ventricle, however, only a minimal interstitial edema was found.

J Biol Chem, 1983 Nov 10, 258(21), 12947 - 51
Position of ester groups in the lipid A backbone of lipopolysaccharides obtained from Salmonella typhimurium; Qureshi N et al.; Lipopolysaccharides extracted from the heptoseless mutant of Salmonella typhimurium G30/C21 were hydrolyzed with either 0.1 N HCl at 100 degrees C or treated twice with 20 mM sodium acetate, pH 4.5, at 100 degrees C for 45 min and finally purified by preparative thin layer chromatography to yield a structural series of mono- and diphosphoryl lipid A, respectively . Positive ion fast atom bombardment mass spectrometry of the diphosphoryl lipid A TLC-3 (a highly acylated major band) showed a major component with (M + H)+ ion of mass 1798, which fragmented to yield a (M - H2PO4)+ ion of mass 1700 . Cleavage at the glycosidic bond gave rise to an oxonium ion fragment of mass 1087 . In conjunction with other studies, this establishes the molecular formula and Mr of the major component to be C94H178N2O25P2 and 1797.2 (as the free acid), respectively . Similar analysis of monophosphoryl lipid A TLC-3 produced an (M + H)+ peak at m/z 1718, (M + Na)+ adduct peak at m/z 1740, and a fragment of mass 1087 . The spectrum of monophosphoryl lipid A TLC-5 was devoid of the m/z 1087 peak and instead contained the phosphorylated oxonium ion of mass 876 . This fragment ion is assigned as the distal subunit, and these results show that the distal subunit of the major lipid A TLC-3 contains two hydroxymyristoyl, one myristoyl, and one lauroyl residues, whereas the reducing end subunit contains two hydroxymyristoyl groups . A revised structure of the lipid A backbone in lipopolysaccharides of S . typhimurium is proposed.

J Biol Chem, 1983 Nov 10, 258(21), 12801 - 3
Complete structure of lipid A obtained from the lipopolysaccharides of the heptoseless mutant of Salmonella typhimurium; Takayama K et al.; A highly purified monophosphoryl lipid A, TLC-3 fraction obtained from the lipopolysaccharides of the heptoseless mutant Salmonella typhimurium G30/C21 was converted to the dimethyl pentatrimethylsilyl derivative and analyzed by proton NMR spectroscopy at 400 MHz . Substantial downfield shifts of the resonances for protons at the 3- and 3'-carbons of the glucosamine disaccharide to 5.06 and 5.15 ppm, respectively, occurred from the normal range of 3.5-4.1 ppm, indicating that these two positions on the sugar rings were acylated . Significant downfield shift of the resonances for protons at the 4- and 6'-carbons did not occur, indicating the absence of acyl groups at these two positions . Since positive ion fast atom bombardment mass spectrometry previously established the presence of hydroxymyristoyl and myristoxymyristoyl esters at the reducing end and distal subunits, respectively, these acyl groups must be attached to the oxygen of the corresponding 3- and 3'-carbons of lipid A . With these results, we can now describe the complete structure of the monophosphoryl lipid A, TLC-3 from S . typhimurium.

J Biol Chem, 1983 Nov 10, 258(21), 12982 - 7
Evidence for a small catalytic domain in the adenylate cyclase from Salmonella typhimurium; Leib TK et al.; Deletions of large portions of the carboxyl-terminal end of the adenylate cyclase (ATP pyrophosphate lyase (cyclizing), EC 4.6.1.1) from Salmonella typhimurium do not significantly affect the enzymatic activity exhibited by the shortened polypeptide . The deletion mutations were generated by nuclease Bal31 digestion from the 3'-end of the cya gene fragment cloned by Wang et al . (Wang, J . Y.-J., Clegg, D . O., and Koshland, D.E . (1981) Proc . Natl . Acad . Sci . U.S.A . 78, 4684-4688); the shortened cya genes were inserted in pBR322 and used to transform a cya- strain of Escherichia coli . The original gene fragment encodes for an enzymatically active polypeptide having an apparent molecular weight of 77,000 . Mutant polypeptides as small as 46,000 Da were found to retain significant enzymatic activity and to confer several cya+ phenotypes on the E . coli host . More extensive deletions resulting in polypeptides as small as 33,000 Da did not have assayable amounts of adenylate cyclase activity, but the biochemical properties of the transformed cya- host implicate the presence of low levels of enzymatic activity . These data suggest that the structure of the intact enzyme is composed of discrete functional domains . Such a structure for this adenylate cyclase should both facilitate investigations of the chemical mechanism of the reaction and allow structure-function relationships in this physiologically important enzyme to be investigated on a molecular level.

Clin Exp Immunol, 1983 Nov, 54(2), 319 - 26
The role of the spleen in the protective effect of C-reactive protein in Streptococcus pneumoniae infection; Nakayama S et al.; C-reactive protein (CRP) is an acute phase serum protein in man which activates complement and has opsonic activity . We have reported that prior injection of CRP into mice can increase their survival following intravenous challenge with Streptococcus pneumoniae type 3 or 4 . In this study the conditions required for protection, and the role of hepatic and splenic clearance of bacteria have been examined . Protection against lethal infection was observed with a minimum dose of 25-50 micrograms CRP per mouse . CRP was most effective when administered between 6 h before and 2 h after challenge . CRP treated mice were not protected against infection with Salmonella typhimurium, LT-2, an organism which does not bind CRP . Mice depleted of C3 by treatment with cobra venom factor were protected against S . pneumoniae infection by CRP . Pre-treatment of mice with CRP did not increase the rate of clearance of viable S . pneumoniae from the bloodstream but did increase splenic and decrease hepatic clearance of radiolabelled bacteria in both normal and complement depleted mice . Although these findings suggest a role for the spleen in CRP protection, mice which had been splenectomized were also protected against lethal pneumococcal infection by CRP treatment.

Mutat Res, 1983 Nov, 124(2), 129 - 43
Genotoxicity studies with a blend of zinc dialkyldithiophosphate lubricant additives; Brooks TM et al.; The mutagenic activity of a blend of primary zinc dialkyldithiophosphate lubricant additives suspended in process oils and a blend of the process oils alone was investigated in agar layer cultures of Salmonella typhimurium TA1535, TA1537, TA1538, TA98 and TA100, both with and without the incorporation of a rat liver microsomal activation system (S9) . Zinc dimethyldithiocarbamate was tested as a structurally-related model bacterial mutagen, and, in additional control experiments, the mutagenic activity of zinc dimethyldithiocarbamate and benzo{a}pyrene was investigated in combination with the blend of process oils in selected bacterial tester strains . Transformation frequencies of BHK cells were determined by colony growth in soft agar culture following treatment with a blend of the zinc dialkyldithiophosphate lubricant additives suspended in process oils, a blend of the process oils, 7,12-dimethylbenzanthracene, both in the presence and in the absence of a blend of the process oils, or zinc dimethyldithiocarbamate . All experiments incorporated a rat liver microsomal activation system (S9) . Application of a blend of the zinc dialkyldithiophosphate additives or a blend of the process oils used in their manufacture did not increase the reverse mutation frequencies of Salmonella typhimurium TA1535, TA1537, TA1538, TA98 or TA100, or significantly increase the transformation frequency of BHK cells under the experimental conditions described . Zinc dimethyldithiocarbamate increased the reverse mutation frequency in some bacterial tester strains, but did not significantly increase the transformation frequency of BHK cells under the described experimental conditions . The addition of the blend of the process oils in combination with the control materials, zinc dimethyldithiocarbamate or benzo{a}pyrene had an inhibitory effect on the mutagenic activity at high doses of each in the bacterial assays, and in the BHK assay the transforming ability of 7,12-dimethylbenzanthracene was suppressed in the presence of the blend of the process oils . Thus, the additive materials showed no evidence of genotoxic activity in the bacterial mutation assays, or in the BHK transformation assay under the experimental conditions described.

Mutat Res, 1983 Nov, 124(2), 121 - 8
Mutagenicity studies of ambient airborne particles . II . Comparison of extraction methods; Krishna G et al.; Organic materials were extracted with acetone from airborne particles by shaking, soxhletion and sonication for varying durations . 4-h, 1-h and 1/8-min extractions by shaking, soxhletion and sonication, respectively gave maximum his+ revertants with the Ames Salmonella/microsome assay . In a comparative study of extraction methods, sonication gave the highest and soxhletion the lowest mutagenic response . It appears that sonication with acetone is the best procedure for the extraction of mutagens from airborne particles as shown by Ames assay and Arar assay systems in Salmonella typhimurium.

Cancer Lett, 1983 Nov, 21(1), 63 - 8
Mutagenic activity of N-nitrosomethamphetamine and N-nitrosoephedrine; Shimizu H et al.; The mutagenicity of N-nitrosomethamphetamine (NMA) and N-nitrosoephedrine (NEP), which were synthesized in our laboratory, was examined by the modified pre-incubation method of Ames assay using Salmonella typhimurium TA100 and TA98 . Both nitroso compounds showed significant mutagenic activity in the presence of hamster S9.

Chem Biol Interact, 1983 Nov, 47(2), 175 - 94
Interrelationships in mice of antipyrine half-life, hepatic monooxygenase activities and liver S9-mediated mutagenicity of aflatoxin B1, benzo{alpha}pyrene 7,8-dihydrodiol, 2-acetylaminofluorene and N-nitrosomorpholine; Roberfroid MB et al.; To evaluate the predictive value of serum antipyrine half-life AP(T1/2) as an index of hepatic carcinogen metabolism, groups of C57BL/6 and DBA/2 mice were treated with various inducers and inhibitors of cytochrome P-450-dependent monooxygenases (pregnenolone-16 alpha-carbonitrile (PCN), phenobarbital (PB), 5,6-benzoflavone (5,6-BF), 3-methylcholanthrene (MC), disulfiram (DIS), 7,8-BF) . Groups of mice were also given ethanol (3% in drinking water) for 12 days . Within each group, mean serum AP-(T1/2) was compared with (i) the in vitro activity of hepatic microsomal benzo{alpha}pyrene (BP) 3-hydroxylase, 2-acetylaminofluorene (AAF)-N-hydroxylase and aldrin monooxygenase, and (ii) the liver S9-mediated mutagenicity of aflatoxin B1 (AFB), trans-7,8-dihydro-7,8-dihydroxybenzo{alpha}pyrene (BP 7,8-diol), 2-acetylaminofluorene and N-nitrosomorpholine (NMOR) in Salmonella typhimurium strains . Serum AP(T1/2) was only correlated negatively with the activity of BP 3-hydroxylase (P less than 0.001) and aldrin monooxygenase (P less than 0.001) . No statistically significant correlation was found between serum AP(T1/2) and liver S9-mediated mutagenicity for any of the four carcinogens . On the basis of these results, we conclude that serum AP(T1/2) may not be a reliable index of the capacity of liver to convert carcinogens into reactive intermediates.

Can J Microbiol, 1983 Nov, 29(11), 1583 - 8
The epidemic spread of Salmonella typhimurium phage type 10 in Canada (1970-1979); Khakhria R et al.; The frequency of Salmonella typhimurium phage type 10 across Canada was monitored during the period 1970-1979 . Phage type 10 isolations increased from 1.2% in 1970 to 68.8% in 1979 among isolates from human sources and from 1.5 to 30.6% in isolates from nonhuman sources . Examination of food-poisoning outbreaks and a study of the animal-host associations of phage type 10 revealed that contaminated poultry products appear to be the most common sources of human infections . The majority (89.3%) of S . typhimurium phage type 10 strains were sensitive to antibiotics . Of the resistant strains, 73.3% were resistant to single antibiotics and 26.7% were multiresistant . Thirty-three different patterns of antibiotic resistance were observed . A number of the resistance determinants were transferable by conjugation and the R plasmids were found to belong to the incompatibility groups HI1, FII, N, I alpha, and C.

J Gen Microbiol, 1983 Nov, 129 ( Pt 11), 3395 - 400
Generalized transduction between Salmonella typhi and Salmonella typhimurium by phage j2 and characterization of the j2 plasmid in Escherichia coli; Mise K et al.; Phage j2, a P1-like phage in Salmonella typhi, was heteroimmune to phage P1 and existed in the lysogenic state as a plasmid of molecular size 58.6 MDal . The phage j2 plasmid was incompatible with the P1 plasmid (IncY group) . A j2-sensitive mutant of Salmonella typhimurium LT2 was isolated by transduction of j2Ap phage into LT2 followed by curing of the prophage . The mutant was used to demonstrate transduction between S . typhi and S . typhimurium by phage j2.

Sci Total Environ, 1983 Nov, 31(2), 181 - 5
Isolation and preliminary toxicological evaluation of arsenobetaine - the water-soluble arsenical constituent from the hepatopancreas of the western rock lobster; Cannon JR et al.; The water soluble arsenic compound present in the hepatopancreas of the western rock lobster (Panulirus cygnus George) has been isolated as the reineckate salt and has been identified as arsenobetaine . Intraperitoneal injection of arsenobetaine into mice at 500 mg kg-1 did not result in mortality, and no symptoms of poisoning were observed . Mice treated with arsenobetaine at 360 mg kg-1 rapidly eliminated the compound in their excreta and no evidence was obtained for metabolic alteration . When tested in the Ames' Salmonella typhimurium system for chemical mutagens, both in the presence and absence of liver microsomal oxidase fraction, arsenobetaine gave consistently negative results.

Genetika, 1983 Nov, 19(11), 1835 - 9
{Experimental analysis and planning using the Salmonella/microsomes test}; Bobrinev EV et al.; A possible statistical treatment of the results obtained in Salmonella typhimurium TA1950, TA1535, TA1537, TA1538, TA98 and TA100 using the Salmonella/microsomes test was investigated . An analysis of independent repeated experiments pointed to the divergence of the data obtained . Consequently, it has been recommended to carry out the statistical treatment of experimental data within the limits of dispersion analysis with the subsequent use of the Scheffe's method for multiple comparisons . To stabilize the dispersion of experimental data, it is suggested to express the number of revertant colonies as lnX . A minimal volume of the data sample needed for resolving experimental tasks has been calculated . In standard experiments aimed at revealing the mutagenic activity of the compounds used, three Petri dishes should be used in each variant of experiments.

Appl Environ Microbiol, 1983 Nov, 46(5), 1243 - 5
Detection of Salmonella spp . in milk by using Felix-O1 bacteriophage and high-pressure liquid chromatography; Hirsh DC et al.; A method is described whereby the presence of less than five salmonellae was detected per milliliter of milk within 24 h of sample collection . Salmonellae were removed from milk by means of electropositive large-pore filters . Eluates from the filters were analyzed for the presence of Salmonella spp . by Felix-O1 bacteriophage and high-pressure liquid chromatographic techniques . The method gave only a positive response when salmonellae were present in the milk . Of the serotypes and strains of Salmonella spp . tested, Salmonella dublin (10 strains), Salmonella typhimurium (5 strains), Salmonella anatum, Salmonella krefeld, and Salmonella saint-paul gave positive responses . One strain of Salmonella agona (three strains tested) and three strains of Salmonella enteritidis (seven strains tested) were not detectable by the method described herein.

Antonie Van Leeuwenhoek, 1983 Nov, 49(4-5), 471 - 84
Indirect induction of SOS functions in Salmonella typhimurium; Barbe J et al.; Infection of non-UV-irradiated cells of Salmonella typhimurium with UV-damaged P22 or KB1 phage induces recA-dependent inhibition of cell division, cell mutagenesis and prophage induction but not inhibition of respiration . On the contrary, respiration and ATP concentration are increased after treatment with UV-damaged phage in both RecA+ and RecA- strains, showing that this increase is not recA-dependent . Furthermore, infection with UV-damaged phage prevents both inhibition of respiration and decrease in ATP level in the UV-irradiated RecA+ strain . This indirect induction of SOS functions is related to degradation of phage DNA as well as to the multiplicity of infection used, suggesting that DNA degradation may play an important role in the mechanism of expression of the SOS system . Our results give also support to the hypothesis that there exists a differentiation in the expression of the various SOS functions.

Mutat Res, 1983 Nov, 124(2), 103 - 12
Mutagenicity testing with the Salmonella/hepatocyte and the Salmonella/microsome assays . A comparative study with some known genotoxic compounds; Bos RP et al.; The applicability of isolated intact hepatocytes as a metabolic factor in bacterial mutagenicity screening was studied . Mutagenic activities of 12 known premutagenic compounds were determined in a Salmonella typhimurium test system comprising hepatocytes and were compared with mutagenicity data obtained with the commonly used Salmonella/microsome plate assay . In a qualitative sense the results obtained with the two systems were, in general, equivalent . However, some specific differences were found depending on the bacterial strain used . For instance, dimethylnitrosamine was only mutagenic for Salmonella strain TA1535 in the hepatocyte suspension system . On the other hand, benzo{a}pyrene was hardly mutagenic towards TA100 with hepatocytes in contrast with the clear-cut effects in the microsome plate assay . In a quantitative respect, for benzidine, 2-acetylaminofluorene, 2-aminoanthracene and dimethylnitrosamine, obviously divergent mutagenic values were recorded with the different procedures . These differences were found to be connected with the presence of intact hepatocytes . This appeared from a comparison between mutagenicities with intact hepatocytes and with S9 prepared from disrupted hepatocytes . The results support previous recommendations that tests with intact cell metabolism should be included in a battery for screening of carcinogens in vitro.

Mutat Res, 1983 Nov, 111(3), 283 - 93
Mutagenesis and anti-mutagenesis in Salmonella: influence of ethionine and caffeine on yields of mutations induced by 2-aminopurine and 9-aminoacridine; MacPhee DG et al.; Ethionine, the ethyl analogue of methionine, slightly reduced the yield of reversions of the hisC3076 frameshift marker induced by 9-aminoacridine (9AA) in an excision-proficient strain of Salmonella typhimurium, but completely abolished mutagenesis by 9AA in the excision-deficient uvrB-deletion strain TA1537 . No toxic effects of ethionine were apparent in either the excision-proficient or the excision-deficient strain . Because of the differential effects of ethionine on mutagenesis in the two strains, it seemed possible that an ethionine-sensitive step in the process(es) leading to fixation of 9AA-induced mutations might be compensated for by the uvrA,B,C+ excision-repair system . To further test this possibility, we used caffeine (a compound known to significantly reduce the efficacy of the excision-repair process) as a co-treatment with ethionine for cells of an excision-proficient strain exposed to 9AA . Treatment with caffeine alone or ethionine alone had very little effect on reversion yield, whereas co-treatment with the two agents abolished 9AA mutagenesis . It appeared, therefore, that either the caffeine-sensitive pathway or the ethionine-sensitive pathway needed to be functioning if 9AA-induced reversions of hisC3076 marker were to be detected . Addition of methionine to cells of the excision-deficient strain exposed to 9AA restored their ability to be mutated by 9AA, however . In a base-pair substitution back-mutation system, ethionine slightly enhanced the yields of revertants of the trpE8 marker induced by 2-aminopurine (2AP) in both an excision-proficient strain (at all 2AP dose levels tested) and an excision-deficient strain (only at the lower dose levels) . In the excision-deficient strain, doses of 2AP above 300 micrograms/plate were highly toxic when ethionine was also present . It was for this reason that no 2AP-induced revertants were recovered at the higher 2AP concentrations . Treatment of the trpE8 strain with methionine also enhanced the yield of 2AP-induced revertants of this marker.

Genetics, 1983 Nov, 105(3), 539 - 57
Selection and endpoint distribution of bacterial inversion mutations; Schmid MB et al.; This paper describes the isolation and characterization of spontaneous inversion mutants of Salmonella typhimurium . The mutants are selected by demanding that an unexpressed hisD gene acquire a new promoter . Chromosome rearrangements that juxtapose the hisD gene and a foreign promoter are obtained by this selection . Although a number of inversions are found, the frequency was lower than expected . The breakpoint of these inversions are not distributed randomly either in the his operon or on the chromosome . The his breakpoint lies in the hisG-hisD intercistronic region, a sequence known to occur at several places on the bacterial chromosome . In most of the inversions, the 'non-his' breakpoint lies across the chromosome, so that the inverted region includes the origin or terminus of DNA replication . The significance of these results is discussed.

Genetics, 1983 Nov, 105(3), 517 - 37
Genetic methods for analysis and manipulation of inversion mutations in bacteria; Schmid MB et al.; A number of genetic methods for the isolation, characterization and manipulation of large chromosomal inversions in Salmonella typhimurium are described . One inversion-carrying mutant is characterized in detail and used to demonstrate a number of unique genetic properties of bacterial inversions . --Contrary to expectation, it was found that large inversion mutations can be repaired by generalized transduction . The repair results from the simultaneous introduction of two wild-type transduced fragments into a single recipient cell . Homologous recombination between the two transduced fragments and the two inversion breakpoints causes the inverted segment to be reinverted . This results in regeneration of the wild-type orientation of this chromosome segment . Similar recombination events allow a large inversion mutation to be introduced into a wild-type strain; two transduced fragments from an inversion strain cause recombination events resulting in inversion of a large chromosome segment . --Genetic methods for mapping the extent of a large inversion mutation by generalized transduction are described and tested . The methods are operationally simple and allow good resolution of the two inversion breakpoints.

Carcinogenesis, 1983 Nov, 4(11), 1477 - 81
Hydroxylation and nitroreduction are required to activate dimethylnitramine into alkylating and mutagenic agents; Malaveille C et al.; Dimethylnitramine (DMNO) was shown to undergo hydroxylation in the presence of 9000 g supernatant from rat liver (S9) to yield hydroxymethyl-methylnitramine (OH-MNO) . OH-MNO displayed a 100-fold higher mutagenic activity in Salmonella typhimurium TA100 strain than DMNO, when compared on a molar basis . The mutagenicity of DMNO in TA100 strain in the presence of S9 paralleled the production of OH-MNO . Acetoxymethyl-methylnitramine (Ac-MNO) and methylnitramine (MNO), two synthetic derivatives of DMNO, were also investigated . Ac-MNO was found to be mutagenic in TA100 strain only in the presence of S9, probably through the release of OH-MNO catalysed by esterase(s); under similar conditions, MNO showed no mutagenicity or toxicity to TA100 strain . OH-MNO showed no alkylating activity towards nicotinamide . These findings implicate OH-MNO as a proximate mutagenic metabolite of DMNO . DMNO and Ac-MNO were found to be more mutagenic in a nitroreductase(s)-proficient (TA100) than in a deficient (TA100 NR) strain . After reduction of OH-MNO with Zn/NH4Cl, it yielded an agent(s) which alkylated nicotinamide . The latter results imply a reduction of the nitro group in OH-MNO to yield a hydroxylamino derivative as the ultimate (or penultimate) mutagenic metabolite . The enzymes and reactive intermediates that may be involved in the activation of DMNO are discussed.

Carcinogenesis, 1983 Nov, 4(11), 1451 - 4
The induction of prophage expression in different Salmonella typhimurium strains by DNA cross-linking and monoadduct forming psoralens and longwave ultraviolet radiation; Connor MJ et al.; The cytotoxicity, and ability to induce the expression of prophage in Salmonella typhimurium LT2 strains has been examined for 4 furocoumarins, 8-methoxypsoralen (8-MOP), 5-methoxypsoralen (5-MOP), 3-carbethoxypsoralen (3-CP), and 5-methylisopsoralen (5-MI) given with ultraviolet-A radiation (u.v.A) . 8-MOP and 5-MOP have a linear tricyclic structure and possess two photoreactive sites, the 3,4 and 4',5' double bonds, enabling them to form both monoadducts and interstrand cross-links with DNA . The angular structure of 5-MI imposes steric constraints preventing it from forming interstrand cross-links with DNA although it possesses both of the photoreactive double bonds . The substituent group at position C-3 in 3-CP blocks the 3,4 reactive site and 3-CP is thus incapable of forming interstrand cross-links; 3-CP is reportedly, unlike the other three furocoumarins, non-carcinogenic in mice . 8-MOP, 5-MOP, and 5-MI were very cytotoxic to both the base-pair (TA1535) and frame-shift (TA1538) tester strains when given with u.v.A . Comparable amounts of 3-CP given with u.v.A were much less toxic . 8-MOP, 5-MOP, and 5-MI were potent inducers of prophage expression in both TA1535 and TA1538 . 3-CP was a very poor inducer of prophage . The cytotoxicity and prophage inducing ability of 5-MI + u.v.A indicate that these actions are not necessarily restricted to the DNA crosslinking psoralens . The lower toxicity of 3-CP + u.v.A is not a simple function of the ability of 3-CP to form only monoadducts with DNA . The ability or inability to induce the expression of prophage in S . typhimurium may be a rapid and useful screen for the potential phototoxicity and carcinogenicity of novel psoralens.

Carcinogenesis, 1983 Nov, 4(11), 1401 - 7
Bovine bladder and liver cell and homogenate-mediated mutagenesis of Salmonella typhimurium with aromatic amines; Hix C et al.; Comparisons of aromatic amine activation were made by using intact cells or cell homogenates (S-9) from bovine bladder urothelium and liver . Since both liver and bladder are thought to contribute carcinogenic metabolites for bladder cancer initiation, comparisons of these two organs' relative ability to activate aromatic amines to mutagens were made . Salmonella typhimurium mutagenesis was used as an indication of mutagen production . Activation occurred in a dose dependent manner and no mutagenic response occurred unless activating cells or S-9 were present . Bladder urothelial cells metabolically activated the carcinogens, 2-amino-fluorene (AF), 2-acetylaminofluorene (AAF), 4-aminobiphenyl (4ABP), benzidine (BZ), and 2-naphthylamine (2NA) but not 1-naphythylamine (1NA), a non-carcinogen . Liver cells were less active than bladder cells in activating AF and AAF; but there was little or no hepatocyte activation of 4ABP, BZ, 2NA and 1NA . Intact bladder cells were more effective than bladder S-9 in activating AAF, but not in activating AF, 4ABP, BZ and 2NA . The liver S-9 showed more mutagenic activity with AF than did intact liver cells; the reverse was true for AAF, and bovine liver S-9 showed little or no activation of 4ABP, BZ, and 2NA . 1NA was not activated by either S-9 preparation . As was the case for intact cells, bladder S-9 was more effective than liver S-9 in activating the aromatic amines studied . The results demonstrate the capacity of bovine bladder urothelium to metabolically activate aromatic amines and suggest a role for the target organ itself in carcinogen activation . Information on the relative usefulness of intact cells versus S-9 preparations as activation systems was also obtained from these studies.

Biochem Pharmacol, 1983 Nov 1, 32(21), 3145 - 9
Role of sulfhydryl compounds in the bactericidal effect of metronidazole; Yeung TC et al.; The bactericidal effect of metronidazole on Escherichia coli and Bacteroides fragilis can be partially reversed by cysteamine under conditions that lead to the formation of an adduct, the thioether, 4-(2-aminoethyl)thio-2-methylimidazole-1-ethanol (4-ATME) . This adduct, which is not mutagenic for the Ames histidine auxotrophs of Salmonella typhimurium, forms at a rate that is independent of live bacterial cells and, therefore, can not be shown to relate to the biological effect of cysteamine . When treated with Raney nickel, this adduct yields 2-methylimidazole-1-ethanol . To determine whether a structurally related adduct forms with bacterial protein, a culture of B . fragilis was incubated with radiolabelled metronidazole and then treated with 5% trichloroacetic acid . That the radiolabel in the precipitate did not yield 2-methylimidazole-1-ethanol when treated with Raney nickel suggests that binding of metronidazole to cellular macromolecules does not involve thioether formation.

Proc Natl Acad Sci U S A, 1983 Nov, 80(21), 6671 - 5
Enzymatic deacylation of the lipid A moiety of Salmonella typhimurium lipopolysaccharides by human neutrophils; Hall CL et al.; Lipid A, the toxic moiety of Gram-negative bacterial lipopolysaccharides (endotoxins), is a glucosamine disaccharide to which fatty acid and phosphate residues are covalently attached . Recent studies of Salmonella lipid A indicate that 3-hydroxytetradecanoic acid (3-OH-14:0) residues are directly linked to the glucosamine backbone and the nonhydroxylated fatty acids (principally dodecanoic and tetradecanoic acids) are esterified to the hydroxyl groups of some of the 3-OH-14:0 molecules . We report here that the granule fraction of human neutrophils contains one or more enzymes that partially deacylate Salmonella typhimurium lipid A by removing the nonhydroxylated fatty acids, leaving almost all of the 3-OH-14:0 residues linked to glucosamine . The available evidence suggests that similar reactions also occur in living neutrophils that ingest lipopolysaccharides by antibody-dependent phagocytosis.

J Bacteriol, 1983 Nov, 156(2), 962 - 5
Anaerobic cultures of Salmonella typhimurium do not exhibit inducible proteolytic function of the recA gene and recBC function; Droffner ML et al.; In a strict anaerobic environment, lack of expression of bacterial recBC function and recA regulatory functions for the SOS repair system is demonstrated by the use of the carcinogenesis-mutagenesis assay and Salmonella phage P22 mutants requiring these host functions for replication . Therefore, we suggest that error-prone repair (SOS repair) is confined to aerobic environments in facultative anaerobes.

J Bacteriol, 1983 Nov, 156(2), 656 - 62
Evidence that thiosulfate assimilation by Salmonella typhimurium is catalyzed by cysteine synthase B; Nakamura T et al.; Mutants carrying defects in cysteine synthase A or B or both were isolated from Salmonella typhimurium LT2 . Parent strains were able to grow on minimal media containing sulfate, sulfite, sulfide, or thiosulfate as sulfur sources . Mutants lacking cysteine synthase B were unable to grow on thiosulfate, whereas mutants lacking cysteine synthase A grew on the four inorganic sulfur sources described above with little difference in their growth rates . Mutants lacking both cysteine synthases failed to grow on media containing any of the inorganic sulfur sources tested . Purification of cysteine synthase B resulted in the copurification of S-sulfocysteine synthase . In addition, the two activities were also cotransduced . These activities appear to be associated with the cysM gene, and this is able to be cotransducted with the cysK gene at a high frequency . From these results, it may be concluded that thiosulfate is assimilated via S-sulfocysteine exclusively with the aid of S-sulfocysteine synthase.

J Bacteriol, 1983 Nov, 156(2), 481 - 6
Two proline porters in Escherichia coli K-12; Stalmach ME et al.; Escherichia coli mutants defective at putP and putA lack proline transport via proline porter I and proline dehydrogenase activity, respectively . They retain a proline uptake system (proline porter II) that is induced during tryptophan-limited growth and are sensitive to the toxic L-proline analog, 3,4-dehydroproline . 3,4-Dehydroproline-resistant mutants derived from a putP putA mutant lack proline porter II . Auxotrophic derivatives derived from putP+ or putP bacteria can grow if provided with proline at low concentration (25 microM); those derived from the 3,4-dehydroproline-resistant mutants require high proline for growth (2.5 mM) . We conclude that E . coli, like Salmonella typhimurium, possesses a second proline porter that is inactivated by mutations at the proP locus.

Immunology, 1983 Nov, 50(3), 359 - 68
Interferon decreases production of hydrogen peroxide by macrophages: correlation with reduction of suppressive capacity and of anti-microbial activity; Boraschi D et al.; Mouse peritoneal macrophages (M phi) expressed enhanced tumoricidal activity upon in vitro stimulation either with the lymphokine M phi-activating factor (MAF) or with fibroblast interferon (IFN-beta) . In contrast, M phi suppressive activity on lymphoproliferation was not affected by MAF pretreatment, but was drastically reduced or abolished by IFN-beta . Catalase, the enzyme involved in the destruction of hydrogen peroxide (H2O2), did significantly decrease M phi suppressive capacity but had no effect on M phi tumoricidal activity . Analysis of the phagocytosis-dependent H2O2 production by IFN-beta-treated M phi demonstrated a strong impairment of the oxygen metabolite release, which strictly paralleled the decreased M phi suppressive capacity . On the other hand, MAF did not modify H2O2 release by M phi . Studies on M phi antibacterial activity against Salmonella typhimurium, a function thought to depend upon H2O2 production, showed that exposure of M phi to IFN-beta significantly impaired their bactericidal and bacteriostatic capacity, again in close correlation with the decrease in H2O2 production . Thus, IFN-beta appears as modulating both suppressive and antibacterial capacities of M phi through reduction of their oxygen metabolism, whereas regulation of M phi anti-tumour activity is possibly controlled by different mechanisms.

Cancer Res, 1983 Nov, 43(11), 5194 - 9
Bovine bladder urothelial cell activation of carcinogens to metabolites mutagenic to Chinese hamster V79 cells and Salmonella typhimurium; Oglesby LA et al.; The ability of bovine bladder urothelial cells to activate genotoxic chemicals to mutagens was examined by cocultivating bladder cells with Chinese hamster V79 cells or Salmonella typhimurium as mutable targets . Activation of test chemicals to mutagenic intermediates by urothelial cells was detected by induction of 6-thioguanine resistance in V79 cells or by induction of histidine revertants in Salmonella . In the bladder cell-mediated V79 cell mutagenesis system, a significant increase in mutation frequency was induced by exposure to 7,12-dimethylbenz(a)anthracene and dimethylnitrosamine . The aromatic amines 2-aminofluorene, 2-acetylaminofluorene, and 4-aminobiphenyl were weakly mutagenic to V79 cells with bladder cell activation, while no mutagenic activity was detected with 1-naphthylamine, 2-naphthylamine, or benzidine . Because the mutagenic activity of the aromatic amines was low with V79 cells as the target, a bladder cell-mediated S . typhimurium system was developed for these chemicals . The aromatic amines 2-aminofluorene, 2-acetylaminofluorene, 4-aminobiphenyl and 2-naphthylamine were mutagenic to S . typhimurium TA98 and TA100 in the presence of bladder cells but not in their absence . Benzidine was mutagenic to TA98 but not to TA100 . The putative noncarcinogen 1-naphthylamine was not mutagenic in the system . In contrast to the V79 data, 7,12-dimethylbenz(a)anthracene and dimethylnitrosamine were not mutagenic with either bacterial strain . Mutagenic responses were related to both the number of bladder cells used for activation and the concentration of test chemical in the Salmonella assay . The data demonstrate that bovine bladder urothelial cells can activate carcinogens from three chemical classes to mutagens and indicate the different sensitivities of V79 cells and S . typhimurium to genotoxic agents.

J Bacteriol, 1983 Nov, 156(2), 743 - 51
Overproduction of Salmonella typhimurium peptidase T; Strauch KL et al.; Pseudorevertants able to use L-leucyl-L-leucyl-L-leucine as a leucine source have been isolated from a Salmonella typhimurium strain carrying stable (nonreverting) mutations in pepN, pepA, and pepB . These strains carry mutations at a locus pto (peptidase T overproducer) tightly linked to pepT that cause an elevated expression of the tripeptidase peptidase T . An F' episome carrying the pto and pepT loci has been constructed and used to show that the pto mutations are cis dominant . Expression of beta-galactosidase from a Mu d1(Apr lac) insertion in pepT is increased by pto mutations . The pto mutations, therefore, define a site affecting the transcription of pepT.

Immunology, 1983 Nov, 50(3), 369 - 76
Immunogenicity of transfer RNA isolated from a two-heptose rough mutant of Salmonella typhimurium LT2 in mouse typhoid infection; Kita E et al.; Transfer ribonucleic acid (tRNA) was isolated from a two-heptose mutant of Salmonella typhimurium LT2 (strain SL1004) and was found to afford 100% mouse protection against challenge with 1000 LD50 of strain LT2 . The intraperitoneal minimum effective dose of tRNA was 5 micrograms RNA per mouse and this dose was significantly lower than that of ribosomal RNA for ddY mouse strain . The protective immunity was independent of the presence of antibodies to cell-surface antigens, and was transferred mainly by T cells . The protective moiety of tRNA was sensitive to ribonuclease digestion which resulted in 85% reduction in the mouse survival rate, but was completely resistant to protease digestion . The present study demonstrates that the immunogenic activity of salmonella RNA is present in both ribosomal RNA and tRNA.

J Mol Biol, 1983 Oct 15, 170(1), 39 - 59
Transcription initiation sites of the leucine operons of Salmonella typhimurium and Escherichia coli; Gemmill RM et al.; Evidence for a transcription attenuation site downstream from the leu promoter was obtained by transcription experiments in vitro . Most transcription initiated in vitro from leuP is terminated prematurely, resulting in the synthesis of a 160 nucleotide leader RNA . We define here the point at which transcription is initiated in vitro and in vivo and demonstrate that the site of premature termination is between the promoter and the first structural gene (leuA) . Additional nucleotide sequences are presented that extend the known sequence 200 base-pairs upstream and 300 base-pairs downstream from leuP . The location of the promoter-proximal end of cistron leuA was deduced by comparing nucleotide sequence data with the sequence of the ten amino acids at the N-terminus of alpha-isopropylmalate synthase . To facilitate the isolation of quantities of material for sequencing experiments, the enzyme was isolated from a plasmid-containing strain, CV605, grown under conditions of leucine limitation . Under such conditions, about 20% of the total soluble protein of strain CV605 is alpha-isopropylmalate synthase and another 20% is beta-isopropylmalate dehydrogenase (leuB product).

Biochem Biophys Res Commun, 1983 Oct 14, 116(1), 141 - 7
Mechanism of activation of proximate mutagens in Ames' tester strains: the acetyl-CoA dependent enzyme in Salmonella typhimurium TA98 deficient in TA98/1,8-DNP6 catalyzes DNA-binding as the cause of mutagenicity; Saito K et al.; The mechanism of activation of proximate mutagens in Ames' tester strains was described . 2-Hydroxyamino-6-methyldipyrido{1,2-a:3',2'-d}imidazole (N-OH-Glu-P-1) and 3-hydroxyamino-1-methyl-5H-pyrido{4,3-b}indole (N-OH-Trp-P-2) were activated to DNA-binding species in the presence of acetyl-CoA by the enzyme(s) in Salmonella typhimurium TA98, and this enzyme was deficient in TA98/1,8-DNP6 . Mutagenicity of N-OH-Glu-P-1 to TA98/1,8-DNP6 was much lower than that to TA98 . Therefore, it was demonstrated that the acetyl-CoA dependent enzyme(s) activated N-OH-Glu-P-1 to the active form which could covalently bind to DNA and subsequently caused mutagenicity.

J Mol Biol, 1983 Oct 5, 169(4), 775 - 97
Nucleotide sequence of the trpD and trpC genes of Salmonella typhimurium; Horowitz H et al.; We have completed the nucleotide sequence determination of trpD and trpC, the second and third genes of the trp operon of Salmonella typhimurium . These genes encode two bifunctional proteins thought to have arisen by gene fusions: the trpD polypeptide contains the glutamine amido transferase and the phosphoribosyl anthranilate transferase activities, and the trpC protein possesses the N-(5'-phosphoribosyl)-anthranilic acid isomerase and the indole-3-glycerol phosphate synthetase activities . The trpD gene consists of 1593 nucleotides encoding 531 amino acids, and possesses an internal promoter (p2) located within a region from about 1400 to 1441 of the nucleotide sequence . The trpC gene contains 1356 nucleotides encoding 452 amino acids . In this paper we compare the trpD and trpC genes of S . typhimurium to those of Escherichia coli with respect to codon usage, nucleotide and amino acid conservation, p2 promoter characteristics and intercistronic regions . The sequence of the two genes we present here completes the sequence determination of the trp operon of S . typhimurium and should prove useful in comparisons with the E . coli trp operon and in future studies of operon structure in S . typhimurium.

J Gen Microbiol, 1983 Oct, 129 (Pt 10), 3075 - 84
Physicochemical surface properties and phagocytosis by polymorphonuclear leucocytes of different serogroups of Salmonella; Xiu JH et al.; Salmonella isolates belonging to different serogroups have been analysed with respect to physicochemical surface properties and interaction with human polymorphonuclear granulocytes (PMNs) . Most (22/34) recent isolates of the different serotypes showed hydrophilic surface properties and little if any negative charge accompanied by resistance to phagocytosis by PMN similar to the old laboratory S strains Salmonella typhimurium 395MS and Salmonella minnesota S99 (main group) . However, all isolates belonging to the serogroups C1 (5 isolates), E4 (2), O43 (1), and one out of three E1 isolates (C1/E4 group) differed from the main group . In aqueous biphasic partition in dextran-polyethyleneglycol (PEG) systems the bacteria in the main group accumulated in the PEG-rich phase to 55-97%, those in the C1/E4 group to less than 10%, and R-mutants only to 1-2% . The bacteria in the C1/E4 group displayed a negative surface charge and a susceptibility to phagocytosis by PMNs that were greater than those for strains in the main group but much lower than those shown by the R-mutants . Bacteria belonging to serogroup C1 also displayed a significant susceptibility to hydrophobic interaction . The results are discussed in relation to the pathogenicity of salmonella.

Vet Microbiol, 1983 Oct, 8(5), 443 - 58
Hemagglutinating and hydrophobic surface properties of salmonellae producing enterotoxin neutralized by cholera anti-toxin; Jiwa SF et al.; Eleven Salmonella strains known to produce enterotoxin under aerobic culture conditions in deferrated (DF) medium at 37 degrees C were shown to produce enterotoxin with and without aeration at 22, 28, 37 and 42 degrees C . Heat-labile enterotoxin was generally produced with growth temperatures up to 37 degrees C irrespective of aeration . Heat-stable enterotoxin was produced up to 42 degrees C, mainly aerobically, as indicated by infant mouse assay (IMA), by six of the eleven strains tested . Nine strains produced heat-stable rapid permeability factor (RPF) in rabbit skin . Cholera anti-toxin neutralized reactivities of Salmonella heat-labile enterotoxin in four different biological assays . Mixed gangliosides also neutralized this activity in the cell-test systems . With guinea-pig erythrocytes, all strains underwent mannose-resistant hemagglutination (MRHA) irrespective of growth temperatures, i.e . 22 and 37 degrees C or medium, i.e., DF, tryptose soy broth (TSB) and colonization factor antigen (CFA) agar . At both growth temperatures, CFA agar-grown cells of each strain caused MRHA of bovine erythrocytes . Excepting three Salmonella typhimurium strains, DF broth-grown cells gave MRHA of bovine, chicken and human group A erythrocytes, CFA agar-grown cells caused MRHA of chicken and human blood, whereas TSB-grown cells caused few MRHA reactions . Salmonellae producing both heat-stable, (ST) and heat-labile, (LT) enterotoxins adsorbed to Phenyl Sepharose whereas salmonellae that produced only LT enterotoxin did not . The presence of MRHA adhesions did not correlate with cell-surface hydrophobicity . However, mannose-resistant hemagglutinins may occur more commonly among salmonellae than has been previously recognized.

Carcinogenesis, 1983 Oct, 4(10), 1239 - 41
Structure-activity relationship amongst biliary acids showing comutagenic activity towards 1,2-dimethylhydrazine; Wilpart M et al.; Secondary biliary acids act, in vitro, as co-mutagenic agents towards 1,2-dimethylhydrazine incubated in the presence of Salmonella typhimurium strain TA 100 . The present report demonstrates an important structure-activity relationship with regard to this effect . The number and position of hydroxyl substituents, the configuration at various C atoms and the stereochemistry of the junction between rings A and B of the steroid moiety are parameters which influence the cogenotoxic activity . Beyond these structural parameters, the basic physico-chemical properties of the biliary acids could be the key factor controlling their effects . Co-incubation of the various biliary acids reveals that the so-called secondary compounds antagonise each other's activity; moreover, in the presence of a constant concentration of primary bile acids, the co-mutagenic effect is directly related to the amount of the secondary bile acids . The co-mutagenic activity of the secondary biliary acids and its modulation by their mixing could be a key factor in the etiology of colon cancer.

Can J Microbiol, 1983 Oct, 29(10), 1339 - 43
Effect of rat polymorphonuclear leukocyte granule components on the growth and survival of Pseudomonas aeruginosa and Salmonella typhimurium; Modrzakowski MC et al.; Granule contents from rat polymorphonuclear neutrophils were prepared by extraction with 0.2 M acetate buffer (pH 4.0), dialyzed against phosphate-buffered saline (pH 7.0), and tested for bactericidal activity against selected target bacteria . Salmonella typhimurium LT-2 and a series of progressively rough lipopolysaccharide outer membrane mutants derived from it were used to monitor antimicrobial activity . Although an antimicrobial potential was present in rat granule contents for S . typhimurium, the growth of Pseudomonas aeruginosa PAO-1 in antimicrobial assay mixtures containing rat granule contents was substantially enhanced over control values . The growth enhancement property of the granule protein was heat resistant and promoted increased oxygen consumption by whole cells.

Food Chem Toxicol, 1983 Oct, 21(5), 557 - 62
Identification and mutagenicity of aflatoxicol-M1 produced by metabolism of aflatoxin B1 and aflatoxicol by liver fractions from rainbow trout (Salmo gairdneri) fed beta-naphthoflavone; Loveland PM et al.; beta-Naphthoflavone (beta NF) fed to rainbow trout (Salmo gairdneri) at 50 or 500 ppm in the diet, modified the in vitro metabolism of aflatoxin B1 (AFB1) by the postmitochondrial fraction (PMF) of the liver . Production of aflatoxicol (AFL) was significantly less in the 500 ppm beta NF-fed group (33.9 ng/mg protein) than in the control group (45.7 ng/mg protein), aflatoxin M1 production was dependent on the dose of beta NF, being greatest in the 500 ppm beta NF-fed group (48.9 ng/mg protein), intermediate in the 50 ppm beta NF-fed group (3.7 ng/mg protein), and was not detected in controls . A new trout metabolite, 4-hydroxyaflatoxicol (aflatoxicol M1, AFLM1) was also detected in small amounts from in vitro metabolism by liver PMF from beta NF-fed trout . Sufficient quantities of AFLM1 for confirmation of identity by ultraviolet spectra, mass spectra and nuclear magnetic resonance spectra were prepared by biotransformation of AFL using liver microsomes and isolation by HPLC . In a modified Ames mutagen assay with Salmonella typhimurium TA98, ALFM1 was 4.1% as mutagenic as AFB1 in a previous determination . The carcinogenicity of AFLM1 to rainbow trout is expected to be considerably less than that of AFB1.

Arch Toxicol, 1983 Oct, 54(2), 167 - 70
Genotoxicity study of CS (ortho-chlorobenzylidenemalononitrile) in Salmonella, Drosophila, and mice . Failure to detect mutagenic effects; Wild D et al.; The lacrimatory agent CS was examined for genotoxic properties . In vitro, Salmonella typhimurium was exposed to CS at concentrations up to 1.5 mg per plate and reverse mutations were assayed . In vivo: male Drosophilae were fed with CS and sex-linked recessive lethal mutations in sperm cells were assayed using the Basc test . Further, mice were exposed to CS by oral or intraperitoneal administration; bone marrow erythrocytes were analysed for chromosomal mutations by means of the micronucleus test . All experiments failed to show a mutagenic activity of CS.

Mutat Res, 1983 Oct, 122(1), 13 - 22
Participation of cytochrome P450 in mutagenic activation of the carcinogen 3'-hydroxymethyl-N,N-dimethyl-4-aminoazobenzene and its N-demethylated compounds by rat liver; Mori Y et al.; Mutagenicity of the hepatocarcinogen 3'-hydroxymethyl-N, N-dimethyl-4-aminoazobenzene (3'-CH2OH-DAB) and its N-demethylated compounds was examined . Rat-liver 9000 X g supernatant (S9) fraction was used together with Salmonella typhimurium TA98 or TA100 as a tester strain . The expression of mutagenicity of 3'-CH2OH-DAB, 3'-hydroxymethyl-N-methyl-4-aminoazobenzene (3'-CH2OH-MAB) and 3'-hydroxymethyl-4-aminoazobenzene (3'-CH2OH-AB) required the presence of both microsomes and cytosol as sources of enzymes as well as NADPH as a cofactor . 3'-CH2OH-AB showed positive mutagenicity on both strains in the presence of liver S9 from untreated rats whereas 3'-CH2OH-DAB and 3'-CH2OH-MAB were negative . The treatment of rats with polychlorinated biphenyls (PCB) or 3-methylcholanthrene (3-MC) resulted in a marked increase in the ability of S9 to activate these three compounds, whereas phenobarbital (PB) induction was not effective, except for the activation of 3'-CH2OH-AB . The mutagenic activities of the three compounds in strain TA98 were considerably decreased by adding cytochrome c to the S9 mixture, but the activation reactions were insensitive to 1-(1-naphthyl)-2-thiourea (NTU) and methimazole, high-affinity flavin-containing monooxygenase (FMO) substrates . Metyrapone and 2-diethylaminoethyl-2,2-diphenylvalerate hydrochloride (SKF-525A, potent inhibitors of cytochrome P450, had no inhibitory effect on the activation of these compounds by S9 from PCB-treated rat livers . In contrast, 7,8-benzoflavone (BF), a specific inhibitor of cytochrome P448, decreased the activities of 3'-CH2OH-DAB and 3'-CH2OH-MAB by 88 and 78%, respectively, but the inhibition was negligible for 3'-CH2OH-AB.

J Reticuloendothel Soc, 1983 Oct, 34(4), 299 - 309
Resistance and susceptibility of mice to bacterial infection . IV . Functional specificity in natural resistance to facultative intracellular bacteria; Cheers C et al.; The effect of opsonic antibody on resistance of susceptibility of three strains of mice, C57Bl/10, BALB/c, and CBA to the intracellular bacteria Listeria monocytogenes, Salmonella typhimurium, and Brucella abortus was tested . Bacteria were opsonized by serum treatment before their injection into mice, or the mice were preimmunized by injection with alcohol killed bacteria which induces antibody without macrophage activation . Antibody did not increase the rate of clearance of Listeria from the bloodstream, nor did it affect the subsequent growth of that organism in the spleen and liver . Blood clearance of S . typhimurium and of B . abortus was increased by preopsonization with specific antibody, indicating that opsonins were a limiting factor in resistance to these two bacteria . However, neither opsonization before infection nor immunization with alcohol killed vaccines had any effect on the strain distribution of resistance/susceptibility, which differs for each of the three intracellular pathogens . Thus, even in the presence of adequate opsonization the three strains of mice showed different patterns of resistance/susceptibility to Listeria, S . typhimurium, and B . abortus . This implies that each has a unique cellular mechanism of early nonspecific resistance.

Food Chem Toxicol, 1983 Oct, 21(5), 615 - 9
Mutagenicity of structurally related aromatic amines in the Salmonella/mammalian microsome test with various S-9 fractions; Shahin MM et al.; The related monocyclic aromatic amines 2,4-diaminoanisole (DAA), 2,4-diaminopropoxybenzene (DAPB) and 2,4-diaminobutoxybenzene (DABB) were tested for mutagenic activity in Salmonella typhimurium strain TA 1538, using S-9 fractions from livers, kidneys and spleens of male Wistar rats for metabolic activation . In the presence of an uninduced liver S-9 fraction, DAA was weakly mutagenic (a two- or threefold increase), and the other compounds were negative . Uninduced S-9 preparations from kidney, spleen or a mixture of kidney, spleen and liver homogenates did not activate any of the compounds . On the other hand, S-9 fractions from rat liver induced with Aroclor 1254 or with a combination of phenobarbital and 5,6-benzoflavone activated both DAA and DAPB, DAA being by far the more mutagenic of the two . S-9 preparations from mixed liver, kidney and spleen homogenates from animals pretreated with Aroclor or with phenobarbital and 5,6-benzoflavone were less effective than the liver homogenates . Aroclor-induced S-9 fractions from kidneys slightly activated DAA, but S-9 fractions from spleen were ineffective in all cases . The mutagenicity ranking of the aromatic amines was DAA greater than DAPB greater than DABB . The latter compound caused little or no increase over the control numbers of revertant colonies . The order of effectiveness of inducers was Aroclor 1254 greater than phenobarbital + 5,6-benzoflavone greater than no inducer, and that of preparations from different organs was liver greater than mixture of liver, kidney and spleen greater than kidney greater than spleen.

Food Chem Toxicol, 1983 Oct, 21(5), 527 - 30
Mutagenic activity at different stages of an industrial ammonia caramel process detected in Salmonella typhimurium TA100 following pre-incubation; Jensen NJ et al.; Mutagenic activity of a commercial ammonia caramel colouring was demonstrated in Salmonella typhimurium TA100 without metabolic activation . The activity in strain TA100 was increased using a 10-min pre-incubation, and a clear dose-response relationship was seen using this method . Investigation of samples taken from the different stages in the industrial process showed a constant level of mutagenic activity in samples from the middle to the end of the heating process with a steep increase in the sample taken after the end of heating . No mutagenic activity was seen in assays with S . typhimurium strains TA1535 and TA98.

Mutat Res, 1983 Oct, 124(1), 25 - 34
Mutagenicity of natural naphthoquinones and benzoquinones in the Salmonella/microsome test; Tikkanen L et al.; The mutagenicities of naturally occurring naphthoquinones and benzoquinones were tested by the pre-incubation method with Salmonella typhimurium strains TA98, TA100 and TA2637, which all contain plasmid pKM101 . 6 of the 16 naphthoquinones tested, i.e., plumbagin, naphthazarin, 2-hydroxy-naphthoquinone, vitamin K3 (menadione), juglone and 7-methyljuglone, were mutagenic to strain TA2637 with metabolic activation . Except for juglone and 7-methyl-juglone, these compounds also had slight mutagenic effects on strain TA98 with S9 mix . All the mutagenic naphthoquinones contain one or two hydroxyl and/or methyl substituents . The naphthoquinone mompain, which has four hydroxyl groups, was not mutagenic . Unsubstituted beta-naphthoquinone, naphthoquinones with a prenyl side chain and all bi-naphthoquinone derivatives tested were non-mutagenic . None of the 13 benzoquinones examined was mutagenic to any of the strains used with or without metabolic activation . These results show that natural naphthoquinones are mutagenic when they have only one or two hydroxyl and/or methyl substituents.

Mutat Res, 1983 Oct, 124(1), 1 - 7
Mutagenicity of chalks . A case in which the test results led to the improvement of the quality of commercial goods; Hayatsu H et al.; Mutagenicity testing, of methanolic extracts of chalks, by the Salmonella/mammalian-microsome system revealed that the blue and the green chalks contained mutagens . A positive mutagenic response was observed on Salmonella typhimurium strain TA98, both in the presence and absence of the microsome system (S9) . The source of the mutagenicity was traced to the blue pigment used for manufacturing these chalks . The pigment, copper phthalocyanine, a product of a Japanese chemical industrial company, was found to contain impurities that were mutagenic . The mutagenic principle giving positive response in the TA98 in the presence of S9 was purified 10(5)-fold from the original pigment . Although its structure is yet to be elucidated, this indirect frame-shift mutagen had a strong activity: 5700 His+ revertants per microgram . This information, delivered in the beginning of 1981, prompted the manufacturer to start supplying a mutagen-free product . As a result, the blue chalks on the market became no longer mutagenic in the summer of 1982.

Mutat Res, 1983 Oct, 111(2), 99 - 118
Bacterial mutagenicity investigation of epoxides: drugs, drug metabolites, steroids and pesticides; Glatt H et al.; Although it has been observed that many epoxides are ultimate mutagens, surprisingly little is known about epoxides to which man may be extensively exposed, e.g., physiological compounds, drugs, drug metabolites and pesticides . We have now investigated 35 such and related epoxides for mutagenicity, using reversion of his- Salmonella typhimurium TA98 and TA100 as biological end-point . None of the tested steroids (12 compounds), vitamin K epoxides (3 compounds) and pesticides (dieldrin, endrin, HEOM (1,2,3,4,9,9-hexachloro-6,7-epoxy-1,4,4a,5,6,7,8, 8a-octahydro-1,4-methanonaphthalene), heptachlor epoxide) showed any mutagenic activity . Negative results were also obtained with the antibiotics oleandomycin, anti-capsin and asperlin, the cardiotonic drug resibufogenin, the widely used parasympatholytic drugs butylscopolamine and scopolamine, the sedatives valtratum, didovaltratum and acevaltratum, the tranquilizer oxanamide as well as with the drug metabolites carbamazepine 10,11-oxide and diethylstilbestrol alpha,beta-oxide . Three barbiturate epoxides, formed by metabolism of allobarbital, alphenal and secobarbital, caused weak but reproducible mutagenic effects at high concentrations . The cytostatic agent ethoglucide was the only drug having substantial mutagenic activity . Its mutagenic potency was similar to those of the control epoxides styrene 7,8-oxide, p-bromostyrene 7,8-oxide and m-bromostyrene 7,8-oxide, but much lower than those of benzo{a}pyrene 4,5-oxide, benzo{e}pyrene 4,5-oxide and 7,12-dimethylbenz{a}anthracene 5,6-oxide . Some epoxides were also tested in other Salmonella typhimurium strains or in the presence of rat-liver S9 mix . Positive results were only obtained with compounds that had already been detected as mutagens in the direct test with strain TA100.

Mutat Res, 1983 Oct, 111(2), 135 - 44
The superiority of hamster liver microsomal fraction for activating nitrosamines to mutagens in Salmonella typhimurium; Lijinsky W et al.; A number of nitrosamines which were carcinogenic in rats were not activated to mutagens in the Salmonella/mammalian microsome assay by the addition of the rat liver microsomal fraction . Some of these nitrosamines induced tumors in the liver of rats and others were carcinogenic to different organs of the rat . Most of these nitrosamines were activated to mutagens by hamster liver microsomal fraction . The use of the hamster preparation showed some compounds to be of very high mutagenic potency . In a few cases the nitrosamines mutagenic with hamster liver activation were more potent carcinogens in the hamster than in the rat . The compounds which were non-mutagenic to Salmonella with either rat or hamster liver activation included the liver carcinogens nitrosomethylethylamine, nitrosodiethanolamine and nitrosoethanolisopropanolamine, the esophageal carcinogens nitrosomethylneopentylamine, nitrosomethylaniline, nitrosomethyl-4-fluoroaniline, nitrosothiomorpholine and nitrosophenylbenzylamine, and the bladder carcinogens nitrosomethyl-3-carboxypropylamine and nitrosodiphenylamine.

Am J Orthod, 1983 Oct, 84(4), 344 - 50
"Single-step" orthodontic bonding systems: possible mutagenic potential; Cross NG et al.; Six commercially available orthodontic direct-bonding resin systems used to attach orthodontic brackets to tooth enamel were tested for bacterial mutagenicity by means of the Ames test . Components of two systems were found to yield positive spot test results with strains of Salmonella typhimurium . Positive spot test results were also obtained on the components applied to orthodontic brackets . Dose response curves for components of these systems were determined for aqueous and DMSO extracts using strain TA-100.

J Reticuloendothel Soc, 1983 Oct, 34(4), 279 - 87
Liposome-encapsulated cephalothin in the treatment of experimental murine salmonellosis; Desiderio JV et al.; The effectiveness of liposome-encapsulated cephalothin was compared with free cephalothin for the treatment of mice experimentally infected with Salmonella typhimurium . Compared with free cephalothin, following intravenous administration, liposome-encapsulated cephalothin was cleared from the circulation more rapidly and concentrated in the liver and spleen . Treatment of infected mice with the liposome antibiotic complex was more efficacious in terms of reducing the number of S . typhimurium in these organs as compared with the free antibiotic . The results suggest that liposome-encapsulated antimicrobial agents may possess a therapeutic advantage in the treatment of diseases caused by facultative intracellular bacteria since this manipulation favors delivery of the entrapped antibiotic to intracellular sites occupied by S . typhimurium.

J Bacteriol, 1983 Oct, 156(1), 471 - 4
Salmonella typhimurium LT2 strains which are r- m+ for all three chromosomally located systems of DNA restriction and modification; Bullas LR et al.; We describe the derivation of two strains of Salmonella typhimurium LT2 which are r- m+ for all three of the known chromosomal genes for the restriction and modification of DNA, hsdLT, hsdSA, and hsdSB; the strains were designated LB5000 and LB5010 . LB5000 is a smooth derivative sensitive to phage P22; LB5010 is a galE strain sensitive to phage P1.

J Bacteriol, 1983 Oct, 156(1), 424 - 8
Identification and characterization of a relA-dependent starvation-inducible locus (sin) in Salmonella typhimurium; Foster JW; By use of Mu cts d1(Ap lac) phage, a strain of Salmonella typhimurium was isolated containing a Mu d insertion in a locus (sinA) which is induced during nicotinate, thiamine, purine, amino acid, phosphate, and carbon starvation conditions . Depending on the starvation condition, a 2- to 10-fold increase in beta-galactosidase activity was demonstrated . The sinA locus, which mapped at 32 U, became induced after a decline in growth rate due to starvation . The introduction of relA into the sinA-lac strain prevented induction by nicotinate starvation and partially prevented induction by phosphate starvation . The data suggest that sinA responds to changes in growth rate due to various nutrient starvation conditions and probably responds in part to changes in guanosine tetraphosphate levels.

J Bacteriol, 1983 Oct, 156(1), 308 - 15
Intracellular activation of albomycin in Escherichia coli and Salmonella typhimurium; Braun V et al.; The antibiotic albomycin is actively taken up by Escherichia coli via the transport system for the structurally similar iron complex ferrichrome . Albomycin is cleaved, and the antibiotically active moiety is released into the cytoplasm, whereas the iron carrier moiety appears in the medium . Besides transport-negative mutants, additional albomycin-resistant mutants were isolated . The mutations were mapped outside the transport genes close to the pyrD gene at 21 min . The mutants were devoid of peptidase N activity . The molecular weight, sensitivity to inhibitors, and cytoplasmic location of the enzyme hydrolyzing albomycin in vitro corresponded to the known properties of peptidase N . The aminoacyl thioribosyl pyrimidine moiety of albomycin apparently has to be cleaved off the iron chelate transport vehicle to inhibit growth . Peptidase N is the major hydrolyzing enzyme . In Salmonella typhimurium peptidase N and peptidase A were equally active in hydrolyzing and activating albomycin.

Zh Mikrobiol Epidemiol Immunobiol, 1983 Oct, (10), 60 - 2
{Changes in the cAMP level in macrophages during the phagocytosis of Salmonella typhimurium . II . Effect of the virulence of microorganisms and the immune status of the macrophages on the dynamics of changes in cAMP levels}; Boichenko MN et al.; The dynamics of changes in the level of intracellular cyclic AMP in nonimmune and immune macrophages in the process of the phagocytosis of S . typhimurium virulent strain, its heated variant and its mutant with low virulence was studied . A transient increase in the level of cyclic AMP was shown to occur during the first 30 minutes of phagocytosis; this increase did not depend on the kind of the phagocytized object and on the activity of macrophages and neither had it any influence on the outcome of phagocytosis . The virulent strain also induced the three-fold increase of the level of cyclic AMP in nonimmune macrophages prior to their disintegration caused by the cytopathogenic action of the microorganism . In immune macrophages the virulent strain did not induce the secondary increase of the level of cyclic AMP.

Infect Immun, 1983 Oct, 42(1), 219 - 23
Enhancement of macrophage-mediated tumor cell killing by bacterial outer membrane proteins (porins); Weinberg JB et al.; Various microbial products are known to influence the function of mouse peritoneal macrophages . Lipopolysaccharide (LPS) and certain lipid A-associated proteins are known to enhance the tumoricidal effects of macrophages . The purpose of this study was to determine whether porins (outer membrane proteins) of Salmonella typhimurium G30/C21 would influence the activity of macrophages from lipid A-responsive and -unresponsive mice . Porins, extracted by a combined sodium dodecyl sulfate-EDTA method from cell walls, were free of LPS as determined by Limulus amebocyte lysate assay and appeared as a band at approximately 36,000 molecular weight on sodium dodecyl sulfate-polyacrylamide gel electrophoresis . In tumor cell killing assays done under LPS-free conditions, the porins in doses of 1 to 10 ng/ml enhanced the tumoricidal effect of macrophages from bacillus Calmette-Guerin-infected C3H/HeN or C3H/HeJ mice . Protein-free LPS enhanced the tumoricidal activity of macrophages from bacillus Calmette-Guerin-infected C3H/HeN but not C3H/HeJ mice . The tumoricidal-enhancing activity of protein-free LPS was blocked by the lipid A-binding antibiotic polymyxin B sulfate, but the effects of porins were not altered by the polymyxin B sulfate . These results suggest that porins, proteins known to alter membrane function, may alter macrophage function by interaction with macrophage membranes.

Carcinogenesis, 1983 Sep, 4(9), 1169 - 73
On the metabolism of quinoline and isoquinoline: possible molecular basis for differences in biological activities; La Voie EJ et al.; Quinoline is a hepatocarcinogen in mice and rats, a mutagen in Salmonella typhimurium, and induces unscheduled DNA synthesis in primary cultures of rat hepatocytes . In contrast, isoquinoline has not been shown to be genotoxic . The metabolites of quinoline and isoquinoline, as formed in vitro with rat liver homogenate, were identified to investigate possible molecular bases for the differences in their biological activity . The ethyl acetate extractable metabolites of quinoline and isoquinoline were analyzed directly by high pressure liquid chromatography and, after silylation, by capillary gas chromatography . The major metabolite of quinoline was 5,6-dihydroxy-5,6-dihydroquinoline . Lesser amounts of 2- and 3-hydroxyquinoline and quinoline-N-oxide were also identified as metabolites . 1-, 4- and 5-Hydroxyiso-quinoline and isoquinoline-N-oxide were detected as metabolites of isoquinoline . 5,6-Dihydroxy-5,6-dihydroiso-quinoline was detected as only a minor metabolite . This difference in the extent to which these isomers are ultimately metabolized to dihydrodiols may be associated with their differences in biological activity . Quinoline, 4-methylquinoline and 7-methylquinoline were bioassayed as tumor initiators on the skin of Sencar mice . While 4-methylquinoline was at least as potent a tumor initiator as quinoline, 7-methylquinoline was not significantly tumorigenic in this assay . These data are consistent with the hypothesis that formation of the 5,6-epoxide of quinoline is associated with its metabolic activation to a tumorigen.

Cancer Lett, 1983 Sep, 20(2), 147 - 55
Mutagenic and DNA damaging activity in muscle of trout exposed in vivo to nitrite; De Flora S et al.; Muscle ether extracts of rainbow trout (Salmo gairdneri) exposed to lake water enriched with nitrite (450 micrograms/l) reverted plasmid-containing his- strains of Salmonella typhimurium, mainly eliciting frameshift mutations, and induced a DNA damage in Escherichia coli reparable through the recA/lexA-dependent SOS functions . The number of revertants was related to their content in nitroso-derivatives and to the physiological condition of the fish . Mutagenicity was efficiently decreased, through NADPH-requiring pathways, by liver S-9 fractions from rats or rainbow trout, while it was not affected by preliminary heating nor by pre-incubation with human gastric juice.

Mutat Res, 1983 Sep, 121(3-4), 185 - 90
Identification of a mutagenic substance, in Rubia tinctorum L . (madder) root, as lucidin; Yasui Y et al.; Mutagenicity of the extract from Rubia tinctorum L . (madder) root was demonstrated on Salmonella typhimurium TA100 and TA98 . The active substance wa purified and characterized by TLC, UV spectrum, IR spectrum, mass spectrum and {1H}NMR spectrum . All the mutagenic activity of the extract from the root of Rubia tinctorum L . was due to lucidin (1,3-dihydroxy,2-hydroxymethyl-9, 10-anthraquinone).

Mutat Res, 1983 Sep, 121(3-4), 177 - 84
Absence of mutagenic activity of fodder proteins in the Ames Salmonella/microsome test; Pahlman R et al.; The mutagenicities of fodder proteins (Pekilo, L-lysine and Orsan) were tested towards Salmonella typhimurium in the plate-incorporation assay in the presence or absence of metabolic activation with a rat-liver S9 preparation . Filtrates and 2-, 5- and 10-fold-concentrated filtrates of saline- or ethanol-soluble fodder proteins were tested . No mutagenic activity was observed.

Can J Microbiol, 1983 Sep, 29(9), 1205 - 12
Derepression of F factor function in Salmonella typhimurium; Sanderson KE et al.; In Salmonella typhimurium LT2 the F factor of Escherichia coli K-12 replicates normally but is repressed; Flac+ cells give no visible lysis on solid media with male-specific phages, low frequency transfer of Flac+ (0.001-0.007 per donor cell), few f2 infective centers (0.002-0.006 per cell), and they propagate male-specific phages to low titers . Thus they display a Fin+ (fertility inhibition) phenotype . This repression, owing to pSLT, a 60 Mdal plasmid normally resident in S . typhimurium, was circumvented by the following materials: (i) Flac+ plasmids from E . coli with mutations in finP or traO; (ii) a S . typhimurium line which had been cured of pSLT; (iii) pKZl, a KmR plasmid in the same Inc group as pSLT, which caused expulsion of pSLT and made Fin- lines; (iv) F-Fin- mutants which originated spontaneously and which are present in most Hfr strains of S . typhimurium . Strains which are derepressed for F function by the above methods give visible lysis on solid media with male-specific phages, ca . 1.0 Lac+ recombinants per donor cell in conjugal transfer, ca . 0.82 f2 infective centers per cell, over 80% of cells with visible F pili, and propagation of male-specific phages to high titer . These data confirm earlier observations that pSLT represses F by the FinOP system . In addition, it shows that there is no other mechanism which represses F function in S . typhimurium . If donor function is derepressed by one of the above methods, and if rough recipient strains are used, F-mediated conjugation in S . typhimurium LT2 is as efficient as in E . coli K-12.

J Infect, 1983 Sep, 7(2), 156 - 8
Recurrent salmonella septicaemia with aortitis, osteomyelitis and psoas abscess; Brooks DJ et al.; A patient with low back pain and recurrent Salmonella typhimurium septicaemia is described . Investigations revealed an aortic aneurysm, lumbar osteomyelitis and a psoas abscess . The importance of thorough investigation of patients with low back pain and salmonella septicaemia is emphasised.

Zh Mikrobiol Epidemiol Immunobiol, 1983 Sep, (9), 40 - 6
{Effect of the R plasmids of Salmonella typhimurium strains of various origins on salmonella virulence}; Iakovleva ON et al.; Antibiotic-multiresistant S . typhimurium strains, phagovars 20 and 25, of different origin (isolated in hospital infections transferred through everyday contacts and by alimentary route, as well as from samples taken from open water basins and sewage) have been found to carry both transmissible and nontransmissible R plasmids . The frequency of the transfer of R plasmids to Escherichia coli K-12 C 600 rif varies within 0.6 X 10(-5) and 0.7 X 10(-3) per donor cell . The direct transfer of plasmids to S . typhimurium has been mostly realized only in the presence of the mobilizing plasmid, the transfer frequency being 1.0 X 10(-7) to 2.2 X 10(-4) per donor cell . S . typhimurium transconjugates show decreased virulence in both enteral and intraperitoneal infection of mice.

Rev Infect Dis, 1983 Sep-Oct, 5 Suppl 4, S702 - 7
Invasive enteric pathogens; Formal SB et al.; Invasive enteric pathogens of the Salmonella or Shigella genera initiate infections by invading the intestinal epithelium . Depending on the species, salmonellae either translocate across the mucosa of the small intestine and cause a systemic febrile disease or they evoke a localized inflammatory response in discreet areas of the infected mucosa . The latter type of infection is characterized by gastroenteritis, and a choleragen-like enterotoxin may contribute to the symptomology . Shigellae can also evoke diarrheal episodes; however, classic shigellosis is characterized by localized invasion of the colonic epithelium, with inflammation and ulceration of the mucosa . Derangement of the colonic mucosa is manifested in the bloody, mucoid stool characteristic of bacillary dysentery . Genetic analysis of invasive enteric pathogens has shown that extrachromosomal elements (plasmids) are required for full expression of virulence in Salmonella typhimurium, Yersinia enterocolitica, Shigella sonnei, and Shigella flexneri . In the latter species, at least three chromosomal regions are also necessary for virulence.

Mutat Res, 1983 Sep, 118(4), 277 - 88
The metabolic activation of dichloromethane and chlorofluoromethane in a bacterial mutation assay using Salmonella typhimurium; Green T; The metabolic activation and mutagenicity of dichloromethane and chlorofluoromethane were investigated using rat liver fractions and Salmonella typhimurium strain TA100 . Both dihalomethanes gave a mutagenic response without the addition of rat-liver fractions . This response has been shown to be due to bacterial metabolism of the test compounds by pathways believed to be similar to those known in the rat . When rat-liver post-mitochondrial supernatant was added to the mutagenicity assay, there was no significant increase in the mutagenicity of dichloromethane, whereas a 2-fold increase was observed for chlorofluoromethane under the same conditions . This increase was derived both from glutathione conjugation and cytochrome P450 oxidative dehydrochlorination . A significant increase in dichloromethane mutagenicity could only be achieved by increasing the concentration of post-mitochondrial supernatant . Under these conditions the increase in mutagenicity was derived solely from glutathione conjugation of dichloromethane . The difference in mutagenic response after the addition of rat-liver fractions can be explained by differences in the half lives of the reactive intermediates rather than a difference in overall metabolic rate between the two compounds.

Mutat Res, 1983 Sep, 118(4), 269 - 76
Genotoxic activity of pulp mill effluent in Salmonella and Saccharomyces cerevisiae assays; Kamra OP et al.; An XAD-2 resin concentrate of chlorination-stage pulp mill effluent was found to induce mutations in Salmonella typhimurium strains TA1535, TA100 and TA98 but not in strains TA1537 or TA1538 . The presence of either S9 mix, S9 mix without cofactors, or heat-inactivated S9 mix, reduced the mutagenic effects . Dose-related increases in gene conversion, mitotic recombination and aberrant colony formation in Saccharomyces cerevisiae strain D7 also were found.

Mutat Res, 1983 Sep, 118(4), 257 - 67
Mutagenicity of Nagara river sediment; Sato T et al.; The sediments of Nagara river and its bystreams were extracted with ether . The mutagenicities of the extracts were determined by the Ames test with Salmonella typhimurium TA100 with S9 mix . The extracts were fractionated on an activated silica-gel column with four kinds of organic solvent, namely iso-octane, iso-octane:benzene (1:1), benzene:ethyl acetate (1:1) and benzene:methanol (1:1) . The highest mutagenicity was observed in the iso-octane-benzene fraction of Arata river by using TA100 with S9 mix . Chemical substances in this fraction were identified by GC-MS and GC, and several kinds of polycyclic aromatic hydrocarbons (PAH) were found . Several peaks were unidentified, but these PAH, especially benzo {b} fluoranthene and benzo {a} pyrene, may contribute substantially to the mutagenicity of this fraction.

Mutat Res, 1983 Sep, 118(4), 229 - 39
A mutagenic metabolite synthesized by Salmonella typhimurium grown in the presence of azide is azidoalanine; Owais WM et al.; A mutagenic azide metabolite was purified from the medium in which Salmonella typhimurium cells were grown in the presence of azide . This metabolite was identified to be azidoalanine based on infrared and mass spectroscopy and elemental analysis . This compound appeared to be identical to the mutagenic compound synthesized in vitro from azide and O-acetylserine by partially purified O-acetylserine sulfhydrylase . The metabolite (azidoalanine) mutagenic efficiency and spectrum in S . typhimurium was similar to that of inorganic azide . The compounds 2-azidoethylamine, 2-bromoethylamine, 3-bromopropionic acid and N-(azidomethyl) phthalimide were also mutagenic with a similar spectrum to azide and azidoalanine, but with lower efficiency . The compounds 3-azidopropylamine, 4-azidobutylamine, 3-chloroalanine and ethylamine were only weakly or nonmutagenic . Numerous other chloro, bromo and azido phthalimide derivatives tested were nonmutagenic . It is suggested that the lack of azide mutagenicity (and perhaps carcinogenicity) in mammalian cells may be due to their inability to convert azide to azidoalanine.

J Infect Dis, 1983 Sep, 148(3), 563 - 70
Intraphagocytic killing of Salmonella typhimurium by liposome-encapsulated cephalothin; Desiderio JV et al.; Multilamellar liposomes (lipid bilayer vesicles) composed of phosphatidylcholine, cholesterol, and phosphatidylserine (molar ratio, 6:3:1) were produced and then made to entrap an aqueous solution of cephalothin . Resident murine peritoneal macrophages were shown to be capable of interiorizing the liposome-antibiotic complex; this event resulted in a relatively high intracellular concentration of cephalothin . In macrophages infected in vitro with Salmonella typhimurium, intracellular killing of the bacteria was maximal at 60 min of incubation; at this time, 60% of the interiorized organisms had been killed . Treatment of infected macrophages with liposome-encapsulated cephalothin enhanced the intraphagocytic killing of S typhimurium over that by macrophages treated with free cephalothin . These results demonstrate the superiority of liposome-encapsulated antibiotics to free antibiotics in effecting the elimination of a facultative intracellular bacterium from its intracellular site . This type of complex may find application in the treatment of diseases caused by this group of microorganisms.

Mutat Res, 1983 Sep, 123(1), 47 - 60
Sensitivity of different E . coli and Salmonella strains in mutagenicity testing calculated on the basis of selected literature; Dyrby T et al.; Two microbial screening test systems for gene (point) mutations, the Salmonella typhimurium assay (TA1535, TA1537, TA1538, TA98 and TA100) and the Escherichia coli WP2 reverse-mutation system (WP2, WP2uvrA, WP2pKM101 and WP2uvrApKM101), were compared with regard to sensitivity toward a broad spectrum of compounds that cause base-pair or frameshift mutations and that have known carcinogenic qualities . Based on available published literature we found that all 44 carcinogens and 9 non-carcinogens examined in both test systems also met with criteria for data acceptance drawn up by us . The results obtained are: firstly, that the Salmonella assay is decidedly better validated than the E . coli WP2 test; and secondly, that the E . coli test system sensitivity (91%) is fully on a par with the sensitivity of the Salmonella assay (72%) . This last is in divergence from earlier reports, e.g . Brusick et al . (1980), and this difference must be ascribed to the new plasmid-containing strains . The many compounds not tested in the E . coli department result in fewer false negatives in the E . coli test system and their omission constitutes a bias in favour of the E . coli assay . By eliminating compounds that are negative in Salmonella and dropped from the WP2 analysis owing to insufficient data, the sensitivity of the Salmonella system is raised to 84% as compared with 91% for the WP2 assay . The results further indicate that some of the tester strains are superfluous, and show an exceedingly sensitive test can be performed by combining the best tester strains from the two test systems.

J Bacteriol, 1983 Sep, 155(3), 1455 - 8
Purification and properties of trimethylamine oxide reductase from Salmonella typhimurium; Kwan HS et al.; The major inducible trimethylamine oxide reductase was purified from Salmonella typhimurium LT2 . The molecular weights of the native enzyme were estimated to be 332,000 by gel filtration and 170,000 by nondenaturing disc gel electrophoresis . In sodium dodecyl sulfate-gel electrophoresis, the enzyme formed a single band of molecular weight 84,000 . The isoelectric point was 4.28 . Maximum activity was at pH 5.65 and 45 degrees C . Reduced flavin mononucleotide, but not reduced flavin adenine dinucleotide, served as an electron donor . The Km for trimethylamine oxide was 0.89 mM and Vmax was 1,450 U/mg of protein . The enzyme reduced chlorate with a Km of 2.2 mM and a Vmax of 350 U/mg of protein.

J Bacteriol, 1983 Sep, 155(3), 1434 - 8
Periplasmic protein associated with the oligopeptide permeases of Salmonella typhimurium and Escherichia coli; Higgins CF et al.; A periplasmic protein essential for the function of the oligopeptide transport system of Salmonella typhimurium was identified . This protein, encoded by the oppA gene, is one of the most abundant proteins in the periplasm and, with an apparent molecular weight of 52,000, is considerably larger than any other known periplasmic transport component . A similarly abundant periplasmic protein forms part of the oligopeptide transport system of Escherichia coli.

Carcinogenesis, 1983 Sep, 4(9), 1179 - 83
Mutagenicity testing of steroids obtained from bile acids and cholesterol; McKillop CA et al.; Twenty bile acid or cholesterol derivatives were tested for mutagenicity by the Ames spot test procedure against five Salmonella typhimurium strains in the presence and absence of rat liver microsomes . No strong mutagens were identified, but four of the compounds increased the number of revertant colonies observed . Three of these compounds were selected for dose response experiments using the Ames plate incorporation assay procedure with strain TA 1538 . No positive results were obtained . These results suggest that none of the twenty bile acid derivatives tested is likely to be the initiating agent in the aetiology of colon cancer.

Cancer Res, 1983 Sep, 43(9), 4078 - 82
Mutagenicity of potassium alkanediazotates and their use as model compounds for activated nitrosamines; Hecker LI et al.; The mutagenicity of a series of potassium alkanediazotates in the Ames assay was studied . These compounds were isolated as solids and are soluble in dimethyl sulfoxide . Upon addition to water, they form diazohydroxides (which are postulated intermediates in the decomposition of alpha-hydroxylated nitrosamines) . The diazohydroxides decompose to electrophilic intermediates which may react with macromolecules or water . In the Ames assay, potassium diazotates produced his+ revertants in Salmonella typhimurium strains TA 100 and TA 1535 but not in strains TA 98, TA 1537, or TA 1538 . Methane, methane-d3, ethane, propane, and phenylmethanediazotates were mutagenic in strain TA 100, and all diazotates with the exception of phenylmethanediazotate, produced revertants in TA 1535 . The order of mutagenic potency of these compounds was: methane approximately equal to methane-d3 greater than ethane, greater than phenylmethane (TA 100) greater than propane greater than phenylmethane (TA 1535) = 0 . All diazotates were direct-acting mutagens and produced revertants even when no liver 9000 X g supernatant (S9) fractions were present . S9 fractions inhibited the mutagenicity of potassium diazotates, and equivalent concentrations of S9 fractions (3 mg protein per plate) from either rat or hamster liver, whether induced or not, were equally effective . Bovine serum albumin was not as effective as S9 fractions in inhibiting diazotate mutagenesis, but heat-inactivated (70 degrees for 20 min) S9 fractions were as inhibitory of methanediazotate mutagenicity as native S9 fractions were at low protein concentrations . The half-lives of mutagenicity of methane- and ethanediazotates in aqueous solutions were identical (less than or equal to 15 sec); after less than 2 min in solution, these diazotates were rendered completely inactive . The implications of these studies for mechanisms of nitrosamine action and the use of potassium alkanediazotates as model compounds for activated nitrosamines are discussed.

J Gen Microbiol, 1983 Sep, 129 (Pt 9), 2951 - 7
Transposition of a gene encoding OXA-2 beta-lactamase; Kratz J et al.; A bla gene encoding OXA-2 beta-lactamase has been transposed from the Salmonella typhimurium R plasmid R1767 . This transposable element which was designated Tn2410 encoded sulphonamide and mercury resistance in addition to the bla gene . It had a size of 18.5 kb and appeared to be flanked by small inverted repeats . Restriction enzyme analysis resulted in a detailed map of Tn2410, which showed a high degree of similarity with the published map of Tn2603, a transposon encoding OXA-1 beta-lactamase . The ampicillin and sulphonamide resistance genes on Tn2410 were mapped in a cluster on the region between the centre and the righ end of the map.

Proc Natl Acad Sci U S A, 1983 Sep, 80(17), 5355 - 8
DNA inversions in the chromosome of Escherichia coli and in bacteriophage Mu: relationship to other site-specific recombination systems; Plasterk RH et al.; The gene product of bacteriophage Mu gin catalyzes a 3,000-base-pair inversion in the DNA of the phage, thus changing its host range . In some strains of Escherichia coli there is a function that can complement Mu gin mutations . This function (pin) was cloned and shown to catalyze an inversion of 1,800 base pairs in the adjacent E . coli DNA (P region) . pin- derivatives carry the P region frozen in the (+) or (-) orientation . The function of the switch is not yet clear . The sequences of gin and pin were determined; they exhibit 70% homology . The sequences around the recombination sites of Gin and Pin are also largely homologous; a consensus sequence is derived for the recombination sites of Gin and Pin, and of Hin in Salmonella typhimurium . The amino acid sequences of Gin, Pin, Hin, and TnpR are compared, and the evolutionary relationship between these prokaryotic site-specific recombination systems is discussed.

J Bacteriol, 1983 Sep, 155(3), 1333 - 42
Characterization of Tn2411 and Tn2410, two transposons derived from R-plasmid R1767 and related to Tn2603 and Tn21; Kratz J et al.; Two transposable elements, Tn2410 and Tn2411, were isolated from Salmonella typhimurium R-factor R1767 . They have sizes of 18.5 and 18.0 kilobases, respectively . Tn2411 mediates resistance to streptomycin, sulfonamides, and mercury . In Tn2410, the streptomycin resistance gene was replaced by a gene coding for the production of the beta-lactamase OXA-2, which is responsible for ampicillin resistance . Physical and functional maps of both transposons were compared with those of Tn21, Tn4, and Tn2603 . From these data it appeared that Tn21 could be an ancestral transposon from which Tn2411, Tn2410, Tn2603, and Tn4 were evolved by the addition or deletion of small DNA segments.

J Bacteriol, 1983 Sep, 155(3), 1147 - 55
Roles for menaquinone and the two trimethylamine oxide (TMAO) reductases in TMAO respiration in Salmonella typhimurium: Mu d(Apr lac) insertion mutations in men and tor; Kwan HS et al.; Three groups of mutants defective in trimethylamine oxide (TMAO) reduction were isolated from Salmonella typhimurium LT2 subjected to transposition mutagenesis with Mu d(Apr lac) . Mutants were identified by their acidic reaction on a modified MacConkey-TMAO medium . Group I consisted of pleiotropic chlorate-resistant mutants which were devoid of TMAO reductase activity . None expressed the lac operon . Group II mutants were partially defective in TMAO reductase . Electrophoretic studies revealed that they lacked the inducible TMAO reductase, but retained the constitutive activity . The genotypic designation tor was suggested for these mutants . The tor mutation in one was located between 80 and 83 U on the S . typhimurium chromosome . Expression of the lac operon in these mutants was not affected by air, TMAO, or nitrate . Group III mutants reduced little or no TMAO in vivo, but their extracts retained full capacity to reduce it with methyl viologen . These mutants also failed to produce hydrogen sulfide from thiosulfate and could not grow anaerobically on glycerol-fumarate . Two subgroups were distinguished . Vitamin K5 restored wild-type phenotype in subgroup IIIa only; vitamin K1 restored wild-type phenotype in both IIIa and IIIb isolates . The genotypic designation men (menaquinone) was suggested for group III isolates . The mutation in IIIa mutants was cotransducible with glpT, which corresponds to the menBCD site in Escherichia coli . That in IIIb mutants was cotransducible with glpK, which corresponds to the menA site in E . coli . Expression of the lac operon in IIIa, but not IIIb, mutants was repressed by air . An additional mutant group isolated on the same medium consisted of strains defective in formate hydrogenlyase.

J Bacteriol, 1983 Sep, 155(3), 1009 - 14
Role of alanine-valine transaminase in Salmonella typhimurium and analysis of an avtA::Tn5 mutant; Berg CM et al.; In Salmonella typhimurium, as in Escherichia coli, mutations in avtA, the gene encoding the alanine-valine transaminase (transaminase C), are silent unless they are combined with mutations involved in isoleucine-valine biosynthesis . avtA is repressed by leucine or alanine but not by valine . Transaminase C is found at reduced levels upon starvation for any one of several amino acids . We hypothesize that this is due to repression of avtA by the elevated alanine and leucine pools found in amino acid-starved cells.

J Microw Power, 1983 Sep, 18(3), 295 - 304
Some basic properties of biological tissues for potential biomedical applications of millimeter waves; Gandhi OP; The paper gives the highlights of the reports in the literature on sharp, distinct resonances in the absorption and action spectra at millimeter wavelengths of various biochemicals, and bacteriological and biological preparations . If true, these properties may be employed for in-vitro diagnostic applications and form a basis for frequency-specific health hazards and for new forms of cancer therapy . Carefully performed experiments in our laboratory have failed to reveal frequency-specific biological effects on BHK-21/C13 mammalian cells, on induction of lambda prophages in lysogenic Escherichia coli and on back-mutation of His Salmonella typhimurium cells . Also on account of the high absorbance of water (13--36 dB/mm) which is an essential part of living tissues, little or no differences have been observed for the absorption spectra biological samples in the 26.5 to 90.0 GHz band . Dielectric characterization of the biological samples is needed and may form a basis for broadband differences in the millimeter wave absorption by various tissues.

Infect Immun, 1983 Sep, 41(3), 888 - 95
Induction of endotoxin tolerance with nonpyrogenic O-antigenic oligosaccharide-protein conjugates; Lindberg AA et al.; We prepared a dodecasaccharide, specific for the O-antigenic polysaccharide chain of Salmonella typhimurium (O-antigens 4 and 12), by the partial hydrolysis of the O-polysaccharide chain, utilizing bacteriophage 28B endo-alpha-L-rhamnosidase . The dodecasaccharide was shown by chemical and spectroscopical analyses to be totally devoid of lipid A and core oligosaccharide . By coupling this dodecasaccharide to human serum albumin, a glycoconjugate (DODECA-4809-ITC-HSA) was prepared and found to be (i) nonpyrogenic, (ii) unable to gelate a Limulus amoebocyte lysate, and (iii) unable to induce early-phase pyrogenic tolerance to endotoxin . Rabbits immunized either intravenously (with the glycoconjugate suspended in saline) or intrapopliteally (with the glycoconjugate suspended in Freund complete adjuvant) developed a significant although modest pyrogenic tolerance against challenge with the O-antigenic homologous S . typhimurium lipopolysaccharide (P less than 0.025 and P less than 0.01 for immunized and control rabbits, respectively) . The evoked tolerance was O-antigen specific since no pyrogenic tolerance against challenge with lipopolysaccharide from S . thompson (possessing identical lipid A and core oligosaccharide structures but differing in the O-antigen polysaccharide chain) could be seen (P greater than 0.1) . These results demonstrate that a nonpyrogenic O-antigenic polysaccharide hapten, when coupled to an immunogenic carrier protein, evokes immune responses which mediate significant, although modest, late-phase tolerance and is capable of partly reducing the pyrogenic activity of the O-antigenic homologous lipopolysaccharide.

Carbohydr Res, 1983 Aug 16, 120, 235 - 49
Carbohydrate specificity of the surface lectins of Escherichia coli, Klebsiella pneumoniae, and Salmonella typhimurium; Firon N et al.; A large number of linear and branched oligosaccharides and several glycosides of D-mannose were tested for their inhibitory activity on the agglutination of yeast cells or guinea pig erythrocytes by three D-mannose-specific enteric bacteria possessing type 1 fimbriae . With Escherichia coli 346, the best inhibitors found are the alpha glycosides of the branched oligosaccharides alpha-D-Manp-(1 leads to 3)-{alpha-D-Manp-(1 leads to 6)}-alpha-D-Manp-(1 leads to 6)-alpha-D-Manp-(1 leads to 3)-D-Manp and alpha-D-Manp-(1 leads to 3)-{alpha-D-Manp-(1 leads to 6)}-alpha-D-Manp- (1 leads to 6)-{alpha-D-Manp-(1 leads to 2)-alpha-D-Manp-(1 leads to 3) }-D-Manp and the trisaccharide alpha-D-Manp-(1 leads to 3)-beta-D-Manp-(1 leads to 4)-D-GlcNAc, all of which are 21-30 times more inhibitory than methyl alpha-D-mannopyranoside . The aromatic glycoside p-nitrophenyl alpha-D-mannopyranoside was also a strong inhibitor (30 times more inhibitory than methyl alpha-D-mannopyranoside), whereas the corresponding beta-D-glycoside was only a weak inhibitor (approximately as methyl alpha-D-mannopyranoside) . A nearly identical pattern of inhibitory activity was observed with the fimbriae . This suggests that the combining site of the E . coli fimbrial lectin is in the form of an extended pocket on the surface of the lectin corresponding to the size of a trisaccharide and fitting best the structure alpha-D-Manp-(1 leads to 3)-beta-D-Manp-(1 leads to 4)-D-GlcNAc . Since p-nitrophenyl alpha-D-mannopyranoside is a strong inhibitor, the existence of a hydrophobic region in the combining site or close to it was assumed . The combining site of the Klebsiella pneumoniae fimbrial lectin is probably similar to that of E . coli, but that of the Salmonella typhimurium fimbrial lectin differs considerably . It appears that the combining sites of the three bacterial lectins tested exhibit preference for structures found in N-glycosylic oligomannoside units of mammalian cell surface glycoproteins.

Eur J Biochem, 1983 Aug 15, 134(3), 497 - 502
Cloning and molecular characterization of the ompA gene from Salmonella typhimurium; Freudl R et al.; The ompA gene from Salmonella typhimurium, encoding a major heat-modifiable protein of the outer membrane, has been cloned and extensively characterized . When expressed in Escherichia coli the gene directs the synthesis of an OmpA protein which is functionally and topologically indistinguishable from that made in S . typhimurium, thus indicating that export and membrane incorporation are very similar in the two organisms . The S . typhimurium protein effectively substitutes for the E . coli polypeptide in F-dependent conjugation and in the uptake of certain colicins, although it cannot serve as the receptor for the OmpA-specific phages K3 and TuII . On examination of the primary sequence of the protein, predicted from the nucleotide sequence of its gene, it was found that those domains likely to be exposed on the cell surface were significantly different to the corresponding regions of the E . coli polypeptide . These differences in the structure of the two proteins have been used to interpret differences in their biological activities.

Nucleic Acids Res, 1983 Aug 11, 11(15), 5223 - 33
N4-aminocytidine, a nucleoside analog that has an exceptionally high mutagenic activity; Negishi K et al.; The reaction of cytidine with hydrazine to give N4-aminocytidine was greatly promoted by addition of a less-than-stoichiometric amount of bisulfite, and the product was isolated in a good yield . N4-Aminocytidine was strongly mutagenic to bacteria (Salmonella typhimurium TA100 and TA1535, and E . coli WP2 uvrA) and to phage (phi X174 am3) . The activity did not require the presence of mammalian microsomal fraction in the system . The mutagenic potency of N4-aminocytidine in these systems was two orders of magnitude greater than that of N4-amino-2'-deoxycytidine, and more than two orders of magnitude greater than that of N4-hydroxycytidine . The greater activity of the riboside than the deoxyriboside was ascribed to the lack of deoxycytidine kinase in these cells . This compound may be useful as a powerful mutagen to induce a transition mutation in microorganisms.

J Virol, 1983 Aug, 47(2), 311 - 6
Identification of a protein bound to the termini of bacteriophage PRD1 DNA; Bamford D et al.; Lipid-containing bacteriophage PRD1 has a double-stranded DNA genome of about 14,500 nucleotide base pairs . The phage can infect Escherichia coli and Salmonella typhimurium as well as other gram-negative bacteria harboring an appropriate plasmid . {35S}methionine label is incorporated into the DNA band early in infection . The label remains associated with DNA through phenol extraction and boiling with sodium dodecyl sulfate . Nuclease treatment of the genome released a protein which migrated as an early phage-specific protein (P8) . This protein is also necessary for phage DNA replication . By restriction enzyme analysis it was shown that protein was associated with the terminal restriction fragments . Extracts of infected cells catalyzed the labeling of protein P8 with {alpha-32P}dGTP.

Biull Eksp Biol Med, 1983 Aug, 96(8), 73 - 5
{Stimulation of DNA synthesis in guinea pig spleen lymphocytes by staphylococcal peptidoglycan}; Khorobrykh VV et al.; The mode of action of peptidoglycan on DNA synthesis in spleen lymphocytes of intact guinea-pigs was studied . It was found that peptidoglycan isolated from Staphylococcus aureus 2287 is mainly mitogenic for B lymphocytes that have IgG receptors on their surface . In contrast to lipopolysaccharide from Salmonella typhimurium, it seems that peptidoglycan is also mitogenic for less differentiated B cells.

Gann, 1983 Aug, 74(4), 483 - 92
Mutagenic activation of selected aminoazo compounds by rat liver: evidence for a cytochrome P-448 dependent reaction; Mori Y et al.; Mutagenicity of 3'-methyl-N,N-dimethyl-4-aminoazobenzene (3'-Me-DAB) and its N-demethylated products was examined using rat liver 9,000 g supernatant fraction (S-9) together with Salmonella typhimurium TA98 or TA100 as a tester strain . The expression of mutagenicity of 3'-Me-DAB required the presence of both microsomes and cytosol as sources of enzymes as well as NADPH as a cofactor . 3'-Me-DAB and its N-demethylated products showed no mutagenicity towards either strain when preincubated with S-9 from untreated rat livers . The involvement of a cytochrome P-450 species in the mutagenic activation was demonstrated with hepatic S-9 by using specific enzyme inducers and inhibitors . The treatment of rats with polychlorinated biphenyls or 3-methylcholanthrene resulted in a marked increase in the ability of S-9 to activate these compounds, whereas phenobarbital induction was not effective . All the mutagenic activities were considerably decreased by adding cytochrome c to the S-9 mixture, but the activation was insensitive to 1-(1-naphthyl)-2-thiourea and methimazole, high-affinity flavin-containing monooxygenase substrates . Carbon monoxide, metyrapone, and 2-diethylaminoethyl-2,2-diphenylvalerate hydrochloride, potent cytochrome P-450 inhibitors, had no inhibitory effect on the mutagenic activation . In contrast, 7,8-benzoflavone, a specific inhibitor of cytochrome P-448, considerably inhibited the reaction . These results suggest that cytochrome P-448 and a cytosol component are involved in the mutagenic activation of 3'-Me-DAB and its N-demethylated products.

J Anim Sci, 1983 Aug, 57(2), 279 - 85
Effect of feeding chlortetracycline or virginiamycin on shedding of salmonellae from experimentally-infected swine; Jones FT et al.; Swine from a herd routinely fed subtherapeutic levels of chlortetracycline (CTC) were fed a diet containing 55 mg of CTC/kg, a diet containing 55 mg of virginiamycin/kg, or a control diet . All animals were inoculated with Salmonella typhimurium that was susceptible to tetracycline . The quantity, duration and prevalence of shedding of S . typhimurium were determined . The infecting organism was first recovered from the animals fed CTC or the control diet on d 2, from animals fed virginiamycin on d 7 and from animals in a second control group on d 10 . The infecting organism was recovered in fewer samples obtained during the initial 7 d postinfection than in those obtained during the last 24 d of the study . Little transfer of resistance to the infecting organism seemed to have occurred from the resident microflora because only two isolates (1%) had resistant patterns that differed from that of the infecting organism . Feeding CTC or virginiamycin to swine did not significantly increase or prolong shedding of an experimentally infected tetracycline-susceptible strain of S . typhimurium . Neither antibiotic affected the drug resistance of the infecting organism.

Mutat Res, 1983 Aug, 118(3), 129 - 52
The genetic toxicology of Kathon biocide, a mixture of 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one; Scribner HE et al.; Kathon biocide, an aqueous solution containing a mixture of 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one in an approximate ratio of 3:1, was tested for mutagenic activity in Salmonella typhimurium, L5178Y mouse lymphoma cells in culture and Drosophila melanogaster . Tests also were conducted for chromosome aberrations in vivo on mouse bone marrow cells, for DNA damage/repair in primary rat hepatocytes in culture, and for morphological transformation in C3H 10T1/2 cells in culture . Kathon biocide produced point mutations in the absence of a rat-liver metabolizing system in bacteria (strain TA 100) and mammalian cells in culture . In the presence of rat-liver metabolizing system a 10-fold higher concentration was required to induce point mutations in mammalian cells in culture . No mutagenic activity was observed with the metabolizing system and S . typhimurium . Negative results were obtained in the sex-linked recessive lethal assay in Drosophila, the in vivo cytogenetic assay in mice, the unscheduled DNA synthesis assay in cultured rat hepatocytes, and the in vitro cell transformation assay.

J Bacteriol, 1983 Aug, 155(2), 831 - 8
Procedure for isolation of bacterial lipopolysaccharides from both smooth and rough Pseudomonas aeruginosa and Salmonella typhimurium strains; Darveau RP et al.; Lipopolysaccharide (LPS) is a major component of the outer membrane of gram-negative bacteria . It is now well established that within a single organism, size heterogeneity of this molecule can exist . We have developed a LPS isolation procedure which is effective in extracting both smooth and rough LPS in high yields (51 to 81% of the LPS present in whole cells as quantitated by using hydroxy fatty acid, heptose, and 2-keto-3-deoxyoctonate yields) and with a high degree of purity . The contamination by protein (0.1% by weight of LPS), nucleic acids (1%), lipids (2 to 5%), and other bacterial products was low . Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the LPS demonstrated the presence of a high degree of size heterogeneity in the isolated smooth LPS as well as the presence of significant amounts of rough-type LPS . The Pseudomonas aeruginosa LPS interacted well with a monoclonal antibody in a variety of immunochemical analyses . The usefulness of the procedure was demonstrated by comparing LPS preparations obtained from wild-type and mutant strains of P . aeruginosa and Salmonella typhimurium . For example, it was shown that the LPS of an antibiotic supersusceptible mutant Z61 of P . aeruginosa, which was previously characterized as identical to wild type with respect to the ratio of smooth to rough LPS molecules isolated by the phenol-water procedure, actually contained only a small proportion of O-antigenic side chains.

Exp Parasitol, 1983 Aug, 56(1), 1 - 8
Toxoplasma gondii: decreased resistance to intracellular bacteria in mice; Wing EJ et al.; The effect of sublethal inocula of Toxoplasma gondii on the course of listeriosis and salmonellosis in mice was investigated . Intravenous injection of T . gondii 24 hr after inoculation of Listeria monocytogenes increased mortality from 16% (L . monocytogenes alone) to 68% (L . monocytogenes + T . gondii) (P less than 0.001) . Multiplication of L . monocytogenes in spleens also was increased significantly in mice given T . gondii . By 3 days after infection, mice that had received T . gondii and L . monocytogenes had approximately 10 times the number of L . monocytogenes per spleen compared to mice receiving L . monocytogenes alone . Similarly, mortality and the number of bacteria in spleens were increased in mice injected with Salmonella typhimurium and then inoculated with T . gondii . An in vitro assay of macrophage listeriacidal activity was used to investigate the mechanism of this decreased resistance . Peritoneal macrophages from mice injected with T . gondii were less bactericidal than macrophages from uninfected mice . Delayed hypersensitivity responses to L . monocytogenes antigen were markedly suppressed in mice injected with T . gondii . T . gondii infection appears to suppress both macrophage and T-lymphocyte function and may result in decreased resistance to infections caused by intracellular bacteria.

Zh Mikrobiol Epidemiol Immunobiol, 1983 Aug, (8), 21 - 7
{Bacteriophage P22 H5 transfection and infection of plasmid Salmonella strains}; Riazanova LA et al.; The results of the Ca2+-dependent transfection of the DNA of bacteriophage P22 H5 to constructed Salmonella typhimurium F'- and R+-strains LT2 WT-R and SA118 demonstrated that in these salmonellae the effectiveness of transfection depended on the specificity of the interrelation of plasmids with host strains . Plasmids RA1, R538-1 and RP1 stimulated the transfection of S . typhimurium strain LT2 WT-R, but suppressed the transfection ability of S . typhimurium strain SA118 . At the same time the expression of the function of plasmids R446b and R64-11 did not depend on the host strain, as the former did not affect and the latter suppressed the release of transfectants in both Salmonella strains . The presence of plasmids R124, RA1, R64-11 and R724 in strain SA118, heat-sensitive in respect to the synthesis of cell-wall lipopolysaccharide, not only led to a decrease in the effectiveness of transfection; the effectiveness of the inoculation of bacteriophage P22 H5 was also suppressed 10(4) times in the presence of plasmid R124 and at least 10(10) times in the presence of 3 other plasmids . The development of resistance to S-specific bacteriophage P22 H5 was not linked with disturbances in the adsorption of this bacteriophage . Besides, the addition of CaCl2 into the medium completely removed the limitation of infection with bacteriophage P22 H5, determined by plasmid R124.

Poult Sci, 1983 Aug, 62(8), 1553 - 8
Influence of age on the temperature response of chickens to Escherichia coli and Salmonella typhimurium endotoxins; Jones CA et al.; An experiment was conducted to investigate the influence of age on the temperature responses of chickens given bacterial endotoxins . Broiler cockerels 1 to 8 weeks of age received a single intravenous injection of either distilled water (controls), Escherichia coli 0127:B8, or Salmonella typhimurium endotoxins . Rectal temperatures were recorded before and after injection, the birds were placed in an environmental chamber preheated to 33 C, and thereafter rectal temperatures were taken every 30 min for 180 min . In one-week-old chicks, a significant temperature loss was found 30 min after E . coli treatment, and this was followed 60 min later by a significant increase in rectal temperature . The E . coli and S . typhimurium treatments caused a .4 and .5 C increase, respectively, in 2-week-old chicks . Birds aged 3 to 8 weeks developed fevers with maximum changes in rectal temperatures ranging from .3 to 1.6 C . Seven- and eight-week-old chicks developed the highest and most persistent fevers . The febrile response of 5 to 8 week-old chicks was of longer duration than that of younger chicks . It was concluded that the febrile response following endotoxin administration is affected by age.

J Biochem (Tokyo), 1983 Aug, 94(2), 433 - 41
Purification and properties of two binding proteins for branched-chain amino acids in Salmonella typhimurium; Ohnishi K et al.; Two leucine-binding proteins isolated from osmotic shock fluid of Salmonella typhimurium LT2 were purified by DEAE-cellulose and DEAE-Sephadex A-50 chromatography, and subsequent isoelectric focusing . These purified binding proteins could be crystallized by adding 2-methyl-2,4-pentanediol . One of the binding proteins, designated as LIVT-binding protein, binds L-leucine, L-isoleucine, L-valine, and L-threonine, while the other, L-binding protein, binds only L-leucine . The level of LIVT-binding protein in the shock fluid was about three-fold higher than that of L-binding protein . The molecular weight of the LIVT-binding protein was estimated to be 35,000 by gel filtration, and 39,000 by gel electrophoresis . The isoelectric point was pH 4.94 . The dissociation constants of this protein for leucine, isoleucine, and valine were 0.43, 0.15, and 0.89 microM, respectively . For the L-binding protein, molecular weights of 34,000 (gel filtration), and 38,000 (gel electrophoresis) were obtained . The isoelectric point was pH 4.74 . The dissociation constant of this protein for leucine was 0.54 microM . The LIVT-binding protein was more heat-stable than the L-binding protein . These two binding proteins showed an antigenic similarity, they could cross-react with each other's antiserum . This similarity was also found between the binding proteins of Salmonella typhimurium and Escherichia coli K-12 . Both LIVT- and L-binding proteins in a regulatory mutant, KA2313, were found to be about three-fold the levels in the wild-type strain.

J Appl Bacteriol, 1983 Aug, 55(1), 89 - 95
Factors affecting the survival of Salmonella and Escherichia coli in anaerobically fermented pig waste; Henry DP et al.; The survival of Salmonella typhimurium was investigated in acidogenic, anaerobically fermented pig wastes and in synthetic media, each containing volatile fatty acids (VFA) . Salm . typhimurium survived at pH 6.8, but not at pH 4.0, when incubated at 37 degrees C for 24 h in either fermented or synthetic medium containing VFA . The minimum inhibiting concentration of VFA for Salm . typhimurium after 48 h incubation at 30 degrees C at pH 4.0 was 0.03 mol/l and for Escherichia coli it was 0.09 mol/l . Fermented pig wastes in a digester, maintained at pH 5.9, were inoculated with Salm . typhimurium and then incubated at 37 degrees C for 24 h . The pH was adjusted to either 4.0 or 5.0 and after a further 48 h at 30 degrees C, Salm . typhimurium survived at pH 5.0 but not at pH 4.0 . It was concluded that pH is critical in determining the survival of this organism in acidogenic anaerobically fermented pig waste.

J Appl Bacteriol, 1983 Aug, 55(1), 101 - 10
Hazard analysis applied to microbial growth in foods: development of mathematical models describing the effect of water activity; Broughall JM et al.; Mathematical models have been developed which describe the effect of lowering the water activity on the growth kinetics of Staphylococcus aureus and Salmonella typhimurium . By treating the lag phase and exponential phase kinetics separately predictions can be made on the extent of microbial growth over successive time/temperature cycles . Staph . aureus was far more tolerant than Salm . typhimurium to lowered water activity and under near growth limiting conditions of water activity and temperature was showing lag periods as long as ca 40 d . The maximum lag period observed for Salm . typhimurium was ca 5 d . Under these conditions the predicted generation times for Staph . aureus were 2-3 d and for Salm . typhimurium.

J Hyg (Lond), 1983 Aug, 91(1), 33 - 45
The excretion of Salmonella typhimurium in the faeces of calves fed milk substitute; Hinton M et al.; A total of 495 calves in 16 batches were examined (117 calves in 4 batches in 1979 and 378 in 12 batches in 1982) . They were purchased in markets, transported by road to a farm in Somerset and reared on a milk substitute diet for a period of up to five weeks . Salmonella typhimurium phage type DT 193 was endemic in 1979 and phage type DT 204c in 1982 . The mortality rates in the two years were 9.4% and 1.9% respectively . The causes of death were not investigated although the majority were probably due to salmonellosis . The rate of isolation of S . typhimurium from the rectal faeces of calves in all groups was either zero or relatively low on arrival . It rose to a peak (which was higher in 1979) in the second or third weeks before declining to low levels by the end of the fourth week of residence on the farm . Data from 162 calves, examined twice weekly for four weeks in 1982, indicated that the distribution of infected calves, based on the number of times that S . typhimurium was isolated from each, was not random . The calves could be assigned to two main categories; those from which the organism was never isolated and those from which it was isolated at least twice . This suggested that salmonella infected calves actively excreted the organism . The association between salmonella excretion and medication of sick animals with antibacterial drugs was strongest during the second week . Over the four-week period nearly 40% of the calves found to be excreting S . typhimurium were not treated, indicating a high incidence of subclinical infection . Salmonella excretion by the calves followed a regular pattern and infection was self-limiting within five weeks . The peak in the salmonella excretion rate and the mortality rate were higher in 1979 when phage type DT 193 was the endemic strain . However, in 1982 the calves received 100 p.p.m . furazolidone in their milk ration during the first week of their stay on the farm, and this may have contributed to the differences noted between the two years.

Mutat Res, 1983 Aug, 121(2), 89 - 94
Structure-function characterization of phenanthridinium compounds as mutagens in Salmonella; Fukunaga M et al.; The mutagenic activity of some phenanthridinium compounds was examined by using Salmonella typhimurium strain TA98 . Microsomal enzyme activation of the compounds was necessary for the detection of frameshift mutagenesis . Amino and/or azido functions at both R3 and R8 were structural requisites for significant mutagenic activity, although mutagenicity was severely reduced for the diazido analog . When an azido or amino group was substituted by hydrogen at either R3 or R8, mutagenic activities were minimal, and the deaminated compound (3,8-dihydro derivative) was not mutagenic . Propidium was only slightly more mutagenic than the monoamino and monoazido analogs . Relationships between mutagenic activity and chemical structure of phenanthridinium compounds are discussed.

Mutat Res, 1983 Aug, 121(2), 107 - 16
Demonstration of a powerful mutagenic dinitropyrene in airborne particulate matter; Tokiwa H et al.; Of the many nitroarenes, dinitropyrenes (DNPs) have the potential to revert Salmonella typhimurium his- mutants . This study was conducted to investigate the potential mutagens present in airborne particulate matter collected in Santiago, Chile . 5 organic substances extracted with dichloromethane showed mutagenic rates of from 38.9 to 287 revertants per m3 of air for S . typhimurium his- strain TA98 without S9 mix . 4 of the samples had greatly reduced mutagenicity for strain TA98/1,8DNP6 but not for strain TA98NR . The 1-nitropyrene (1-NP) content accounted for 0.06-0.15 microgram per g of particulate, as determined by high-performance liquid chromatography (HPLC), but the contribution of the compound to mutagenicity was less than 1% of the total activity . On the other hand, by using two columns in the HPLC, DNPs of 1,6- and 1,8-isomers were detected in the samples pooled after the determination of 1-NP, and the amount of the derivatives was about 0.2 microgram per g of particulate matter.

Mutat Res, 1983 Aug, 118(3), 177 - 89
High mutagenic potency of several polycyclic aromatic hydrocarbons induced by liver postmitochondrial fractions from control and xenobiotic-treated immature carp; Protic-Sabljic M et al.; The metabolism of carcinogens in fish was examined by measuring the activation of different polycyclic aromatic hydrocarbons (PAH) by carp (Cyprinus carpio L.) liver post-mitochondrial fractions (S9) using the Salmonella typhimurium TA100 reverse mutation assay . For this study, 1 non-carcinogen, anthracene (AN), and 4 carcinogens, chrysene (CHR), benzo{a}pyrene (BaP), 3-methylcholanthrene (3MC) and 7,12-dimethylbenzanthracene (DMBA), were chosen . The bioactivating potency of the metabolic systems of carp pretreated with phenobarbital (PB), 3MC or Aroclor 1254 (ARO) were compared to uninduced carp liver . The results show that carp liver has the ability to metabolize carcinogenic PAH into mutagenic metabolites, which is enhanced when carp are pretreated with 3MC or ARO, but not with PB . A positive correlation between the induction of aryl hydrocarbon hydroxylase (AHH) activity in carp liver and the mutagenic potencies of CHR, BaP, DMBA and 3MC, has been observed . The bioactivating ability of carp liver S9 was compared with the ability of the same fractions from female Wistar rats (this study) as well as from Sprague-Dawley rats (literature data) . When the mutagenic potencies of selected PAH had been normalized on the activity of BaP, the following order of mutagenic activities with S9 fractions from ARO-treated animals was obtained: (1) BaP (1) greater than DMBA (0.26) greater than 3MC (0.22) greater than CHR (0.05) greater than AN (0) for carp; (2) BaP (1) greater than 3MC (0.48) greater than CHR (0.31) greater than DMBA (0.16) greater than AN (0) for Sprague-Dawley rats; and (3) BaP (1) greater than 3MC (0.17) greater than DMBA (0.11) greater than CHR (0) = AN (0) for female Wistar rats . We conclude that carp and rats are very similar in their ability to activate carcinogenic PAH into mutagenic metabolites, which suggests that carp may be very susceptible to the carcinogenic activity of these compounds . According to our results from the mutagenicity study, as well as from the enzyme induction study, we propose the use of carp as a suitable model system for the study of chemical carcinogens.

Mutat Res, 1983 Aug, 118(3), 167 - 76
Genotoxic properties of 2,4,7-trinitro-9-fluorenone; Sorenson WG et al.; The genotoxic effects of 2,4,7-trinitro-9-fluorenone (TNF) were studied in assays employing procaryotic (Salmonella typhimurium and Escherichia coli) and eucaryotic (Saccharomyces cerevisiae, mouse lymphoma L5178Y and Chinese hamster ovary) cells . The results show that TNF is a potent mutagen for procaryotes . It causes both frame-shift and base-pair substitution mutations, although frame-shift mutations were predominant . In Saccharomyces cerevisiae, this compound appeared to be too toxic to permit detection of genotoxic effects . TNF was also toxic to mouse lymphoma cells and Chinese hamster ovary cells but the toxic effects were reduced by metabolic activation . TNF induced a clear increase in sister-chromatid exchanges in CHO cells and in mutant frequency in mouse lymphoma cells both in the presence and absence of metabolic activation.

Mutat Res, 1983 Aug, 118(3), 153 - 65
The capacity of some nitro- and amino-heterocyclic sulfur compounds to induce base-pair substitutions; Voogd CE et al.; The capacity of 27 heterocyclic sulfur compounds to induce base-pair substitutions was investigated with Klebsiella pneumoniae ur- pro- and Salmonella typhimurium TA100 as test organisms . Among the compounds tested, all sulfur compounds with nitro groups and some thiazoles with an amino group were mutagenic . Among the nitrothiazoles, the most potent mutagen was niridazole, followed by 2-acetamido-5-nitrothiazole, 2-bromo-5-nitrothiazole, N-(5-nitrothiazol-2-yl)benzamide, and 2-amino-5-nitrothiazole . Of the nitrothiophenes, 2-nitrothiophene was more mutagenic than 3-nitrothiophene and 2,4-dinitrothiophene . 4-Nitroisothiazole was also mutagenic . Of the aminothiazoles, 2-amino-5-bromothiazole and 2-amino-5-chlorothiazole were mutagenic to both test organisms . With 2-amino-5-(p-nitrophenylsulfonyl)thiazole, a mutagenic action was only found with Salmonella typhimurium TA100, whereas 2-aminothiazole and 2-amino-4-methylthiazole were only mutagenic with Klebsiella pneumoniae . With the other 13 compounds, no mutagenic activity was observed . Of the coccidiostatics, 2-acetamido-5-nitrothiazole was also mutagenic on Escherichia coli K12 and Saccharomyces cerevisiae D4 but non-mutagenic on Salmonella typhimurium TA1530, TA1535, TA1537 and TA98, while 2-amino-5-nitrothiazole was mutagenic on Escherichia coli K12, Salmonella typhimurium TA1530, TA1535 and TA98, and non-mutagenic on strain TA1537 and on Saccharomyces cerevisiae D4.

Mutat Res, 1983 Aug, 110(2), 243 - 62
Curing and induction of the Fels 1 and Fels 2 prophages in the Ames mutagen tester strains of Salmonella typhimurium; Affolter M et al.; A method is described for curing the Ames Salmonella mutagen tester strains of their Fels 1 and Fels 2 prophages with the aid of the antitumor drug daunorubicin . Non-lysogenic derivatives corresponding to TA100 and TA1535 were isolated and designated TAQ100 and TAQ1535 respectively . In addition, the Fels 1 monolysogens TAQ100F1 and TAQ1535F1, as well as the Fels 2 monolysogens TAQ100F2 and TAQ1535F2, were obtained . Finally, strains corresponding to TA98 and TA1538 cured of Fels 2, but retaining a cryptic Fels 1 (F1d) prophage were isolated and designated TAQ98F1d and TAQ1538F1d respectively . The various cured derivatives were identified by colony hybridization with 32P-labeled probes of Fels 1 and Fels 2 DNA . Southern blot hybridizations confirmed that phage-specific Fels DNA sequences were missing from the cured strains . The Fels 2-cured strains were resistant to Fels 2, but Fels 1 grew, albeit poorly, on the Fels 1-cured strains . Strains TAQ100F1, TAQ1535F1, TAQ100F2 and TAQ1535F2 were used in prophage induction assays, in the presence of rat-liver extract where necessary . Daunorubicin, bleomycin, mitomycin C, aflatoxin B1, 2-amino-dipyrido{1,2-a:3',2'-d}imidazole (Glu-P-2) were found to induce Fels 1 and/or Fels 2 in at least one of these strains . The induction of the Fels prophages in the TAQ monolysogens may provide a useful complement to the Ames test for the detection of DNA-damaging agents and potential carcinogens.

Mutat Res, 1983 Aug, 110(2), 181 - 219
Quantitative comparison of carcinogenicity, mutagenicity and electrophilicity of 10 direct-acting alkylating agents and of the initial O6:7-alkylguanine ratio in DNA with carcinogenic potency in rodents; Bartsch H et al.; The quantitative relationship between carcinogenicity in rodents and mutagenicity in Salmonella typhimurium was examined, by using 10 monofunctional alkylating agents, including N-nitrosamides, alkyl methanesulfonates, epoxides, beta-propiolactone and 1,3-propane sultone . The compounds were assayed for mutagenicity in two S . typhimurium strains (TA1535 and TA100) and in plate and liquid assays . The mutagenic activity of the agents was compared with their alkylating activity towards 4-(4'-nitrobenzyl)pyridine and with their half-lives (solvolysis constants) in an aqueous medium . No correlations between these variables were found, nor was mutagenic activity correlated with estimates of carcinogenicity in rodents . There was a positive relationship between carcinogenicity and the initial ratios of 7-:O6-alkylguanine formed or expected after their reaction with double-stranded DNA in vitro . The results suggest that alkylation of guanine at position O6 (or at other O atoms of DNA bases) may be a critical DNA-base modification that determines the overall carcinogenicity of these alkylating agents in rodents.

Infect Immun, 1983 Aug, 41(2), 751 - 7
Salmonella typhimurium infection in calves: cell-mediated and humoral immune reactions before and after challenge with live virulent bacteria in calves given live or inactivated vaccines; Lindberg AA et al.; Groups of six calves, 4 to 5 weeks old, were vaccinated either orally with a live auxotrophic Salmonella typhimurium (O-antigen 1,4,12) SL1479 vaccine (10(8) bacteria on day zero, 10(10) bacteria on days 7 and 14) or subcutaneously with a heat-inactivated (56 degrees C, 30 min) S . typhimurium SVA1232 vaccine (10(10) bacteria suspended in 30% {vol/vol} aluminum hydroxide on days zero, 7, and 14) . The calves were then orally challenged with either 10(6) (approximately 100 X the 25% lethal dose) or 10(9) (approximately 100,000 X the 25% lethal dose) live bacteria of the calf-virulent S . typhimurium SVA44 strain . The immune reactivity of these calves and of nonvaccinated control calves was followed before and after the challenge infection up to 42 days by (i) intradermal injection of S . typhimurium crude extract, outer membrane protein preparation (porins), and lipopolysaccharide (LPS), (ii) in vitro stimulation of peripheral blood lymphocytes estimated by using uptake of {3H}thymidine, with S . typhimurium crude extract, porins, LPS, and polysaccharide (O-antigenic polysaccharide chain free of lipid A), and Salmonella sp . serotype thompson (O-antigen 6,7) strain IS40 LPS and polysaccharide, and (iii) estimation of the class-specific immunoglobulin G (IgG) and IgM antibody responses against S . typhimurium LPS and porins, and Salmonella sp . serotype thompson LPS . The immune studies showed that in calves given the live vaccine orally, the skin test reactivity and lymphocyte stimulation indices were significantly higher (P values ranging from less than 0.025 to less than 0.0005) against homologous, but not heterologous, antigens than those seen in calves given the heat-inactivated vaccine subcutaneously . In contrast, the IgG and IgM antibody titers against homologous LPS and porins were significantly higher (P less than 0.0005) in sera collected on day 21 from calves given the heat-inactivated vaccine than in calves given the live vaccine . After the oral challenge, calves given the live vaccine showed reduced cell-mediated immune reactions, in agreement with the observation that the host defense could eradicate the challenge organism, whereas calves given the heat-inactivated vaccine showed significantly increased cell-mediated immune reactions (P values ranging from less than 0.025 to less than 0.005), in agreement with the observation that in these calves, the challenge strain caused enteritis as well as systemic invasion . The increased cell-mediated immune reactivity in calves given the live vaccine correlated well with the excellent protection against challenge infection seen in these animals.

Cancer Res, 1983 Aug, 43(8), 3674 - 9
Effect of dietary protein concentration on yield of mutagenic metabolites from 1,2-dimethylhydrazine in mice; Kari FW et al.; The effects of varying dietary protein concentrations on the metabolism of 1,2-dimethylhydrazine (DMH) to mutagenic products by male C57BL/6 X C3H F mice were assayed by in vivo and in vitro methods . DMH and its metabolite, azoxymethane (AOM), did not increase the mutation frequency of Salmonella typhimurium (strain G-46) in vitro alone or in the presence of mouse liver homogenates capable of activating the promutagen dimethylnitrosamine . Methylazoxymethanol (MAM), another metabolite of DMH, was mutagenic in vitro without activation . S.c . administration of DMH, AOM, or MAM at dosages ranging from 0.2 to 0.8 mmol/kg of body weight caused dose-dependent increases in mutations of S . typhimurium in the host-mediated assay, and molar potencies increased progressively from DMH to AOM to MAM . S.c . or i.p . injections of AOM increased host-mediated mutagenesis within 20 min, while increases in mutagenesis by DMH required at least 1 hr . When {14C}DMH was administered, {14C}azomethane was expired immediately, while 14CO2 began to appear 1 hr after DMH administration . The percentage of administered {14C}DMH expired as azomethane varied inversely with dietary protein concentration, while AOM-induced host-mediated mutagenesis was directly proportional to dietary protein (p less than 0.01) . The percentage of DMH converted to mutagenic end products was limited by losses of the volatile metabolite azomethane, especially in protein-deficient mice . Greater expiration of azomethane and decreased conversion of AOM to MAM, both seen with restriction of dietary protein, were associated with a smaller body burden of DMH metabolites.

Cell, 1983 Aug, 34(1), 143 - 9
Evidence that a nucleotide sequence, "boxA," is involved in the action of the NusA protein; Friedman DI et al.; We report the isolation of a mutation, boxA1, in the nutR region of the phage lambda genome . The nutR region, located downstream of the pR promoter, includes the site nutR where the lambda N protein is thought to act to render subsequent transcription termination-resistant . We have previously suggested that the boxA sequence, 5'CGCTCTTA3' (or its RNA analog), located 8 bp promoter-proximal to nutR, might be the recognition site for the E . coli host factor, NusA, which has been shown to be necessary for N action . The boxA1 mutation, an A:T to T:A transversion, results in a changed boxA sequence upstream of nutR, CGCTCTTT . This change is necessary for lambda to effectively use the NusA of Salmonella typhimurium, a NusA function not normally active with the N product of lambda . Other lambdoid phages with unique N functions and nut sites that are normally active with the NusA of Salmonella have boxA sequences with the terminal three Ts . Moreover, sequences closely resembling boxA have been found near transcription termination sequences in E . coli operons where NusA has been shown to be involved in termination . These findings identify boxA as an important recognition signal for the NusA protein.

Proc Natl Acad Sci U S A, 1983 Aug, 80(16), 4894 - 8
Replacement and amplification of bacterial genes with sequences altered in vitro; Gutterson NI et al.; An efficient method for the replacement of chromosomal DNA by segments altered in vitro has been developed for bacteria . The method requires (i) a recombinant plasmid with a ColE1-like replicon and (ii) a strain defective in DNA polymerase I (polA), which is unable to replicate the plasmid extrachromosomally . This method is of general use since there are a number of suitable vectors and polA strains are available in both Escherichia coli and Salmonella typhimurium, the two most widely studied bacterial species . Using the method, we have constructed two chromosomal deletions in the chemotaxis gene region of S . typhimurium . In addition, plasmid sequences integrated into the chromosome have been amplified up to 30-fold by varying the concentration of ampicillin or tetracycline in the growth medium.

J Bacteriol, 1983 Aug, 155(2), 578 - 85
Cloning and physical mapping of the cysB region of Salmonella typhimurium; Jagura-Burdzy G et al.; The cysB region of Salmonella typhimurium was cloned in pBR322 and localized to a 1.75-kilobase HincII fragment . Two-dimensional protein electropherograms showed levels of the cysB polypeptide chain that were several fold higher in plasmid-bearing strains than in the wild type . Fully derepressed levels of sulfite reductase and O-acetylserine sulfhydrylase in cysB plasmid-bearing strains were only 25% higher than in the wild type, suggesting that the product of this regulatory gene ordinarily is not a limiting factor in the expression of the cysteine regulon . The mapping of cysB deletions by Southern blots showed a good correlation between the genetic and the physical maps of this gene . The supX gene was initially cloned with cysB and is within 0.7 kilobase of cysB.

J Med Microbiol, 1983 Aug, 16(3), 371 - 80
Haemagglutinins and adhesion of Salmonella typhimurium to HEp2 and HeLa cells; Tavendale A et al.; When fimbriate (Fim+) strains of Salmonella typhimurium were grown in static broth, many bacteria were in the fimbriate phase and bore fimbrial mannose-sensitive haemagglutinin (MSHA) that enabled them to adhere to guinea-pig and other erythrocytes and to agglutinate them in rocked tile and static settling tests . When either Fim+ or Fim- strains were grown on phosphate-buffered nutrient agar, the bacteria formed a diffusible, mannose-resistant haemagglutinin (MRHA) that gave dispersed sediments with sheep and pig erythrocytes in static settling tests, but without evidence of bacterial adhesion to the erythrocytes . On exposure, from above or from below, to cultured HEp2 and HeLa cells for 30 or 90 min at 37 degrees C, motile MSHA-rich, MRHA-negative broth-grown bacteria adhered to the cells in large numbers (e.g., 20-100/cell), but motile MSHA-negative, MRHA-negative broth-grown bacteria and non-motile MSHA-negative, MRHA-rich agar-grown bacteria adhered in only small numbers (usually less than 1/cell) . Thus, strong adhesiveness of bacteria for cultured cells in vitro appears to depend upon the presence of MSHA, not MRHA, and as Fim- (MSHA-negative) strains of S . typhimurium are known to be highly infective in animals, a strong reaction in the in-vitro model does not reflect a property of the bacteria essential for infectivity in vivo.

Biochem Biophys Res Commun, 1983 Jul 29, 114(2), 626 - 31
Ultimate forms of mutagenic and carcinogenic heterocyclic amines produced by pyrolysis; Nagao M et al.; A mutant strain of Salmonella typhimurium TA98/1,8-DNP6 isolated by McCoy et al . (1) was reported to be defective in esterifying activity . We have found that 2-amino-6-methyldipyrido{1,2-a:3',2'-d}imidazole (Glu-P-1), 2-aminodipyrido{1,2-a:3',2'-d}imidazole (Glu-P-2), 2-amino-3-methylimidazo-{4,5-f}quinoline (IQ), 2-amino-3,4-dimethylimidazo{4,5-f}quinoline (MeIQ) and 2-amino-3,8-dimethylimidazo{4,5-f}quinoxaline (MeIQx) were not mutagenic to TA98/1,8-DNP6 with S9 mix, while these compounds were strongly mutagenic to the original TA98 with S9 mix . The mutagenicities of some of these heterocyclic amines to TA98 were inhibited by pentachlorophenol, an aryl sulfotransferase inhibitor . These results indicate that the ultimate forms of these heterocyclic amines are probably sulfate esters of heterocyclic amine N-hydroxides . Contrary to this, 3-amino-1,4-dimethyl-5H-pyrido{4,3-b}indole (Trp-P-1), 3-amino-1-methyl-5H-pyrido{4,3-b}indole (Trp-P-2), 2-amino-9H-pyrido{2,3-b}indole (A alpha C) and 2-amino-3-methyl-9H-pyrido{2,3-b}indole (MeA alpha C) were definitely mutagenic to TA98/1,8-DNP6, although less than to TA98.

FEBS Lett, 1983 Jul 25, 158(2), 239 - 42
Phosphorylation of isocitrate dehydrogenase in Escherichia coli mutants with a non-functional glyoxylate cycle; Reeves HC et al.; The phosphorylation of NADP-specific isocitrate dehydrogenase in an isocitrate lyase and in a malate synthase mutant of Escherichia coli has been investigated . The results clearly demonstrate that isocitrate dehydrogenase may undergo an acetate-induced phosphorylation in organisms which do not have a functional glyoxylate cycle . This observation, together with those reported in Salmonella typhimurium, suggest that the current notion concerning the interrelationship between the glyoxylate cycle and the reversible phosphorylation of NADP-isocitrate dehydrogenase in microbial physiology should be reevaluated, and that phosphoenolpyruvate may be a key factor in the regulation of the reversible covalent modification of this enzyme in vivo.

Biochemistry, 1983 Jul 19, 22(15), 3594 - 603
L-serine binds to arginine-148 of the beta 2 subunit of Escherichia coli tryptophan synthase; Tanizawa K et al.; Inactivation of the beta 2 subunit and of the alpha 2 beta 2 complex of tryptophan synthase of Escherichia coli by the arginine-specific dicarbonyl reagent phenylglyoxal results from modification of one arginyl residue per beta monomer . The substrate L-serine protects the holo beta 2 subunit and the holo alpha 2 beta 2 complex from both inactivation and arginine modification but has no effect on the inactivation or modification of the apo forms of the enzyme . This result and the finding that phenylglyoxal competes with L-serine in reactions catalyzed by both the holo beta 2 subunit and the holo alpha 2 beta 2 complex indicate that L-serine and phenylglyoxal both bind to the same essential arginyl residue in the holo beta 2 subunit . The apo beta 2 subunit is protected from phenylglyoxal inactivation much more effectively by phosphopyridoxyl-L-serine than by either pyridoxal phosphate or pyridoxine phosphate, both of which lack the L-serine moiety . The phenylglyoxal-modified apo beta 2 subunit binds pyridoxal phosphate and the alpha subunit but cannot bind L-serine or L-tryptophan . We conclude that the alpha-carboxyl group of L-serine and not the phosphate of pyridoxal phosphate binds to the essential arginyl residue in the beta 2 subunit . The specific arginyl residue in the beta 2 subunit which is protected by L-serine from modification by phenyl{2-14C}glyoxal has been identified as arginine-148 by isolating a labeled cyanogen bromide fragment (residues 135-149) and by digesting this fragment with pepsin to yield the labeled dipeptide arginine-methionine (residues 148-149) . The primary sequence near arginine-148 contains three other basic residues (lysine-137, arginine-141, and arginine-150) which may facilitate anion binding and increase the reactivity of arginine-148 . The conservation of the arginine residues 141, 148, and 150 in the sequences of tryptophan synthase from E . coli, Salmonella typhimurium, and yeast supports a functional role for these three residues in anion binding . The location and role of the active-site arginyl residues in the beta 2 subunit and in two other enzymes which contain pyridoxal phosphate, aspartate aminotransferase and glycogen phosphorylase, are compared.

Chem Biol Interact, 1983 Jul 15, 45(2), 153 - 69
Mutagenicities of glycidyl ethers for Salmonella typhimurium: relationship between mutagenic potencies and chemical reactivity; Sugiura K et al.; The lethal and mutagenic effects of ethyl, benzyl, 1-naphthylmethyl, 2-naphthylmethyl, 1-naphthylethyl, 2-naphthylethyl and 9-anthrylmethyl glycidyl ethers on Salmonella typhimurium (TA100, TA1535, TA98 and TA1538) were investigated . LD30-value became smaller with an increase in compound hydrophobicity . The mutagenicities of these compounds in TA100 increased in the order: 1-naphthylethyl glycidyl ether less than 2-naphthylethyl glycidyl ether less than benzyl glycidyl ether less than 2-naphthylmethyl glycidyl ether less than 1-naphthylmethyl glycidyl ether less than 9-anthrylmethyl glycidyl ether . 1-Naphthylmethyl and 2-naphthylmethyl glycidyl ethers were mutagenic toward TA1535 . In TA98, 1-naphthylmethyl and 9-anthrylmethyl glycidyl ethers showed mutagenic activity and 9-anthrylmethyl glycidyl ether was more mutagenic than 1-naphthylmethyl glycidyl ether . 9-Anthrylmethyl glycidyl ether was also active in TA1538 . In the reaction of glycidyl ethers with deoxyguanosine and related compounds, glycidyl ethers attacked at only N-7 of guanine . The alkylation rates of glycidyl ethers toward guanine residues in DNA were determined and the exciplex-formation ability of 7-substituted guanines was studied . The reactivity of glycidyl ethers with guanine residues in DNA has not provided a sufficient explanation for the variation in mutagenic potencies of glycidyl ethers.

J Biol Chem, 1983 Jul 10, 258(13), 7991 - 7
The x-ray structure of the periplasmic galactose binding protein from Salmonella typhimurium at 3.0-A resolution; Mowbray SL et al.; The x-ray structure of the periplasmic galactose binding protein from Salmonella typhimurium, the specific receptor for taxis toward, and high-affinity transport of, galactose has been solved at 3.0-A resolution using multiple isomorphous replacement . The path of the polypeptide chain has been traced, and a model structure consisting of 292 amino acids has been fit to the electron density map . The overall shape of the molecule is that of a prolate ellipsoid, with dimensions 35 X 35 X 65 A . The protein consists of two similar domains of roughly equal size, related by an axis of pseudosymmetry, and separated by a deep cleft about 8 A wide . Each domain has a core of parallel beta sheet surrounded by five alpha helices, built by alternating strands of sheet and helix in a repeating pattern . Approximately 36% of the residues are involved in alpha helices, and 27% in beta sheet . The tertiary structure has been compared to that of the Escherichia coli arabinose binding protein (Gilliland, G.L., and Quiocho, F . A . (1981) J . Mol . Biol . 146, 341-362), a periplasmic receptor which is involved in transport, but not in chemotaxis . The overall folding of these two molecules is very similar, with the exception of two areas on the surface of the molecule on the long sides of the prolate ellipsoid . The observed variations are adequate to explain the differences in interaction of L-arabinose binding protein and galactose binding protein with the membrane proteins for transport and chemotaxis.

Mutat Res, 1983 Jul, 121(1), 39 - 45
Induction of chromosomal alterations as an assay for cytostatic drug activity in plasma; Natarajan AT et al.; Information about the extent and persistence of cytostatic activity in blood plasma after administration of a cytostatic drug into the body is needed for a better evaluation of the inter-individual variations in drug metabolism and disposition . As an assay for cytotoxic activity, a test system was chosen in which Chinese hamster ovary cells (CHO) were incubated with plasma containing active metabolites of cyclophosphamide (from human patients or rats), after which the frequencies of induced sister-chromatid exchanges per cell were determined . The treatment with plasma increased the frequencies of SCEs very effectively at concentrations of metabolites that were negative in the Salmonella typhimurium back-mutation test with strain TA100 . The results obtained indicate that the SCE test system offers the possibility to follow the cytotoxic activity of plasma at various time intervals after administration of cyclophosphamide.

Cancer Res, 1983 Jul, 43(7), 3132 - 7
Identification and mutagenicity of metabolites of 1-nitropyrene formed by rat liver; El-Bayoumy K et al.; The metabolism of 1-nitropyrene by rat liver 9000 X g supernatant was investigated . Under aerobic conditions, ring oxidation to 1-nitropyren-3-ol, 1-nitropyren-6-ol, 1-nitropyren-8-ol, and 4,5-dihydro-4,5-dihydroxy-1-nitropyrene and nitroreduction to 1-aminopyrene were observed . Metabolites were identified by their ultraviolet, mass, and nuclear magnetic resonance spectra; by chemical transformations; and by comparison to reference standards . When incubations were carried out in an atmosphere of 4% O2 in N2, 1-aminopyrene was the major metabolite . The mutagenic activities of 1-nitropyren-3-ol, 1-nitropyren-6-ol, and 1-nitrosopyrene were assessed in Salmonella typhimurium strains TA 98 and TA 100 . In strain TA 98, without activation, doses of 0.5 micrograms/plate or less of these three compounds were more mutagenic than was 1-nitropyrene; however, their activities decreased rapidly at higher doses . In the presence of rat liver 9000 X g supernatant, they were less mutagenic than was 1-nitropyrene at all doses tested . In S . typhimurium TA 100, without activation, 1-nitropyren-3-ol, 1-nitropyren-6-ol, and 1-nitrosopyrene were more mutagenic than was 1-nitropyrene at doses of 0.25 micrograms/plate or less, but their activities decreased at higher doses . In strain TA 100, with activation, only 1-nitropyren-6-ol was more mutagenic than was 1-nitropyrene . The results of this study indicate that both nitroreduction and ring oxidation may be involved in the mutagenic activity of 1-nitropyrene.

Infection, 1983 Jul-Aug, 11(4), 227 - 31
Efficacy of intravenous immunoglobulin preparations against viral and bacterial infections in mouse protection tests; Stephan W et al.; Our investigation indicates that pretreatment of human immunoglobulin for the elimination of the anticomplementary activity is associated with a loss of activity, the extent of which depends on the type of treatment applied . Laboratory preparations of human IgG were tested in a mouse protection assay using influenza A2-Taiwan virus, tetanus toxin and Salmonella typhimurium as the challenge . There was a 7-28% reduction in efficacy in an intravenous 7S preparation in comparison with an untreated 7S IgG . F(ab')2 fragments showed a 24-65% and Fab fragments an 80-100% reduction in efficacy . Two commercial human 7S products showed approximately 90% efficacy in the Salmonella assay; a commercial, pepsin-treated preparation showed 65-74% efficacy when compared with untreated 7S IgG.

Antimicrob Agents Chemother, 1983 Jul, 24(1), 107 - 13
Polycations sensitize enteric bacteria to antibiotics; Vaara M et al.; Polymyxin B nonapeptide, a polymyxin B derivative which lacks the fatty acyl part and the bactericidal activity of polymyxin, was shown to sensitize smooth encapsulated Escherichia coli (O18:K1) and smooth Salmonella typhimurium to hydrophobic antibiotics (novobiocin, fusidic acid, erythromycin, clindamycin, nafcillin, and cloxacillin) . The polymyxin B nonapeptide-treated bacteria were as sensitive to these antibiotics as are deep rough mutants . A lysine polymer with 20 lysine residues (lysine 20) had a largely similar effect . Larger lysine polymers and the protamine salmine were bactericidal but, at sublethal concentrations, sensitized the strains to the antibiotics mentioned above, whereas lysine4, streptomycin, cytochrome c, lysozyme, and the polyamines cadaverine, spermidine, and spermine had neither bactericidal nor sensitizing activity.

Zh Mikrobiol Epidemiol Immunobiol, 1983 Jul, (7), 47 - 51
{Processes of bacterial L transformation and L form reversion in the body of argasid ticks}; Levina GA et al.; The experimental infection of tampan ticks (Ornithodoros moubata) with the bacterial cultures of Listeria monocytogenes and Salmonella typhimurium, as well as with their L-forms, was carried out . These experiments demonstrated that both the L-transformation of bacteria and the reversion of their L-forms into the initial bacterial culture could occur in the body of the ticks.

J Reticuloendothel Soc, 1983 Jul, 34(1), 29 - 44
Killing of Listeria monocytogenes by human neutrophils and monocytes, but not by monocyte-derived macrophages; Czuprynski CJ et al.; Acquired resistance to listeriosis is thought to require immunological activation of mononuclear phagocytes to an enhanced microbicidal state . In this study we found that both neutrophils and mononuclear phagocytes from nonimmunized human donors killed Listeria monocytogenes in vitro as well as they killed Salmonella typhimurium and Escherichia coli . Bactericidal activity was detectable using both adherent cell and cell suspension bactericidal assays; however, bactericidal activity was greater when the suspension assay was used . Perhaps more surprising, freshly-obtained monocytes were more bactericidal than were monocytes cultured in vitro for 5-7 days, even though monocytes cultured in vitro acquire many characteristics of mature macrophages . These data suggest that newly emigrated monocytes and neutrophils may be particularly effective cell types in resistance to listeriosis.

J Bacteriol, 1983 Jul, 155(1), 186 - 95
sn-Glycerol-3-phosphate transport in Salmonella typhimurium; Hengge R et al.; Salmonella typhimurium contains a transport system for sn-glycerol-3-phosphate that is inducible by growth on glycerol and sn-glycerol-3-phosphate . In fully induced cells, the system exhibited an apparent Km of 50 microM and a Vmax of 2.2 nmol/min . 10(8) cells . The corresponding system in Escherichia coli exhibits, under comparable conditions, a Km of 14 microM and a Vmax of 2.2 nmol/min . 10(8) cells . Transport-defective mutants were isolated by selecting for resistance against the antibiotic fosfomycin . They mapped in glpT at 47 min in the S . typhimurium linkage map, 37% cotransducible with gyrA . In addition to the glpT-dependent system, S . typhimurium LT2 contains, like E . coli, a second, ugp-dependent transport system for sn-glycerol-3-phosphate that was derepressed by phosphate starvation . A S . typhimurium DNA bank containing EcoRI restriction fragments in phage lambda gt7 was used to clone the glpT gene in E . coli . Lysogens that were fully active in the transport of sn-glycerol-3-phosphate with a Km of 33 microM and a Vmax of 2.0 nmol/min . 10(8) cells were isolated in a delta glpT mutant of E . coli . The EcoRI fragment harboring glpT was 3.5 kilobases long and carried only part of glpQ, a gene distal to glpT but on the same operon . The fragment was subcloned in multicopy plasmid pACYC184 . Strains carrying this hybrid plasmid produced large amounts of cytoplasmic membrane protein with an apparent molecular weight of 33,000, which was identified as the sn-glycerol-3-phosphate permease . Its properties were similar to the corresponding E . coli permease . The presence of the multicopy glpT hybrid plasmid had a strong influence on the synthesis or assembly of other cell envelope proteins of E . coli . For instance, the periplasmic ribose-binding protein was nearly absent . On the other hand, the quantity of an unidentified E . coli outer membrane protein usually present only in small amounts increased.

G Batteriol Virol Immunol, 1983 Jul-Dec, 76(7-12), 290 - 9
{Biological effects of the combined action of laser radiation and hematoporphyrin on a strain of Salmonella typhimurium (TA 100)}; Curci E et al.; The AA . have studied biological effects of Laser radiation and Haematoporphyrin (HPD) on Salmonella typhimurium TA 100 strain . Their results do not show a growth of letal effect that they demonstrated on antecedent trials, only dependent from Laser radiation . Nome mutagenetic effect was demonstrated . They think that HPD is not capable of binding or penetrating in bacterial cell owing to complexity of bacterial capsule and wall; therefore HPD can not increase Laser radiation effect, though its photodynamic action.

Mikrobiyol Bul, 1983 Jul, 17(3), 186 - 90
{Salmonella meningitis}; Ceyhan M et al.; A four - month old boy with Salmonella Typhimurium meningitis is presented . This patient was admitted to the hospital with a diagnosis of staphylococcal pneumonia, pyo-pneumothorax, cardiac failure and anemia . He has been treated for 18 days and he was discharged in good condition . Two days after discharge patient was readmitted with a fever, vomiting and feeding problem . In physical examination, stiff neck and bulging of the fontanel were remarkable . Examination of cerebrospinal fluid (CSF) has revealed meningitis and cultures of blood and CSF specimens were positive for S . typhimurium . It was sensitive only to trimethoprim sulphamethoxazole and netilmicin . Trimethoprim sulphamethoxazole (IM) and netilmicin (IV) were given . At the fifth day of this treatment patient expired . Postmortem examination has revealed the same agent in both meninges tissue and CSF cultures.

Avian Dis, 1983 Jul-Sep, 27(3), 632 - 43
Evaluation of turkey cecal microflora in protecting day-old poults from Salmonella typhimurium challenge; Reid CR et al.; The oral administration of a 1:20 (wt/vol) dilution of adult turkey cecal contents to poults on the day of hatching protected more than 80% of the poults against challenge at 24 hr of age with approximately 10(3) colony-forming units (CFU) of a nalidixic-acid-resistant strain of Salmonella typhimurium . All untreated poults similarly challenged were colonized . Protection was lost when the challenge dose was 10(6) or greater . When the microflora treatment followed salmonella challenge by 6 hours or more, protection was reduced . If poults were colonized by S . typhimurium, the organisms were found always in the ceca and infrequently in other parts of the intestinal tract . When poults shedding salmonella were mixed with treated poults, more than 70% of the latter remained free of the organism.

Avian Dis, 1983 Jul-Sep, 27(3), 602 - 15
Use of two vaccines (live G30D or killed RW16) in the prevention of Salmonella typhimurium infections in chickens; Suphabphant W et al.; Several properties of a galactose epimerase mutant strain (G30D) of Salmonella typhimurium were investigated in white leghorn and white rock chickens . More chickens shed G30D when it was administered orally at 1 day of age than when given at 1, 2, or 4 weeks of age . In another experiment, the mean cumulative data obtained for 52 days on the shedding rate of virulent RW16 in the unvaccinated challenged controls were significantly higher (P less than 0.05) than data in challenged groups that had been vaccinated subcutaneously with live G30D . In a third experiment, chickens vaccinated twice with live G30D or killed RW16 were less likely to shed RW16 than unvaccinated controls following challenge with live RW16 . Vaccination with both live G30D and killed RW16 was significantly more beneficial (P less than 0.05) than using either vaccine alone twice . The route of administration of the vaccines made no difference in the reduction of shedding.

Avian Dis, 1983 Jul-Sep, 27(3), 577 - 83
Infection and immune responses in chickens exposed to Salmonella typhimurium; Lee GM et al.; The transmission of Salmonella typhimurium among adult chickens maintained in wire-floored cages was examined . Within 6 days, organisms had spread from infected seed chickens to the majority of uninoculated chickens . Initially, organisms were found in the intestinal tract alone, but by day 20, all chickens were infected, and most of these had organisms in the liver, spleen, and intestinal tract . Antibodies to whole bacterial cells and lipopolysaccharide were detected in the serum and bile of all chickens from day 24 . Clearance of organisms from the tissues was not apparent until after day 33 . Cell-mediated immunity to salmonella antigens was also induced in chickens that naturally acquired the infection . The role of these parameters of immunity in the clearance of organisms is discussed.

Poult Sci, 1983 Jul, 62(7), 1211 - 6
Survival of Salmonella typhimurium and Staphylococcus aureus in eggs cooked by different methods; Baker RC et al.; Shell eggs inoculated with Salmonella typhimurium and Staphylococcus aureus were cooked by recommended procedures for boiling, poaching, and frying . Except for poaching, the recommended procedures were inadequate in destroying the inoculum placed in the yolk . Boiling for 7 min was necessary for complete destruction of S . typhimurium and it took 12 min of boiling to destroy Staph . aureus . Cooking time-temperature relationship for complete kill depended on the cooking method with fried eggs . Four minutes and 70 C were needed for covered eggs, 3 min on each side at 64 C for turned over eggs, while cooking for 7.5 min at 64 C for sunnyside eggs was not sufficient for destruction of both of the test organisms . None of the test organisms could be recovered from omelets baked by the recommended procedure (86 C for 25 min) . Scrambling for 1 min at 74 C was required for the complete destruction of S . typhimurium and 2 min at 78 C for Staph . aureus.

Appl Environ Microbiol, 1983 Jul, 46(1), 28 - 31
Immune response of Tilapia aurea exposed to Salmonella typhimurium; Baker DA et al.; Tilapia aurea showed a specific immune response to Salmonella typhimurium . S . typhimurium was introduced into the gut of T . aurea by force-feeding . S . typhimurium was isolated from the fish viscera after 15 days, but at 30 days viable cells were not detected . T . aurea had an antibody titer to S . typhimurium after 30 days which was fivefold greater than the natural background antibody titer . An elevated antibody titer was not indicative of active bacterial infection.

Sci Total Environ, 1983 Jul, 29(1-2), 143 - 54
Mutagenic potential of laboratory chlorinated river water; Maruoka S et al.; Sample water was taken from a river and chlorinated at a concentration of 5 mg 1(-1) chlorine for 20 h in the laboratory in order to examine the effect of chlorination on the mutagenic potential of organic extracts that were recovered using XAD-2 resin and diethyl ether . It was found that the XAD extracts recovered from the river water showed per se strong mutagenic activity, in the presence of S-9 mix, towards Salmonella typhimurium TA 1538 . When the mutagenic activity of the XAD extracts was related to the initial water volume, chlorination increased both the direct-acting and the S-9 dependent mutagenic activity . This suggests that chlorination produced de novo direct-acting and S-9 dependent mutagens and/or increased pre-existing mutagenic activities . In addition, in this study XAD extracts recovered from chlorinated and unchlorinated river water were divided into a neutral, basic and acidic fraction respectively . When the mutagenic activity of each fraction was related to the initial water volume, the neutral fraction showed the most marked increase in mutagenic activity with, and without, the S-9 mix in the chlorinated river water.

J Infect Dis, 1983 Jul, 148(1), 7 - 11
The plasmid pattern as an epidemiologic tool for Salmonella typhimurium epidemics: comparison with the lysotype; Brunner F et al.; In the study of a limited epidemic of Salmonella typhimurium infections, the plasmid content (pattern) of bacteria was used as an epidemiologic tool outside the hospital environment . Comparisons were made with lysotyping, resistance pattern determination (14 antibiotics), and biotyping . Plasmid pattern determination was found to be as useful and accurate as lysotyping, whereas resistance pattern determination was of more limited interest . However, in this report biotyping was of no use.

Cancer Lett, 1983 Jul, 19(3), 343 - 5
Non-mutagenicity of 3-dimethylamino-psi-saccharin to Salmonella typhimurium; Ashby J et al.; 3-Dimethylamino-psi-saccharin has been confirmed as non-mutagenic to Salmonella typhimurium when evaluated in vitro in the presence of induced rat liver S9 mix.

Proc Soc Exp Biol Med, 1983 Jul, 173(3), 319 - 23
Circadian variation in circulating pyrogen: possible role in resistance to infection; Ucar DA et al.; In the rat, body temperature (bt) is highest, and plasma iron (Fe) and zinc (Zn) concentrations are lowest at night while the rat is most active; the inverse is true during the day . Based on data implicating endogenous pyrogen (EP) as a mediator of the rise in body temperature and fall in plasma trace metal levels during infection we hypothesized that the circadian rise in body temperature and fall in plasma Fe and Zn levels may be attributed to a cyclic release of EP . To test this hypothesis: (1) Rats were injected ip with an antipyretic dose of sodium salicylate (300 mg/kg) . The result was a reduction (P less than 0.05) in bt at night . (2) Rats were injected during the day with 1 ml each of plasma collected from rats during the night . As a control, rat plasma collected during the day was injected at this same time point . A rise (P less than 0.05) in bt was observed only in animals who had received plasma collected at night . These results support the hypothesis that a pyrogen, perhaps EP, is present in the plasma of rats at night . The release of EP during periods of greatest activity may have an adaptive role since rats are more likely to come into contact with pathogens during these times . If EP were released during periods of activity, the likelihood of severe infection occurring would be diminished . To test this hypothesis, two groups of rats were injected with Salmonella typhimurium, one group at midnight (A) and one group at noon (B) . The mortality rate was 25% in group A and 60% in group B (P less than 0.025) . These data support the hypothesis that the immune/host defense of rats to S . typhimurium is more effective at night, possibly due to an increased level of circulating pyrogen.

Mutat Res, 1983 Jul, 121(1), 17 - 23
The basis of the insensitivity of Salmonella typhimurium strain TA98/1,8-DNP6 to the mutagenic action of nitroarenes; McCoy EC et al.; Salmonella typhimurium tester strain TA98/1,8-DNP6 is resistant to the mutagenicity of 1,8-dinitropyrene because it lacks an esterification enzyme which is needed for the formation of the ultimate mutagen, presumably the corresponding hydroxamic acid ester . This enzyme does not appear to be required for the activation of all nitroarenes and arylamines, as some of these are fully active in TA98/1,8-DNP . It is suggested that these form electrophilic arylnitrenium ions nonenzymatically from nitroso- and N-hydroxylamino-arenes intermediates . The esterification enzyme appears to be a transacetylase . An assay using 2-aminofluorene as the acetyl acceptor is described . Derivatives of S . typhimurium TA100 also lacking this enzyme were obtained by Tn5-mediated mutagenesis.

Mutat Res, 1983 Jul, 118(1-2), 49 - 59
The evaluation of mutagenicities of 19 structurally related aromatic amines and acetamides in Salmonella typhimurium TA98 and TA100; Connor TH et al.; 19 aromatic amines were assayed for mutagenicity using Salmonella typhimurium strains TA98 and TA100 with and without the addition of S9 from Aroclor-1254-induced rat liver . These included: naphthalenes (1-amino-, 1-acetamido-, 2-amino-, 2-acetamido-, 1-amino-4-nitro- and 2-amino-1-nitro-), biphenyls (2-amino-, 2-acetamido-, 4-amino- and 4-acetamido-), fluorenes (2-amino- and 2-acetamido-), anthracenes (1-amino-, 1-acetamido-, 2-amino- and 2-acetamido-), 3-aminofluoranthene, 1-aminopyrene and 6-aminochrysene . None of the compounds were mutagenic when tested without S9 . With S9, 15 of 19 were mutagenic for TA98 and 16 of the 19 were mutagenic for TA100 . Overall, 2-aminoanthracene was the most potent mutagen . When compared to the parent amines, the respective acetamido derivatives were consistently less mutagenic.

Mutat Res, 1983 Jul, 118(1-2), 43 - 7
Variable mutagenic activity of commercial preparations of ABTS (2,2'-azino-di(3-ethyl-benz-thiazoline) sulphonic acid; Moore WB et al.; Different batches of ABTS obtained from the same commercial source varied in their capacity to effect direct mutation in the strains of Salmonella typhimurium used routinely in the incorporation test of Ames . One batch, obtained in 1976, and another obtained early in 1979, both exhibited direct base-pair substitution and frame-shift activities . These activities, however, were absent from each of two batches obtained after 1979, and also from a highly purified preparation from a different source . The possible presence of the unsulphonated immediate precursor of ABTS as a mutagenic impurity is an unlikely explanation for the activity of the mutagenic preparations . It is more probable that the commercial synthesis generated other, mutagenic, impurities which remained in the batches obtained in 1976 and early in 1979, but were absent or were removed from later batches . The identity of these active impurities is unknown . Pure ABTS is neither a direct nor an indirect mutagen.

J Bacteriol, 1983 Jul, 155(1), 97 - 106
Reconstitution of maltose transport in Escherichia coli: conditions affecting import of maltose-binding protein into the periplasm of calcium-treated cells; Brass JM et al.; The reconstitution of active transport by the Ca2+ -induced import of exogenous binding protein was studied in detail in whole cells of a malE deletion mutant lacking the periplasmic maltose-binding protein . A linear increase in reconstitution efficiency was observed by increasing the Ca2+ - concentration in the reconstitution mixture up to 400 mM . A sharp pH optimum around pH 7.5 was measured for reconstitution . Reconstitution efficiency was highest at 0 degree C and decreased sharply with increasing temperature . The time necessary for optimal reconstitution at 0 degree C and 250 mM Ca2+ was about 1 min . The competence for reconstitution was highest in exponentially growing cultures with cell densities up to 1 X 10(9)/ml and declined when the cells entered the stationary-growth phase . The apparent Km for maltose uptake was the same as that of wild-type cells (1 to 2 microM) . Vmax at saturating maltose-binding protein concentration was 125 pmol per min per 7.5 X 10(7) cells (30% of the wild-type activity) . The concentration of maltose-binding protein required for half-maximal reconstitution was about 1 mM . The reconstitution procedure appears to be generally applicable . Thus, galactose transport in Escherichia coli could also be reconstituted by its respective binding protein . Maltose transport in E . coli was restored by maltose-binding protein isolated from Salmonella typhimurium . Finally, in S . typhimurium, histidine transport was reconstituted by the addition of shock fluid containing histidine-binding protein to a hisJ deletion mutant lacking histidine-binding protein . The method is fast and general enough to be used as a screening procedure to distinguish between transport mutants in which only the binding protein is affected and those in which additional transport components are affected.

J Bacteriol, 1983 Jul, 155(1), 435 - 7
Motility development of Salmonella typhimurium cells with flaV mutations after addition of exogenous flagellin; Kagawa H et al.; Cells of Salmonella typhimurium with flaV mutations developed motility after exogenous addition of flagellin, similar to what is observed with flbC mutants of Escherichia coli K-12.

Toxicol Lett, 1983 Jul, 17(3-4), 233 - 40
Mutagenicity and in vivo disposition of biliary metabolites of benzo(a)pyrene; Chipman JK et al.; Rabbits and rats administered {3H}benzo(a)pyrene (BP; 40 mumol/kg, i.v.) excreted, via the bile, metabolites which increased reverse gene mutation frequency in Salmonella typhimurium TA98 when incubated with beta-glucuronidase . Glucuronic acid conjugates of BP 4,5-diol, BP 1,6-, 3,6- and 6,12-quinones were detected in rat bile with low levels of 3- and 9-OH BP and BP 7,8- and 9,10-diols . In rabbits BP 9,10-diol was the major aglycone along with smaller amounts of BP 1,6- and 3,6-quinones, BP 4,5- and 7,8-diols and 3- and 9-OH BP . Qualitatively similar metabolic profiles were found when animals were given 3 mumol/kg {3H}BP . When 3H-labelled biliary metabolites, which contained the mutagenic component, were administered intraduodenally to rats, radioactivity reached the systemic circulation but DNA adducts were not detectable (less than 0.03 pmol/mg DNA) in tissues (intestinal wall, liver and lung) exposed to the reabsorbed metabolites.

J Bacteriol, 1983 Jul, 155(1), 213 - 21
An indispensable gene for NAD biosynthesis in Salmonella typhimurium; Hughes KT et al.; We have located the nadD locus between lip and leuS at 14 min on the Salmonella typhimurium chromosome, and we have shown it to be the structural gene for nicotinic acid mononucleotide adenylyltransferase . This is the first indispensable gene of pyridine nucleotide metabolism that has been identified . Mutants altered at this locus, isolated by their 6-aminonicotinamide resistance phenotype, accumulate abnormally large pools of nicotinic acid mononucleotide in vivo; many exhibit a temperature-sensitive lethal phenotype . Enzyme assays reveal markedly lower transferase activity in mutant extracts than in nadD+ extracts . The partial dominance of nadD mutants when placed in a nadD+/nadD diploid suggests that nicotinic acid mononucleotide adenylyltransferase is a multimeric enzyme.

Antimicrob Agents Chemother, 1983 Jul, 24(1), 114 - 22
Polycations as outer membrane-disorganizing agents; Vaara M et al.; The outer membrane-disorganizing effect of a short (10-min) treatment with polycationic agents was studied with smooth Salmonella typhimurium used as a test organism . The polycationic agents were the protamine salmine, a lysine polymer with 20 lysine residues (lysine20), and the deacylated polymyxin B derivative polymyxin B nonapeptide . Two different types of outer membrane-disorganizing were found . Protamine and lysine20 released 20 to 30% of the lipopolysaccharide from the outer membrane and sensitized the bacteria to the anionic detergent sodium dodecyl sulfate but did not (under these conditions) make the bacteria permeable to the hydrophobic probes fusidic acid and actinomycin D . In contrast, polymyxin B nonapeptide did not release lipopolysaccharide or sensitize the bacteria to sodium dodecyl sulfate but made the outer membrane permeable to the hydrophobic probes . None of the agents was bactericidal under the conditions used or caused any leakage of periplasmic beta-lactamase . Polymyxin B was used as a reference and showed characteristic outer membrane-disorganizing action . In thin-section electron microscopy, polymyxin B nonapeptide caused the appearance of long, narrow, finger-like projections on the outer membrane . Protamine and lysine20 caused a distinctly wrinkled appearance of the outer membrane but no projections.

J Bacteriol, 1983 Jul, 155(1), 82 - 9
Nucleotide sequence of the control regions for the glnA and glnL genes of Salmonella typhimurium; Hanau R et al.; We have partially characterized a DNA fragment encoding glutamine synthetase in Salmonella typhimurium . Restriction mapping and RNA polymerase binding studies identified two regions within the fragment which exhibit promoter activity when fused to lacZ in pMC1403, a plasmid used to detect transcriptional and translational control signals . DNA sequence analysis revealed that one region encodes amino acids corresponding to the amino terminus of the glutamine synthetase protein . The second region codes for the amino acids corresponding to the carboxy terminus of glutamine synthetase followed by a 330-nucleotide sequence containing an ideal Pribnow heptamer and a possible translation initiation signal . The location of this region is analogous to the position of the beginning of the glnL gene identified in Escherichia coli, and it is likely that the Pribnow heptamer is the RNA polymerase binding site for the glnL gene.

J Biol Chem, 1983 Jun 10, 258(11), 6827 - 34
Diadenosine 5',5"'-P1,P4-tetraphosphate and related adenylylated nucleotides in Salmonella typhimurium; Lee PC et al.; Salmonella typhimurium LT2 rapidly accumulates high levels of a family of five adenylylated nucleotides following exposure to a bacteriostatic quinone, 6-amino-7-chloro-5,8-dioxoquinoline . These compounds have been analyzed using our recently described two-dimensional thin layer chromatographic method . The five dinucleotides, which cannot be detected in exponentially growing cells, have been identified as diadenosine 5',5"'-P1,P4-tetraphosphate (AppppA), ApppGpp (guanosine 3'-diphosphate-5'-adenosine-5'-(P1,P3-triphosphate)), AppppG (adenosine 5'-guanosine-5'-(P1,P4-tetraphosphate)), ApppG (adenosine 5'-guanosine-5'-(P1,P3-triphosphate)), and ApppA (diadenosine 5',5"'-P1,P3-triphosphate) . AppppA has been previously detected in vitro as an enzymatic product of aminoacyl-tRNA synthetases and in vivo at submicromolar levels in eucaryotic cells . The induced intracellular concentration of AppppA and the other adenylylated nucleotides in S . typhimurium is approximately 100-fold higher than that found in eucaryotic cells . We propose that these dinucleotides are alarmones, regulatory molecules signaling a particular metabolic stress.

Science, 1983 Jun 3, 220(4601), 1016 - 20
Separation of signal transduction and adaptation functions of the aspartate receptor in bacterial sensing; Russo AF et al.; In order to investigate the functions of stimulus recognition, signal transduction, and adaptation, the aspartate receptor gene for bacterial chemotaxis in Salmonella typhimurium has been sequenced and modified . A carboxyl-terminal truncated receptor was shown to bind aspartate and to transmit a signal to change motility behavior . However, the truncated receptor showed greatly reduced methyl-accepting capacity, and did not allow adaptation to the sensory stimulation . The separation of receptor functions by alteration of primary structure emphasizes that the receptor is directly involved in adaptation and is not solely a device for transmitting a signal across a membrane.

Clin Nephrol, 1983 Jun, 19(6), 288 - 94
Depressed polymorphonuclear leukocyte functions associated with normal cytotoxic functions of T and natural killer cells during chronic hemodialysis; Charpentier B et al.; The cytotoxic capacities of T lymphocytes and natural killer (NK) cells and the phagocytic functions of polymorphonuclear leukocytes were determined in a group of 20 patients with end stage disease who were being maintained on hemodialysis . The mononuclear cells from these patients were able to mediate normal T-cytotoxic functions in a xenogeneic cell-mediated lympholysis assay and normal NK cytotoxic capacity when tested against K562 target cells . Contrarily, polymorphonuclear functions in these patients were severely impaired . The reduction of Nitroblue tetrazolium in dark formazan (NBT test) and the direct phagocytosis of 2 pyogenic strains (Staphylococcus aureus and Salmonella typhimurium) were equally and deeply depressed in almost all patients . This defect was not restored either by 4 hr of hemodialysis nor by 12 months of treatment . This study confirms a major role for a defect of polymorphonuclear cell functions in the depressed defence of patients on chronic hemodialysis against infections.

J Natl Cancer Inst, 1983 Jun, 70(6), 1077 - 80
Organ, species, and compound specificity in the metabolic activation of primary aromatic amines; Poupko JM et al.; For the evaluation of the role of target tissue activation in the induction of bladder cancer, microsome-mediated N-hydroxylation of the bladder carcinogen 4-biphenylamine (4-BA) was studied in bovine and canine bladder mucosae, relative to the activity in liver . Bovine bladder microsomes mediated the N-hydroxylation of 4-BA at an exceptionally high rate, whereas no detectable activity was found with bovine liver microsomes . Dog bladder microsomes were 40-100 times less active than bovine bladder microsomes and contained approximately one-third the amount of cytochrome P450 . Dog liver microsomes were as active as dog bladder microsomes per nanomole P450 and an order of magnitude more active when normalized to microsomal protein . Rat liver microsomes contained the highest level of P450 of all the preparations studied, and N-hydroxylase activity was approximately twice the rate of that of dog liver . The rate of N-hydroxylation of 2-naphthylamine (2-NA) and 1-naphthylamine (1-NA) was compared in bovine bladder mucosa and was found to correlate well with the relative potency of these compounds as bladder carcinogens (4-BA greater than 2-NA greater than 1-NA) . Such a comparison could not be made with dog bladder mucosa because of its low N-hydroxylation activity . In addition, bovine bladder mucosa S-9 mutagenic activation of 4-BA, 2-NA, and 1-NA was investigated in Salmonella typhimurium and found to parallel the carcinogenic potency of these compounds . These results demonstrate considerable tissue, species, and compound specificity for the metabolic activation of aromatic amines and provide further evidence in support of bladder activation as a mechanism of aromatic amine-induced bladder cancer.

Mutat Res, 1983 Jun, 112(3), 147 - 68
Deletion induction in bacteria . I . The role of mutagens and cellular error-prone repair; Balbinder E et al.; The amber mutation trpD28 of Salmonella typhimurium shows a complex reversion pattern on anthranilate (AA)-supplemented minimal medium . Under such conditions it is possible to recover revertants of two phenotypes, prototrophs (MM+) and anthranilate utilizers (AA+), each phenotype brought about by several mutational events . Since one class of AA+ revertants is caused by deletion of the trpD28 mutation, this constitutes a useful system for quantitative studies of the effects of mutagenic agents and cellular factors on the production of deletions . In the present study we have tried to assess the relative contribution of chemical mutagens vs . cellular mutator factors in causing this class of mutations . Strains of S . typhimurium in which the spontaneous reversion rate of trpD28 was modified by pKM101, (strain SO1007), mutL (strain SO1018) and both (strain SO1008), as well as the wild type (strain SO939) were treated with nitrous acid (HNO2) and mitomycin C (MC), mutagens reported to induce deletions in bacteria . The results showed that while the absolute frequency of deletions increased exponentially with dose of mutagen in parallel with the total reversion frequency, the relative frequency (percent) of these mutations was characteristic for each strain and for the most part unaffected by the dose of mutagen . It appears that deletions, spontaneous or induced, occur as a fixed percentage of total mutations and are brought about by the cells' own repair capacity and characteristic DNA metabolism . Perhaps these mutations are the result of untargeted events during SOS misrepair.

J UOEH, 1983 Jun 1, 5(2), 207 - 12
{Structure-function characterization of phenanthridinium compounds as mutagens in salmonella and yeast}; Fukunaga M et al.; The relation between the mutagenic activities and chemical structure of phenanthridinium derivatives were tested by using Salmonella typhimurium strain TA 98 and yeast Saccharomyces cerevisiae . The 3,8-diamino analog and amino-azido isomers caused frameshift type mutation in Salmonella . However, mutagenicity was severely reduced for the diazido analog, and mutagenic activities of monoamino and monoazido analogs were minimal . The deaminated analog was not mutagenic . Diamino analog and two amino-azido isomers induced mitochondrial mutation of yeast in both resting and growing conditions . Two monoamino and deaminated analogs were mutagenic only in growing yeast but not in resting cells . Two monoazido and diazido analogs were less mutagenic even in the growing conditions.

Can J Microbiol, 1983 Jun, 29(6), 670 - 5
Bactericidal photoproducts in medium containing riboflavin plus aromatic compounds and MnCl2; Chelala CA et al.; Exposure to visible light of growth medium containing riboflavin and indole at low concentrations created photoproducts highly toxic to Salmonella typhimurium and other bacteria . No toxicity was detected in the dark or when either of these two components was present singly . Other aromatic compounds (serotonin, indole-3-acetic acid, indole-3-propionic acid, tryptophan, tyrosine, phenylalanine, and p-aminobenzoic acid) tested in place of indole produced various degrees of toxicity . The presence of MnCl2 significantly enhanced the toxicity . Addition of catalase eliminated the toxicity, indicating an important role for hydrogen peroxide.

Food Chem Toxicol, 1983 Jun, 21(3), 319 - 23
Detection of genotoxicity in fried bacon by the Salmonella/mammalian microsome mutagenicity assay; Miller AJ et al.; The potential for mutagen formation in fried bacon and the possible reduction or elimination of this hazard was examined in the Salmonella/mammalian microsome mutagenicity assay using Salmonella typhimurium strain TA98 . Alkaline dichloromethane extracts were prepared from green pork bellies, commercial bacon (nitrite-treated and nitrite-free), and pilot-plant bacon (nitrite-free) . When fried, all forms of bacon and the green belly samples gave positive mutagenic responses with the plate-incorporation technique . Unfried samples were not mutagenic . Aroclor-activated rat-liver S-9 fractions plus NADPH were essential to demonstrate a mutagenic response . When the frying temperature was held constant (171 degrees C) maximum mutagen formation was observed in samples fried for 6 min; when samples were fried for 6 min a mutagenic response which increased with temperature, in a linear manner, was observed at temperatures above 125 degrees C . Volatile nitrosamines were not detected in the bacon samples . The data indicate the generation of one or more mutagens in fried bacon and green pork belly, the levels of which can be reduced by decreasing heating temperature and/or time.

Food Chem Toxicol, 1983 Jun, 21(3), 299 - 303
Acute toxicity of 3-deoxy-4-sulphohexosulose in rats and mice, and in vitro mutagenicity in the Ames test; Walker R et al.; 3-Deoxy-4-sulphohexosulose (DSH) is formed in sulphited foods by the interaction of SO2 and intermediates of the Maillard reaction . The acute intragastric toxicity of DSH has been studied in rats and mice, and the LD50 was found to exceed 5 g/kg body weight in both species . The only adverse effect seen in a 14-day post-dosing period was a transient diarrhoea in the first 24 hr . DSH was shown to be non-mutagenic in four strains of Salmonella typhimurium in the Ames test, with and without metabolic activation by S-9 mix from Aroclor-treated rats.

Mutat Res, 1983 Jun, 120(4), 207 - 17
Genetic toxicity of methyl methanethiosulfonate on Salmonella typhimurium, Saccharomyces cerevisiae and Nicotiana tabacum; Dorange JL et al.; The genetic toxicity of methyl methanethiosulfonate (MMT), a hydrolytic derivative of the insecticide methomyl, or lannate (Du Pont), was studied in Salmonella typhimurium, Saccharomyces cerevisiae and Nicotiana tabacum . At low concentrations, a lethal action was observed in all 3 models . Nuclear genetic effects of the product were not detected on the Xanthi x NC 95 hybrid of N . tabacum or on the diploid strain D7 of S . cerevisiae . At the cytoplasmic level, an effect on chloroplasts was observed on tobacco, but MMT did not induce cytoplasmic 'petites' in yeast . Ames tests with and without metabolic activations by S9 mix and/or fecalase were negative . MMT cannot be considered to be mutagenic on these models; consequently it is unlikely to be genotoxic in man, although these experiments do not exclude eventual co-genetic effects.

J Bacteriol, 1983 Jun, 154(3), 1493 - 7
Stability of plasmids R1-19 and R100 in hyper-recombinant Escherichia coli strains and in Salmonella typhimurium strains; Gomez-Eichelmann MC et al.; Plasmids R1-19 and R100 dissociate in hyper-recominant Escherichia coli strains in a way that is similar to but slower than dissociation in Salmonella typhimurium . The results presented suggest that the molecular mechanism for plasmid dissociation in hyper-recombinant E . coli strains is different than that in S . typhimurium strains.

J Bacteriol, 1983 Jun, 154(3), 1485 - 8
Identification of the enzymatic reactions encoded by the purG and purI genes of Escherichia coli; Houlberg U et al.; The chromosomal locations of the genes purG and purI on the Escherichia coli linkage map are the opposites of those of Salmonella typhimurium . By methods which permit the identification of lesions in any of the five early enzymes of the purine de novo pathway, the gene-enzyme relationships of the purG and purI loci have been reevaluated in these two organisms . The results demonstrate that the relative locations of the genes encoding the two enzymes (phosphoribosylformylglycinamidine synthetase and phosphoribosylaminoimidazole synthetase) are similar in the two organisms . The gene products have been correctly determined in S . typhimurium . The gene products currently listed for the loci in E . coli are incorrect . The E . coli purG locus is equivalent to the S . typhimurium purI locus, and the E . coli purI locus is equivalent to the S . typhimurium purG locus.

J Bacteriol, 1983 Jun, 154(3), 1462 - 6
Lipopolysaccharide core mutants of Salmonella typhimurium containing D-glycero-D-manno-heptose; Branes LV et al.; Mutants resistant to several hydrophobic membrane antagonists were isolated from a "deep rough" (rfaC) mutant of Salmonella typhimurium . The resistance was due to an alteration in the core region lipopolysaccharide composition as evidenced by altered bacteriophage and complement sensitivity and by compositional analysis . The principal change in carbohydrate composition was the predominance of the unusual heptose isomer D-glycero-D-manno-heptose . The unusually wide pleiotropic phenotype of this organism is suggested to be due to a fundamental change in the properties of the bacterial outer membrane.

Infect Immun, 1983 Jun, 40(3), 1234 - 5
A BALB/c congenic strain of mice that carries a genetic locus (Ityr) controlling resistance to intracellular parasites; Potter M et al.; BALB/c.DBA/2 Idh-1b-Ityr-Pep-3b congenic mice were developed by introgressively backcrossing the Idh-1b and Pep-3b markers of DBA/2 mice onto the BALB/c pi mice . This introduced a 30-centimorgan chromosome 1 segment of DBA/2 chromatin that contained the Ityr gene . BALB/c.DBA/2 Idh-1b-Ityr-Pep-3b mice were resistant to in vivo infections by Salmonella typhimurium, Mycobacterium bovis, and Leishmania donovani.

Zh Mikrobiol Epidemiol Immunobiol, 1983 Jun, (6), 56 - 8
{Ultrastructure of Salmonella typhimurium forms with unbalanced growth induced by lithium chloride}; Konstantinova ND et al.; The action of 1.0 and 1.5 M LiCl on S . typhimurium induces the appearance of unbalanced growth forms capable of growing and multiplication, when subcultured in a medium with this preparation . In this culture the prevalence of cells differing in their structure from the initial Salmonella cells and from stable L-form cultures is observed . Cells characteristic of the initial culture and cells resembling the L-forms occur in lesser numbers . LiCl seems to affect peptidoglycan and the cytoplasmic membrane, which brings about disturbances in the permeability of the surface structures of the cell.

Acta Pathol Microbiol Immunol Scand {B}, 1983 Jun, 91(3), 163 - 8
Prevalence and molecular epidemiology of antibiotic-resistant Salmonella typhimurium and Salmonella dublin in Danish cattle; Jorgensen ST; Among 130 strains of S . typhimurium and 191 strains of S . dublin, all from cattle, 80% and 63%, respectively, were resistant to one, two or three antibiotics . Mono-resistance to sulphonamides was most common . Plasmid load was analysed by conjugation, transformation, extraction of plasmid DNA and subsequent electrophoresis in agarose gels . Plasmid DNA from 38 strains was further analysed by restriction with endonuclease EcoR1 . On the basis of this, the strains were classified into four groups . Two groups held S . typhimurium, one held S . dublin and one group held both serotypes . This suggests that dissemination of strains and plasmids mainly occurs through clonal spread of strains . However, plasmid transfer per se also takes place, as exemplified by the fact that indistinguishable plasmids were found in two different serotypes . Strains of one group had contaminated a water-course . Strains of this group were furthermore isolated from humans in the same area as the infected cattle . Strains of this group had an R pattern and a phage-type similar to the R pattern and phage-type of the early isolates of a strain that became epidemic in British cattle . It is discussed whether Denmark, which was previously almost free of cattle salmonellosis, is experiencing the first warnings of an epidemic similar to the one in the UK.

J Bacteriol, 1983 Jun, 154(3), 1502 - 4
The Salmonella typhimurium LT2 uvrD gene is regulated by the lexA gene product; Pang PP et al.; The uvrD gene product apparently plays a role in the repair of UV damage, in mismatch repair, and in genetic recombination . A lower level of expression of the Salmonella typhimurium LT2 uvrD gene was observed in maxicells prepared from an Escherichia coli strain that contained a lexA+ plasmid than in maxicells prepared from an E . coli strain that lacked functional LexA protein . These results suggest that the uvrD+ gene is repressed by the LexA protein and is thus a member of the set of genes whose expression is increased by "SOS"-inducing treatments.

Infect Immun, 1983 Jun, 40(3), 917 - 23
Effect of erythrocyte ingestion on macrophage antibacterial function; Hand WL et al.; Individuals with sickle cell anemia are subject to serious infections caused by a number of bacteria, including Salmonella species and Staphylococcus aureus . It has been suggested that in sickle cell anemia, extensive erythrophagocytosis by macrophages may interfere with their antibacterial function and thereby predispose to infection . As a means of investigating this possibility, we evaluated the effects of erythrocyte ingestion on the Killing of Salmonella typhimurium by peritoneal macrophages and of S . aureus by alveolar macrophages . Monolayers of rabbit macrophages were exposed to erythrocytes or latex particles immediately before and during bacterial challenge . Erythrophagocytosis markedly inhibited intracellular killing of S . typhimurium by peritoneal macrophages (bacterial survival was 181% of control) and of staphylococci by alveolar macrophages (bacterial survival was greater than 200% of control) . Exposure to latex particles depressed the bactericidal activity of alveolar macrophages to a lesser degree . Next we investigated the possibility that erythrophagocytosis inhibits oxidative bactericidal mechanisms in macrophages . Hexose monophosphate shunt activity was stimulated by erythrocyte ingestion . However, zymosan-induced superoxide generation and chemiluminescence were suppressed by erythrocytes . Furthermore, a cell-free (hypoxanthine-xanthine oxidase) system for chemiluminescence generation was also depressed in the presence of erythrocytes (intact or lysate) or by purified hemoglobin . These studies reveal that erythrophagocytosis inhibits macrophage antibacterial function, probably because of interactions between erythrocyte components and reactive products of phagocyte oxygen metabolism . This host defense abnormality may predispose to bacterial infection in certain hemolytic anemias.

J Bacteriol, 1983 Jun, 154(3), 1126 - 36
6-Aminonicotinamide-resistant mutants of Salmonella typhimurium; Hughes KT et al.; Resistance to the nicotinamide analog 6-aminonicotinamide has been used to identify the following three new classes of mutants in pyridine nucleotide metabolism . (i) pncX mutants have Tn10 insertion mutations near the pncA locus which reduce but do not eliminate the pncA product, nicotinamide deamidase . (ii) nadB (6-aminonicotinamide-resistant) mutants have dominant alleles of the nadB gene, which we propose are altered in feedback inhibition of the nadB enzyme, L-aspartate oxidase . Many of these mutants also exhibit a temperature-sensitive nicotinamide requirement phenotype . (iii) nadD mutants have mutations that affect a new gene involved in pyridine nucleotide metabolism . Since a high proportion of nadD mutations are temperature-sensitive lethal mutations, this appears to be an essential gene for NAD and NADP biosynthesis . In vivo labeling experiments indicate that in all the above cases, resistance is gained by increasing the ratio of NAD to 6-aminonicotinamide adenine dinucleotide . 6-Aminonicotinamide adenine dinucleotide turns over significantly more slowly in vivo than does normal NAD.

J Bacteriol, 1983 Jun, 154(3), 1054 - 63
IlvHI locus of Salmonella typhimurium; Squires CH et al.; In Escherichia coli K-12, the ilvHI locus codes for one of two acetohydroxy acid synthase isoenzymes . A region of the Salmonella typhimurium genome adjacent to the leucine operon was cloned on plasmid pBR322, yielding plasmids pCV47 and pCV49 (a shortened version of pCV47) . This region contains DNA homologous to the E . coli ilvHI locus, as judged by hybridization experiments . Plasmid pCV47 did not confer isoleucine-valine prototrophy upon either E . coli or S . typhimurium strains lacking acetohydroxy acid synthase activity, suggesting that S . typhimurium lacks a functional ilvHI locus . However, isoleucine-valine prototrophs were readily isolated from such strains after mutagenesis with nitrosoguanidine . In one case we found that the Ilv+ phenotype resulted from an alteration in bacterial DNA on the plasmid (new plasmid designated pCV50) . Furthermore, a new acetohydroxy acid synthase activity was observed in Ilv+ revertants; this enzyme was similar to E . coli acetohydroxy acid synthase III in its lack of activity at low pH . This new activity was correlated with the appearance in minicells of a new polypeptide having an approximate molecular weight of 61,000 . Strains carrying either pCV49 or pCV50 produced a substantial amount of ilvHI-specific mRNA . These results, together with results from other laboratories, suggest that S . typhimurium has functional ilvB and ilvG genes and a cryptic ilvHI locus . E . coli K-12, on the other hand, has functional ilvB and ilvHI genes and a cryptic ilvG locus.

Lancet, 1983 May 28, 1(8335), 1187 - 91
Acquired immunodeficiency with intestinal cryptosporidiosis: possible transmission by Haitian whole blood; Andreani T et al.; A 31-year-old Frenchman had an acquired immunodeficiency syndrome (AIDS) with profound depression of cellular immunity and relative sparing of humoral immunity . The clinical picture included intractable secretory diarrhoea, vomiting, abdominal pain, and weight loss . Gastrointestinal cryptosporidiosis was present and a perfusion technique showed profuse secretion of fluid in the proximal small bowel . The patient also had recurrent Salmonella typhimurium septicaemia, cytomegalovirus infection, and cerebral toxoplasmosis and he died within 13 months . This patient did not belong to any of the groups known to be affected by this type of acquired immunodeficiency (homosexuals, drug addicts, haemophiliacs, Haitians) but had been transfused with Haitian blood 4 years before onset of symptoms . This case supports the notion that some forms of AIDS may be transmitted by blood, with a long incubation period.

Science, 1983 May 27, 220(4600), 961 - 3
Mutagenicity of glutathione and cysteine in the Ames test; Glatt H et al.; Postmitochondrial supernatant from rat liver and kidney homogenates transformed cysteine into a mutagen that reverted bacteria of the strain Salmonella typhimurium TA100 to histidine independence . Glutathione was also activated by kidney postmitochondrial supernatant but not by liver preparations . Hence, important endogenous compounds of mammals are positive in the most commonly used short-term test for carcinogenicity and mutagenicity . Glutathione is positive in the test even at concentrations found in mammalian tissues.

J Biol Chem, 1983 May 25, 258(10), 6450 - 7
A possible nucleotide-binding domain in the tertiary fold of phosphoribosyltransferases; Argos P et al.; Comparison of the primary structures of three phosphoribosyltransferases (human hypoxanthine-guanine, Salmonella typhimurium ATP, and Escherichia coli glutamine) showed no significant amino acid sequence homology except for a 35-residue span in hypoxanthine-guanine and glutamine phosphoribosyltransferases . However, comparison of smoothed plots of amino acid physical characteristics thought to control protein folding with amino acid sequence number resulted in a substantial correlation for a 120-residue stretch in each of the phosphoribosyltransferases . A secondary structure prediction analysis of the regions indicated a dinucleotide-binding fold with its characteristic beta alpha beta secondary structural pattern . Furthermore, the physical parametric correlation analysis suggested a common catalytic domain fold for hypoxanthine-guanine and glutamine phosphoribosyltransferases which was consistent with the register of the sequence homology . A possible binding mode of the phosphoribosyltransferase substrates is discussed . The physical parametric approach to protein sequence comparison may be generally applicable for distantly related proteins which maintain similar structural folds without any apparent sequence homology.

Nucleic Acids Res, 1983 May 25, 11(10), 3207 - 26
The expression of prokaryotic tRNA genes in frog oocytes; Bossi L et al.; A tRNA gene cluster in Salmonella typhimurium includes the genes for tRNAArg, tRNAHis, tRNA1Leu and tRNAPro . DNA clones were constructed with different portions of this tRNA gene cluster . These clones were microinjected into the nuclei of Xenopus laevis oocytes and assayed for expression . Two of the bacterial tRNA genes (tRNAArg and tRNAPro) are transcribed at high rates and the primary transcripts are processed into mature tRNAs . Transcription and processing are largely independent of whether the two genes are injected individually or as part of a tRNA gene cluster . A third tRNA gene (tRNA1Leu) is expressed less efficiently . Synthesis of this tRNA is totally abolished by a deletion removing 22 bp in the first half of the tRNA1Leu coding sequence . The expression of the fourth tRNA gene (tRNAHis) is very inefficient and dependent upon the gene organization within the injected DNA . No significant tRNA synthesis is detected upon injection of a clone containing only the tRNAHis gene . Evidence is presented suggesting that the impaired expression of the tRNAHis gene is not caused by inefficient transcription, but rather by defective processing of the primary transcript . The prokaryotic tRNAs synthesized in the oocytes show a modification pattern that is specific of eukaryotic tRNAs . Overall, our results are consistent with the hypothesis that the intragenic signals for eukaryotic tRNA gene transcription have appeared early in evolution for reasons other than gene expression.

Biochem Biophys Res Commun, 1983 May 16, 112(3), 833 - 42
Anti-mutagenic chalcones: antagonizing the mutagenicity of benzo(a)pyrene on Salmonella typhimurium; Torigoe T et al.; Several chalcone derivatives; e.g . Ro 09-0204, Ro 09-0323 and Ro 09-0501 were found to reduce markedly the revertant increase of Salmonella typhimurium TA100 by benzo(a)pyrene during the incubation with S-9 Mix . The antimutagenic activity was 100 - 700 times stronger than that of L-ascorbic acid . Effect on other mutagens, the structure activity relationship and the possible mechanism of action are briefly discussed.

J Biol Chem, 1983 May 10, 258(9), 5634 - 7
The introduction of specific sites for heavy metal binding in a crystalline protein; Mowbray SL et al.; Heavy metal derivatives of the galactose binding protein of Salmonella typhimurium were obtained by the treatment of crystals with carbon disulfide under anaerobic conditions, followed by exposure to mercury-containing reagents . Carbon disulfide reacts with protein amino groups to give a metastable dithiocarbamate, which is susceptible to covalent derivatization by mercurials . The number of amino groups which react for any particular crystalline protein will depend on the pH, the composition of the crystal mother liquor, and the steric accessibility limitations imposed by crystal packing . Direct reaction with protein crystals, rather than solution derivatization followed by purification and subsequent crystallization, is used to promote isomorphism of the derivative crystal with the native and to limit the number of available sites . For the S . typhimurium galactose binding protein, carbon disulfide treatment, followed by reaction with 2-chloromercuri-4-nitrophenol, resulted in binding at two sites at pH 8.0 . Similar treatment with dimercury acetate gave one binding site for the dimercurial at the same pH . Both derivatives were isomorphous with the native crystal to a resolution of at least 3.5 A . These heavy atom derivatives have been used to produce an interpretable electron density map of the protein at 3-A resolution.

Proc Natl Acad Sci U S A, 1983 May, 80(10), 2912 - 6
Presence of 1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid, a precursor of a mutagenic nitroso compound, in soy sauce; Wakabayashi K et al.; After treatment with nitrite, Japanese soy sauce was strongly mutagenic to Salmonella typhimurium TA100 without S9 mixture . Two precursors of the mutagen were isolated from Japanese soy sauce, and these were identified as (-)-(1S,3S)-1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid {(-)-(1S,3S)-MTCA} and its stereoisomer (-)-(1R,3S)-MTCA . After treatment with nitrite, 1-mg samples of these compounds induced 17,400 and 13,000 revertants of TA100, respectively, without S9 mixture . Quantitative analysis of various kinds of soy sauces produced in Japan showed the presence of 82-678 micrograms of MTCA per ml . The mutagenicities of these compounds with nitrite accounted for 16-61% of the total mutagenicity of soy sauce with nitrite . Most soy sauces produced in the United States were less mutagenic than those produced in Japan and little, if any, of these two precursors of the mutagen was found in them . A major reaction product of (-)-(1S,3S)-MTCA and nitrite was a compound having a nitroso substitution at position N-2, but this compound was not mutagenic . Thus, the mutagen(s) formed from (-)-(1S,3S)-MTCA and nitrite was a minor product(s), and its specific mutagenic activity must be very high.

Infect Immun, 1983 May, 40(2), 713 - 9
In vitro propagation of antigen-specific T lymphocytes that adoptively transfer resistance to Listeria monocytogenes; Kearns RJ et al.; Murine T cells generated against heat-killed Listeria monocytogenes or Listeria intracellular product (LIP) were propagated in a source of Interleukin 2 . Both T-cell cultures were greater than 98% Lyt 1+, 2/3- and proliferated specifically against LIP and L . monocytogenes crude whole-cell antigen in vitro . Proliferation of both T-cell cultures required the presence of antigen and accessory cells syngeneic to the T cells at the left end of the major histocompatibility complex . The ability of these cultures to adoptively transfer protection against challenge with viable Listeria cells was dramatically different . As few as 10(6) LIP-specific T cells conferred significant protection against a lethal challenge of Listeria cells, whereas cultures induced against crude whole-cell antigen showed little or no protective function . The resistance conferred by LIP-specific T cells was specific in that the cells did not reduce the mortality seen after challenge with Salmonella typhimurium.

Ann Microbiol (Paris), 1983 May-Jun, 134A(3), 319 - 28
{Epidemiology of Salmonella typhimurium biotype 6 strains, isolated in Belgium from 1969 to 1982}; Pohl P et al.; Strains of S . typhimurium biotype 6 possess neither tetrathionate reductase nor arginine dihydrolase; they use trehalose, but not inositol and glycerol . Most are multi-resistant to antibiotics and are responsible for numerous outbreaks of salmonellosis . They have been divided into four groups . Groups I includes strains of phage type 207, and was predominant in Belgium from 1969 to 1976 . Group II includes strains of a classical variety belonging to phage types 49, 193 and 204 . Group III includes strains of the copenhagen variety belonging to the same phage types . Strains of groups II and III are generally resistant to trimethoprim . They have predominated in Belgium since 1978 (mainly phage type 193) . Group IV contains a few strains of various phage types, generally non-resistant, which have caused no epidemics.

J Biochem (Tokyo), 1983 May, 93(5), 1391 - 9
Structural requirements of endotoxic glycolipid for antitumor and toxic activity; Amano K et al.; Endotoxic glycolipids extracted from the polysaccharide heptose-less Re mutant of Salmonella typhimurium were hydrolyzed with alkaline and acid reagents . Treatment with hydroxylamine caused the liberation of all O-ester linked fatty acids and resulted in abrogation of the toxicity (lethality to chick embryos) and ability to regress tumors (line-10 tumors in strain 2 guinea pigs) . Treatment with dilute sodium hydroxide caused partial removal of O-ester linked fatty acids without loss of these activities . Toxicity and tumor-regressive potency were retained after removal of 2-keto-3-deoxyoctonate (KDO) by exposing the glycolipids to sodium acetate solution at pH 4.5 . The majority of the glycolipids of the endotoxic extracts were rendered non-toxic but retained antitumor activity when hydrolyzed with boiling 0.1 N hydrochloric acid, which split KDO and glycosidic phosphate from the glycolipid molecules . Non-toxic glycolipid fractions possessing antitumor activity were separated from the acid hydrolysate by means of preparative thin layer chromatography . It was concluded that glycosidic bound phosphate and at least a portion of the fatty acids of the lipid A moiety are essential for toxicity, but that this phosphate is not an essential structural feature for tumor-regression activity.

Infection, 1983 May-Jun, 11(3), 137 - 43
The influence of bacterial exotoxins and endotoxins on the phagocytic activity of human macrophages in culture; D'Onofrio C et al.; The effect of bacterial exotoxins and endotoxins on phagocytosis was tested on human macrophages in monolayer cultures by determining the rate of zymosan particle ingestion at different toxin concentrations and incubation times . The exotoxins tested were staphylococcal alpha-toxin and diphtheria-toxin . The endotoxins used were lipopolysaccharides from Salmonella typhi, Salmonella typhimurium, Shigella flexneri and Serratia marcescens . Phagocytosis was significantly impaired after prolonged incubation with diphtheria toxin whereas alpha-toxin was ineffective . Endotoxin-treated macrophages showed a wide range of phagocytic activity . Enhancement of phagocytosis was observed with a low concentration of endotoxin (1 microgram/ml) from S . typhi, S . typhimurium and S . flexneri . Higher concentrations (2.5 and 5 micrograms/ml) depressed phagocytosis to varying extents, except for S . typhi lipopolysaccharide, which did not induce a significant decrease in phagocytosis in comparison to the controls.

Eur J Cancer Clin Oncol, 1983 May, 19(5), 641 - 7
Mutagenicity of eight anthracycline derivatives in five strains of Salmonella typhimurium; Marzin D et al.; The mutagenicity of eight anthracycline derivatives, doxorubicin (adriamycin, ADM), daunorubicin (DNR), rubidazone (zorubicin), detorubicin (DTR), 4'-epi-adriamycin (4' epi-ADM), AD 32, N-leucyl daunorubicin (N-leu DNR) and aclacinomycin A, has been tested on Salmonella typhimurium TA 100, Ta 98, TA 1535, TA 1537 and TA 1538 . All but aclacinomycin A were mutagenic . Adriamycin and daunorubicin were mutagenic in all five strains, but only at very high doses (40-100 micrograms/plate) in TA 1535 and 1537 . TA 98 was the most sensitive strain . In general S9 mix (liver homogenate) increased the mutagenicity of the low doses of both compounds . Zorubicin, 4'-epi-adriamycin and detorubicin were mutagenic for TA 98 and TA 100 and slightly mutagenic in TA 1538 . They were also activated by S9 mix . N-leu DNR and AD 32 were slightly but significantly mutagenic for TA 98 and TA 1538 and were also activated by S9 mix . Aclacinomycin A lacked mutagenic activity in the five strains even at cytotoxic doses, both in the presence and absence of S9 mix . The results with AD 32 N-leu DNR and aclacinomycin A strengthen the hypothesis according to which amino moiety of the anthracycline glycosides is essential for mutagenesis.

Appl Environ Microbiol, 1983 May, 45(5), 1548 - 54
Longevity of Salmonella typhimurium in Tilapia aurea and water from pools fertilized with swine waste; Baker DA et al.; Salmonella typhimurium declined rapidly when inoculated into Tilapia aurea culture pools fertilized with fresh swine waste . Within the water column, a 95% decline of viable cells occurred during the first 6 h . Isolation of viable salmonellae was possible at 16 days post-inoculation, but not at 32 days . Similarly, salmonellae could be detected in the viscera and epithelium of T . aurea at 16 days, although not at 32 days . Salmonellae were not isolated from the fish flesh, nor was there evidence of septicemic infection.

Toxicol Lett, 1983 May, 16(3-4), 347 - 50
Mutagenic effect of chlordiazepoxide hydrochloride in mice by host-mediated assay; Susheela M et al.; Chlordiazepoxide hydrochloride, a benzodiazepine tranquilizer was tested for its mutagenic ability by host-mediated assay using Salmonella typhimurium G46 strain as indicator organism and mice as host . Three concentrations of the drug were used: 187.5, 375, and 562 mg/kg body weight corresponding to three sublethal doses 1/4, 1/2, and 3/4 of LD50 . The results show that chlordiazepoxide induced point mutations in Salmonella typhimurium G46 at all three doses . The mutations were increased 2- to 4-fold in the experimental groups compared to the control . The statistical analysis of the data clearly showed significant values at all dose levels; further, the drug also showed a dose-related increase in the mutation rate.

Proc Natl Acad Sci U S A, 1983 May, 80(10), 2879 - 83
In vitro synthesis of the tryptophan operon leader peptides of Escherichia coli, Serratia marcescens, and Salmonella typhimurium; Das A et al.; We used an in vitro DNA-dependent protein-synthesizing system to demonstrate de novo synthesis of the leader peptide specified by the tryptophan (trp) operons of several bacterial species . Peptide synthesis was directed by self-ligated short restriction fragments containing the trp promoter and leader regions . Synthesis of leader peptides was established by demonstrating that they were labeled in vitro only by those amino acids predicted to be present in the peptides . Leader peptide synthesis was abolished by the addition of the Escherichia coli trp repressor . The E . coli trp leader peptide was found to be extremely labile in vitro; it had a half-life of 3-4 min . In a highly purified DNA-dependent peptide-synthesizing system, synthesis of the di- and tripeptides predicted from the Salmonella typhimurium trp operon leader sequence, fMet-Ala and fMet-Ala-Ala, also was observed . Using this dipeptide synthesis system, we demonstrated that translation initiation at the ribosome binding site used for trp leader peptide synthesis was reduced 10-fold when the transcript contained a segment complementary to the ribosome binding site.

Mutat Res, 1983 May-Jun, 117(3-4), 279 - 300
Genetic effects of chromium compounds; Bianchi V et al.; Seven different test systems were utilized to investigate the genetic activity of chromium compounds: infidelity of DNA replication in vitro by DNA pol alpha from calf thymus, damage of DNA detected by alkaline elution in treated mammalian cells or in DNA purified and treated in vitro, DNA repair synthesis in mammalian cells in vitro detected by autoradiography or scintillation counting after labelling with {3H}dThd, gene mutations in the Salmonella typhimurium Ames test, gene mutations (6TG resistance) in cultured hamster cells, sister-chromatid exchanges in different rodent cell cultures, and transformation to anchorage-independent growth of hamster cells in vitro (soft-agar assay) . Potassium dichromate and chromium chloride were used as water-soluble Cr(VI) and Cr(III) salts . Several reference mutagens (EMS, MMS, MMC, 4NQO) were included in the single tests as positive controls . Cr(VI) was active in all the tested systems, except in the induction of DNA damage and DNA repair synthesis in cultured cells . Cr(III), on the other hand, was absolutely inactive unless a direct interaction with purified DNA was permitted by the test conditions . The relevance of data from the various tests to the understanding of the mechanisms of the genotoxic activity of chromium is discussed . Effects other than the direct interaction of Cr(III) with DNA are inferred, which can cause infidelity of the DNA polymerase functions.

Mutat Res, 1983 May-Jun, 117(3-4), 225 - 36
Studies on mutagenicity of 2 bronchodilators under development in Cuba; Jimenez MA et al.; 2 pyridoquinazolones, 2-amino-11H-pyrido{2,1-b}quinazolin-11-one (2-APQ) and 11H-pyrido{2,1-b}quinazolin-11-one (PQ), under development as anti-asthma drugs, were studied for mutagenicity . 2-APQ was found to be a strong mutagen in 5 strains of Salmonella typhimurium and a mild one in the forward-mutation system of the yeast Schizosaccharomyces pombe . Furthermore, 2-APQ had strong clastogenic effects in mouse bone marrow . Because of these results, development of 2-APQ as a bronchodilator was stopped . PQ, on the other hand, did not induce mutation in the 5 Salmonella strains or in S . pombe . S9 mix generally increased the response of 2-APQ in Salmonella dramatically . On the contrary, the mutagenic effectiveness of this compound in S . pombe was only slightly higher in the presence of S9 than without it, suggesting that metabolic activation was not effective in this system.

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