Salmonella typhimurium

Cancer Res, 1981 Nov, 41(11 Pt 1), 4518 - 22
Species difference in N-hydroxylation of a tryptophan pyrolysis product in relation to mutagenic activation; Yamazoe Y et al.; Metabolic activation of a tryptophan pyrolysate, 3-amino-1-methyl-5H-pyrido{4,3-b}indole (Trp-P-2), in liver microsomes from rats, mice, hamsters, guinea pigs, and rabbits was studied to know whether N-hydroxylation is a common obligatory step for mutagenic activation of Trp-P-2 . Among hepatic microsomes obtained from untreated animals, the highest activity of Trp-P-2 N-hydroxylase was observed in microsomes from hamsters, followed by those from guinea pigs, mice, and rabbits . In rats, the activity was low, and there was no appreciable difference between the sexes . The activity of Trp-P-2 N-hydroxylase in microsomes was increased by pretreating the animals with a polychlorinated biphenyl mixture . The induction was most profound in rats, and the activity was enhanced 257-fold, as compared to that of untreated animals . The activity was also enhanced in microsomes from polychlorinated biphenyl mixture-treated rabbits, mice, and hamsters, while the activity was increased only slightly in guinea pigs and was thereby lowest among microsomes from the polychlorinated biphenyl mixture-treated animals . In bacterial mutagenesis test systems using Salmonella typhimurium TA 98, the number of revertants induced by Trp-P-2 was increased in parallel with the microsomal ability of the N-hydroxylation . These results indicate that in all species examined N-hydroxylation is an essential metabolic step for mutagenic activation of Trp-P-2.

J Bacteriol, 1981 Nov, 148(2), 426 - 34
Increased outer membrane resistance to ethylenediaminetetraacetate and cations in novel lipid A mutants; Vaara M; Polymyxin-resistant pmrA mutants of Salmonella typhimurium differed from their parents in that they were resistant to tris(hydroxymethyl)aminomethane-ethylenediaminetetraacetate-lysozyme, tris(hydroxymethyl)aminomethane-ethylenediaminetetraacetate-deoxycholate, and tris(hydroxymethyl)aminomethane-ethylenediaminetetraacetate-bacitracin . Tris(hydroxymethyl)aminomethane-ethylenediaminetetraacetate released about 50% less lipopolysaccharide from the pmrA strains than from the parental strains when the bacteria were grown in L-broth containing 2 mM Ca2+ . Protamine, polylysine, octapeptin, benzalkonium chloride, cold NaCl, cold MgCl2, or cold tris(hydroxymethyl)aminomethane hydrochloride (pH 7.2) caused no leakage or markedly less leakage of periplasmic beta-lactamase from a pmrA mutant than from its parent strain . pmrA mutants were more resistant than their parent strains to protamine and polylysine but not to octapeptin or benzalkonium chloride, as measured by the ability of these agents to kill the bacteria or to sensitize them to deoxycholate-induced lysis . The pmrA strains did not differ from their parent strains in sensitivity to several antibiotics, in porin function (as measured by cephaloridine diffusion across the outer membrane), or in outer membrane-associated phospholipase A activity.

Fundam Appl Toxicol, 1981 Nov-Dec, 1(6), 415 - 8
Absence of mutagenic activity of trifluoroethanol and its metabolites in Salmonella typhimurium; Blake DA et al.; Trifluoroethanol, trifluoroacetaldehyde and trifluoroacetate were found to have no mutagenic activity in the standard Salmonella typhimurium reverse mutation assay (Ames test) using a closed incubation system . Negative results were also obtained when incubation mixtures included 9000 x g supernatant fractions of rat liver or testes homogenates along with an NADPH generating system . Rats were pretreated with a polychlorinated biphenyl mixture to induce biotransforming enzyme activity . These results suggest that the previously reported mutagenic activity of fluroxene is not due to metabolites arising from the trifluoroethyl side of the molecule and that inhibition of spermatogenesis in rats by trifluoroethanol is not mediated through a mutagenic mechanism.

Mutat Res, 1981 Nov, 90(3), 247 - 54
The influence of procarbazine (MIH) on the induction of prophage lambda in Escherichia coli K12 and toxic effects on Salmonella typhimurium; Lackner F et al.; Natulan R (MIH, procarbazine) was tested for its ability to induce prophage lambda in Escherichia coli GY5027 . E . coli Gy4015 served as indicator strain . A weak phage-inducing effect was observed at concentrations from 2 to 12 mg/plate in presence of S9 prepared from rats . This effect was found not to be due to the formation of hydrogen peroxide . It was confirmed that, even at the same high concentrations, no mutagenic effect can be detected with the Ames test in strains TA98 and TA100 of S . typhimurium . However, a toxic effect was observed in presence of S9 in S . typhimurium.

Infect Immun, 1981 Nov, 34(2), 328 - 32
Immunization with major outer membrane protein (porin) preparations in experimental murine salmonellosis: effect of lipopolysaccharide; Kuusi N et al.; A crude major outer membrane (porin) preparation, obtained from a rough strain of Salmonella typhimurium earlier shown to be protective both in active and passive immunization of mice against challenge with smooth S . typhimurium, was further purified . Removal of the main impurities, lipopolysaccharide (LPS) and lipoprotein, was accompanied by loss of protective capacity in passive immunization experiments . Reconstitution with rough LPS restored the protective capacity . Protection was, however, concluded not to be due to anti-LPS, because a large fraction of the anti-LPS antibodies could be removed from the protective rabbit antiserum with an LPS immunosorbent without loss of protection.

Vet Rec, 1981 Oct 31, 109(18), 398 - 401
Salmonella infection in horses in England and Wales, 1973 to 1979; Wray C et al.; During the period 1973 to 1979 the number of recorded incidents of equine salmonellosis increased from 23 in 1973 to a peak of 111 incidents in 1976, but has since decreased to 32 in 1979 . Of the 416 incidents recorded during the period of the survey 292 were caused by Salmonella typhimurium and 121 by 33 different serotypes; in three instances rough strains of salmonella were involved . The number of incidents caused by serotypes other than S typhimurium increased from one in 1973 to 32 in 1976 . The number of different salmonella serotypes increased from two in 1973 to 23 in 1977 and has subsequently declined . Drug resistance monitoring of salmonella strains from horses showed that most of the strains were resistant to streptomycin and sulphonamides, although resistance to other antibacterial drugs used was low . Seventeen different patterns of antibiotic resistance were observed but resistance to more than two antibiotics was uncommon.

Biochemistry, 1981 Oct 13, 20(21), 5973 - 81
Antibacterial peptide from normal rat serum . 1 . Isolation from whole serum, activity, and microbicidal spectrum; Carroll SF et al.; A procedure is described for purification of the primary bactericidal component of normal rabbit serum active in vitro against Bacillus subtilis . A 65 000-fold increase in specific bactericidal activity per milligram of serum protein was obtained, yielding a low molecular weight, heat-stable polypeptide fraction (PC-III) exhibiting biological activity at protein concentrations below 10 ng/mL . This preparation appeared homogeneous as judged by column chromatography and analytical NaDodSO4-polyacrylamide gel eletrophoresis; recovery of serum bactericidal activity was routinely greater than 80% . Analysis of dansylated or 125I-labeled samples in peptide-resolving polyacrylamide gels revealed a single band with an Mr of 1800 . Optimal antibacterial activity of PC-III against B . subtilis occurred at an ionic strength of 0.24 and was absolutely dependent upon divalent cations; calcium was the most effective . Under optimum conditions, 4 ng/mL of PC-III reduced the viability of B . subtilis test innocula by 90% within 10 min at 37 degrees C . Listeria monocytogenes, Escherichia coli, and Salmonella typhimurium were all sensitive to the action of PC-III, but higher bactericide concentrations were required to produce similar reductions in viability as observed with B . subtilis . All strains were killed by PC-III concentrations well below 1 microgram/mL, roughly that found in normal serum . The activity of PC-III preparations was significantly reduced by pretreatment with trypsin or proteinase K but not by neuraminidase or periodate.

Appl Environ Microbiol, 1981 Oct, 42(4), 688 - 91
Thermal inactivation of eight Salmonella serotypes on dry corn flour; VanCauwenberge JE et al.; Dry heat was used to inactivate Salmonella newington, Salmonella typhimurium, Salmonella anatum, Salmonella kentucky, Salmonella cubana, Salmonella seftenberg, Salmonella thompson, and Salmonella tennessee in corn flour at 10 and 15% moisture . The flour was spray inoculated at 10(5) Salmonella cells per g and then stored at 49 degrees C (120 degrees F); viable Salmonella cells were counted on Trypticase (BBL Microbiology Systems) soy agar plates every 30 min for the first 4 h and then at 4-h intervals for 20 additional h of storage . After 24 h, 99.9% of all Salmonella cells were killed . S . thompson and S . tennessee were more resistant to heat inactivation than the other serotypes . Naturally occurring contamination by Salmonella spp . in dry food products could be significantly reduced with this treatment.

Poult Sci, 1981 Oct, 60(10), 2203 - 9
Eimeria tenella infection enhances Salmonella typhimurium infection in chickens; Arakawa A et al.; Three experiments were conducted to investigate the effects of concurrent infections of Salmonella typhimurium and Eimeria tenella on establishment of salmonella infection in chickens . There were four groups in all experiments: noninfected controls, birds infected with 50,000 E . tenella oocysts, birds infected with approximately 10(4) S . typhimurium, and birds infected with a combination of E . tenella S . typhimurium . In the first experiment with three identical trials of 80 birds each, chickens were infected with the organisms and necropsied 1, 3, 5, and 7 days later . Concurrent infections of coccidia and salmonella did not significantly enhance salmonella infection in terms of number of salmonella in the ceca and the number of positive birds for salmonella . In the second experiment, consisting of three replications of 80 chickens each, birds were exposed to salmonella on the day of coccidia exposure, 2, 4, or 6 days thereafter, and killed 1 day late . Salmonella in the ceca of coccidia-infected chickens did not increase significantly as compared with salmonella exposure alone . In the third experiment, with three replication of 60 birds each, chickens were exposed consecutively to salmonella 1 through 5 days and killed 7, 10, and 14 days after coccidia infection . There was a significant increase in number of salmonella in coccidia-infected ceca and number of chickens positive for salmonella in ceca or in liver when compared with those of salmonella infection alone.

Can J Comp Med, 1981 Oct, 45(4), 366 - 70
The isolation of salmonellae, Newcastle disease virus and other infectious agents from quarantined imported birds in Canada; Rigby CE et al.; Necropsy and culture results are presented for 269 consignments of imported birds (mainly psittacine and passerine species) examined between January 1977 and August 1980 . Consignments were submitted for diagnosis of clinical illness or deaths occurring among these birds while they were in quarantine before entry into Canada . Enteritis and injury were the most frequent diagnoses . Pathogens or potential pathogens were isolated from 77% of consignments . Newcastle disease virus was isolated nine times, and Chlamydia psittaci was isolated once . Escherichia coli (from 113 consignments) and salmonellae (from 49) were the most common bacteria isolated, and reoviruses (from 22) and paramyxoviruses other than Newcastle disease virus (from 22) were the most common viruses . Salmonella typhimurium was the most common Salmonella serovar . Salmonella hadar was isolated from turkey poults imported from Great Britain . The possible public health significance of the role of imported birds in the introduction of exotic Salmonella serovars, or of serovars resistant to several antimicrobials is discussed.

Mutat Res, 1981 Oct, 90(2), 111 - 8
Mutagenicity of a series of hexacoordinate chromium (III) compounds; Warren G et al.; 17 chromium(III) compounds have been tested for DNA-damaging capabilities using an E . coli differential repair assay and for mutagenicity in strains of Salmonella typhimurium . 4 of these compounds were active in both assays . Another 4 compounds were positive only in the repair assay and 9 were devoid of activity in both assays . Most of the doubly active complexes contain aromatic amine ligands like 2,2'-bipyridine and 1,10-phenanthroline . Closely related complexes of ligands derived from saturated amines are much less active . It appears that chromium(III) in the proper ligand environment can have considerable genetic toxicity and could represent one of the several possible ultimate species in a mechanism for chromium mutagenesis and carcinogenesis.

Mutat Res, 1981 Oct, 83(3), 349 - 59
The effects of mutations in the polA and recA genes on mutagenesis by nitrosoguanidine in Salmonella typhimurium; Diver WP et al.; Results of semi-quantitative plate tests indicated that polA and recA mutants of Salmonella typhimurium strain LT2 trpB1 might be significantly less mutable by nitrosoguanidine (MNNG) than were their repair-proficient parents strains . Quantitative data obtained in treat-and-plate experiments showed that this was not the case, at least for low doses of MNNG, and also that the recA strain was significantly more mutable at low doses than its Rec+ parent . On the basis of these results it is suggested that cells of S . typhimurium may possess a recA+-dependent repair pathway capable of error-free removal of MNNG-induced pre-mutational lesions from their DNA.

Mutat Res, 1981 Oct, 85(5), 323 - 33
Human saliva inactivates mutagenicity of carcinogens; Nishioka H et al.; Mutagenicities of AF-2, MNNG, 4NQO, aflatoxin B1, benzo {a} pyrene and Trp-P-1, with or without metabolic activation, were inactivated by treatment with human saliva to a great extent in the Ames test with Salmonella typhimurium test strains TA98 and TA100 . Mutagenic activities of quercetin, pyrolysates of beef, salmon and sodium glutamate, and condensate of cigarette smoke were also decreased to some extent by saliva treatment, but no significant effect was found on the activity of MMS and pyrolysate of polypeptone . These effects showed individual variations . The inhibition of AF-2 mutagenicity by saliva varied with temperature in TA100 but not in TA98 cultures . Boiled saliva inactivated AF-2 mutagenicity in TA98 to some extent but not in TA100 cultures . Inactivation of AF-2 mutagenicity by saliva treatment was completed within 30 sec . Complex mechanisms may be involved in the inactivation of mutagenicity of carcinogens by saliva, including biochemical reactions with enzymes, vitamins, etc . and/or adsorption with high molecular weight substances in saliva such as proteins, bacterial cells, mucous materials, etc.

Mutat Res, 1981 Oct, 85(5), 309 - 21
Modified fluctuation test for the direct detection of mutagens in foods with Salmonella typhimurium TA98; Levin DE et al.; A modified fluctuation test (Green) with the Ames' tester strain Salmonella typhimurium TA98 has been examined for sensitivity to histidine feeding and for detection of minimal concentrations of daunomycin and S9 activated benzo{a}pyrene . The fluctuation test was found operable over a range of histidine concentrations between 0.25 and 1.25 microgram/ml using 48 tube assays and microtitre plates with 120 wells . The agar plate method yielded a comparable operational range for histidine concentration . With daunomycin, the microtiter fluctuation test was 48-fold greater in sensitivity than the macroscale fluctuation test . With benzo {a} pyrene, the microtiter fluctuation test was 4.8-fold greater in sensitivity than the macroscale test . The microtiter assay was 2.4 and 2.5-fold more sensitive than the plate and treat method with daunomycin and benzo {a} pyrene respectively.

Cancer Lett, 1981 Oct, 14(1), 93 - 9
Mutagen formation during the cooking of fish; Krone CA et al.; Compounds mutagenic toward Salmonella typhimurium strains sensitive to frameshift mutation (1537, 1538 and TA98) were formed when fish flesh was fried at 190 degrees c . Four species of marine fish commonly consumed in the United States were cooked in an electric skillet and broiled beneath the elements of an electric oven . Organic extracts of the fish were tested in the Salmonella mutagenic assay using strains 1535, 1537, 1538, TA98 and TA100 . Basic organic extracts of fried but not raw or broiled samples exhibited significant mutagenicity with metabolic activation . Mutagenic activity ratios ranging from 3.3 to 15.7 for the extract from 20 g of fish were observed . The mutagenicity produced during the frying of fish was dependent on time . Frying times of less than 6 min produced no mutagenic activity, while at 6 min or greater substantial mutagenicity was generated.

J Hyg (Lond), 1981 Oct, 87(2), 257 - 69
Change of drug resistance patterns and genetic properties of R plasmids in Salmonella typhimurium of bovine origin isolated from 1970 to 1979 in northern Japan; Makino S et al.; A total of 321 Salmonella typhimurium strains of bovine origin obtained in northern Japan during the period 1970-1979 were tested for drug resistance and detection of conjugative R plasmids . Three hundred and eighteen (99.1%) of these strains were resistant to one or more drugs . The isolation frequently of multiply drug-resistant strains tended to increase year by year . Two hundred and thirty-seven (74.5%) of these resistant strains carried conjugative R plasmids . A total of 308 R plasmids including 174 (56.5%) thermosensitive (ts) R plasmids were derived from the 237 drug-resistant strains, indicating that 71 (30.0%) strains have two different conjugative R plasmids in a single host cell . Of the 308 R plasmids examined for fertility inhibition (fi), 167 ts and 131 non-ts R plasmids were fi- . Of the 60 ts r plasmids examined for incompatibility, 50 were classified into H1 group and 10 into H2 group . Of the 52 non-ts R plasmids examined, 35 were classified into the I alpha-group and the remaining plasmids were untypable in our tests . Mercury resistance marker was found in about 20% of H1 R plasmids coding for multiresistance, and all of H2 R plasmids coded for resistance to tellurite . The clonal distribution of an S . typhimurium strain which carried an H1 R plasmid coding for resistance to six drugs and mercury was recognized in 1978 and 1979.

J Bacteriol, 1981 Oct, 148(1), 394 - 6
Genetic mapping of the Salmonella typhimurium pncB locus; Foster JW et al.; The nicotinic acid phosphoribosyltransferase locus pncB was located on the Salmonella typhimurium linkage map counterclockwise relative to pyrC . P22 and P1 transductional analyses revealed linkage of pncB with aroA and pyrD, indicating a pncB map position of approximately 20 map units . The results of these cotransduction experiments also indicated that the genetic map distance between gal and pyrD is greater than the published 2.2 map units.

J Bacteriol, 1981 Oct, 148(1), 283 - 93
Influence of lipopolysaccharide and protein in the cell envelope on recipient capacity in conjugation of Salmonella typhimurium; Sanderson KE et al.; In crosses of Salmonella typhimurium FfinP301 lac+ to F- strains of S . typhimurium in broth, recipient strains which were rough mutants affected in the outer core region of the lipopolysaccharide gave an average of 1.4 Lac+ transconjugants per donor cell and over 50% of the donor and recipient cells in mating aggregates, whereas smooth recipient strains gave 0.08 Lac+ transconjugants and few cells in mating aggregates . Strains with mutations affecting the inner core of the lipopolysaccharide were usually poor recipients . When cells were mated on Millipore membrane filters, both smooth and rough strains gave ca . 1.0 Lac+ transconjugants per donor cell . Plasmids in Inc groups FI, FII, M, J, and I beta gave more transconjugants with rough than smooth strains, but there were no difference in crosses with plasmids in Inc groups T, L, P, N, and W . Strains with mutations in the ompA gene (deficient in Omp Ap = 33K = II* = conjugation protein) yielded only 0.02 Lac+ transconjugants per donor cell and few cells in mating aggregates . There was no indication of a deficiency of Omp Ap in smooth strains compared with rough strains . Reduced fertility of smooth recipients may occur because the O side chains of the lipopolysaccharide shield the recipient and reduce the frequency of stabilization of mating aggregates . However, gradient-of-transmission experiments indicated that once these mating aggregates are stabilized, they are equally stable in both smooth and rough recipients . Fertility was high in crosses of S . typhimurium Flac+ to Escherichia coli K-12 F- (0.75 Lac+ transconjugants per donor cell; over 50% of the cells in mating aggregates) . In crosses of E . coli K-12 Flac+ to S . typhimurium smooth F-, ca . 10(-5) Lac+ transconjugants per donor cell were obtained; in crosses to rough recipient strains, fertility was increased 14-fold, and when the recipient was defective in the SA and LT host restriction systems, fertility was increased in additional 100-fold . Thus, both the lipopolysaccharide and the protein in the cell envelope of S . typhimurium were shown to be important in the recipient function in F-mediated conjugation.

J Bacteriol, 1981 Oct, 148(1), 257 - 64
Isolation of IIIGlc of the phosphoenolpyruvate-dependent glucose phosphotransferase system of Salmonella typhimurium; Scholte BJ et al.; We report a procedure for the isolation of IIIglc of Salmonella typhimurium, a protein component of the phosphoenolpyruvate-dependent sugar phosphotransferase system . IIIGlc is a soluble protein with a molecular weight of 21,000, as determined by gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis . The purified protein is involved in the phosphoenolpyruvate-dependent phosphorylation of methyl alpha-glucoside in vitro . Its affinity for octyl-Sepharose may be an indication of the partial hydrophobic nature of IIIGlc . A specific antiserum against purified IIIGlc was prepared . Growth on different carbon sources did not affect the synthesis of IIIGlc, as determined by quantitative immunoelectrophoresis . Mutations which lower the adenosine 3',5'-phosphate level, such as cya and pts, do not alter the IIIGlc level . The closely related enteric bacteria Escherichia coli and Klebsiella aerogenes contain a protein factor which is closely related to IIIGlc of S . typhimurium, whereas Staphylococcus aureus does not.

J Bacteriol, 1981 Oct, 148(1), 210 - 9
Wild-type isopropylmalate isomerase in Salmonella typhimurium is composed of two different subunits; Fultz PN et al.; The isopropylmalate isomerase in Salmonella typhimurium is the second enzyme specific for leucine biosynthesis . It is a complex enzyme composed of two subunits which are coded for by two genes of the leucine operon, leuC and leuD . The two polypeptides have been shown to copurify through successive ammonium sulfate fractionations and have been identified on sodium dodecyl sulfate-polyacrylamide gels as having molecular weights of 51,000 (leuC gene product) and 23,500 (leuD gene product) . They have also been shown to be fairly stable, since in vitro complementation of cell-free extracts of leuC and leuD mutant strains was demonstrated, with only a 40% loss of activity 16 h after preparation of the extracts . The native isopropylmalate isomerase was shown to have a Km for its substrate alpha-isopropylmalate of 3 x 10(-4)M.

Antimicrob Agents Chemother, 1981 Oct, 20(4), 558 - 62
Mode of antibiotic action of 4-hydroxy-3-nitrosobenzaldehyde from Streptomyces viridans; Yang CC et al.; The free ligand, deferroviridomycin A, and its iron(II) complex, viridomycin A, were detected in culture supernatant fluids of Streptomyces viridans 1671 and were structurally characterized as 4-hydroxy-3-nitrosobenzaldehyde and tris(4-hydroxy-3-nitrosobenzaldehydato-N3,O4)ferrate(II), respectively . We investigated the antibiotic activity of the above compounds and of the chemically synthesized bis copper(II), tris cobalt(III), and tris nickel(II) complexes against Escherichia coli NIHJ, Salmonella typhimurium LT-2Z, Staphylococcus aureus 209P, Streptococcus faecium 10541, and Bacillus cereus, T . The free ligand and its kinetically labile copper(II) and nickel(II) complexes displayed activity against all of the above organisms, whereas the kinetically inert iron(II) and cobalt(III) complexes displayed activity only against S . aureus and B . cereus . The antibiotic activity of the substitutionally labile metal complexes was attributed to dissociation of the free ligand . The mode of antibiotic action of the free ligand against E . coli appears to be interference with the structural and functional integrity of the cell membrane.

J Pharmacobiodyn, 1981 Oct, 4(10), 803 - 11
Studies on aspirin derivatives with very little side effect . II . Potent platelet anti-aggregant activity and no mutagenicity of aspirin-isopropylantipyrine (AIA); Aonuma S et al.; The effect of a new aspirin derivative, aspirin-isopropylantipyrine (AIA), with very little gastric ulcerogenic activity and very slight acute toxicity and with analgesic, antipyretic anti-inflammatory, and platelet aggregation inhibitory activities was evaluated in vitro and ex vivo and compared with those of aspirin and isopropylantipyrine (IA) . In vitro, AIA, aspirin and IA (50-200 microM) caused concentration-dependent inhibition of collagen-induced aggregation in rabbit platelets although AIA was several-fold more active than the others Arachidonic acid-induced aggregation was inhibited by all three agents (200 microM) in the following magnitude; IA greater than aspirin greater than AIA . Three agents did not influence primary ADP-induced aggregation . The in vitro effects on the release-inducing aggregants were confirmed by ex vivo experiments in rats . These demonstrated that AIA and aspirin (50 mg/kg) exhibited almost identical inhibitory potencies in the extent and the rate of collagen-induced aggregation 4 h after subcutaneous injection . AIA was still effective 24 h after administration as well as aspirin . IA was less effective, differing from the results in vitro . AIA had no effect on plasmin activity and blood flow through the common carotid artery . AIA (1 mM) maintained spreading and beating of myocardial cells in a serum-free culture . As special toxicity trials on AIA mutagenecity tests were made by the Rec-assay with Bacillus subtilis, by the plate culture with Escherichia coli, and by the Ames system with Salmonella typhimurium . AIA was found to have no mutagenic effect under any of those methods and to have no effect on the mutagenic action of 3, 4-benzopyrene under the liver microsome test using the Ames system.

Proc Natl Acad Sci U S A, 1981 Oct, 78(10), 6038 - 42
Two periplasmic transport proteins which interact with a common membrane receptor show extensive homology: complete nucleotide sequences; Higgins CF et al.; The hisJ and argT genes of Salmonella typhimurium encode two periplasmic binding proteins, J and LAO, which are involved in histidine and arginine transport, respectively, and which interact with a common membrane-bound component, the P protein . The complete nucleotide sequences of these two genes have been determined . The two genes show extensive homology (70%) and presumably arose by tandem duplication of a single ancestral gene . The two encoded proteins now perform distinct functions but still retain sufficient homology to permit interaction with the same site on the membrane-bound P protein . Three lines of evidence have allowed both the amino acid-binding site and the site involved in the interaction with the P protein to be assigned to specific regions of each binding protein: (i) the distribution of amino acid differences between the two proteins; (ii) the properties of a functional chimeric protein, produced by a deletion mutant in which the first half of the argT gene is fused to the second half of the hisJ gene; (iii) the sequence change in a mutant J protein unable to interact with P.

Mech Ageing Dev, 1981 Oct, 17(2), 163 - 71
Metabolic activation of aflatoxin B1 by liver tissue from male fischer F344 rats of various ages; Jayaraj A et al.; The effect of aging on the ability of the liver to activate chemical procarcinogens was studied using 12-, 18-, and 27-month-old male Fischer F344 rats . The cytochrome P-450 content of the S9 and microsomal fractions of the liver decreased approximately 30% between 12 and 18 months of age . The structural conformation of cytochrome P-450 in microsomes from 12-, 18-, and 27-month-old rats was studied using electron-spin resonance spectroscopy . An age-related decrease in the amount of cytochrome P-450 ferric iron in the liver microsomes was observed . The conversion of the chemical procarcinogen aflatoxin B1 to mutagenic compounds by the S9 and microsomal fractions of liver was measured using the Salmonella typhimurium bioassay . A 40-50% decrease in the metabolic activation of aflatoxin B1 was observed between 12 and 18 months of age . However, the activation of aflatoxin B1 did not change after 18 months of age . The age-related decrease in the activation of aflatoxin B1 by liver appears to be due to a decrease in the metabolic activity of the mixed-function oxidase system.

J Gen Microbiol, 1981 Oct, 126(Pt 2), 405 - 11
Phage Folac: an Folac plasmid-dependent bacteriophage; Bradley DE et al.; By enriching sewage with Escherichia coli or Salmonella typhimurium strains harbouring the plasmid EDP208, a constitutive pilus-producing derivative of plasmid F olac, a phage was isolated which plated on these two organisms but not on isogenic strains without the plasmid . The phage was named F olac; it has a hexagonal outline with a diameter of 28 nm, contained RNA, was resistant to chloroform, and probably adsorbed preferentially to the sides of EDP208 pili very near the tip . Phage multiplication could be demonstrated on E . coli or S . typhimurium strains carrying the plasmid F olac, but an increase in titre did not occur on E . coli strains carrying plasmids of the F complex . Results of phage multiplication experiments on strains carrying the depressed pilus-producing plasmids R71 or TP224-Tc, which determine pili serologically related to those of EDP208, were inconclusive . Phage F olac was found to be serologically related to phage UA-6, another isolate specific for EDP208.

Biochim Biophys Acta, 1981 Sep 28, 655(2), 221 - 9
A computer method for construction of secondary structure from polynucleotide sequence . Possible structure of the bacterial replication origin; Ooi T et al.; A computer method to search the possible secondary structure of a long polynucleotide was developed . As a criterion for the stabilization of a secondary structure, free energy originating from base-pairing was employed, since the structure in solution would be at the free energy minimum . The method is summarized as follows: all possible helices are collected from a given nucleotide sequence under restrictions that the length of a helix is greater than N0 bases (e.g., four bases) and the free energy of the helix calculated according to free energies of two successive sequence-dependent basepairs is lower than E0 (e.g., -5 kcal/mol) . The search of secondary structures of low free energy is performed by connecting one helix to another without allowing any base-pairing between loops . For connecting single-stranded regions, destabilizing free energy of 2--3 kcal/mol is added . The method was first applied to several tRNAs and the clover-leaf structure of tRNA was obtained as a free energy minimum . Then, possible secondary structures of the replication origin regions of the Escherichia coli and Salmonella typhimurium chromosomes were examined by the method, assuming that one of the strands in the origin region takes a specific secondary structure . The lowest-energy structure for the E . coli origin was found to be approximately identical to that for the S . typhimurium origin region.

J Biol Chem, 1981 Sep 25, 256(18), 9762 - 6
Enzymatic properties of the purified putA protein from Salmonella typhimurium; Menzel R et al.; In the previous paper (Menzel, R., and Roth, J . (1981) J . Biol . Chem . 256, 9755-9761) we have described the purification of a protein, the putA gene product, which has both proline oxidase and pyrroline-5-carboxylic acid dehydrogenase activities . In this paper we demonstrate that these enzyme activities are distinct with respect to a number of characteristics . The oxidase activity proceeds by a ping-pong mechanism involving the reduction of an enzyme-bound flavin . The dehydrogenase activity utilizes an ordered reaction mechanism.

J Biol Chem, 1981 Sep 25, 256(18), 9755 - 61
Purification of the putA gene product . A bifunctional membrane-bound protein from Salmonella typhimurium responsible for the two-step oxidation of proline to glutamate; Menzel R et al.; In this paper we report the purification of a protein which is able to catalyze both the proline oxidase and the pyrroline-5-carboxylic acid dehydrogenase activities necessary for the oxidation of proline to glutamic acid . The purification involves the preparation of a crude membrane pellet, detergent solubilization, ammonium sulfate fractionation, and DEAE-chromatography . We are able to obtain an essentially pure preparation (greater than 95% pure) after only a 52-fold purification, demonstrating that the protein is a major protein in cells fully induced for proline utilization . Both proline oxidase and pyrroline-5-carboxylic acid dehydrogenase activities co-purity throughout our purification . Velocity sedimentation of the purified protein demonstrates that both proline oxidase and pyrroline-5-carboxylic acid dehydrogenase activities co-sediment . Early in the purification procedure we are able to detect two species of protein which have both proline oxidase and pyrroline-5-carboxylic acid dehydrogenase activities . Our procedure purifies only the larger molecular weight species . The purified protein is a dimer composed of identical 132,000-dalton subunits . Analysis of mutants defective for proline utilization demonstrate that the bifunctional enzyme is the putA gene product.

Cancer Treat Rep, 1981 Sep-Oct, 65(9-10), 835 - 40
Phase I trial of PCNU administered by 5-day courses; Earhart RH et al.; PCNU was selected for clinical trials based on high activity in both standard and intracisternally transplanted murine tumors . PCNU was administered of five daily to 24 patients with refractory advanced solid tumors by courses of five daily iv injections every 6 weeks . The total dose ranged from 25 to 125 mg/m2/course . The major dose-limiting toxicity was reversible thrombocytopenia, with the nadi at 28-49 days and recovery by 2 weeks later . At a dose of 125 mg/m2/course, the mean nadir platelet count was 77 X 10(3)/mm3 (range, 16-201 X 10(3)/mm3) . Recovery time was prolonged with successive courses in four patients, suggesting cumulative toxicity . The mean nadir of leukopenia at this dose was 2.6 X 10(3) cells/mm3 (range, 1.2-5.0 X 10(3) cells/mm3) and tended to occur with a later median at Day 44 . Nausea and vomiting were unusually mild for a nitrosourea . Sporadic transaminasemia and elevated LDH may have been related to the vehicle, N,N'-dimethylacetamide . Other major organ toxic effects were not encountered, and there were no objective responses . PCNU was found to be a base-substitution mutagen in the Salmonella typhimurium assay . A starting dose of 125 mg/m2, divided into five daily doses, is suggested for phase II trails in patients with no significant hematologic compromise from prior chemotherapy or radiation, and a dose of 75 mg/m2 is recommended for all others.

Zentralbl Bakteriol Mikrobiol Hyg {B}, 1981 Sep, 173(6), 452 - 6
{Studies on survival of salmonellae on agricultural areas (author's transl)}; Platz S; Subsequent to experimental contamination of grass plots, the persistence of Salmonella typhimurium has been investigated under outdoor climatic conditions . The studies showed the following results: -in the usually shaded zones of the blade of grass near the subsoil and in the superficial soil layer itself, the Salmonella could be reisolated over a period of 28-77 days by Salmonella enrichment methods . On the other hand, the indicator bacteria could be reisolated from the apical zone of the blade of grass for only a maximum of 5 days by the same microbiological methods . In general however, regular isolations of Salmonellae were possible for only a third part of the maximal survival time, which could be detected in the actual experiments . -longer periods of sunshine in connection with only few rainfall seemed to reduce the survival times of the indicator bacteria . The results lead to the conclusion, that an interval of 6 weeks between spreading of liquid manure and the first drive to pasture will result in decreased risk of bacterial infection for grazing animals.

Mutat Res, 1981 Sep, 90(1), 57 - 65
Mutagenicity of reaction products of sulpyrine with nitrite; Sakai A et al.; The mutagenicity of three N-nitroso compounds produced by the reaction of sulpyrine with nitrite, 1-diketobutyryl-1-phenyl-2-methyl-2-nitrosohydrazide hydrate (DPMN), 4-(N-methyl-N-nitroso) aminoantipyrine (MNAA) and 1-acetyl-1-methyl-2-nitroso-2-phenylhydrazine, was tested on Salmonella typhimurium TA100 and TA98 . The mutagenicity of related compounds, 4-methyl-aminoantipyrine, 1-acetyl-1-methyl-2-phenylhydrazine, 4-hydroxyantipyrine, sulpyrine and sodium nitrite was also examined . DPMN and MNAA, which are main reaction products in the nitrosation of sulpyrine, and sodium nitrite were mutagenic to TA100, but not to TA98 . The other compounds were not mutagenic to either strain . MNAA required metabolic activation with rat-liver microsomal preparation (S9 mix) for the mutagenic activity, while DPMN did not require S9 mix . The mutagenicity of DPMN was remarkably increased by the addition of L-cysteine or glutathione . The enhancing effect was proportional to the concentrations of cysteine (0.4-2.1 mumoles/plate) or glutathione (0.8-6.5 mumoles/plate) added.

Mutat Res, 1981 Sep, 90(1), 21 - 30
Frameshift mutations: relative roles of simple intercalation and of adduct formation; McCoy EC et al.; The contribution of "simple" intercalation and of adduct formation on the expression of frameshift mutations in Salmonella typhimurium was investigated using 9-aminoacridine and derivatives capable of either only intercalating between DNA base pairs or of forming adducts with DNA as well . For a chemical capable of intercalating as well as of forming an adduct, only a small portion of the frameshift mutagenicity is due to "simple" intercalation . Analogs only able to induce frameshift mutations as a result of intercalation generally display only a fraction (approx . 1%) of the frameshift activity of the analog capable of forming DNA adducts.

Mutat Res, 1981 Sep, 90(1), 1 - 10
Frameshift mutagenesis of 9-aminoacridine derivatives in Salmonella typhimurium; Young PR et al.; It has been noted that 9-aminoacridine reverts a his C frameshift but not one in his D in the Salmonella strains used in the Ames test, without metabolic activation . The 2 sites differ in the arrangement of G and C residues present . We show here that a series of 9-aminoacridine derivatives exhibits the same selectivity as 9-aminoacridine provided there is at least one exocyclic amino hydrogen at the central ring position in acridines, or the analogous site in aminoquinolines . The results are consistent with a model derived from NMR experiments on 9-aminoacridine binding to dinucleoside phosphates, in which the N-H group is situated in the duplex so as to participate in a hydrogen bond with one base while excluding its complementary partner, thereby provoking mismatching . We also report a strong difference in the dose-response behavior of 9-aminoacridine, quinacrine and a bifunctional derivative of quinacrine.

Gene, 1981 Sep, 14(4), 309 - 19
DNA sequence of the araBAD-araC controlling region in Salmonella typhimurium LT2; Horwitz AH et al.; The araB and araC genes of Salmonella typhimurium have been cloned onto the plasmid pBR322 . Restriction analysis and subcloning of restriction fragments localized these genes to a 4.4 kb DNA fragment . Complementation analysis revealed that the cloned araB and araC genes from S . typhimurium complemented araB and araC mutant strains of escherichia coli . Conversely, cloned araB and araC genes from E . coli complemented araB and araC mutant strains of Escherichia coli . Conversely, cloned araB and araC genes from E . coli complemented araB and ara C mutant strains of S . typhimurium . The DNA sequence was determined for the S . typhimurium araB and araC controlling region and for the initially translated portions of these genes . The nucleotide sequence of the araB promoter was 87% homologous with the same region in E . coli and contained no deletions or insertions relative to the E . coli sequence . The presumed AUG codon corresponding to the amino terminus of the S . typhimurium araC protein was in the same location as in E . coli . There was, however, considerable divergence for the E . coli sequence preceding the translation start site . The nucleotide sequence of the initial 237 bp in the open reading frame of the S . typhimurium araC gene was 78% homologous with the same sequence in E . coli . By comparison, the amino acid sequence for this region was 91% conserved.

J Clin Microbiol, 1981 Sep, 14(3), 281 - 7
Detection of Salmonella infections by polyvalent enzyme-linked immunosorbent assay; Lentsch RH et al.; Serum immunoglobulin G (IgG) and IgM were measured for individual Salmonella species by the enzyme-linked immunosorbent assay (ELISA) . F344 rats were experimentally infected with Salmonella typhimurium (serogroup B), S . enteritidis (serogroup D), and S . rubislaw (serogroup G.) Endotoxin extracted from each serogroup served as the antigen in a classical indirect ELISA . Antibody specific for each Salmonella serogroup was detected by ELISA . Normal gut flora from control animals appeared not to cause cross-reactions in the ELISA . Specificity and sensitivity of the IgG ELISA were determined by statistically evaluating false-positives and false-negatives . Ideal values of 90% or better were achieved in nearly all instances . Each antigen was also tested with heterologous antisera in an effort to develop a polyvalent assay for Salmonella species . No single antigen detected all positive heterologous antisera . Therefore, a polyvalent antigen composed of the three serogroup antigens was tested . The results suggested that Salmonella infections can be detected by measuring serum IgG levels with a polyvalent ELISA 6 to 9 days postinfection.

J Bacteriol, 1981 Sep, 147(3), 986 - 96
Hydrophobic peptide auxotrophy in Salmonella typhimurium; Branes LV et al.; The growth of a pleiotropic membrane mutant of Salmonella typhimurium with modified lipopolysaccharide composition was found to be strictly dependent on the peptone component of complex media . Nutritional Shiftdown into minimal media allowed growth for three to four generations . Of 20 commercial peptones, only enzymatic digests supported growth to varying degrees . Neither trace cations, amino acids, vitamins, carbohydrates, lipids, glutathione, polyamines, carbodimides, nor synthetic peptides stimulated growth; however, cells still metabolized carbohydrates, and amino acid transport systems were shown to be functional . A tryptic digest of casein was fractionated into four electrophoretically different peptide fractions of 1,000 to 1,200 molecular weight which supported growth to varying degrees . The best of these was further fractionated to two highly hydrophopic peptides . N-terminal modifications eliminated biological activity . Fluorescein-conjugated goat antibody to rabbit immunoglobulin G was used as a probe to detect antipeptide antibody-peptide complexes on membrane preparations . Cells grown on peptone distributed the peptide into both inner and outer membranes . The peptide could be removed with chaotropic agents, and cells had to be pregrown in peptone-containing media to bind the hydrophobic peptide . The gene (hyp) responsible for peptide auxotrophy was mapped at 44 to 45 units by conjugation.

J Bacteriol, 1981 Sep, 147(3), 925 - 30
Degradation of abnormal proteins in peptidase-deficient mutants of Salmonella typhimurium; Miller CG et al.; The degradation of abnormal proteins produced as a result of incorporation of the arginine analog L-canavanine or generated by exposure to puromycin was studied in wild-type and multiply peptidase-deficient strains of Salmonella typhimurium . Both types of abnormal protein were rapidly degraded during growth of Pep+ strains of this organism . Peptidase--deficient mutants (lacking peptidases N, A, B, and D) could also degrade these abnormal proteins, although the rate of production of trichloroacetic acid-soluble degradation products was slower in the mutant strain than in a strain carrying a normal complement of peptidases . Analysis of these trichloroacetic acid-soluble degradation products of ion-exchange chromatography showed that free amino acid was the major breakdown product produced by the wild-type strain . The acid-soluble degradation product produced by the mutant strain, however, was a complex mixture that contained a variety of small peptides as well as free amino acids . These results indicate that the same group of peptidases shown previously to function in the degradation of exogenously supplied peptides and in protein turnover during carbon starvation also lie on the pathway by which abnormal proteins are degraded.

Cancer Res, 1981 Sep, 41(9 Pt 1), 3441 - 7
Mutagenicity, tumor-initiating activity, and metabolism of methylphenanthrenes; LaVoie EJ et al.; The mutagenicity, in vitro metabolism, and tumor-initiating activity of methylphenanthrenes were evaluated . The only monomethyl isomers which were mutagenic toward Salmonella typhimurium were 1- and 9-methylphenanthrenes . Among the disubstituted phenanthrenes assayed for mutagenicity, only 1,4-dimethylphenanthrene was active in the presence of metabolic activation . Studies on the in vitro metabolism of methylphenanthrenes were performed by incubation of the various isomers with the 9000 X g supernatant from Aroclor-treated rat livers . Comparison of mutagenicity with metabolites formed in vitro indicated that inhibition of 9,10-dihydrodiol formation was positively associated with mutagenic activity . Among the metabolites of 1- and 9-methylphenanthrenes, significant mutagenic activity was associated only with the 3,4- and/or 5,6-dihydrodiol . Metabolism to the 1,2- or 7,8-dihydrodiol, the requisite dihydrodiols for formation of "bay-region" dihydrodiol-epoxides, was most significant in the case of 4-methylphenanthrene . None of the isomeric methylphenanthrenes were active when assayed as tumor initiators on mouse skin . In contrast, 1,4-dimethylphenanthrene was found to have potent tumorigenic activity . These results suggest that inhibition of 9,10-dihydrodiol formation, the influence of a 4-methyl substituent in directing dihydrodiol formation at the 1,2- or 7,8-positions, and the presence of a bay-region methyl group may be responsible for eliciting a tumorigenic response for 1,4-dimethylphenanthrene.

Mutat Res, 1981 Sep, 87(2), 191 - 210
Bacterial systems for carcinogenicity testing; Mohn GR; During the past 30 years, bacterial test systems have been extensively refined in their ability to detect not only mutagenic agents but, in many cases, carcinogenic ones as well . Since many carcinogens are known to be activated within the mammalian body, major improvements in bacterial test systems were made when representative parts of mammalian metabolism were included as part of the test protocol . Presently, systems of great simplicity and convenience are available for the efficient detection of gene mutations, lysogenic induction of prophages, and differential DNA repair . These qualities render bacterial systems potentially useful in distinguishing between carcinogens and non-carcinogens, in characterizing induced mutation spectra, and possibly in quantifying mutagenic potency that may be used to predict tumor-initiating potency . Sensitive strains of Salmonella typhimurium . Escherichia coli and Bacillus subtilis with altered DNA-repair capacities have been constructed which accurately identify many carcinogens . Comparative studies have shown that techniques using these strains can be standardized to some extent and that the majority of carcinogens are active in all adequately sensitive genetic systems . Because of this redundancy, it may be sufficient to employ only one standardized set of tester strains and methodology . However, serveral classes of known carcinogens are undetected or underestimated when assayed in standard testing procedures . Some of these chemicals can be efficiently recognized as mutagens upon varying the methodology, the genetic endpoint, or the mammalian activation system . Thus, to modify and adjust the experimental protocol to the particular type of chemical under study and to calibrate the system with appropriate carcinogenic and non-carcinogenic reference compounds is advisable . It is noteworthy that chemical carcinogens which probably act by non-genotoxic mechanisms thus far remain undetected in bacterial tests . Newly developed systems which measure specific types of genetic events, such as transpositions of DNA segments and derepression of genes, presently are being tested for their ability to detect such carcinogens . A final matter of growing concern is the increasing number of environmental chemicals that are found to be mutagenic in bacteria but for which information about carcinogenic activity in vivo is insufficient . The possible use of bacteria for quantifying mutagenic potency and extrapolating this information to tumor-initiating potency can be envisaged in three ways: (i) direct extrapolation from standard in vitro tests, (ii) indirect extrapolation making use of an in vitro/in vivo comparison of induced effects (the parallelogram method) as devised by Sobels {138} on the basis of identical dose (to DNA), and (iii) host-mediated assays to assess mutagenic potency of carcinogens in selected organs of mammals...

Mutat Res, 1981 Sep, 90(1), 49 - 55
Mutagenicities of carbadox and olaquindox--growth promoters for pigs; Yoshimura H et al.; Carbadox and olaquindox were examined for mutagenicities in the repair tests with Bacillus subtilis (rec assay) and Salmonella typhimurium (uvr assay) and in the reverse mutation test (TA100 and TA98 of S . typhimurium) . Both compounds were positive in the rec and uvr assays, and were highly mutagenic for strains TA100 and TA98 . Carbadox was about 6 times move mutagenic than olaquindox in the absence of S9 mix . When incubated in S9 mix or bacterial cytosol (BC) mix for various times at 37 degree C, carbadox was found to lose its mutagenic activities easier than olaquindox . The mutagenicity of carbadox was almost inactivated at 10 min after incubation with S9 mix, but olaquindox still retained its activities even at 20 min . While carbadox required 20 min to be inactivated in BC mix, olaquindox was not completely inactivated even if incubated for 60 min.

J Bacteriol, 1981 Sep, 147(3), 827 - 35
Spontaneous mutators of salmonella typhimurium LT2 generated by insertion of transposable elements; Shanabruch WG et al.; Spontaneous mutators of Salmonella typhimurium LT2 were generated by inserting the transposable element Tn5 or Tn10 into the bacterial chromosome . Two mutators mapped at the position of the mutH and mutL loci of S . typhimurium, and two other mutators mapped at positions corresponding to the mutS and uvrD loci of Escherichia coli . A fifth mutator, mutB, did not map at a position corresponding to any of the known mutators of S . typhimurium or E . coli . The mutH,L,S and uvrD alleles increased the frequency of both spontaneous base substitution and frameshift mutations, whereas the mutB allele increased the frequency only of spontaneous base substitution mutations . The increased frequency of base substitution mutations was recA+ independent in the mutH, mutL, and uvrD strains and partially recA+ independent in the mutS strain . The uvrD mutation decreased the resistance of the cells to killing by ultraviolet irradiation . The mutH,L,S and uvrD strains showed an increased sensitivity to mutagenesis by the alkylating agents methyl methane sulfonate and ethyl methane sulfonate, but not to mutagenesis by 4-nitroquinoline-1-oxide.

Cancer Res, 1981 Sep, 41(9 Pt 1), 3400 - 6
Relationship between benzo(a)pyrene-induced DNA base modification and frequency of reverse mutations in mutant strains of Salmonella typhimurium; Fahl WE et al.; Salmonella typhimurium cells (TA98 and TA100) were incubated with {3H}benzo(a)pyrene ({3H}BP) and induced rat liver microsomes . The BP-induced cytotoxicity and His+ reverse-mutation frequencies were determined, and bacterial DNA hydrolysates were chromatographed on Sephadex LH-20 . Analysis indicated three principal DNA adducts formed from two diastereoisomeric BP diol-epoxides and a 9-hydroxy-benzo(a)pyrene metabolite . An 8.6-fold increase in TA100 cell concentration in the microsome incubation was paralleled by a 7.2-fold decrease in total adducts per cell and a 7.4-fold decrease in mutation frequency . Separate TA98 incubations were titrated with increasing concentrations of {3H}(+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene ({3H}anti BP diol-epoxide), {3H}(+/-)-7 beta, 8 alpha-dihydroxy-9 beta, 10 beta-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene {3H}syn BP diol-epoxide), or {3H}9-hydroxybenzo(a)pyrene . Linear, nonsaturated increases in DNA adduct levels were seen up to the highest observed concentrations of 4.00 microM BP diol-epoxide or 6.00 microM 9-hydroxybenzo(a)pyrene in both TA98 and TA100 cells . The increasing adduct levels were accompanied by linearly increasing mutation frequencies . At equivalent concentrations of the two DP diol-epoxides, an average of 8.2-fold more base substitution mutations (TA100) were seen than frameshift mutations (TA98) . The results also indicate significant differences in absolute mutagenic efficiency (mutation frequency/unit modified DNA) between these three covalent DNA ligands (TA98, syn BP diolepoxide greater than 9-hydroxy-4,5-epoxy-benzo(a)pyrene greater than anti BP diol-epoxide; TA100, 9-hydroxy-4,5-epoxy-benzo(a)pyrene greater than syn BP diol-epoxide greater than anti BP diol-epoxide).

Infect Immun, 1981 Sep, 33(3), 750 - 7
Immunochemical characterization of major outer membrane components from Salmonella typhimurium; Kuusi N et al.; We used crossed immunoelectrophoresis to study detergent-solubilized components of the outer membrane of Salmonella typhimurium under nondenaturing conditions . The antisera used were raised against nondenatured outer membrane preparations . Lipopolysaccharide and lipoprotein were identified easily as discrete precipitates when they were solubilized with Triton X-100 . However, solubilization of the porins with Triton X-100 resulted in a complex precipitate pattern, indicating incomplete dissociation of protein-protein interactions . A clear-cut pattern was obtained when the porins were first solubilized and denatured with hot sodium dodecyl sulfate, followed by removal of the sodium dodecyl sulfate and renaturation in the presence of Triton X-100 . Our findings suggested that crossed immunoelectrophoresis can be used to study the antigenicity of nondenatured porins and the antibody responses to them.

J Biol Chem, 1981 Aug 25, 256(16), 8807 - 14
Bacterial cell envelopes with functional flagella; Eisenbach M et al.; Our aim was to isolate from bacteria a flagellated, subcellular system whose content could be changed at will . Because the control of bacterial chemotaxis resides in the direction of rotation of the flagella, such a system would be ideal for the study of this control mechanism . By incubating bacteria with penicillin and then lysing them osmotically, we were able to isolate cell envelopes from Escherichia coli and Salmonella typhimurium . These envelopes have the same sidedness and similar shape and dimensions as the original bacteria; they are practically free of cytoplasm; they are osmotically sensitive, having intact the cytoplasmic membrane and at least part of the cell wall; and they have flagella . This preparation was used to find out what is required to restore flagellar rotation, which had been lost during osmotic lysis . By visualizing the image of individual flagella with high intensity light microscopy or by tethering the cell envelopes, we found that adding artificial electron donors as an energy source is enough to restore rotation . This seems to indicate that no cytoplasmic components are required and that the proton electrochemical potential is indeed the driving force for flagellar rotation . However, the rotation was almost entirely counterclockwise, while in intact bacteria the flagella rotate in both directions . This may indicate that a cytoplasmic component is required to allow clockwise rotation . The significance of these results for the study of chemotaxis is discussed.

Poult Sci, 1981 Aug, 60(8), 1822 - 6
Effect of five cycle rapid freeze-thaw treatment in conjunction with various chemicals for the reduction of Salmonella typhimurium; Olson VM et al.; A five cycle rapid freeze-rapid thaw process was used in conjunction with chemicals to reduce numbers of Salmonella typhimurium cells on poultry meat . The second portion of chicken wings consisting of ulna and radius with attached skin and muscle was inoculated with 400 to 900 colony forming units (CFU/g) of a nalidixic acid resistant strain of S . typhimurium . Chemicals used were 20 ppm chlorine, 5% potassium sorbate, 5% lactic acid, and 5% calcium propionate . The wings were either sprayed with or dipped into all chemicals before the freeze-thaw process . Wings were also chemically treated and not subjected to the freeze-thaw process . Numbers of S . typhimurium were determined by the most probable number procedure . The relative effectiveness of combinations of chemicals and the freeze-thaw process was compared to a control with the following percentage reductions of numbers of S . typhimurium cells: lactic acid, 98%; calcium propionate, 96%; potassium sorbate, 96%; chlorine, 95%; and freeze-thaw process without chemicals, 95% . There were no statistically significant differences among the treatments . In pilot plant study simulating commercial conditions, a carbon dioxide freezer was used for the rapid freeze and a microwave oven was used for the rapid thaw . Treatment of wings with 5% lactic acid plus freeze-thaw process resulted in statistically significant fewer numbers of S . typhimurium cells when compared to the freeze-thaw process without chemical treatment or to wings chemically treated without the freeze-thaw process.

J Med Chem, 1981 Aug, 24(8), 1016 - 8
Syntheses of 9-acridine- and 2-phenanthridinemethanols as potential antimalarials; Muth CW et al.; alpha-(1-Piperidinylmethyl)-9-acridinemethanol (3), alpha-{(dibutylamino)ethyl}-9-acridanmethanol (4a), and alpha-{(dibutylamino)methyl}-2-phenanthridinemethanol (5) have been made and all are ineffective as antimalarials against Plasmodium berghei in mice . 9-Acridinyloxirane showed no significant mutagenicity for strains TA 98 or TA 100 of Salmonella typhimurium.

Teratology, 1981 Aug, 24(1), 1 - 11
Modification of the mutagenicity and teratogenicity of cyclophosphamide in rats with inducers of the cytochromes P-450; Hales BF; Cyclophosphamide must be enzymatically activated to be either mutagenic or teratogenic . This activation is thought to be catalyzed by the cytochrome P-450 monooxygenase system . To study the relationship between the mutagenic and teratogenic metabolites of cyclophosphamide, the mutagenicity and teratogenicity of this drug were compared after activation by rats pretreated with chemicals (phenobarbital and beta-naphthoflavone) inducing different cytochromes P-450 . Activation of cyclophosphamide to mutagenic metabolites by enzyme fractions from rats on day 13 of gestation was measured with the Ames test using Salmonella typhimurium TA1535 . Teratogenicity was assessed in vivo by treatment of rats with cyclophosphamide on day 13 of gestation . Cyclophosphamide was activated to mutagenic metabolites to the same extent (on a tissue wet weight basis) by enzyme fractions from maternal liver, kidney and placenta, despite differences in cytochrome P-450 content . Fetal homogenates did not activate cyclophosphamide . Phenobarbital pretreatment increased the activation of cyclophosphamide to mutagenic metabolites by maternal liver microsomes 10-fold and liver cytochrome P-450 content 1.8 fold; however, this drug did not alter the activation of cyclophosphamide by maternal kidney, by placenta or by the fetus . Phenobarbital pretreatment increased the teratogenicity of cyclophosphamide in rats on day 13 of gestation (increased incidence of malformed embryos, decreased fetal weight) . Pretreatment with beta-naphthoflavone did not induce liver cytochrome P-450 in the pregnant rat and did not change the activation of cyclophosphamide to mutagenic metabolites by liver, kidney, placenta or the fetus . Pretreatment with this polycyclic aromatic hydrocarbon had no effect or decreased the teratogenicity of cyclophosphamide . Thus, these experiments suggest that the mother, rather than the fetus, is the site of activation of cyclophosphamide; after phenobarbital pretreatment the predominant site of cyclophosphamide activation is the maternal liver . There appears to be a correlation between the teratogenicity and mutagenicity of cyclophosphamide after induction of the cytochromes P-450 . We can speculate that the "proximate teratogen" of cyclophosphamide may also be the "proximate mutagen".

Mutat Res, 1981 Aug, 83(1), 39 - 48
A comparison of aflatoxin B1-induced cytotoxicity, mutagenicity and prophage induction in Salmonella typhimurium mutagen tester strains TA1535, TA1538, TA98 and TA100; Wheeler L et al.; Treatment of Ames mutagen tester strains with aflatoxin B1 (AFB1) and S9 mix results not only in the production of a potent mutagen, but induces a pathway that leads to the induction of prophages present in all Ames tester strains . Characterization of the prophage induction and mutagenic response following AFB1 treatment showed that plasmid pKM101 dramatically enhances mutagenesis, but suppressed prophage induction . Spontaneous release of phage by TA98 and TA100 was also lower than in TA1535 and TA1538 . In addition to mutagenesis and prophage induction, survival of all 4 tester strains was quantitated after AFB1 treatment . The data show that the frameshift tester strains (TA1538 and TA98) are more sensitive to the bactericidal action of AFB1 than the base-pair tester strains (TA1535 and TA100), survival being significantly affected above 100 ng . One of several hypotheses examined was the difference in the number and types of prophages present in base-pair tester strains that are not detectable in the frame-shift tester strains . These data suggest that prophage induction can detect DNA damage that is non-mutagenic; and that it is important to characterize the lysogenic nature of the Ames strains since it may influence the observed histidine revertant rate and the survival of the tester strain.

Infect Immun, 1981 Aug, 33(2), 643 - 5
Bactericidal activity in fractionated granule contents from human polymorphonuclear leukocytes: studies with leukocytes from normal individuals; Modrzakowski MC et al.; Sephadex G-100 chromatographic fractions of granule extracts from normal human polymorphonuclear leukocytes, exhibiting differences from fractions previously obtained from leukemic polymorphonuclear leukocytes, possessed cationic proteins with distinct bactericidal activity against cell wall mutants of Salmonella typhimurium LT2.

Environ Health Perspect, 1981 Aug, 40, 163 - 72
Effects of metals in in vitro bioassays; Sirover MA; The capacity of in vitro bioassays to detect the potential carcinogenicity of metal compounds is reviewed . The in vitro bioassays discussed include: bacterial reversion analysis to determine the capacity of metal salts to revert Salmonella typhimurium histidine auxotrophs or to revert Escherichia coli WP 2 tryp- to tryptophan prototrophy; examination of the ability of metal salts to preferentially inhibit cell growth in Bacillus subtilis cells deficient in DNA repair pathways; determination of the ability of metal salts to induce resistance to base analogs in mammalian cells; the capacity of metal salts to enhance viral transformation of mammalian cells or to transform cells in the absence of virus; and the ability of metal salts to induce chromosomal aberrations in mammalian cells . Using each of these in vitro bioassays, diverse metal compounds have been identified as potential carcinogens . Furthermore, the use of different compounds of a specific metal may allow a determination of the valence which may be required for carcinogenesis.

Zentralbl Bakteriol A, 1981 Aug, 249(3), 350 - 61
{High-immunogenic mutants of Salmonella with two independently of each other attenuating markers as potential vaccines from bacteria capable of multiplication . 2 . Communication: spontaneous chromosomal resistance against antibiotics as a possibility for isolation of clones with decreased virulence (author's transl)}; Linde K; Mutants of Salmonella typhimurium with spontaneous chromosomal resistance against oleandomycin, streptothricin, nalidixic acid and rifampicin were investigated for their virulence behaviour with the i.p . mouse model . The strains resistant against the special antibiotic consists of a spectrum of various clones with a different behaviour of virulence: Additionally to obvious unchanged virulent strains there are such with a weak or strong attenuation . The majority of the attenuated strains protect the immunized mice against a following lethal wild strain infection . High-immunogenic attenuated double-marker mutants for application as potential vaccine strains may be isolated with the aid of a step by step introduction of a second attenuating "resistance"-marker in a one-marker strain, attenuated for another reason . These strains show the following parameters: -stability under the conditions of practical vaccine application, because a simultaneous back-mutation in both attenuating markers by reason of the unrealizable germ numbers will not occur, -immunogenicity by one immunization only, -separation from homologous wild strains of another origin with simple laboratory methods . This obvious generally acting biological principle is explained on the basis of molecular biological considerations and by referring to the literature . A test for orientation using an attenuated RNA-polymerase mutant showed, the resistance against rifampicin and attenuation are transferred together by co-transduction.

J Bacteriol, 1981 Aug, 147(2), 390 - 400
Molecular cloning of chemotaxis genes and overproduction of gene products in the bacterial sensing system; DeFranco AL et al.; The chemotaxis genes cheR, cheB, cheY, cheZ, and tar of Salmonella typhimurium were cloned into bacteriophage lambda vectors and onto pBR322 plasmids by recombinant DNA techniques . The genes were linearly arranged in the order tar-cheR-cheB-cheY-cheZ (and were read from a promoter on the upstream side of the tar or cheR gene) . However, their stoichiometries of expression were found to be 4:1:1:18:3, respectively . The overexpression of the cheY gene appeared to be a function of translational control . These five che genes were placed on a multicopy plasmid, and the gene products were overproduced in the cells, as shown by enzyme assays . The overproduction of the products of these five genes relative to those of the other che genes caused some changes in chemotactic properties, but no dramatic destruction of sensing ability.

Cancer Res, 1981 Aug, 41(8), 3205 - 10
Mutagenicity studies in Salmonella typhimurium on some carcinogenic N-nitramines in vitro and in the host-mediated assay in rats; Khudoley V et al.; N-Nitrodimethylamine, N-nitrodiethylamine, N-nitromorpholine and their N-nitroso analogs, N-nitrosodimethylamine, N-nitrosodiethylamine, and N-nitrosomorpholine, were tested in Salmonella typhimurium strains TA100 and TA1530 . The mutagenicity of all compounds, except N-nitrodiethylamine, was demonstrated in liquid incubation assays in at least one of the tester strains; it required the presence of a postmitochondrial supernatant from the liver of Aroclor-treated rats, reduced nicotinamide adenine dinucleotide phosphate-generating system, and oxygen . When compared on a molar basis with their N-nitroso analogs, N-nitromorpholine was about 10 times less mutagenic and N-nitrodimethylamine about 70 times less mutagenic . Addition of disulfiram to the assays at a final concentration of 0.1 mM efficiently inhibited mutagenesis by all nitro and nitroso compounds; ascorbic acid at a 7.4 mM concentration produced less inhibition . Mutagenic activity of the three nitramines was also determined in the host-mediated assay in rats . After p.o . administration of each of the N-nitramines, cells of S . typhimurium strains TA1530 and TA100 that had been injected i.p . were isolated from the peritoneal liquid after 1, 3, and 6 hr . All three nitramines were found to be mutagenic for strain TA1530 but not for TA100 . Mutation frequencies (number of histidine revertants per 10(6) surviving cells) were in the descending order N-nitromorpholine greater than N-nitrodiemethylamine greater than N-nitrodiethylamine . After a p.o . dose of N-nitrodiethylamine to rats, bacteria were also isolated from liver, lungs, and kidneys . Mutation frequency was highest in bacteria recovered from the liver but was not increased in those obtained from lungs and kidneys . The data suggest that carcinogenic nitramines exert their mutagenic effects through the formation of alkylating intermediates.

Can J Microbiol, 1981 Aug, 27(8), 843 - 6
Changes in the activity of antifungals in mixed cultures of bacteria and yeasts; Domon MH et al.; When Candida cells were grown in mixed cultures with Escherichia coli, Salmonella typhimurium, or Pseudomonas aeruginosa, their sensitivity to antifungal agents affecting sterol metabolism or functioning (polyenes and miconazole) was increased by several log units . This phenomenon was overcome by the addition to the culture medium of sugars utilized either by the bacteria or the yeast . Antifungals without direct effect on sterol metabolism (5-fluorocytosine, methylparaben, and 4-hydroxyquinazoline) were not more active in mixed than in pure cultures.

Eur J Biochem, 1981 Aug, 118(1), 125 - 30
Evidence for an essential lysine at the active site of L-histidinol:NAD+ oxidoreductase; a bifunctional dehydrogenase; Burger E et al.; Histidinol dehydrogenase (EC 1.1.1.23) from Salmonella typhimurium is inhibited by formaldehyde and pyridoxal 5-phosphate (pyridoxal-P) . epsilon-Pyridoxyl-lysine is isolated upon acid hydrolysis of pyridoxal-P-treated enzyme reduced by sodium borohydride . In the presence of formylhistidinol and formylhistidine (specific ligands of the enzyme) inactivation of histidinol dehydrogenase by pyridoxal-P is prevented . Extrapolation of the initial part of the inactivation curve caused by pyridoxal-P indicates that modification of two essential lysine residues results in inactivation of the dimeric enzyme . The essential lysine residues appear to participate in the reversible oxidation/reduction reaction converting histidinol to histidinal.

Proc Natl Acad Sci U S A, 1981 Aug, 78(8), 4684 - 8
Molecular cloning and amplification of the adenylate cyclase gene; Wang JY et al.; A segment of DNA containing cya, the gene for adenylate cyclase {ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1}, has been isolated from Salmonella typhimurium . The phage lambda gt4 was used as a cloning vector and adenylate cyclase-positive hybrid phages were isolated that complemented adenylate cyclase-negative bacteria . The cloned DNA fragment encodes a polypeptide of molecular weight 81,000 that gives rise to adenylate cyclase activity . This protein represents a functional mutant of the bacterial adenylate cyclase . When the cya gene was amplified by inserting into a multicopy plasmid, the enzyme activity was overproduced 20-fold, but the cyclic AMP level increased only 60%, suggesting several probable regulatory mechanisms . Overproduction of enzymes by recombinant DNA techniques can be a useful probe of relationships in the metabolizing organism in vivo.

Mutat Res, 1981 Aug, 83(1), 61 - 8
Nitrite converts 2-amino-alpha-carboline, an indirect mutagen, into 2-hydroxy-alpha-carboline, a non-mutagen, and 2-hydroxy-3-nitroso-alpha-carboline, a direct mutagen; Tsuda M et al.; 2-Amino-alpha-carboline {26148-68-5} which was isolated from a pyrolysate of soybean globulin and which was mutagenic to Salmonella typhimurium in the presence of a rat-liver microsomal fraction (S9 mix), was converted into non-mutagenic 2-hydroxy-alpha-carboline by treatment with nitrite in acidic conditions . However, on prolonged treatment with nitrite and acid, 2-hydroxy-alpha-carboline was further converted into a new mutagen which did not require S9 mix for exhibition of the mutagenicity . This direct-acting mutagen was found to be 2-hydroxy-3-nitroso-alpha-carboline by mass and proton magnetic resonance spectroscopies.

J Bacteriol, 1981 Aug, 147(2), 679 - 81
Escherichia coli and Salmonella typhimurium supX genes specify deoxyribonucleic acid topoisomerase I; Trucksis M et al.; Mutations of the Escherichia coli or Salmonella typhimurium supX genes eliminated deoxyribonucleic acid topoisomerase I . Suppression of a supX amber mutation partially restored the topoisomerase . Multicopy plasmids carrying supX+ caused overproduction of topoisomerase . Thus, these supX genes were identified as topA genes which specify deoxyribonucleic acid topoisomerase I.

J Bacteriol, 1981 Aug, 147(2), 401 - 9
Physical map of the Salmonella typhimurium histidine transport operon: correlation with the genetic map; Ardeshir F et al.; A detailed restriction map of a 12.4-kilobase EcoRI fragment of Salmonella typhimurium deoxyribonucleic acid (DNA) containing the entire histidine transport operon and the argT gene is presented . Subclones of specific regions of the transport operon of S . typhimurium were constructed in plasmid vectors . An accurate correlation between the restriction map and the location of genetically defined deletions was obtained by hybridizing restriction digests of chromosomal DNA from strains carrying each deletion with cloned transport operon DNA as a probe . These data were used to position the histidine transport genes on the cloned 12.4-kilobase fragment of DNA.

J Bacteriol, 1981 Aug, 147(2), 382 - 9
Defective enzyme II-BGlc of the phosphoenolpyruvate:sugar phosphotransferase system leading to uncoupling of transport and phosphorylation in Salmonella typhimurium; Postma PW; Transport and phosphorylation of glucose via enzymes II-A/II-B and II-BGlc of the phosphoenolpyruvate:sugar phosphotransferase system are tightly coupled in Salmonella typhimurium . Mutant strains (pts) that lack the phosphorylating proteins of this system, enzyme I and HPr, are unable to transport or to grow on glucose . From ptsHI deletion strains of S . typhimurium, mutants were isolated that regained growth on and transport of glucose . Several lines of evidence suggest that these Glc+ mutants have an altered enzyme II-BGlc as follows . (i) Insertion of a ptsG::Tn10 mutation (resulting in a defective II-BGlc) abolished growth on and transport of glucose in these Glc+ strains . Introduction of a ptsM mutation, on the other hand, which abolishes II-A/II-B activity, had no effect . (ii) Methyl alpha-glucoside transport and phosphorylation (specific for II-BGlc) was lowered or absent in ptsH+,I+ transductants of these Glc+ strains . Transport and phosphorylation of other phosphoenolpyurate:sugar phosphotransferase system sugars were normal . (iii) Membranes isolated from these Glc+ mutants were unable to catalyze transphosphorylation of methyl alpha-glucoside by glucose 6-phosphate, but transphosphorylation of mannose by glucose 6-phosphate was normal . (iv) The mutation was in the ptsG gene or closely linked to it . We conclude that the altered enzyme II-BGlc has acquired the capacity to transport glucose in the absence of phosphoenolpyruvate:sugar phosphotransferase system-mediated phosphorylation . However, the affinity for glucose decreased at least 1,000-fold as compared to the wild-type strain . At the same time the mutated enzyme II-BGlc lost the ability to catalyze the phosphorylation of its substrates via IIIGlc.

J Bacteriol, 1981 Aug, 147(2), 452 - 62
Molecular cloning and expression of the ilvGEDAY genes from Salmonella typhimurium; Blazey DL et al.; The ilvGEDAY genes of Salmonella typhimurium were cloned in Escherichia coli K-12 by in vitro recombination techniques . A single species of recombinant plasmid, designated pDU1, was obtained by selecting for Valr Ampr transformants of strain SK1592 . pDU1 was shown to contain a 14-kilobase EcoRI partial digestion product of the S . typhimurium chromosome inserted into the EcoRI site of the pVH2124 cloning vector . The ilvGEDAY genes were found to occupy a maximum length of 7.5 kilobases . Restriction endonuclease analysis of the S . typhimurium ilv gene cluster provided another demonstration of the gene order as well as established the location of ilv Y between ilvA and ilvC . The presence of a ribosomal ribonucleic acid operon on the pDU1 insert, about 3 kilobases from the 5' end of ilvG, was shown by Southern hybridization . The expression of the ilvGEDA operon from pDU1 was found to be elevated, reflecting the increased gene dosage of the multicopy plasmid . A polarity was observed with respect to ilvEDA expression which is discussed in terms of the possible translational effects of the two internal promoter sequences, one located proximal to ilvE and the other located proximal to ilvD.

Nucleic Acids Res, 1981 Jul 24, 9(14), 3419 - 32
The DNA sequence of the promoter-attenuator of the ilvGEDA operon of Salmonella typhimurium; Taillon MP et al.; The isolation of a lambda gt . ilvGEDA . S.t . hybrid transducing phage has permitted the characterization of the promoter-attenuator region of the ilvGEDA operon of Salmonella typhimurium . In vitro transcription and Southern hybridization indicate that the promoter-attenuator resides on a 400 nucleotide Rsa I restriction fragment . DNA sequence analysis shows only seven base pair differences exist between the DNA sequence of the ilvGEDA promoter-attenuator of S . typhimurium and that previously published for Escherichia coli K12.

J Med Chem, 1981 Jul, 24(7), 859 - 64
A comparison of mutagenic and carcinogenic activities of aniline mustards; Leo A et al.; A set of 15 derivatives of aniline mustard (I) was tested to give a quantitative measure of mutagenicity in Salmonella typhimurium TA-1535 and TA-100 and also carcinogenicity as lung tumors in strain-A mice . The structural variation in the set was chosen to minimize collinearity between hydrophobic, electronic, and molar refractive properties . By these measures, there was not a direct relationship between mutagenicity and carcinogenicity; in fact, since the 4-OPh analogue ranked highest in mutagenicity and among the lowest in carcinogenicity, while the reverse was noted for the 3,5-(NHCONH2)2 analogue, an inverse relationship was marginally significant . S-9 activation was required in the Ames test using TA-100, and the dose-response curve, prior to toxicity, appeared biphasic.

J Gen Microbiol, 1981 Jul, 125(Pt 1), 173 - 83
Natural resistance of mice to Salmonella typhimurium: bactericidal activity and chemiluminescence response of murine peritoneal macrophages; Blumenstock E et al.; The phagocytic capacity of peritoneal macrophages from resistant C3Hf mice and sensitive C57Bl/6 mice was studied in vitro using a virulent and an avirulent strain of Salmonella typhimurium . Virulent and avirulent 3H-labelled bacteria opsonized with normal mouse serum were killed to an equal extent (about 40%) by macrophages from C3Hf mice and C57Bl/6 mice within 5 min after contact . Killing of both bacterial strains by macrophages from C3Hf mice continued at a lower rate for the next 30 min until about 40% of the remaining bacteria were killed . In this later phase macrophages from C57Bl/6 mice killed avirulent S . typhimurium to an extent comparable with the killing by macrophages from C3Hf mice, whereas macrophages from C57Bl/6 mice were unable to kill virulent S . typhimurium . Cytochalasin B did not inhibit the rapid initial killing of bacteria opsonized with normal mouse serum, but completely inhibited the slower phase of killing . From these results it is concluded that the resistance of the mice to infection with S . typhimurium correlates with the bactericidal activity of their peritoneal macrophages, and that killing of the bacteria occurs in an early extracellular phase followed by an intracellular phase . It is only the latter phase which reflects the animal's resistance to infection . The chemiluminescence response to macrophages to opsonized live S . typhimurium was independent of the susceptibility of the mice from which the macrophages were taken . Cytochalasin B and 2-deoxy-D-glucose reduced the chemiluminescence generated by opsonized or non-opsonized S . typhimurium . Comparison of the kinetics as well as inhibition, by cytochalasin B and 2-deoxy-D-glucose, of chemiluminescence and killing of S . typhimurium showed that the killing reaction of the peritoneal macrophages was not related to their chemiluminescence response.

Cancer Lett, 1981 Jul, 13(2), 147 - 52
Mutagen production during pan-broiling compared with microwave irradiation of beef; Nader CJ et al.; Segments of beef were cooked either by broiling on a hot plate or by irradiation at 2450 MHz in a microwave oven . Extracts of surface layers of the cooked meat were tested for mutagenic activity using Salmonella typhimurium TA98 and TA100 with and without S-9 liver microsomal preparation . The broiled beef extracts with S-9 activation exhibited marked frame-shift mutagenicity, which increased with cooking time . No such activity was detected with beef cooked by microwave irradiation, with exposures ranging from normal to 3 times the normal cooking period.

Vopr Pitan, 1981 Jul-Aug, (4), 63 - 7
{Analysis of the mutagenic activity of nitrofurylacrylic acid}; Zhurkov VS et al.; The mutagenic activity of the vine stabilizer, sodium salt of 3-(5-nitro-2-furyl)acryl acid (5-NFA), was studied . Use was made of a cytogenetic analysis of mouse bone marrow cells, the dominant lethality test on male mice, analysis of chromosome aberrations in human lymphocyte culture and the Salmonella typhimurium test with metabolic drug activation in the body of mice . 5-NFA was administered intragastrically or given in drinking water . In tests on somatic and sexual cells of mammals, 5-NFA did not manifest mutagenic activity . The preparation increased the frequency of mutations in Salmonella on administration to mice in doses amounting to 1/5-1/4 of or exceeding the LD50.

Mutat Res, 1981 Jul, 89(3), 197 - 202
Mutagenicity studies with o-tolidine and 4,4'-tetramethyldiaminodiphenylmethane; Waalkens DH et al.; This paper confirms the mutagenicity of 2 carcinogenic chemicals, o-tolidine and 4,4'-tetramethyldiaminodiphenylmethane (TDDM) . o-Tolidine and TDDM were both tested in the Salmonella/mammalian-microsome test and in the sister-chromatid exchange (SCE) test with rabbit lymphocytes in vitro . The number of revertants was increased in the presence of S9 mix by o-tolidine in the Salmonella typhimurium strains TA98 and TA1538, and by TDDM in strains TA98 and TA100 . Both compounds showed weak SCE-inducing activity in cultured rabbit lymphocytes in the absence, but not in the presence, of an exogenous metabolic system.

Mutat Res, 1981 Jul, 89(3), 187 - 96
The extraordinary mutagenicity of nitropyrenes in bacteria; Mermelstein R et al.; Nitropyrenes cause frameshift mutations in Salmonella typhimurium . This activity which is restricted to frameshift mutations is unusual in several respects: (a) Nitropyrenes, as a class, are the most mutagenic chemicals reported in the literature; (b) The mutagenicity depends upon the formation of adducts between DNA and nitropyrene metabolites; (c) The penultimate intermediates responsible for mutagenic activity (hydroxylamines) are not obtained in all instances by reduction of the nitro function by the "classical" nitroreductase (the one that acts on nitrofurans and other simple nitrated polycyclic aromatic hydrocarbons) but by another nitroreductase which appears to be specific for higher nitrated polycyclic aromatic hydrocarbons; (d) The mutagenicity of nitropyrenes is enhanced when resting rather than growing bacterial cultures are used.

Mutat Res, 1981 Jul, 82(2), 275 - 83
Structure--activity relationships in the mutagenicity of quinone methides of 7-hydroxyflavylium salts for Salmonella typhimurium; Sweeny JG et al.; Several synthetic 7-hydroxyflavylium salts related to apigeninidin, a natural 3-deoxyanthocyanidin, have been studied in the Ames mutagenicity test using strain TA1537 of Salmonella typhimurium . Under the neutral pH conditions of the test, these flavylium salts are deprotonated through ionization of the C7-OH (pK'a = 4.2-4.4) to form quinone methides . Only the quinone methides of 4-methyl-7-hydroxyflavylium chloride and 4'-methoxy-4-methyl-7-hydroxy-flavylium chloride showed mutagenicity . Responses of 4-8 times the background were observed at the higher doses (1000 micrograms/plate), both with and without metabolic activation . It was concluded that the induction of frameshift mutagenicity by this group of compounds is caused by those quinone methides that have non-ionic, stable polycyclic structures at neutral pH.

Immunology, 1981 Jul, 43(3), 547 - 54
Acquired immunity to Salmonella typhimurium and delayed (footpad) hypersensitivity in BALB/c mice; Hormaeche CE et al.; BALB/c mice are extremely susceptible to salmonella infections . Previous reports have suggested that this natural susceptibility is due to a defect in cell-mediated immunity (CMI) which correlates with their inability to develop a delayed (footpad) hypersensitivity reaction to a salmonella extract when immunized with attenuated salmonellae . We have shown that mice thus immunized are in fact highly resistant to superinfecting intravenous challenge with virulent organisms, at a time when the footpad test is still negative . The footpad test becomes positive 2-3 weeks later, after the appearance of CMI, which is already present at 1 week as measured by determining the fate of a superinfecting challenge in the RES . The positive footpad reactions that develop in BALB/c mice--and also in B10, and CBA and (B10XA/J)F1 mice--are transferable to normal recipients by thetasensitive spleen cells . However, although B10 mice give positive delayed hypersensitivity (DH) reactions, they are more susceptible to salmonellae of intermediate virulence than the DH negative BALB/c strain . We have also shown that previous reports which suggested that susceptible mice did not develop immunity when vaccinated with live organisms are probably due to the salmonella strain used for vaccination, which does not establish a carrier state . A strain which does establish a carrier state effectively immunizes the susceptible BALB/c strain against virulent challenge, indicating that natural susceptibility does not preclude the development of acquired immunity to reinfection . X

Cancer Res, 1981 Jul, 41(7), 2654 - 7
Isolation of a nontoxic lipid A fraction containing tumor regression activity; Takayama K et al.; Galanos-type endotoxin obtained from the heptose-less mutant of Salmonella typhimurium was converted to Lipid A by two cycles of treatment with sodium acetate, pH 4.5, at 100 degrees and separated on a DEAE-cellulose column into several fractions (Fractions III to VII) . Tumor regression studies with strain 2 guinea pigs and syngeneic line 10 hepatocellular carcinoma showed that all fractions were effective when combined with trehalose dimycolates and an additional tumor regression factor (previously designated ACP) and incorporated into oil droplets (78 to 100% cures) . A low polar fraction (Fraction IV) was relatively nontoxic {the medium lethal dose for 11-day-old chick embryos inoculated i.v . (CELD50) was more than 10 micrograms} and nonpyrogenic {the dose estimated to give a fever index (area under fever curve) of 40 sq cm in rabbits when 1 hr and 1 degrees are plotted as 1 (FI40) was 5 micrograms} as compared to the unfractionated Lipid A (CELD50 of 0.0546 micrograms; FI40 of 0.046 micrograms) . All other fractions were toxic and pyrogenic and caused severe endotoxic shocks when combined with N-acetylmuramyl-L-seryl-D-isoglutamine and injected i.v . into guinea pigs . Fraction IV plus N-acetylmuramyl-L-seryl-D-isoglutamine did not cause endotoxic shock . The phosphate content of Fraction IV was about one-half of that detected in the toxic fractions.

Cancer Res, 1981 Jul, 41(7), 2589 - 97
Mutagenicity of the bay-region diol-epoxides and other benzo-ring derivatives of dibenzo(a,h)pyrene and dibenzo(a,i)pyrene; Wood AW et al.; The mutagenic activities of dibenzo(a,h)(pyrene, dibenzo(a,i)pyrene, and a total of 11 of their benzo-ring derivatives were evaluated in bacterial and mammalian cells in the absence or presence of a mammalian metabolic activation system . trans-1,2-Dihydroxy-1,2-dihydrodibenzo(a,h)pyrene and trans-3,4-dihydroxy-3,4-dihydrodibenzo(a,i)pyrene, the expected dihydrodiol precursors of bay-region diol-epoxides, were metabolized to products which were more mutagenic to strains TA98 and TA100 of Salmonella typhimurium than were the metabolic products formed from their respective parent hydrocarbons . For each dihydrodiol, replacement of the benzo-ring double bond adjacent to the diol moiety with a single bond resulted in tetrahydrodiol derivatives which could not be metabolically activated, suggesting that one or both diastereomeric bay-region diol-epoxides were the bioactivated metabolites . The authentic bay-region diol-epoxide diastereomers of dibenzo(a,h)pyrene and dibenzo(a,i)pyrene in which the benzylic hydroxyl group and the epoxide oxygen are trans (diol-epoxide 2 series) were highly mutagenic in strains TA98 and TA100 of S . typhimurium and in cultured Chinese hamster V79 cells . Neither diol-epoxide was significantly, if at all, metabolized by epoxide hydrolase . The bay-region diol-epoxide of dibenzo(a,i)pyrene was from 1.5 to 5 times more active as a mutagen than the diol-epoxide of dibenzo(a,h)pyrene, and in strain TA98 of S . typhimurium as well as Chinese hamster V79 cells, it had activity comparable to that of the highly carcinogenic bay-region diol-epoxide of benzo(a)pyrene.

Immunology, 1981 Jul, 43(3), 483 - 91
The growth-promoting effect of bacterial iron for serum-exposed bacteria; Mellencamp MW et al.; Bacterial ability to obtain iron in bovine serum or in media containing transferrin (Tr) or conalbumin (Ca) was investigated by using serum-resistant (virulent) and serum-sensitive (avirulent) strains of Escherichia coli and Salmonella typhimurium . Bacteria growing in bovine serum enriched with radioactive iron-saturated Tr or with radioactive iron-saturated enterobactin (E) did not acquire radioactive iron . It has been found that the passage of siderophore (Si)-iron complexes into bacteria is blocked in serum by Tr and in Ca-containing medium by Ca . The investigation of bacterial ability to take iron in synthetic media showed that bacteria take in Si-bound but no Tr-bound radioactive iron . In the absence of free iron, the growth of serum-exposed virulent bacteria was supported by their stored iron . Virulent bacteria passaged in medium void of usable iron became depleted in stored iron and did not grow in animal sera unless sera were enriched by the addition of exogenous iron . Experiments with serum-exposed avirulent bacteria showed that their growth in Si-enriched serum should not be attributed to the iron-providing activity of Si but to the stimulating effect of Si which facilitates the use of stored iron . As distinct from avirulent bacteria, virulent bacteria used stored iron without the stimulating activity of extracellular Si.

J Bacteriol, 1981 Jul, 147(1), 13 - 24
Genetic analysis of a temperature-sensitive Salmonella typhimurium rho mutant with an altered rho-associated polycytidylate-dependent adenosine triphosphatase activity; Housley PR et al.; A conditional-lethal rho mutant of Salmonella typhimurium LT2 has been isolated . The mutation was selected as a suppressor of the polarity of an insertion sequence (IS)2-induced mutation (gal3) carried on an F' plasmid . In addition to suppression of IS2-induced polarity, the rho-111 mutation suppressed nonsense and frameshift polarity . The rho-associated polycytidylic acid-dependent adenosine triphosphatase activity in the mutant strain was elevated 15-fold above that in the parental strain, and the mutant rho protein was thermally unstable . A temperature-resistant revertant of the mutant strain did not suppress polarity and contained normal levels of polycytidylic acid-dependent adenosine triphosphatase, suggesting that the phenotype of the rho-111-bearing strain is the consequence of a single mutation . The rho-111 mutation was located on the S . typhimurium linkage map midway between the ilv and cya loci by phage P22 cotransduction studies . F' plasmid maintenance was not impaired in the mutant strain, and the mutation was recessive to the wild-type allele . The rho-111 mutation did not alter in vivo expression of either the tryptophan or histidine operons.

J Bacteriol, 1981 Jul, 147(1), 124 - 34
Cloning and restriction map of the first part of the histidine operon of Salmonella typhimurium; Barnes WM; The first part of the histidine operon of Salmonella typhimurium, hisGpeaGD, has been cloned onto the vector plasmid mini-ColE1 (pVH51) . The resulting plasmid, pWB91, has a single EcoRI site and is 11,500 base pairs in size . The HindII restriction map was determined by the method of two-dimensional cross-annealing between a partial digest pattern and a complete digest pattern . The restriction fragment containing the genetic control region was identified with the aid of the small (35-base pair) internal deletion 01242 and the observation that heteroduplexed restriction fragments containing this deletion have markedly reduced mobility on polyacrylamide gels . The genetic control region was then mapped in more detail with other restriction enzymes . The genetic orientation of the restriction map was determined with the aid of several deletions of integral HindII fragments generated in vitro.

J Bacteriol, 1981 Jul, 147(1), 101 - 9
Biosynthesis of bacterial glycogen: purification and structural properties of Rhodospirillum tenue adenosine diphosphate glucose synthetase; Yung SG et al.; Adenosine diphosphate glucose synthetase from the photosynthetic bacterium Rhodospirillum tenue has been purified greater than 95% . The molecular weight of the enzyme is approximately 215,000, with a subunit molecular weight of about 51,000 . The enzyme appears to be composed of four similar if not identical subunits . Although the amino acid composition of the enzyme is similar to that of Escherichia coli and Salmonella typhimurium, no apparent homology has been observed between their N-terminal amino acid sequences . Antisera prepared against the R . tenue enzyme can partially inhibit the activities of adenosine diphosphate glucose synthetases from other photosynthetic bacteria.

Biochemistry, 1981 Jun 23, 20(13), 3738 - 44
Pausing of RNA polymerase during in vitro transcription of the tryptophan operon leader region; Winkler ME et al.; RNA polymerase molecules pause at a single site during in vitro transcription of the tryptophan (trp) operon leader region . Pausing was observed when DNA templates derived from Escherichia coli . Salmonella typhimurium, and Klebsiella aerogenes were used . Fingerprint analyses showed that the major RNA species produced by the transcriptional pause is 91 nucleotides long . A minor RNA species 90 nucleotides long was also detected . Single-round transcription experiments were used to study the kinetics of pausing . Time course, pulse-chase, and delayed-labeling experiments suggest that every RNA polymerase molecule transcribing the trp leader region pauses . A suboptimal ribonucleoside triphosphate concentrations, the half-life of paused-leader RNA was approximately 3 min at 22 degrees C and 0.7 min at 37 degrees C . At near-optimal ribonucleoside triphosphate concentrations, the half-time of the paused species dropped to about 0.3 min at 22 degrees C . The appearance and half-life of the paused species were unaffected by salt concentration, rho factor, guanosine 3'-5'-bis(diphosphate), or point mutations in the trp attenuator region . It is postulated that transcriptional pausing may play a role in maintaining the synchronization of transcription and translation that is vital in the control of transcription termination at the trp operon attenuator.

Vet Immunol Immunopathol, 1981 Jun, 2(3), 233 - 52
The role of serum and biliary antibodies and cell-mediated immunity in the clearance of S-typhimurium from chickens; Lee GM et al.; The development of three parameters of immunity in response to a non-lethal infection of Salmonella typhimurium in adult chickens has been examined . Intravenous inoculation of 1 X 10(6) organisms established infection in the liver, spleen and intestinal tract of all birds; the organism persisted in these sites until day 9 of the infection, after which it was cleared rapidly from all sites . High levels of agglutinating and haemagglutinating antibodies were found in serum and bile 5 days after infection; they peaked at days 7 to 10, and detectable antibody was still present in both fluids 6 weeks after infection . The presence of this antibody did not appear to cause a significant reduction in organism numbers in any of the sites examined . Cell mediated immunity was detected at day 14 . It is suggested that cells mediated immunity is responsible for clearance of the organisms from the tissues.

Mutat Res, 1981 Jun, 89(2), 145 - 9
Mutagenicity of smoke condensates induced by CO2-laser irradiation and electrocauterization; Tomita Y et al.; Smoke condensates generated from mucous membrane of the canine tongue irradiated with a CO2 laser showed mutagenicity on Salmonella typhimurium TA98 under metabolic activation with S9 mix . Strain TA100 was not so sensitive to the condensates with or without S9 mix . Smoke condensates from electrocauterization on the mucosa of the canine tongue also showed mutagenic activity on TA98 and TA100 with S9 mix . The revertant number per mg of the smoke condensates from laser irradiation was one-half that of the smoke condensates from electrocauterization (1623 and 3371) in TA98 . The mutagenic potency observed was comparable to that of cigarette smoke . The amount of these smoke condensates from 1 g of tissue was equivalent to those from 3--6 cigarettes as to total mutagenicity.

Mutat Res, 1981 Jun, 82(1), 31 - 9
The relationship between frameshift mutagenicity and DNA-binding affinity in a series of acridine-substituted derivatives of the experimental antitumour drug 4'-(9-acridinylamino)methanesulphonanilide (AMSA); Ferguson LR et al.; The mutagenicity of DNA-binding affinity of members of a series of acridine-substituted derivatives of 4'-(9-acridinylamino)methanesulphonanilide (AMSA) have been compared . The series includes compounds ranging from highly active to inactive in the L1210 murine leukaemia . Binding to DNA was measured by an ethidium displacement technique, with a correction being made for acridine-induced quenching of ethidium . Mutagenicity was assessed by measuring the reversion frequencies of the frameshift tester strain Salmonella typhimurium TA1537 in liquid culture . The results indicate that maximum mutagenicity is found in a "window" of DNA-binding affinities between 10(6) and 5 X 10(6) M-1 (determined at 0.01 ionic strength) . Compounds with binding affinities below 10(6) M-1 generally lacked both antitumour and mutagenic activity, whereas those with affinities above 5 X 10(6) M-1 were active against L1210 leukaemia but virtually inactive in inducing frameshift mutations.

J Toxicol Environ Health, 1981 Jun, 7(6), 973 - 89
Evaluation of the genetic activity of industrially produced carbon black; Kirwin CJ et al.; Commercially produced oil furnace carbon black (Chemical Abstract Service Registry No . 1333-86-4) has been evaluated by five different assay for genetic activity . These were the Ames Salmonella typhimurium reverse mutation test, sister chromatid exchange test in CHO cells, mouse lymphoma test, cell transformation assay in C3H/10T1/2 cells, and assay for genetic effects in Drosophila melanogaster . Limited cellular toxicity was exhibited but no significant genetic activity was noted.

Ann Rheum Dis, 1981 Jun, 40(3), 312 - 4
Suppurative coxitis due to Salmonella typhimurium in systemic lupus erythematosus; Shiota K et al.; A 36-year-old woman with systemic lupus erythematosus (SLE) developed septicaemia and subsequently suppurative coxitis due to Salmonella typhimurium . Although systemic treatment with antibiotics eradicated salmonella from the arterial blood, cup arthroplasty and irrigation of the operative wounds with effective antibiotics were needed for eradication of the organism from the affected joints.

J Bacteriol, 1981 Jun, 146(3), 914 - 9
Genetic mapping of a mutation conferring sensitivity to bacteriophage Mu in Salmonella typhimurium LT2; Faelen M et al.; Two strains of Salmonella typhimurium LT2, SA1475 and MA411, were fortuitously found to be sensitive to bacteriophage Mu . The Mu-sensitivity allele of SA1475 was called musA1 and shown to be linked to the histidine operon both in conjugation and transduction experiments . The Mus allele of MA411 was unlinked to the his region and was tentatively designated musB2 . Strains carrying large deletions of the his operon were also tested for Mu sensitivity; those of which the his-rib region is deleted were also sensitive to Mu . Transduction data led to the order zee-2 hisOGDCBAHFIE gnd musA . An Hfr injecting the his operon early (HfrK9) an carrying hisG9424::Tn10 delta 4 delta 11 and musA1 was isolated; this Hfr made it possible to introduce the Mus character into most derivatives of S . typhimurium LT2 . Since strain SA1475 is resistant to bacteriophage P1, it could be used to select a new P1-Mu hybrid which has the host range of Mu and the transduction properties of P1.

J Bacteriol, 1981 Jun, 146(3), 895 - 901
Genetics of L-proline utilization in Escherichia coli; Wood JM; L-Azetidine-2-carboxylate (AC) and 3,4-dehydro-D,L-proline (DHP) are toxic L-proline analogs that can be used to select bacterial mutants defective for L-proline transport . Mutants resistant to AC and DHP are defective for proline transport alone (putP mutants), and mutants resistant to AC but not to DHP are defective both in putP and in the closely linked proline dehydrogenase gene putA . Proline dehydrogenase oxidizes DHP but not AC, probably detoxifying the former compound . These observations were exploited in preparing an otherwise isogenic set of Escherichia coli K-12 strains with well-defined defects in the putP and putA genes . The results of this study suggest that the genetic and biochemical characteristics of proline utilization in E . coli K-12 are closely analogous to those of Salmonella typhimurium.

Cancer Res, 1981 Jun, 41(6), 2305 - 7
Effect of genotype on mutagenicity of niridazole in nitroreductase-deficient bacteria; Speck WT et al.; The mutagenicity of niridazole for Salmonella typhimurium depends upon the enzymic reduction of the nitro function . The response of niridazole nitroreductase-deficient bacteria to niridazole is reduced to 4.4 and 0.19% that exhibited by the enzyme-proficient parent strain when the deficiency is the result of a base substitution and frame-shift mutation, respectively . The results are taken to indicate that the residual activity (4.4%) seen in the strain with a base substitution mutation reflects the activity of an enzyme with an amino acid substitution, while the basal level (0.19%) of activity indicates the action of a different nitroreductase with a low specificity for niridazole.

Nippon Yakurigaku Zasshi, 1981 Jun, 77(6), 579 - 96
{Antitumor activities of bamboo leaf extracts (BLE) and its lignin (BLL)}; Kuboyama N et al.; Antitumor activity of bamboo leaf against various transplantable mouse tumor strains, such as Sarcoma 180 and Ehrlich ascites carcinoma has previously been demonstrated by Sakai et al.7) and Yammamoto et al.9) . The present investigation was undertaken to determine the antitumor activities of BLE and BLL against the spontaneous tumor induced by benzopyrene (BP) and 4-nitroquinoline-1-oxide (4NQO) in mice and rats . The possible mechanism of antitumor action was also discussed as related to Kada's Rec-assay and Ames test in vitro . The in vivo antitumor test was performed using 16 groups of mice given the following solutions ad libitum for 120 days; Groups 1-4, 5-8, 9-12 and 13-16 were given water, 1% and 10% BLe, 0.1% BLL, and each respective group was treated with no injection (control), oil/s.c., BP 1 mg/s.c., and 4NQO 0.5 mg/s.c . Rat respective group was treated 30 days after in initiation of experiment with no injection (control), oil/s.c., BP 2.4 mg/s.c . Antitumor activities of the BLE and BLL were determined by the tumor incidence index and average weight of tumor . In vitro Rec-assay, cold incubation method, and Ames test were performed in the usual manner . Antitumor activity against BP induced tumor was the highest with 1.0% BLE (0.71 mg/ml), but no significant difference was found between the groups of the 10% BLE, 0.1% BL and control . A weak trend toward DNA damage was seen in the case of BLE, in the Rec-assay . His+ revertants with S-9 mix on Salmonella typhimurium TA98 were found in the case of BLL . It was concluded that antitumor activity against BP- and 4NQO-induced tumors was the highest with 1% BLE (0.71 mg/ml), and a direct action of BLE on tumor cells was indicated.

Mutat Res, 1981 Jun, 82(1), 41 - 6
Antimutagenic effect of selenium on acridine orange and 7,12-dimethylbenz{alpha}anthracene in the Ames Salmonella/microsomal system; Martin SE et al.; The antimutagenic effects of selenium as sodium selenite were investigated using the Ames Salmonella/microsome mutagenicity test . The compounds examined were acridine orange and 7,12-dimethylbenz{alpha}anthracene . Selenium (22 ppm) reduced the number of histidine revertants caused by 20 microgram acridine orange and 20 microgram 7,12-dimethylbenz{alpha}anthracene by 52 and 74%, respectively . Increasing the quantity of selenium added to the plates further suppressed the mutagenicity of the test compounds . The antimutagenic effects of selenium cannot be explained by lethality of Salmonella typhimurium.

J Bacteriol, 1981 Jun, 146(3), 997 - 1002
Coregulation of oxidized nicotinamide adenine dinucleotide (phosphate) transhydrogenase and glutamate dehydrogenase activities in enteric bacteria during nitrogen limitation; Liang A et al.; The relationship between oxidized nicotinamide adenine dinucleotide (phosphate) {NAD(P)+} transhydrogenase (EC 1.6.1.1) and NAD(P)+ glutamate dehydrogenase in several enteric bacteria which differ slightly in their regulation of nitrogen metabolism was studied . Escherichia coli strain K-12 was grown on glucose and various concentrations of NH4Cl as the sole nitrogen source . In the range of 0.5 to 20 mM NH4Cl, the energy-independent transhydrogenase increased two to threefold . Comparable changes occurred in NAD(P)+-linked glutamate dehydrogenase . NH4Cl concentrations of 20 to 60 mM resulted in relatively constant specific activities for both enzymes . Higher exogenous NH4Cl, however, led to a decline in both activities . Isocitrate dehydrogenase, another potential source of cellular NADPH, was insensitive to NH4Cl limitation . Similar studies in the presence of glutamate and different exogenous NH4Cl concentrations again showed concerted effects on both enzymes . Growth on glutamate as the sole nitrogen source led to severe repression of both transhydrogenase and glutamate dehydrogenase . In Salmonella typhimurium, both enzymes were unaffected by limiting NH4Cl or growth on glutamate as the sole nitrogen source . Both were, however, repressed by growth on aspartate, a potential source of cellular glutamate . Coordinate changes in glutamate dehydrogenase and transhydrogenase were also evident in Klebsiella aerogenes, particularly under conditions in which glutamate dehydrogenase was regulated inversely to glutamate synthetase . Coordinate changes in glutamate dehydrogenase and transhydrogenase in enteric bacteria are discussed in terms of the possible involvement of the latter enzyme as a direct source of NADPH in the ammonia assimilation system.

Proc Natl Acad Sci U S A, 1981 Jun, 78(6), 3446 - 9
ATP-driven active transport in right-side-out bacterial membrane vesicles; Hugenholtz J et al.; Membrane vesicles from Salmonella typhimurium induced for phosphoglycerate transport, were loaded with pyruvate kinase and ADP by lysing spheroplasts under appropriate conditions . Vesicles so prepared catalyze active transport of proline and serine in the presence of phosphoenolpyruvate; this activity is abolished by the protonophore carbonyl cyanide-m-chlorophenylhydrazone and by the H+-ATPase inhibitor N,N' dicyclohexylcarbodiimide but not by anoxia or cyanide . In contrast, D-lactate-driven active transport is abolished by the hydrazone and by anoxia or cyanide but not by the carbodiimide . Moreover, phosphoenolpyruvate does not drive transport effectively in vesicles that lack the phosphoglycerate transport system . The results are consistent with an overall mechanism in which phosphoenolpyruvate gains access to the interior of the vesicles by means of the phosphoglycerate transporter and is then acted on by pyruvate kinase to phosphorylate ADP . ATP formed inside of the vesicles is then hydrolyzed by the H+-ATPase, leading to the generation of a proton electrochemical gradient that drives H+/solute symport . By using pBR322 as vector and Escherichia coli as host, a fragment of S . typhimurium DNA coding for the phosphoglycerate transport system has been cloned . E . coli membrane vesicles containing the phosphoglycerate transport system also catalyze transport in the presence of phosphoenolpyruvate when they are loaded with pyruvate kinase and ADP.

Infect Immun, 1981 Jun, 32(3), 1123 - 7
Induction of immunoenhancing factors for murine splenocyte cultures by Salmonella typhimurium ribosome and ribonucleic acid extracts; Butler RC et al.; Ribosomal and ribonucleic acid (RNA)-rich preparations derived from Salmonella typhimurium were examined for their ability to enhance the primary in vitro antibody response of normal mouse spleen cell cultures to sheep erythrocytes . Both of these fractions were consistently more active in elevating the antibody response of normal mouse splenocytes from lipopolysaccharide (LPS) responder mice than was LPS . Furthermore, injection of mice with either the ribosomal or RNA-rich fraction induced antibody response helper factor activity in 2-h post-treatment serum similar to that induced by LPS . Endotoxin low-responding C3H/HeJ mice were stimulated to release helper factors by ribosomes and the RNA extracts but not by LPS . Treatment of the ribosomes and RNA fractions with ribonuclease destroyed their ability to stimulate the production of the helper factor in serum of treated mice . Therefore, it appears likely that ribosomes and RNA-rich fractions stimulated an intermediate helper factor due to the presence of RNA and not LPS.

J Biol Chem, 1981 May 10, 256(9), 4640 - 8
The identification of distinct protein kinases and phosphatases in the prokaryote Salmonella typhimurium; Wang JY et al.; The finding of protein phosphorylation in prokaryotes (Wang, J . Y . J., and Koshland, D . E . (1978) J . Biol . Chem . 253, 7605-7608) has been pursued further . The prokaryotic organism Salmonella typhimurium is shown to contain at least 10 phosphorylated proteins with serine or threonine phosphates which are produced by the action of at lest four protein kinases . The protein kinases are distinguished by their substrate specificity, their chromatographic behavior, and their inhibition patterns . The phosphorylations are reversible, and more than one protein phosphatase activity exists in these cells . The presence of specific protein kinases and phosphatases suggests that this form of protein covalent modification is involved in the regulation of different cellular functions in prokaryotes as it is in eukaryotes.

Cancer Lett, 1981 May, 12(4), 279 - 85
Relationships between mutagenic potency, reversion mechanism and metabolic behaviour within a class of chemicals (hydrazine derivatives); De Flora S et al.; Homogeneous mutagenicity data, available for 16 hydrazine derivatives assayed in the Salmonella/microsome test, were tentatively associated with their chemical structure . Some possible relationships were detected between chemical features and the following parameters in vitro: (a) mutagenic potency, expressed as revertants per micromole compound, which varied over a 3200-fold range without S-9 mix and a 7000-fold range with S-9 mix; (b) reversion mechanism, as inferred from the selective sensitivity of 5 Salmonella typhimurium tester strains; (c) metabolic behaviour in the presence of S-9 mix containing rat liver, mouse liver or mouse lung /-9 fractions from animals treated with Aroclor-1254.

J Gen Microbiol, 1981 May, 124(Pt 1), 225 - 8
Transfer of RP4::Mu to Salmonella typhimurium; Beacham IR et al.; Restriction-proficient strains of Salmonella typhimurium are shown to be ineffective as recipients of normal RP4::Mucts62 due to the operation of two restriction systems (hsdSA and hsdLT) on the Mu moiety of this plasmid . Strains mutant in both these hsd loci are excellent recipients.

Mutat Res, 1981 May, 81(3), 295 - 309
Azido analogs of acridine: photoaffinity probes for frameshift mutagenesis in Salmonella typhimurium; Firth WJ 3rd et al.; In order to identify a photoaffinity probe for 9-aminoacridine frameshift mutagenesis, 20 azido analogs of acridine were synthesized and tested in Ames' Salmonella tester strains, TA1535, TA1537, TA1538 and their corresponding excision-repair-coefficient strains TA1975, TA1977 and TA1978, to determine their mutagenicity and toxicity relative to 9-aminoacridine . The substituent-mutagenicity patterns observed for these compounds agree very well with those obtained previously for non-azidoacridines . The results presented here show that the 2-azido-analog of 9-aminoacridine demonstrates biological activity similar to 9-aminoacridine prior to photolytic activation . With light activation, however, the 9-amino-2-azido derivative becomes more effective at producing frameshift mutations characteristic of 9-aminoacridine . Furthermore, this photolytic enhancement of mutagenesis appears to be due to the repairable lesion suggesting that covalent attachment of the drug occurs.

J Toxicol Sci, 1981 May, 6(2), 123 - 8
{Mutagenicity tests on mequitazine (author's transl)}; Sono A et al.; Microbial backward mutation test, Ames Salmonella/microsome plate assay, on six bacterial strains (Salmonella typhimurium TA 98, 100, 1535, 1537, 1538 and E . coli WP 2uvrA) and micronucleus test in mice were carried out to detect mutagenic activity of mequitazine . Mequitazine caused no increases of revertants at doses from 1 to 1000 microgram/plate in every bacterial strains irrespective of metabolic activation . Similarly, mequitazine induced no significant increases of micronucleated polychromatic erythrocytes in mice over the control level at doses from 0.12 (clinical dose) to 48 mg/kg (approx . LD 50) . From above results, we concluded that mequitazine has no mutagenic activity per se.

Appl Environ Microbiol, 1981 May, 41(5), 1173 - 6
Combined effect of acetate and reduced water activity in survival of Salmonella typhimurium 7136; Meyer LB et al.; Whereas Salmonella typhimurium 7136 will not grow at reduced water activity (aw), it was survival in such items as intermediate-moisture foods is of interest . Initial studies demonstrated that the addition of 0.3 M acetate (pH 4.7) to glycerol-Trypticase soy broth (BBL Microbiology Systems) solutions (aw 0.86) reduced the viability of S . typhimurium cells . The extent of death of cells exposed to reduced aw was increased by decreasing the pH or increasing the concentration of acetate . Acidification of glycerol-Trypticase soy broth reduced the D40 degrees C value exhibited by cells exposed to a range of aw solutions (0.65 to 0.92) . Acetate appeared to affect survival more dramatically as aw values approached the minimum growth limit . Acidification with acetate also reduced cell survival in a variety of humectant solutions with an aw of 0.86 (glycerol, dextrose, and NaCl).

Am J Vet Res, 1981 May, 42(5), 896 - 7
Biotyping of Salmonella typhimurium strains isolated from animals and birds in northern Japan; Ishiguro N et al.; Strains of Salmonella typhimurium (n = 175) isolated from animals and birds in northern Japan were differentiated into 5 biovars (1, 2, 7, 10, and untypeable) by 6 kinds of fermentation tests (inositol, bitter-xylose, rhamnose, xylose, Stern's glycerol, and trehalose) of Brandis' scheme, and were subdivided into 9 primary and 38 full biovars by a new biotyping method, using additional biochemical reactions . The full biovar classified by the new biotyping method was considered to be a marker for assessing the widespread outbreaks of infection with S typhimurium . In particular, strains of biovars 25hi and 27hi were characteristically found in pigeons, quail, and fantails, and were thought to be of avian origin.

Infect Immun, 1981 May, 32(2), 497 - 502
Artificial Salmonella vaccines: Salmonella typhimurium O-antigen-specific oligosaccharide-protein conjugates elicit opsonizing antibodies that enhance phagocytosis; Jorbeck HJ et al.; Outbred NMRI mice and rabbits were vaccinated with different artificial Salmonella typhimurium immunogens and the specificity and activity of elicited antibodies were studied in in vivo and in vitro phagocytosis assays . The Salmonella immunogens used were: (i) the synthetic disaccharide, abequose (formula see text) D-mannose, representative of Salmonella O antigen 4, covalently linked to bovine serum albumin (BSA); (ii) the octa- and dodecasaccharides, (formula see text) covalently linked to BSA; and (iii) whole heat-killed Salmonella . Rabbit antibodies passively administered to mice significantly enhanced the clearance of intravenously injected S . typhimurium challenge bacteria from the bloodstream . The clearance rate and the titer of anti-O-antigen-specific antibodies correlated . The clearance rate of an S . thompson (O6,7) strain, which has a different O antigen, was the same irrespective of the rabbit serum given . NMRI mice actively immunized with the various oligosaccharide-BSA conjugates had a significantly increased clearance rate of S . typhimurium only . In the in vitro assay, mouse antioligosaccharide-BSA sera promoted phagocytosis of S . typhimurium, but not S . thompson, when incubated with complement and mouse peritoneal exudate cells activated with Freund complete adjuvant.

Eur J Biochem, 1981 May, 116(1), 137 - 42
Patterns of product inhibition of a bifunctional dehydrogenase; L-histidinol:NAD+ oxidoreductase; Burger E et al.; The steady-state kinetic patterns of the bifunctional enzyme histidinol dehydrogenase from Salmonella typhimurium (EC 1.1.1.23) are compatible with a bi-uni uni-bi ping-pong mechanism . Studies of product inhibition make it possible to determine the sequence of substrate binding and product dissociation . Histidinol binds first to the enzyme, followed by the binding of NAD+; histidine is the last product to dissociate from histidinol dehydrogenase . Five of ten kinetic constants defined are determined from linear intercept and slope replots; Km for histidinol was found to be 16 +/- 3 microM and for NAD+ 1 +/- 0.3 mM; K2 for NAD+ was determined to be 0.8 +/- 0.4 mM and K3 for NADH to be 0.3 +/- 0.07 mM . K1 for histidine was found to be 2.1 +/- 0.5 mM.

Mutat Res, 1981 May, 91(3), 193 - 7
Mutagenic and inhibitory properties of some new purine analogs on Salmonella typhimurium TA1530; Janion C et al.; Mutagenic and growth-inhibitory effects of 2-amino-N6-hydroxyadenine, 2-amino-N6-methoxyadenine and 2-amino-N6-methyl-N6-hydroxyadenine were examined on S . typhimurium TA1530 . All compounds showed strong mutagenic activity, and 2-amino-N6-hydroxyadenine induced mutations at a dose as low as 1 microgram/ml . 2-Amino-N6-hydroxyadenine and, to a lesser extent, 2-amino-N6-methyl-N6-hydroxyadenine (but not 2-amino-N6-methoxyadenine) exerted inhibitory effects on bacterial growth . The specificity of mutagenic action of these base analogs, as well as the target for reversion of the his- marker in TA1530, is discussed.

Mutat Res, 1981 May, 91(3), 183 - 91
Dependence of the mutagenic power of heteroatomic dyes on their DNA-base-pair specificity; Mennigmann HD et al.; 23 compounds structurally related to proflavine were tested with Salmonella typhimurium TA1537 for their ability to induce mutants in the quantitative mutagenicity test of Ames et al . Of these compounds, 13 were mutagenic . Their mutagenic power decreased with increasing GC specificity of the dye . Because the mutational site in the tester strain is assumed to consist of a run of 4 adjacent GC pairs of the same polarity we conclude that for mutation to occur the dye should not be bound within this run of identical base pairs . Some of the compounds showed a negative slope at higher concentrations . Because these dyes also showed a comparatively high tendency to dimerize we conclude that mutation induction requires the intercalator to be bound as a monomer . Those compounds that were not mutagenic either did not intercalate or were inactivated by reduction.

Mutat Res, 1981 May, 91(3), 167 - 76
Mutagenicity of methylated fluorenes and benzofluorenes; Lavoie EJ et al.; Methylated fluorenes were assayed for mutagenic activity towards Salmonella typhimurium TA98 and TA100 . None of these methylfluorenes were mutagenic in the absence of metabolic activation . In the presence of 9000 X g supernatant from Aroclor-induced rats, 9-methylfluorene and 1,9-dimethylfluorene were active towards TA98 and TA100 . The structural requirement for mutagenic activity within this series was the presence of a single methyl substituent at the 9-position . Enhanced mutagenic activity was also observed for benzofluorenes similarly methylated at their benzylic positions.

Mutat Res, 1981 May, 91(3), 155 - 61
Isolation of an azide mutagenic metabolite in Salmonella typhimurium; Owais WM et al.; A scheme that employs a cation-exchange column and high-pressure liquid chromatography (HPLC) is devised to isolate and process large quantities of azide metabolite produced by S . typhimurium TA1530 strain . The mutagenic metabolite adheres strongly to the cation-exchange column, thus providing a convenient way to separate the metabolite from unreacted azide (N3-) . The metabolite is very polar and only sparingly soluble in most organic solvents . Recrystallization in a methanol-carbon tetrachloride solvent system gave rise to microcrystalline material that decomposes with charring and gas evolution at 173-176 degrees C . The infrared spectrum indicates the presence of a covalently bound azide moiety.

Mutat Res, 1981 May, 89(1), 9 - 20
The mutagenicity of isoniazid in Salmonella and its effects on DNA repair and synthesis in human fibroblasts; Wade DR et al.; A commercial sample of the tuberculostatic drug isoniazid (INH) was found to have a weak mutagenic activity towards Salmonella typhimurium strains TA100 and TA1535 . The addition of a rat or mouse liver homogenate to the test system decreased the mutagenic effect of INH . Hydrazine, an impurity of the INH sample, was also weakly mutagenic in strains TA100 and TA1535, but not in the extent that could account for the mutagenicity of the INH sample . An inhibition of DNA synthesis in human fibroblasts was observed for INH, this effect being potentiated by the addition of manganese to the test system . There was no induction of unscheduled DNA synthesis in human cells by INH except in the presence of manganese.

J Bacteriol, 1981 May, 146(2), 444 - 52
R-factor cointegrate formation in Salmonella typhimurium bacteriophage type 201 strains; Helmuth R et al.; The genetic and molecular properties of the plasmids in Salmonella typhimurium phase type 201 isolated are described . Such strains are resistant to streptomycin, tetracycline, chloramphenicol, ampicillin, kanamycin, and several other antimicrobial drugs, and are highly pathogenic for calves . These strains have been encountered with increasing frequency since 1972 in West Germany and The Netherlands . We show that isolates of this phage type constitute a very homogeneous group with regard to their extrachromosomal elements . These bacteria carry three small plasmids: pRQ3, a 4.2-megadalton (Md) colicinogenic plasmid; pRQ4, 3.4-Md plasmid that interferes with the propagation of phages; and pRQ5, a 3.2-Md cryptic plasmid . Tetracycline resistance resides on a conjugative 120-MD plasmid pRQ1, belonging to the incompatibility class H2 . Other antibiotic resistance determinants are encoded by a nonconjugative 108-Md plasmid pRQ2 . Transfer of multiple-antibiotic resistance to appropriate recipient strains was associated with the appearance of a 230-Md plasmid, pRQ6 . It appears that pRQ6 is a stable cointegrate of pRQ1 and pRQ2 . This cointegrate plasmid was transferable with the same efficiency as pRQ1 . Other conjugative plasmids could mobilize pRQ2, but stable cointegrates were not detected in the transconjugants . Phase type 201 strains carry a prophage, and we show that phage pattern 201 reflects the interference with propagation of typing phages effected by this prophage and plasmid pRQ4 in strains of phage type 201.

Cancer Lett, 1981 May, 12(4), 287 - 94
Parameters for detection of mutagenesis of 1,2-dimethylhydrazine using an in vitro Bacillus subtilis system; Wells BC et al.; Parameters for detection of mutagenesis of 1,2-dimethylhydrazine (DMH) using a Bacillus subtilis microbial assay are defined . His+ and his met mutations were induced in B . subtilis TKJ6321 in the absence of rat liver S-9 Mix . This B subtilis mutant showed a greater sensitivity to this chemical than did Salmonella typhimurium TA1535 . Protein-binding studies with bovine serum albumin showed the capacity for DMH to bind non-specifically to protein . S-9 mix from Aroclor pretreated animals appeared to decrease the mutagenic response . Kinetics of mutagen stability were also shown, thereby demonstrating the need for more complete investigation of known chemical carcinogens which give negative results in the Ames bioassay alone.

Proc Natl Acad Sci U S A, 1981 May, 78(5), 3113 - 7
Spontaneous tandem genetic duplications in Salmonella typhimurium arise by unequal recombination between rRNA (rrn) cistrons; Anderson P et al.; A method is described to detect and measure the frequency of spontaneous tandem genetic duplications located throughout the Salmonella genome . The method is based on the ability of duplication-containing strains to inherit two selectable alleles of a single gene during generalized transductional crosses . One allele of the gene carries an insertion of the translocatable tetracycline-resistance element Tn10; the other allele is a wild-type copy of that gene . Using this technique, we have measured the frequency of tandem duplications at 38 chromosomal sites and the amount of material included in 199 independent duplications . These results suggest that, in one region of the chromosome, tandem duplications are particularly frequent events . Such duplications have end points within rRNA (rrn) cistrons and probably arise by unequal cross-over between these dispersed repeated sequences . Spontaneously duplications of this type are harbored by as much as 3% of the bacterial population . Preliminary evidence suggests that such duplications may play a significant regulatory role under conditions of rapid growth . Our analysis has suggested the position on the genome of an additional rRNA cistron.

Mutat Res, 1981 May, 89(1), 1 - 7
Microbial short-term assays with thiram in vitro; Zdzienicka M et al.; The fungicide thiram was assayed in the following tests in vitro, with and without metabolic activation: (1) prophage lambda induction of Escherichia coli K12; (2) repair test in Salmonella typhimurium (strains TA1538 and TA1978); (3) induction of gene mutations in Aspergillus nidulans (methA1 suppressor induction) . Thiram was positive in the repair test and in the A . nidulans forward-mutation test (4-6 fold increase) in the absence of metabolic activation . A slight increase was observed in prophage lambda induction with thiram in the presence of the metabolic activation system.

Proc Natl Acad Sci U S A, 1981 May, 78(5), 2747 - 51
Mutations in the gene coding for Escherichia coli DNA topoisomerase I affect transcription and transposition; Sternglanz R et al.; Mutations in top, the structural gene for Escherichia coli DNA topoisomerase I, have been identified and mapped at 28 min on the chromosome, near cysB . Strains carrying deletions of the top gene are viable . The top mutations, however, do exert pleiotropic effects on transcription and transposition . Mutants lacking DNA topoisomerase I have a more rapid rate of induction and a higher level of catabolite-sensitive enzymes including tryptophanase and beta-galactosidase . This general activation of transcription by top mutations can be attributed to an increase in the negative superhelicity of the DNA in vivo when the topoisomerase activity is abolished . The frequency of transposition of Tn5, a transposon carrying kanamycin resistance, is decreased by a factor of 40 or more in top mutants . A direct or indirect role of the topoisomerase in transposition is discussed . The transposition frequency of Tn3, however, is not dependent on top . Based on the studies of the E . coli top mutants, it appears that the supX gene, which was originally studied in Salmonella typhimurium {Dubnau, E . & Margolin, P . (1972) Mol . Gen . Genet . 117, 91-112} is likely to be the structural gene for DNA topoisomerase I.

Mech Ageing Dev, 1981 May, 16(1), 29 - 35
Activation of promutagens by liver homogenates isolated from female mice at different ages; lack of significant differences; Guttenplan JB et al.; Liver S-9 (9000 g supernatant) fractions isolated from 2-, 12- and 26-month untreated female Swiss-Webster mice were compared under different assay conditions as to their abilities to activate 2-acetylaminofluorene, benzo(a)pyrene, and dimethylnitrosamine to mutagens in Salmonella typhimurium tester strain TA 100 . All fractions activated these compounds to mutagens, although 2-acetylaminofluorene was only weakly mutagenic . Some differences in the activating abilities of the three age groups were observed but they were for the most part relatively small.

Science, 1981 May 1, 212(4494), 546 - 7
Mutation caused by human phagocytes; Weitzman SA et al.; Histidine-requiring mutants of Salmonella typhimurium TA100 were incubated with human peripheral blood leukocytes . More of these bacteria reverted to histidine independence than controls not incubated with cells . Phagocyte-rich suspensions were mutagenic, while heat-killed cells, lymphocytes, or mixed blood leukocytes of a patient with chronic granulomatous disease were not . Production of reactive oxygen metabolites could explain the capacity of phagocytes to induce mutation.

Drug Metab Dispos, 1981 May-Jun, 9(3), 292 - 6
Structural elucidation of a mutagenic metabolite of 3-amino-1-methyl-5H-pyrido{4,3-b}indole; Yamazoe Y et al.; Metabolic activation of a tryptophan pyrolysate, 3-amino-1-methyl-5H-pyrido{4,3-b}indole (Trp-P-2) by liver microsomes was studied . Trp-P-2 was converted to at least four metabolites (M-1 to M-4), which were separable by HPLC or TLC . Among them, the major metabolite (M-3) was extremely mutagenic to Salmonella typhimurium TA 98 in the absence of activating enzymes and the activity accounted for almost all mutagenic effects of Trp-P-2 . Metabolite M-3 was identified as 3-hydroxyamino-1-methyl-5H-pyrido{4,3-b}indole by mass spectrometry and by conversion to the 4-chloro derivative of Trp-P-2 by treatment with hydrochloric acid . The latter compound was identified by NMR and mass spectrometry.

J Bacteriol, 1981 May, 146(2), 535 - 41
Gene rfaH, which affects lipopolysaccharide core structure in Salmonella typhimurium, is required also for expression of F-factor functions; Sanderson KE et al.; Mutations in gene rfaH of Salmonella typhimurium at 84 units on the linkage map make lipopolysaccharide of chemotypes Ra, Rb2, Rb3, and Rc (A . A . Lindberg and C . G . Hellerqvist, J . Gen . Microbiol, 116:25--32, 1980) . F-factor expression in RfaH- strains was reduced in the following properties when compared with RfaH+ strains: transfer of Flac, number of phage f2 infective centers, lysis by and propagation of phages f2 and M13, proportion of cells with visible F-pili, and formation of mating aggregates with F- cells . Inhibition of multiplication of Br60, a female-specific phage, was not reduced in RfaH- Flac strains . Plasmid transfer from RfaH- strains was reduced for Inc groups FI, FII, and T, unaffected for Inc groups beta, I alpha, L, N, P, and W . and increased for Inc group M when compared with plasmid transfer from RfaH+ strains . Reduced F-factor function in RfaH- strains was not due to defective lipopolysaccharide since strains with mutations in other rfa genes were unaffected in plasmid transfer . Gene rfaH appears to be homologous with gene sfrB in Escherichia coli K-12, which maps at the same location, influences F-factor function, and affects synthesis of lipopolysaccharide . The gene product of sfrB has been proposed to be a transcription antiterminator.

Rev Argent Microbiol, 1981 May-Aug, 13(2), 41 - 4
Effect of RNA on the immunological response of rats, induced by Salmonella typhimurium; Molteni OA et al.; Rats treated with RNA from normal rat spleen were challenged 5 days later with Salmonella typhimurium . The primary response was delayed and antibody titers significantly lower than controls were observed . Forty eight hours after the secondary challenge the antibody titers were also lower; this difference disappeared five days later . This study confirms the immunological depression produced by RNA . Moreover, it is demonstrated that the RNA action is transitory and that the recovery of secondary response occurs seven days after the second challenge . This action is probably explained at macrophage level.

Mol Cell Biochem, 1981 Apr 27, 36(2), 95 - 104
Purification and properties of several transfer RNA methyltransferases from S . typhimurium; Cimino F et al.; A fast method for a single-step fractionation of a number of tRNA methyltransferases from Salmonella typhimurium is described . The method basically consists of ion-exchange chromatography on a phosphocellulose column and permits the separation of the enzymes forming mt6A, m1G, m5U, m7G . The enzyme fractions appear sufficiently purified to allow the estimation of some molecular and kinetic properties . The apparent KM for adenosylmethionine range between 1.5 to 3.2 X 10(-5) M, whereas KM for undermethylated tRNA range between 3.1 X 10(-5) M to 3.1 X 10(-4) M . Glycerol gradient determination indicates the following Mr for the native proteins: 25 X 10(3), 40 X 10(3), 50 X 10(3) and 65 X 10(3) for m7G-, mt6A-, m1G- and m5U-forming enzymes, respectively . A complete analysis of methylated nucleosides formed in vivo in S . typhimurium has been obtained: it also allowed us to infer the pattern of the various tRNA methyltransferases for this prokaryote . The tRNA methyltransferase forming mt6A has been isolated for the first time from any type of cell.

Lancet, 1981 Apr 18, 1(8225), 881 - 4
Person-to-person spread of Salmonella typhimurium phage type 10 after a common-source outbreak; Palmer SR et al.; An outbreak of gastroenteritis caused by Salmonella typhimurium phage type 10 in a university hall of residence affected 66 students and one member of staff . Results of a questionnaire survey of students suggested that the main wave of (53) cases was due to consumption of contaminated cottage pie, but the remaining cases could best be explained by person-to-person spread of infection . Investigation of the outbreak was greatly assisted by rigorous case finding, the screening of those at risk for symptomless excretors, and the collection of food histories from those who remained well . The possibility of person-to-person spread of salmonella food-poisoning serotypes should be borne in mind when outbreaks are investigated in closed communities such as institutions, families, and ships.

Nucleic Acids Res, 1981 Apr 10, 9(7), 1743 - 55
Comparison of the nucleoside sequence of trpA and sequences immediately beyond the trp operon of Klebsiella aerogenes . Salmonella typhimurium and Escherichia coli; Nichols BP et al.; The nucleotide sequence of trpA of Klebsiella aerogenes is presented and compared with the trpA sequences of Salmonella typhimurium and Escherichia coli . The majority of the approximately 200 differences between each pair of trpA's are single nucleotide pair changes that do not alter the amino acid sequence . Codon usage conforms to the general patterns revealed by examination of other prokaryotic gene sequences . However, codon usage in K . aerogenes trpA reflects the high G+C content of the genome of this organism . The DNA sequences just beyond trpA, the presumed transcription termination region, are also compared for the three species . Perusal of these sequences indicates that the secondary structure of the transcript segment just beyond trpA has been preserved, while the primary sequence has diverged appreciably.

Cancer Res, 1981 Apr, 41(4), 1469 - 82
DNA-damaging activity in vivo and bacterial mutagenicity of sixteen hydrazine derivatives as related quantitatively to their carcinogenicity; Parodi S et al.; Sixteen hydrazine derivatives (hydrazine, 1,1-dimethylhydrazine, 1,2-dimethylhydrazine, phenylhydrazine, procarbazine, isoniazid, isocarboxazid, nialamide, 2,4-dinitrophenylhydrazine, phenelzine, hydralazine, dihydralazine, carbamylhydrazine, mebanazine, iproniazid, and 1-carbamyl-2-phenylhydrazine) were tested for DNA-damaging activity by the alkaline elution technique and for mutagenic activity in the Salmonella-microsome (Ames) test . The first nine compounds listed (56%) were found to induce a significant DNA fragmentation in the liver and/or in the lung of i.p.-treated male Swiss mice . The DNA-damaging potency varied over an approximately 30-fold range . Thirteen of the first 14 compounds listed (81% of the total), isocarboxazid being inactive, were positive in the Ames test, with a broad range of activity towards the five bacterial strains of Salmonella typhimurium used (TA1535, TA100, TA1537 . TA1538, and TA98) and of metabolic behavior in the presence of S-9 mix containing rat liver, mouse liver, or mouse lung postmitochondrial preparations from Aroclor-treated animals . The mutagenic potency varied over an almost 7000-fold range . For 11 of the 16 hydrazine derivatives tested, homogeneous carcinogenicity data (induction of pulmonary tumors in mice chronically treated p.o.) were available from literature . Elaboration of these data showed that carcinogenic potency varied over an approximately 1900-fold range . The five most potent carcinogens were all positive in the DNA damage test . Their carcinogenic potency varied over a 130-fold rage and their DNA-damaging potency varied over a 22-fold range . DNA-damaging potency seemed to vary on a more compressed scale, but regression analysis indicated the existence of a strong positive correlation between in vivo DNA-damaging and carcinogenic potencies, while a lack of correlation was found between mutagenic and carcinogenic potencies . There was no correlation between DNA-damaging and mutagenic potencies.

Cancer Res, 1981 Apr, 41(4), 1389 - 96
Species-specific enhancement by 7,8-benzoflavone of hepatic microsomal metabolism of benzo{e}pyrene 9,10-dihydrodiol to bay-region diol epoxides; Thakker DR et al.; Metabolism of benzo{e}pyrene 9,10-dihydrodiol to the bay-region 9,10-diol-11,12-epoxides by hepatic microsomes from human, rat, mouse, guinea pig, hamster, and rabbit has been examined in the presence and absence of 7,8-benzoflavone . In the absence of 7,8-benzoflavone, the formation of bay-region diol epoxides from benzo{e}pyrene 9,10-dihydrodiol was low in all species except the hamster . With hamster liver microsomes, greater than 60% of total metabolites formed were bay-region diol epoxides, whereas human and mouse liver formed less than 5% of total metabolites as bay-region diol epoxides . Addition of 7,8-benzoflavone to the microsomal incubations stimulated the formation of diol epoxides, but this stimulation was species dependent . The most dramatic stimulation was observed with human and rabbit liver microsomes . In a parallel study, metabolic activation of benzo{e}pyrene 9,10-dihydrodiol to mutagens toward Salmonella typhimurium strain TA 100 by hepatic microsomes from the above species was examined in the presence and absence of 7,8-benzoflavone . In the absence of 7,8-benzoflavone, hepatic microsomes from all the species only weakly activated benzo{e}pyrene 9,10-dihydrodiol to mutagens . 7,8-Benzoflavone enhanced the metabolic activation catalyzed by microsomes from all species except rats and hamsters . Particularly high stimulation was observed with human and rabbit liver microsomes . 9,10-Dihydroxy-9,10,11,12-tetrahydrobenzo{e}pyrene, a compound which cannot be metabolized to a bay-region diol epoxide, was not metabolically activated to mutagenic metabolites in the presence or absence of 7,8-benzoflavone by any of the species examined . These results indicated that the effect of 7,8-benzoflavone on the enhanced mutagenic activity of benzo{e}pyrene 9,10-dihydrodiol is mediated by bay-region diol epoxides, which is consistent with the metabolism studies.

J Gen Microbiol, 1981 Apr, 123(Pt 2), 209 - 14
The synergistic contribution of macrophages and antibody to protection against Salmonella typhimurium during the early phase of infection; Akeda H et al.; The contribution of phagocytes and antibody to protection against Salmonella typhimurium during the early phase of infection in mice was analysed . Following intravenous injection, most of the bacteria were trapped in the liver and spleen within 10 to 60 min and killed within 6 h; surviving organisms began to multiply in these tissues after 24 h and reached a maximum at 5 to 7 d . The transient killing phase was abrogated by treatment with carrageenan, a macrophage blocker, but not by whole-body X-irradiation . These observations suggest that carrageenan-sensitive, but radio-resistant macrophages play an important role in the early phase of the infection . Actively immunized mice showed accelerated trapping and killing; the protection observed at the early stage of infection in immunized mice could be passively transferred to normal mice, whereas carrageenan-treated mice did not kill the bacterial even after receiving immune serum . It seems that the synergistic action of macrophages and antibody provided the main initial primary defence in immune animals.

Poult Sci, 1981 Apr, 60(4), 768 - 70
Sampling of broiler carcasses for Salmonella with low volume water rinse; Cox NA et al.; The uneven distribution and low numbers of salmonella usually present on broiler carcasses make whole carcass rinsing the most sensitive sampling procedure for detecting this organism on the raw product . However, 270 ml of water or medium has been the smallest volume used in past published research . We found that 100 ml was adequate to recover Salmonella typhimurium, S . california, or S . montevideo from freshly processed broiler carcasses that had been inoculated with the organism at the rate of 50 cells/carcass . When carcasses were inoculated with 20 cells or S . heidelberg, then stored at -23 C for 3 or 6 months, sampling with 100 ml was adequate to detect the organism on all carcasses . The advantages of using the smallest volume of rinsing medium that will consistently lead to detection of salmonella present are: 1) less enrichment medium is required, 2) less incubator space is required, and 3) the concentration of cells in the selective enrichment medium at the end of incubation is greater; hence, the greater are the chances of salmonella detection when a drop is subsequently transferred to the selective plating medium.

J Pharmacobiodyn, 1981 Apr, 4(4), 269 - 74
Characterization of aminoindamines and aminoindoanilines formed by oxidative hair dyeing and their mutagenicity; Matsuki Y et al.; 2-Amino-5-methoxy-2'(or 3')-methylindamine and 2-amino-5-methoxy-2'(or 3')-methylindoaniline were isolated from a coloring matter formed by oxidative condensation of 2,5-diaminotoluene with 2,4-diaminoanisole, and their structures were elucidated on the basis of nuclear magnetic resonance and mass spectral data . These two main components of the oxidation product formed at the early stage exhibited a positive result in the mutagenicity test on the thin-layer chromatography plate . The mutagenic activities of purified aminoindamines and aminoindoanilines against Salmonella typhimurium TA 98 were as strong as that of 2-acetamidofluorene . It was also demonstrated that 5-methoxy-2'(or 3')-methylindamine was formed in 10% yield under the conditions used for hair dyeing and the yield was dependent upon the molar ratio of 2,5-diaminotoluene to 2,4-diaminoanisole.

Mutat Res, 1981 Apr, 88(4), 337 - 42
Mutagenicity of irradiated solutions of nucleic acid bases and nucleosides in Salmonella typhimurium; Wilmer J et al.; Solutions of nucleic acid bases, nucleosides and a nucleotide, saturated with either N2, N2O or O2, were irradiated and tested for mutagenicity towards Salmonella typhimurium, with and without pre-incubation . Irradiated solutions of the nucleic acid bases were all non-mutagenic . Irradiated solutions of the nucleosides showed mutagenicity in S . typhimurium TA100 (pre-incubation assay) . Generally, the mutagenicity followed the order: N2O greater than N2 greater than O2 . The results show that the formation of mutagenic radiolytic products is initiated by attack of mainly OH radicals on the 2-deoxy-D-ribose moiety of the nucleosides . With irradiated solutions of the nucleotide, thymidine-5'-monophosphate, no mutagenicity could be detected.

Proc Natl Acad Sci U S A, 1981 Apr, 78(4), 2169 - 73
Procedure for production of hybrid genes and proteins and its use in assessing significance of amino acid differences in homologous tryptophan synthetase alpha polypeptides; Schneider WP et al.; Hybrid tryptophan synthetase alpha and beta polypeptides were produced by genetic recombination between the trpB--trpA regions of Escherichia coli and Salmonella typhimurium contained on compatible, multicopy plasmids . Intragenic recombination was decreased but still evident in recA cells . Genetic exchange occurred at many sites within trpA, but every recombinant gene produced a functional alpha polypeptide despite many amino acid differences from one or the other of the parental polypeptides . The five hybrid tryptophan synthetase alpha subunits examined resembled the parental polypeptides in catalytic function but differed in thermostability . The stability differences suggest that, as amino acid changes occurred in these proteins during the course of evolution, subsequent changes were limited to those that would allow retention of a desired protein conformation.

Immunology, 1981 Apr, 42(4), 569 - 76
The fate of temperature-sensitive salmonella mutants in vivo in naturally resistant and susceptible mice; Hormaeche CE et al.; The in vivo net growth rate of salmonellae in mice is faster with virulent than with attenuated strains, and slower in resistant than in susceptible mice, the latter difference being controlled by a single host gene (Ity) . Mice were injected intravenously (i.v.) with nonreplicating temperature-sensitive (TS) salmonellae mutants: TS mutants from virulent parents survived better in the RES than those from attenuated or non-virulent parents as if the latter were more susceptible to bactericidal mechanisms . However, a TS mutant from a virulent parent (Salmonella typhimurium C5) did not consistently survive better in susceptible C5) did not consistently survive better in susceptible Itys than in resistant Ityr mice, suggesting that this gene may not operate by a bactericidal mechanism . In many animals the TS salmonellae caused septic arthritis which first appeared at 2--3 weeks . Subcutaneous inoculation in the tail caused local lesions and the organism spread to the RES, but did not cause arthritis in the short term.

Eur J Biochem, 1981 Apr, 115(3), 525 - 31
Phosphate-containing proteins of Salmonella typhimurium and Escherichia coli . Analysis by a new two-dimensional gel system; Ferro-Luzzi Ames G et al.; The pattern of post-translational protein modifications involving a phosphate group was determined in the prokaryotes Salmonella typhimurium and Escherichia coli . A special two-dimensional gel electrophoretic separation was developed which utilizes acidic urea in the first dimension and neutral sodium dodecyl sulfate in the second dimension . This system allows survival and visualization of a number of proteins which are otherwise lost in systems employing basic conditions . The total number of phosphate-containing proteins thus obtained is approximately twenty . Among them are included proteins containing nucleotidylyl groups; two of these have been identified: glutamine synthetase (adenylylated) and regulatory protein PII (uridylylated) . Two phosphate-containing proteins are shown to be regulated by the level of K+ . The pattern of phosphorylation is shown to change with changing growth conditions and with specific mutations.

J Bacteriol, 1981 Apr, 146(1), 298 - 304
Genetic characterization of the araE gene in Salmonella typhimurium lt2; Lee JH et al.; Six L-arabinose transport-deficient mutants of Salmonella typhimurium LT2 were isolated on the basis of their inability to ferment low concentrations of L-arabinose . The mutations were localized between serA and lys on the S . typhimurium genetic map and assigned to the araE locus . An araE-lac fusion strain was constructed and used to determine that the direction of araE transcription was counterclockwise on the S . typhimurium genetic map . beta-Galactosidase activity was induced by L-arabinose in the araE-lac fusion strain, suggesting that araE expression is controlled at the level of transcription.

J Bacteriol, 1981 Apr, 146(1), 170 - 8
Role of the supX gene in ultraviolet light-induced mutagenesis in Salmonella typhimurium; Overbye KM et al.; Salmonella typhimurium strains with supX mutations are more sensitive than wild type to killing by ultraviolet (UV) irradiation . Studies with strains bearing the leuD21 mutation revealed that inactivation of the supX locus by a nonsense mutation or a deletion results in a complete lack of ability to produce induced Leu+ reversion mutations after UV irradiation . Suppression of the nonsense supX mutation or the presence of an Escherichia coli K-12 F'-borne supX+ allele restored the capacity for induced reversions and increased cell survival after UV irradiation . Introduction of plasmid pKM101 into supX mutant strains also restored their capacity for UV mutagenesis as well as increased survival . The possible nature of the supX gene product and mechanisms by which it may affect expression of the inducible SOS error-prone repair system are considered.

Infect Immun, 1981 Apr, 32(1), 295 - 9
Heparin inhibits phagocytosis by polymorphonuclear leukocytes; Victor M et al.; Phagocytosis of unopsonized Salmonella typhimurium 395, MR-10, opsonized Salmonella typhimurium 395 MS, and Staphylococcus epidermidis by rabbit polymorphonuclear leukocytes was inhibited by heparin at concentrations as low as 0.5 U/ml . Inhibition was dose dependent and nearly complete at 20 U/ml . Provided that heparin concentrations did not exceed 100 U/ml, inhibition could be largely reversed by washing . Heparin also reversibly inhibited the adherence of polymorphonuclear leukocytes to glass . In contrast, hexose monophosphate shunt activity of polymorphonuclear leukocytes stimulated by noningested S . typhimurium MR-10 or Streptococcus pyogenes B14 was not inhibited by heparin at concentrations as high as 100 U/ml.

Infect Immun, 1981 Apr, 32(1), 137 - 44
Protein synthesis in HeLa or Henle 407 cells infected with Shigella dysenteriae 1, Shigella flexneri 2a, or Salmonella typhimurium W118; Hale TL et al.; The incorporation of {14C}leucine into protein was studied in two mammalian cell lines which had been infected with strains of Shigella dysenteriae 1, Shigella flexneri 2a, or Salmonella typhimurium W118 . These cell lines differed in susceptibility to the effects of exogenously applied Shiga cytotoxin . All invasive shigella strains (which synthesize this toxin to a greater or lesser degree) were found to inhibit protein synthesis in both cell lines with equal efficiency . Leucine accumulation continued in these cells, but the labeled amino acid was preferentially incorporated into bacterial protein . S . typhimurium W118, which has not been shown to elaborate a Shiga-like toxin, had little effect on protein synthesis in infected host cells.

Mutat Res, 1981 Apr, 88(4), 363 - 74
Mutagenicity of fractions of cigarette smoke condensate in Neurospora crassa and Salmonella typhimurium; DeMarini DM; The mutagenicities of selected fractions of cigarette smoke condensate (CSC) were studied in Neurospora crassa for the presence of direct-acting mutagens . CSCs from the University of kentucky Reference Cigarette 1R1 were assayed in a forward-mutation test at the adenine-3 (ad-3) region in resting conidia of a 2-component heterokaryon . Direct-acting mutagenic activity was found in an enriched polycyclic aromatic hydrocarbons (EPAH) fraction and in a basic fraction (Swain 5) . No direct-acting mutagenic activity was detected in an acidic fraction (Swain 8), although it was highly toxic to resting conidia . The EPAH fraction also was tested in the presence of S9 mix prepared from Aroclor-1254-induced rat liver . It was found to be mutagenic, but higher doses were required than in the absence of S9 mix . In addition, the mutagenicities of CSC and 10 fractions of CSC were investigated in Salmonella typhimurium TA1538 by the incorporation and preincubation methods . In general, preincubation did not enhance the mutagenicities of the fractions, and the two rankings of mutagenic potency of the condensates that were obtained by the two methods were not significantly different . This is the first report of the presence of potent direct-acting mutagenicity in the EPAH and Swain 5 fractions of CSC.

Chem Biol Interact, 1981 Apr, 35(1), 71 - 91
Mutagenicities of styrene oxide derivatives on bacterial test systems: relationship between mutagenic potencies and chemical reactivity; Sugiura K et al.; The reaction products of deoxyguanosine with 3,4-dimethyl-, p-methyl-, m-methyl-, m-methoxy-, p-bromo-, m-chloro- and unsubstituted styrene oxide were isolated and characterized . The reaction followed second-order kinetics . The reactive site was the N-7 site of guanine . The normal isomer (attack at CH2 of styrene oxides) and the abnormal isomer (attack at CH) were obtained . The Hammett reaction constant (rho) for the normal reaction was +0.42 and that for the abnormal reaction was -1.1 . The difference of acid dissociation constant, rate of imidazole ring opening and rate of glycosidic bond cleavage was not found between the normal adduct and the abnormal adduct . Styrene oxides have been tested for toxicity and mutation in a liquid suspension assay using Escherichia coli WP2 and some of its repair deficient derivatives . Salmonella typhimurium TA100 was also employed . The mutation frequency of 3,4-dimethylstyrene oxide was higher in CM571 than in WP2 . The greatest mutability was found with the WP2uvrA strain . 3,4-Dimethylstyrene oxide also acted as an inducer of E . coli K-12 (kappa) . The mutagenicity of 3,4-dimethylstyrene oxide may depend on a combination of the recA-dependent and recA-independent action mechanisms . The mutagenicities of these compounds in WP2uvrA and TA100 increased in the order: m-chlorostyrene oxide = p-bromostyrene oxide less than m-methoxystyrene oxide less than styrene oxide less than m-methylstyrene oxide less than p-methylstyrene oxide less than 3,4-dimethylstyrene oxide . There was no correlation between the mutagenicities and the total reaction rates . On the other hand, the reaction rates of these compounds for the abnormal reaction correlated with their mutagenicities . The results indicate that the mutagenic effect of a chemical is not dependent simply on the quantity of the adducts, but may vary with structure of its adducts.

Proc Natl Acad Sci U S A, 1981 Apr, 78(4), 2164 - 8
Identification and localization of a gene that specifies production of Escherichia coli DNA topoisomerase I; Trucksis M et al.; A gene that specifies production of Escherichia coli DNA topoisomerase I (omega protein) was identified with the aid of a radioimmunoassay for this protein . E . coli DNA topoisomerase I was produced by Salmonella typhimurium merodiploids that harbored E . coli plasmid F' 123, but not by strains that lost this plasmid . Analysis of strains with spontaneous deletions of F' 123 showed that the gene, topA, required for production of the E . coli omega protein was between the trp operon and the cysB gene . Deletions that eliminated topA also eliminated the supX gene . We suggest that topA is the structural gene of E . coli DNA topoisomerase I and that topA is identical to supX.

Proc Natl Acad Sci U S A, 1981 Apr, 78(4), 2135 - 9
Nitrogen regulatory locus "glnR" of enteric bacteria is composed of cistrons ntrB and ntrC: identification of their protein products; McFarland N et al.; The nitrogen regulatory locus "glnR" of Escherichia coli and Salmonella typhimurium is composed of two cistrons, which we propose to call ntrB and ntrC (nitrogen regulation B and C) . Frameshift mutations in ntrB and ntrC were isolated on a lambda phage that carries the E . coli ntrB and ntrC genes and the closely linked glnA gene, the structural gene encoding glutamine synthetase {L-glutamate:ammonia ligase (ADP-forming), EC 6.3.1.2}; mutations were selected as suppressors of glnF (which we propose to rename ntrA), a selection used previously to isolate glnR mutations . Phage DNA from one mutant (ntrB) failed to direct synthesis of a 36-kilodalton (kDal) protein whose synthesis was directed by DNA from the parent phage (ntrB+) in a coupled in vitro transcription/translation system . DNA from three other mutants (ntrC) failed to direct synthesis of a 54-kDal protein; DNA from two of these mutants instead directed synthesis of smaller proteins, 53 and 50 kDal, respectively . In all four cases, DNA from frameshift revertants directed synthesis of both the 36-kDal and 54-kDal proteins . These results suggested that ntrB and ntrC were separate genes which encoded 36-kDal and 54-kDal protein products, respectively . Frameshift mutations in ntrB and ntrC complemented each other with regard to regulation of glnA expression in vivo and growth on arginine as nitrogen source, another nitrogen-controlled phenotype; this confirmed that ntrB and ntrC are separate cistrons that encode diffusible products . The ntrB and ntrC genes were also defined in S . typhimurium . Studies of mutant strains provided information on the roles of the ntrB and ntrC products in activation and repression of glnA expression and raised the possibility that these products function as a protein complex in regulating expression of nitrogen-controlled genes.

Nouv Presse Med, 1981 Mar 21, 10(13), 1039 - 41
{Renal transplantation and Salmonella typhimurium infection . Epidemiological study of lysotypes and biotypes (author's transl)}; Schoutens E et al.; During an 8-year period (1970-1977), 24 strains of Salmonella spp . were isolated in 24 renal transplant recipients . In 19 cases (79%) the infection had an unusual presentation (extradigestive focus or bacteraemia), and 15 of the offending strains belonged to the serotype typhimurium . During the same period 161 strains of Salmonella spp . were isolated in 159 adult patients admitted to units other than the renal transplantation unit; 52% of the infections presented as gastroenteritis, and S . typhimurium accounted for only 25% of unusual presentations . However, the lysotypes and biotypes of S . typhimurium were as diverse in the renal transplantation unit as in other hospital units . The study failed to demonstrate interhuman transmission of Salmonella spp . within the renal transplantation unit.

J Toxicol Environ Health, 1981 Mar-Apr, 7(3-4), 519 - 31
Mutagenicity of N-nitroso derivatives of carbofuran and its toxic metabolites; Nelson J et al.; Carbofuran (CF), an insecticide and nematocide, is metabolically oxidized to two less toxic forms, 3-hydroxycarbofuran and 3-ketocarbofuran . The N-nitroso derivatives of carbofuran and its metabolites were synthesized by reaction with nitrite under acidic conditions . Products of the reaction were obtained by extraction, identified by thin-layer chromatography, and purified by silica gel column chromatography . All three nitroso derivatives reacted positively with Gries reagent and gave characteristic triplet absorption spectra (387, 402, and 422 nm) . Structural confirmation was by nuclear magnetic resonance and mass spectroscopy . Mutagenicity was determined by the Ames assay method with Salmonella typhimurium strains TA98 and TA100 . The nitroso derivatives of all three compounds responded similarly, given a mutation ratio of 45 at 5 micrograms per plate on TA100 . In addition, all three produced chromosome aberrations in Chinese hamster ovary (CHO) cells . Only two of the three (nitrosocarbofuran and 3-hydroxynitrosocarbofuran) were also capable of inducing large numbers of sister chromatid exchanges in the same cells . Observed variations in maximum mutagenicity in the Ames test and the ability to induce sister chromatid exchanges in CHO cells are consistent with the stability of the compounds in aqueous solution.

Cancer Lett, 1981 Mar, 12(1-2), 93 - 7
Formation of mutagens in cooked foods . IV . Effect of fat content in fried beef patties; Spingarn NE et al.; Cooking beef patties results in the formation of mutagens detectable by Salmonella typhimurium TA98 with metabolic activation . We now show that the amount of fat in beef affects the quantity of mutagens formed . While char increases with increasing fat, over the range of 5-309% of added fat content, mutagenicity reaches a peak at 10% added fat and subsequently decreases . Thus, char formation is not an accurate measure of mutagenicity . These results suggest that fat plays an important role in mutagen formation in fried beef.

Cancer Lett, 1981 Mar, 12(1-2), 81 - 6
Formation of nitroso compounds and mutagens from tranquilizers by drug/nitrite interaction; Takeda Y et al.; The formation of nitroso compounds and mutagens by drug/nitrite interaction was screened for 14 tranquilizers . The drug (0.05 M) was reacted with nitrite (0.5 M) at pH 3-3.5 . After 4 h at 37 degrees C, nitroso compound formation was observed for flupentixol, chlordiazepoxide, spiperone, thiothixene, and chlorprothixene in more than 40% yield . Mutagenicity was found in the reaction products of opipramol, chlordiazepoxide, bromazepam, thiothixene, and carpipramine by the Ames assay using Salmonella typhimurium TA98 and TA100 as tester strains.

Cancer, 1981 Mar 1, 47(5), 889 - 94
Nitrite-induced volatile mutagens from normal human feces; Rao BG et al.; Volatile mutagens (putative carcinogens) were produced from normal human and animal feces upon incubation with sodium nitrite in saline at 37 C for 48 hours . The mutagens were detected by using Ames' Salmonella typhimurium tester strain TA1535 without microsomes, on plates inverted over samples in sealed containers . Mutagenicity was maximal at 0.2 to 0.6 M NaNO2 and at pH 6.2 to 6.8 . Reversions per plate varied from approximately 30 to 450 (1.5 to 25 x background) within the normal human population . Sodium ascorbate and alpha-Tocopherol (at one-half {NaNO2}) each reduced the mutagenicity by approximately 30% . Two standard N-nitroso-compounds were mutagenic in the system . We propose that the mutagenicity in our system is probably caused by the formation of volatile N-nitroso-compounds and that addition of nitrite to human feces in vitro enhances a process that occurs in vivo.

J Toxicol Environ Health, 1981 Mar-Apr, 7(3-4), 643 - 53
Quantifying the toxic and mutagenic activity of complex mixtures with Salmonella typhimurium; Somani SM et al.; The toxicity and mutagenicity of 11 compounds individually and in mixtures were quantified in Salmonella typhimurium strains TA98, TA100, and TA1537 by a modification of the Ames spot test . The distance (millimeters) from the center of the petri dish to the bacterial growth front represented the toxic response . When mutagenicity occurred, the distance from the inner radius to the outer radius of the mutagenic growth represented the mutagenic response . Multiple regression analysis was used to quantify the toxicity and mutagenicity of individual compounds in the mixtures . The results indicate that the effects of compounds in mixtures are generally additive.

J Dairy Sci, 1981 Mar, 64(3), 454 - 8
Subtherapeutic tetracycline effects on recovery patterns of calves after Salmonella typhimurium challenge; Remillard RL et al.; Holstein calves were maintained on a subtherapeutic dose of chlortetracycline to determine if an oxytetracycline therapy, given after a Salmonella typhimurium challenge, would be compromised by the previous subtherapy . Two of the four groups of seven calves were maintained on a subtherapeutic amount of chlortetracycline . All calves then were challenged with Salmonella typhimurium, and with the onset of clinical symptoms one group with and one group without subtherapy were given a therapeutic dose of oxytetracycline . The two groups receiving a therapeutic dosage of oxytetracycline had the most quickly declining body temperatures and the highest average body weights post-challenge . Two calves died in the group receiving no antibiotic treatments, and one calf died in the group receiving only the subtherapeutic treatment . There were no differences in postchallenge body temperatures or body weight changes between subtherapeutic and nonsubtherapeutic groups of calves . The conclusion was that the subtherapeutic dosing of chlortetracycline did not affect the therapeutic treatment effects of oxytetracycline after a Salmonella typhimurium challenge.

Mutat Res, 1981 Mar, 88(3), 255 - 72
The mutagenicity of diesel-exhaust particle extracts collected under smog-chamber conditions using the Salmonella typhimurium test system; Claxton LD et al.; This study was designed to detect the effect that different environmental conditions have upon diesel-exhaust organics . In this study, diesel exhaust was injected into the Calspan smog chamber under different conditions, and the resulting particles were collected upon Pallflex glass-fiber filters . After extraction from the particles with methylene chloride, the organics were solvent exchanged to dimethyl sulfoxide and tested in the Salmonella typhimurium plate-incorporation test . Results demonstrate that the irradiation of propylene, SO2, NO and NO2 produces ozone and a mutagenic moiety . Unless another mitigating factor (e.g., ozone) was present or formed, irradiation did not alter the mutagenic response of the organics . The production or injection of ozone into chamber tended to reduce the mutagenic response of the collected organics . In summary, this study demonstrates that ambient conditions can alter the mutagenic response of diesel-exhaust organics.

Mutat Res, 1981 Mar, 81(1), 11 - 9
Mutagenicity of structurally related oxiranes: derivatives of benzene and its hydrogenated congeners; Jung R et al.; The mutagenicities of 17 closely related oxiranes were determined in 4 tester strains (Salmonella typhimurium TA98, TA100, TA1535, TA1537) . The test compounds comprised all possible oxides of benzene and its partially hydrogenated congeners . In TA100 and TA1535, 12 of the tested oxiranes were weak to moderate mutagens . 4 of these were also active in TA98 . No mutagenicity was observed with the remaining 5 compounds in any of the 4 strains . The presence of a double bond in formal conjugation with the epoxide ring increased the mutagenicity relative to that of the saturated oxirane . Interestingly, additional epoxide rings within the same molecule did not markedly increase the mutagenic activity, and for the oxiranes that are not activated by a double bond, the relationship between mutagenic activity and the number of epoxide rings in the molecule was even inverse . The influence of bromo and hydroxyl substitution on oxirane mutagenicity is discussed . Most notably, a compound having a 4-hydroxyl group in syn position to a 1,2-epoxide ring fused to the cyclohexane ring, a structure which has been suggested to increase the electrophilic reactivity of dihydrodiol epoxides through hydrogen bonding, was almost inactive.

Mutat Res, 1981 Mar, 81(1), 1 - 10
Activation of phenanthrene to mutagenic metabolites and evidence for at least two different activation pathways; Oesch F et al.; Phenanthrene, generally considered to be a non-carcinogen, was converted by mammalian tissue preparations to products that were mutagenic for Salmonella typhimurium TA100 and TA1537 . In TA100 the mutagenic response was highly dependent on the activation system used . High amounts of 9000 x g supernatant fraction from the liver of rats induced by Aroclor 1254 were required . Equivalent amounts of microsomal or cytosolic fraction alone did not activate phenanthrene to an observable extent . Furthermore, this activation was only observed when the rats had been treated with Aroclor . Liver preparations from control rats and from rats treated with phenobarbital, beta-naphthoflavone, a mixture of both, and transstilbene oxide failed to activate phenanthrene to mutagens for TA100 . Interestingly, liver microsomes and 9000 x g supernatant fractions of Aroclor-treated mice also failed significantly to activate phenanthrene to mutagens for this strain . Addition of pure epoxide hydrolase to the S9 mix had no influence on this activation . Glutathione (GSH) decreased the mutagenicity, but uridine diphosphate glucuronic acid (UDPGA) had only minor effects . An adenosine-3'-phosphate-5'-sulfate phosphate (PAPS) generating system, however, increased the number of his+ revertants from TA100 (2.7-fold) . TA1537 was reverted by mutagens produced from phenanthrene by liver microsomes or 9000 x g supernatant fraction, when the microsomal epoxide hydrolase was inhibited by 1,1,1-trichloropropene oxide . This activation pathway exists in Aroclor-treated rats and mice . The results show that at least 2 different pathways for metabolic activation of phenanthrene exist which were observed in 2 differentially sensitive tester strains and distinguished by their different metabolic requirements . Furthermore, the study shows that earlier suggestions do not hold that equivalent results can be obtained by inducing animals with a combination of phenobarbital and beta-naphthoflavone instead of the environmentally persistent Aroclor 1254 . Moreover, the study provides a striking example that the use of 9000 x g supernatant in amounts corresponding to standard practice but sub-optimal for a particular compound only impede the detection of a weak mutagen and that the rapid inactivation of active metabolites by inactivating enzymes may be responsible for negative results in mutagenicity testing.

J Infect Dis, 1981 Mar, 143(3), 465 - 9
Virulence in mice of epidemic strains of Salmonella typhimurium isolated from children; Peluffo CA et al.; The virulence of 30 multiresistant strains of Salmonella typhimurium, which produced nine severe outbreaks in children's hospitals, was tested in mice . The arithmetic mean of the 50% lethal dose (LD50) for mice was 1.37 x 10(7) colony-forming units (cfu) compared with a mean LD50 of 2.65 x 10(5) cfu for 18 normal strains (P less than 0.005) . Thirteen of the epidemic strains had an LD50 of greater than 10(7) cfu and on the average were 80 times less virulent than strain CDC 9, which has been kept in the laboratory for greater than 40 years . The unexpected results show that apparently the factors determining virulence for children are not the same as those for mice, and they raise doubts about the validity of using mice to study the salmonella host-parasite relationship in humans . Genetic material carried by the transfer factor may be responsible for the altered virulence of the epidemic strains.

South Med J, 1981 Mar, 74(3), 382 - 3
Splenic abscess due to Salmonella typhimurium bacteremia; Rodan BA et al.; We have described a case of splenic abscess due to Salmonella typhimurium bacteremia . We believe abdominal roentgenograms and computed tomography are most effective in the preoperative evaluation of splenic abscess . Salmonella infections should be considered in the differential diagnosis of splenic abscess.

Chem Biol Interact, 1981 Mar 1, 34(2), 129 - 43
The metabolism of drugs and carcinogens in isolated subcellular fractions of Drosophila melanogaster . I . Activation of vinyl chloride, 2-aminoanthracene and benzo{a}pyrene as measured by mutagenic effects in Salmonella typhimurium; Hallstrom I et al.; The capacity of microsomal fractions from different Drosophila strains to activate three premutagens, 2-aminoanthracene (2-AA), vinyl chloride (VCM) and benzo{a}pyrene (BP) was investigated, using Salmonella typhimurium as the indicator organism . A significant increase in the mutation response in the Salmonella test system was obtained with all three substances in the presence of a metabolizing system (S9) from Drosophila larvae . 2-AA was converted to highly mutagenic metabolite(s) by the Drosophila S9 and the mutagenic effect was further increased after pretreatment with Aroclor 1254 (PCB) or beta-naphthoflavone (BNF) . BP had only marginal mutagenic effects, causing less than a 2-fold increase in the number of mutants over the control . The data indicate that the metabolic conversion of BP is different in the Drosophila as compared to the rat liver microsomal fraction . In accordance with mutagenic data on Drosophila in vivo, vinyl chloride was a fairly weak mutagen in this Drosophila/Salmonella in vitro system.

Mutat Res, 1981 Mar, 88(3), 241 - 54
Reverse mutation tests in Salmonella typhimurium and chromosomal aberration tests in mammalian cells in culture on fluorinated pyrimidine derivatives; Yajima N et al.; Reverse mutation (Ames) tests with Salmonella typhimurium TA98, TA100 and TA1537, and chromosomal aberration tests in vitro with a Chinese hamster fibroblast cell line (CHL), were carried out on fluorinated pyrimidine derivatives, such as 5-fluorouracil (5-FU), 1-(2-tetrahydrofuryl)-5-fluorouracil (FT), 5-fluorodeoxyuridine (FUdR), 1,3-bis(2-tetrahydrofuryl)-5-fluorouracil (FD-1) and a mixture of uracil and FT in the molar ratio 4 : 1 (UFT) (Fujii et al., 1978) . For comparison, similar tests were also carried out on 4 anti-metabolic agents, a metabolite of FD-1 and a component of UFT, such as cytosine-1-beta-D-arabinofuranoside (AraC), 6-mercaptopurine (6-MP), 6-thioguanine (6-TG), 8-azaguanine (8-AG), 3-(2-tetrahydrofuryl)-5-fluorouracil (3-FT) and uracil . The anti-bacterial action of 4 fluorinated pyrimidine derivatives such as 5-FU, FT, FD-1 and UFT to TA100 was tested under the condition that buffer, S9 mix, S9 and albumin were present . 6-MP was only positive in the Ames test with TA100 in the system without S9 mix, while all others failed to show mutagenic activity . On the other hand, all compounds tested, except uracil, induced chromosomal aberrations on CHL cells in the system without metabolic activation . FT was degraded by S9, but there was no significant difference in the killing activity of FT among with buffer, S9 mix and albumin . The killing activity of 5-FU was the strongest with buffer, and it was slightly binding to albumin . The killing activity of 5-FU was mostly decreased by S9 mix . FD-1 showed the strongest anti-bacterial action when S9 mix was present but it was degraded by S9 . UFT showed no anti-bacterial action in any conditions.

J Biol Chem, 1981 Feb 25, 256(4), 1935 - 9
The amino acid sequence of the histidine binding protein of Salmonella typhimurium; Hogg RW; The amino acid sequence of the histidine binding protein of Salmonella typhimurium was determined by automated sequence analysis of reduced and S-pyridylethylated histidine binding protein and fragments derived by chemical and enzymatic cleavage of the native protein . The fragments were the products of cleavage at methionine residues by cyanogen bromide, cleavage at tryptophan residues by 2-nitrophenylsulfenyl-3-methyl-3-bromo-3H-indole (BrNps-skatole), limited enzymatic digestion at arginine residues, and enzymatic digestion at Glu-X bonds by the Staphylococcus aureus V8 protease . The sequence of the COOH-terminal residues was determined using bovine carboxypeptidases A and B and amino acid analysis . The histidine binding protein was found to contain 238 amino acid residues and to have a molecular weight of 26,104 calculated from sequence.

Cancer Lett, 1981 Feb, 11(4), 295 - 302
Mutagenicity of paint removers containing dichloromethane; Nestmann ER et al.; A volatile component of commercially available paint and varnish removers was mutagenic in strains of Salmonella typhimurium TA1535, TA100 and TA98 . Levels of dichloromethane in exposure chambers were determined by gas chromatography and were related directly to mutational dose-effect curves observed for the products.

Toxicol Lett, 1981 Feb, 7(4-5), 311 - 9
Effect of several factors on the liver extract mediated mutagenicity of acrylonitrile and identification of four new in vitro metabolites; Duverger-Van Bogaert M et al.; The mutagenicity of acrylonitrile (ACN) was tested with Salmonella typhimurium TA1530 after a preincubation period of the chemical with a rat liver post-mitochondrial fraction in liquid medium . Several pretreatments were applied to the animals before the preparation of the liver fractions and different compounds added to the incubation mixture, which were shown to modify the liver mediated mutagenic activity of ACN . Four metabolites: cyanoacetic acid, cyanoethanol, acetic acid and glycolaldehyde were identified after incubation of ACN with the rat liver homogenate . From both sets of results, an in vitro metabolic scheme is proposed to ACN, which postulates the intermediate formation of a radical species and an epoxide.

Biochimie, 1981 Feb, 63(2), 113 - 7
Identification of the esterase peptide and its interaction with the cheZ peptide in bacterial sensing; Snyder MA et al.; Previous genetic evidence has indicated that the methylesterase activity of the chemotaxis system in Escherichia coli and Salmonella typhimurium resides with the cheB gene product, and that this protein may interact with the cheZ protein . In this article we report biochemical evidence for association of the cheB protein with esterase activity . We also show that while the cheZ gene product is not needed for catalysis, certain mutations in it can eliminate esterase activity in vitro, suggesting association of cheZ and cheB in an oligomeric protein complex.

Mutat Res, 1981 Feb, 88(2), 165 - 73
Mutagenicity of a series of hexacoordinate rhodium(III) compounds; Warren G et al.; 19 rhodium(III) compounds have been tested for genetic damaging capabilities using an Escherichia coli differential repair assay and for mutagenicity in the strains of Salmonella typhimurium . 10 of these were active in both assays . Presence of the plasmid pKM101 was required for mutagenicity in Salmonella . Both the composition of the ligands and the free-dimensional structures of the coordination complexes profoundly affect genetic activity . In general, the structure--activity relationships appear to favor complexes with (1) a +1 charge, (2) 2-relatively labile leaving groups with 4 more strongly bonded amine ligands, and (3) a relatively slow rate of exchange of the ligands which is characteristic of substitutionally inert coordination complexes.

Mutat Res, 1981 Feb, 88(2), 155 - 64
Studies on mutagenic constituents of apple brandy and various alcoholic beverages collected in western France, a high incidence area for oesophageal cancer; Loquet C et al.; Apple brandies, alcoholic spirits produced in the west of France, as well as other types of alcoholic beverage (rums, whiskies, armagnacs, cognacs) were tested for mutagenicity on Salmonella typhimurium TA98 and TA100 in the plate-incorporation assay in the presence or the absence of rat-liver S9 . The mutagenic activity of acrolein, gamma-butyrolactone, furfural and glycidol, chemicals usually found in these spirits, was assayed by the same procedure . Glycidol was mutagenic in TA1535 and TA100 without metabolic activation . We found higher and more frequently positive responses in home-made apple brandies than in the other beverages; therefore, further fractionation for isolation of the mutagenic compound(s) was performed by using spinning band column distillation, HPLC and gas chromatography . The fractions contained various types of mutagen, i.e., frameshift and/or base-pair substitution mutagens; some required metabolic activation and others did not in either the alcoholic, aqueous or non-volatile fractions . The results indicate that the high incidence of oesophageal cancer correlated with the alcoholic consumption in these areas might be at least partially attributable to the presence of mutagens in apple brandies.

Mutat Res, 1981 Feb, 88(2), 147 - 54
Mutagenicity of alcoholic beverages; Nagao M et al.; The mutagenicities of evaporated residues of alcoholic beverages were tested by the Ames method with the modification of pre-incubation, by using Salmonella typhimurium TA100 and TA98 . 12 of 13 brands of whisky were mutagenic to TA100 without S9 mix . Addition of S9 mix decreased or abolished these mutagenicities . 5 brands of brandy and 1 apple brandy were tested, and all showed a similar type of mutagenicity to that of whisky . A fraction of brand-K whisky, containing a major mutagen(s), eluted from XAD-2 column with water, gave 3800 revertants of TA100 per plate at a dose equivalent to 10 ml of whisky.

Can J Microbiol, 1981 Feb, 27(2), 226 - 37
Isolation and characterization of hemin-permeable, envelope-defective mutants of Salmonella typhimurium; Janzer JJ et al.; From Salmonella typhimurium LT2 hemA (delta-aminolevulinic acid requiring) 15 mutants were isolated which grew on the hydrophobic compound hemin . All had increased sensitivity to antibiotics such as vancomycin, bacitracin, novobiocin, erythromycin, rifampin, and oleandomycin, and were considered to be envelope mutants (Env-) . Half the mutants were rough , based on altered bacteriophage sensitivity and deoxycholate sensitivity, whereas the remainder were smooth; three of the smooth mutants were studied in detail . They gave increased uptake of gentian violet but no increase in leakage of a periplasmic protein, RNase I . The total membranes and fractions from sucrose gradient centrifugations representing inner and outer membranes of the wild type and three mutants were examined by sodium dodecyl sulfate - polyacrylamide gel electrophoresis (SDS-PAGE) and isoelectric focussing - PAGE (IEF-PAGE) . The major outer membrane proteins (molecular weights (MW)33 000, 34 000, 35 000, and 36 000) showed no or very little alterations in the Env- mutants . In SA1926 (env-52) one protein spot at MW 48 000, proven to be an outer membrane protein, was missing, whereas a new spot appeared nearby, and other proteins in this area of the gel were reduced . An Env+ transductant selected from this strain had the wild-type protein pattern restored . The two other Env- mutants had similar but not identical changes in protein composition.

J Bacteriol, 1981 Feb, 145(2), 984 - 9
Organization and regulation of the ilvGEDA operon in Salmonella typhimurium LT2; Berg CM et al.; A total of 102 isoleucine- and isoleucine-valine-requiring (ilv) mutants induced by insertion of the transposable element Tn10 have been classified to cistron by growth requirement, cross-feeding behavior, and enzyme assays . The mutations are in a polycistronic operon transcribed in the order ilvGEDA and in a monocistronic operon ilvC . Analysis of distal gene expression in these polar insertion mutants revealed the existence of two constitutive interval promoters, one preceding ilvE and the other preceding ilvD.

J Bacteriol, 1981 Feb, 145(2), 796 - 802
Regulation of derepressed synthesis of arylsulfatase by tyramine oxidase in Salmonella typhimurium; Murooka Y et al.; The participation of tyramine oxidase in the regulation of arylsulfatase synthesis in Salmonella typhimurium was studied . Arylsulfatase synthesis was repressed by inorganic sulfate, cysteine, methionine, or taurine . This repression was relieved by tyramine, octopamine, or dopamine, which induced tyramine oxidase synthesis, although the level of arylsulfatase activity was very low . The induction of tyramine oxidase and derepression of arylsulfatase by tyramine were strongly inhibited by glucose and ammonium chloride, and the repression of both enzymes was relieved by use of xylose as a carbon source after consumption of glucose or by use of tyramine as the sole source of nitrogen, irrespective of the carbon source used . The initial rates of tyramine uptake by cells grown with glucose and xylose were similar . Results with tyramine oxidase-constitutive mutants showed that constitutive expression of the tyramine oxidase gene resulted in derepression of arylsulfatase synthesis in the absence of tyramine . Thus, catabolite and ammonium repressions of arylsulfatase synthesis and the induction of the enzyme by tyramine seem to reflect the levels of tyramine oxidase synthesis . These results in S . typhimurium support our previous finding that the specific regulation system of arylsulfatase synthesis by tyramine oxidase is conserved in enteric bacteria.

J Bacteriol, 1981 Feb, 145(2), 1095 - 8
A Salmonella typhimurium mutant dependent upon carbamyl aspartate for resistance to 5-fluorouracil is specifically affected in ubiquinone biosynthesis; Zak VL et al.; The isolation and properties of a mutant dependent upon exogenous carbamyl aspartate for resistance to 5-fluorouracil are described . The mutant was deficient in the synthesis of ubiquinone and accumulated a quinone provisionally identified as the ubiquinone precursor 2-octaprenyl-3-methyl-6-methoxy-1,4-benzoquinone . The mutation resulted in an alteration in the regulation of synthesis of enzymes involved in de novo pyrimidine biosynthesis but did not establish a functional block in dihydroorotate dehydrogenase activity in vivo . Conditional resistance to 5-fluorouracil apparently occurred through an inhibition of the conversion of the analog to the nucleotide level.

J Bacteriol, 1981 Feb, 145(2), 1082 - 4
Passive rotation of flagella on paralyzed Salmonella typhimurium (mot) mutants by external rotatory driving force; Ishihara A et al.; Salmonella typhimurium mot mutants are unable to rotate their flagella . Dark-field light microscopy showed that the flagella could be rotated passively by an external rotatory driving force.

J Bacteriol, 1981 Feb, 145(2), 958 - 65
In vivo and in vitro chemotactic methylation in Bacillus subtilis; Ullah AH et al.; Two doublets of Bacillus subtilis membrane proteins with molecular weights of 69,000 and 71,000 and of 30,000 and 30,800, were labeled by C3H3 transfer in the absence of protein synthesis . In addition, there was intense methylation of several low-molecular-weight substances . Both doublets were missing in a chemotaxis mutant . The equivalent proteins in Escherichia coli and Salmonella typhimurium are believed to be the methyl-accepting chemotaxis proteins . The higher-molecular-weight doublet bands were increased in degree of methylation upon addition of attractant to the bacteria . A methyltransferase from B . subtilis that methylates the wild-type membrane significantly better than the mutant membrane, using S-adenosylmethionine, has been partly purified . The methylated product was alkali labile and is probably a gamma-glutamyl methyl ester, as in E . coli and S . typhimurium . Ca2+ ion inhibited the methyltransferase, with a Ki of about 80 nM . Analysis of the in vitro methylation product showed labeling of the 69,000-dalton methyl-accepting chemotaxis protein and a low-molecular-weight protein, using wild-type membrane . Labeling of the low-molecular-weight protein but not of the 69,000 dalton protein was observed when the mutant membrane was used . The chemotaxis mutant tumbled much longer than the wild type when diluted away from attractant.

J Appl Toxicol, 1981 Feb, 1(1), 11 - 4
Promutagen activation with mammalian and avian S9 liver microsomes; Tometsko AM et al.; Metabolic activation activity of Aroclor 1254 induced rat liver microsomes (S9) were compared with uninduced microsomes obtained from beef, pig, sheep and chicken liver . Using the Ames Salmonella typhimurium mutagenesis assay (strains TA98 and TA100), in conjunction with benzo(a)pyrene and 2-aminoanthracene, the highest promutagen activation levels were obtained with chicken liver S9 . The S9 from the other domestic animals gave results which were close to those of the induced rat S9 values . Enhanced promutagen activation activity was observed with chicken S9 following freeze drying and reconstitution of the S9 preparation.

Antimicrob Agents Chemother, 1981 Feb, 19(2), 328 - 31
Treatment of experimental Salmonella typhimurium infection with mecillinam and ampicillin; Butler T et al.; The activities of mecillinam and ampicillin, alone and in combination, were evaluated in mice infected with the LT-2 strain of Salmonella typhimurium . The minimal inhibitory concentrations of mecillinam and ampicillin for this strain were, respectively, 6.2 and 0.4 microgram/ml of culture medium . In vitro synergy was demonstrated . CF-1 mice inoculated intraperitoneally with 10(4) colony-forming units of the LT-2 strain were used in the therapeutic assessments . Treatment of subgroups with graded doses of the respective penicillins or their combination was initiated 24 h after inoculation and repeated at 6-h intervals for 5 consecutive days . Animals were observed during 21 days for mortality or sacrificed for quantitative cultures of spleen homogenates at the end of the treatment . Ampicillin in doses of greater than or equal to 0.03 mg and mecillinam in doses of greater than or equal to mg reduced mortality rates from 77% in the saline-treated controls to a range of 0 to 4% (P less than 0.05) . The same doses of antibiotics also extended the median times to death and lowered significantly the means of splenic bacterial counts . When both drugs were combined in doses that were partially effective or subinhibitory alone, no synergistic effects were observed . These results showed that mecillinam and ampicillin given alone were effective in treating S . typhimurium infection but that combinations of the two drugs were not synergistic in controlling the course of infections.

J Bacteriol, 1981 Feb, 145(2), 990 - 1001
Aerotaxis in Salmonella typhimurium: role of electron transport; Laszlo DJ et al.; Sensory transduction in aerotaxis required electron transport, in contrast to chemotaxis, which is independent of electron transport . Assays for aerotaxis were developed by employing spatial and temporal oxygen gradients imposed independently of respiration . By varying the step increase in oxygen concentration in the temporal assay, the dose-response relationship was obtained for aerotaxis in Salmonella typhimurium . A half-maximal response at 0.4 microM oxygen and inhibition by 5 mM KCN suggested that the "receptor" for aerotaxis is cytochrome o . The response was independent of adenosine triphosphate formation via oxidative phosphorylation but did correlate with changes in membrane potential monitored with the fluorescent cyanine dye diS-C3-(5) . Nitrate and fumarate, which are alternative electron acceptors for the respiratory chain in S . typhimurium, inhibited aerotaxis when nitrate reductase and fumarate reductase were induced . These results support the hypothesis that taxis to oxygen, nitrate, and fumarate is mediated by the electron transport system and by changes in the proton motive force . Aerotaxis was normal in Escherichia coli mutants that were defective in the tsr, tar, or trg genes; in S . typhimurium, oxygen did not stimulate methylation of the products of these genes . A cheC mutant which shows an inverse response to chemoattractants also gave an inverse response to oxygen . Therefore, aerotaxis is transduced by a distinct and unidentified signally protein but is focused into the common chemosensory pathway before the step involving the cheC product . When S . typhimurium became anaerobic, the decreased proton motive force from glycolysis supported slow swimming but not tumbling, indicating that a minimum proton motive force was required for tumbling . The bacteria rapidly adapted to the anaerobic condition and resumed tumbling after about 3 min . The adaptation period was much shorter when the bacteria had been previously grown anaerobically.

J Bacteriol, 1981 Feb, 145(2), 1106 - 9
Genetic dissection of catalytic activities of the Salmonella typhimurium mannitol enzyme II; Leonard JE et al.; Approximately 60 mutants of Salmonella typhimurium were isolated which exhibited altered levels of the activities of the mannitol enzyme II . The mutants were grouped into six distinct categories based on their mannitol fermentation, transport, chemotaxis, and phosphorylation activities.

Cancer Lett, 1981 Feb, 11(4), 265 - 75
Antimutagenic properties of liver homogenates, proteins and glutathione on diesel exhaust particulates; Wang YY et al.; Diesel exhaust particulates contain mutagens which are active in the Ames Salmonella typhimurium assay . The mutagens do not require liver enzymes for activation and, in fact, the addition of liver homogenates (S-9) to the Ames system decreases the mutagenicity of diesel exhaust samples . We have examined here the properties and components of S-9 that account for its antimutagenic effect . The antimutagenic effect of S-9 is not changed by heating S-9 in a boiling water bath for 5 min or by omission of the NADPH-generating system in the cofactor mixture . These experiments showed that the antimutagenic effect on S-9 is not enzymatic . The antimutagenicity of S-9 disappeared after the protein component of S-9 was removed by filtration . Exogenous albumin added to the Ames system mimicked the antimutagenic effect . Analysis of the albumin content of liver cytosol showed that 90% of the antimutagenic effect could be accounted for by the amount of albumin present . Glutathione added to diesel exhausts reduced mutagenicity, but the qualities of glutathione present in S-9 are too small to account for the antimutagenic effect of S-9 . We conclude that the antimutagenic effect of S-9 is non-enzymatic and is most likely the result of non-specific protein binding of mutagens to liver albumin . The antimutagenic effect of glutathione on diesel exhausts suggests that the mutagens present are electrophiles.

J Bacteriol, 1981 Feb, 145(2), 1002 - 9
Pyridine nucleotide cycle of Salmonella typhimurium: in vitro demonstration of nicotinamide adenine dinucleotide glycohydrolase, nicotinamide mononucleotide glycohydrolase, and nicotinamide adenine dinucleotide pyrophosphatase activities; Foster JW; Extracts of Salmonella typhimurium were chromatographed by using Sephadex G-150 to separate the various enzymes involved with pyridine nucleotide cycle metabolism . This procedure revealed a previously unsuspected nicotinamide adenine dinucleotide (NAD) glycohydrolase (EC 3.2.2.5) activity, which was not observed in crude extracts . In contrast to NAd glycohydrolase, NAD pyrophosphatase (EC 3.6.1.22) was readily measured in crude extracts . This enzyme possessed a native molecular weight of 120,000 . Other enzymes examined included nicotinamide mononucleotide (NMN) deamidase (EC 3.5.1.00), molecular weight of 43,000; NMN glycohydrolase (EC 3.2.2.14), molecular weight of 67,000; nicotinic acid phosphoribosyl transferase (EC 2.4.2.11), molecular weight of 47,000; and nicotinamide deamidase (EC 3.5.1.19), molecular weight of 35,000 . NMN deamidase and NMN glycohydrolase activities were both examined for end product repression by measuring their activities in crude extracts prepared from cells grown with and without 10(-5) M nicotinic acid . No repression was observed with either activity . Both activities were also examined for feedback inhibition by NAD, reduced NAD, and NADP . NMN deamidase was unaffected by any of the compounds tested . NMN glycohydrolase was greatly inhibited by NAD and reduced NAD, whereas NADP was much less effective . Inhibition of NMN glycohydrolase was found to level off at an NAD concentration of ca . 1 mN, the approximate intracellular concentration of NAD.

Chem Biol Interact, 1981 Feb, 34(1), 95 - 107
Some biochemical and pharmacological properties of an epoxide metabolite of alclofenac; Slack JA et al.; The properties of an epoxide metabolite of alclofenac have been investigated in a number of in vitro and in vivo tests . Alclofenac epoxide was shown to inhibit the activity of yeast alcohol dehydrogenase and form a conjugate with cysteine . The epoxide, but not alclofenac itself, showed mutagenic effects on strains of Salmonella typhimurium sensitive to alkylating agents, but had no effect on strains sensitive to intercalating agents . In addition the epoxide was active in a cell transformation assay using as a target Syrian hamster cells . No acute toxic reactions were observed in mice treated with alclofenac epoxide and the compound was devoid of analgesic and acute antiinflammatory activity . Alclofenac epoxide was found to be a sensitising agent in the guinea-pig when administered either by injection with complete Freud's adjuvant or topically as an ethanolic solution . It is postulated that the formation of the epoxide may explain some of the therapeutic and toxicological properties of alclofenac in man.

Nucleic Acids Res, 1981 Jan 24, 9(2), 375 - 87
Studies on the miscoding properties of 1,N6-ethenoadenine and 3,N4-ethenocytosine, DNA reaction products of vinyl chloride metabolites, during in vitro DNA synthesis; Barbin A et al.; 1,N6-Ethenoadenine (epsilon A) and 3,N4-ethenocytosine (epsilon C) are formed when electrophilic vinyl chloride (VC) metabolites, chloroethylene oxide (CEO) or chloroacetaldehyde (CAA) react with adenine and cytosine residues in DNA . They were assayed for their miscoding properties in an in vitro system using Escherichia coli DNA polymerase I and synthetic templates prepared by reaction of poly(dA) and poly(dC) with increasing concentrations of CEO or CAA . Following the introduction of etheno groups, an increasing inhibition of DNA synthesis was observed . dGMP was misincorporated on CAA- or CEO-treated poly(dA) templates and dTMP was misincorporated on CAA- or CEO-treated poly(dC) templates, suggesting that epsilon A and epsilon C may miscode . The error rates augmented with the extent of reaction of CEO or CAA with the templates . Base-pairing models are proposed for the epsilon A.G . and epsilon C.T pairs . The potentially miscoding properties of epsilon A and epsilon C may explain why metabolically-activated VC and its reactive metabolites specifically induce base-pair substitution mutations in Salmonella typhimurium . Promutagenic lesions may represent one of the initial steps in VC- or CEO-induced carcinogenesis.

J Biol Chem, 1981 Jan 10, 256(1), 382 - 9
Periplasmic phosphatases in Salmonella typhimurium LT2 . A biochemical, physiological, and partial genetic analysis of three nucleoside monophosphate dephosphorylating enzymes; Uerkvitz W et al.; Three periplasmic nucleoside monophosphate-splitting phosphatases from Salmonella typhimurium, 2':3'-cyclic nucleotide 2'-phosphodiesterase, nonspecific acid phosphatase I, and nonspecific acid phosphatase II, were separated by column chromatography . They are characterized with respect to their substrate specificities, Km values, pH optima, molecular weights, and sensitivity to inhibition by Pi and EDTA . Nonspecific acid phosphatase II has not been reported previously . The physiological roles of the various phosphatases are assessed by studies on mutant strains . Selection procedures were developed for the isolation of mutants defective in the synthesis of one or more of the phosphatase activities . Analysis of these mutant strains revealed that 2':3'-cyclic nucleotide 2'-phosphodiesterase is the major 3'-nucleotide dephosphorylating activity, and nonspecific acid phosphatase II is most active against 5'-nucleotides at concentrations below 1 mM . Triple mutants, lacking all periplasmic nucleotide-splitting activities, are viable . Regulatory mutants with elevated levels of nonspecific acid phosphatase II activity were isolated . The gene for 2':3'-cyclic nucleotide 2'-phosphodiesterase (pde) was located between purA and argI at 135 min on the S . typhimurium linkage map.

Toxicology, 1981-82, 22(4), 345 - 52
Mutagenicity and alpha-hydroxylation of N-nitrosopyrrolidine and N-nitrosopiperidine: a possible correlation; Gilbert PJ et al.; N-Nitrosopyrrolidine (NPyrr) and N-nitrosopiperidine (NPip) are carcinogenic and mutagenic cyclic nitrosamines . Their biotransformation by rat liver post-mitochondrial fraction into 1,4-butanediol and 1,5-pentanediol, respectively, is evaluated by determining these ultimate metabolites with a sensitive and suitable method . Their mutagenic activity towards the Salmonella typhimurium strain TA 1530 was simultaneously observed . A relationship exists between their metabolism and their mutagenicity . alpha-Hydroxylation is probably the critical metabolic metabolism of cyclic nitrosamines.

Microbiol Immunol, 1981, 25(9), 929 - 37
Mitogenicity and adjuvanticity of a marine bacterium, Vibrio anguillarum, in mice; Shimizu T et al.; The effects of whole cells of three different O serotypes of Vibrio anguillarum on the murine immune response were studied . The addition of different doses (1-100 microgram/ml) of V . anguillarum cells, as well as Salmonella typhimurium lipopolysaccharide, markedly increased the incorporation of {3H}thymidine into in vitro cultured spleen cells of C57BL/6 mice . All three serotype strains of V . anguillarum were able to induce the mitogenic effect at 10 microgram /ml and 100 microgram/ml, but serotype I strains were more potent than the others . Since pretreatment of spleen cells with rabbit anti-mouse thymocyte antiserum did not affect the mitogenic activity of V . anguillarum, Vibrio cells may be a B-lymphocyte mitogen . When sheep or horse erythrocytes and Vibrio cells were injected intraperitoneally into ddY mice, Vibrio cells exhibited an enhancing effect on antibody response in vivo, regardless of the different serotypes . Vibrio cells, when injected intraperitoneally into mice before the antigen, markedly suppressed the antibody response . Several days after the injection of Vibrio cells, these mice showed an enhanced carbon clearance activity . Acid phosphatase activity in their peritoneal cells was also augmented, suggesting that Vibrio cells activated macrophages in the mice.

Equine Vet J, 1981 Jan, 13(1), 53 - 5
Serum levels of amoxycillin following its oral administration to thoroughbred foals; Love DN et al.; Amoxycillin trihydrate was administered orally to 6 foals at dose rates of 13 mg/kg (low), 20 mg/kg (medium) and 30 mg/kg (high) and serum concentrations determined at intervals up to 8 h . Therapeutic serum levels of 1 microgram/ml persisted for 268 mins at a dose rate of 13 mg/kg, for 339 mins at 20 mg/kg and for 381 mins at 30 mg/kg . A 2 micrograms/ml serum level persisted for 198 mins at a dose rate of 13 mg/kg, for 268 mins at 20 mg/kg and for 311 mins at 30 mg/kg . To determine the spectra of its antibacterial activity, the minimum inhibitory concentrations of amoxycillin against 8 genera of common pathogenic bacteria in foals were examined . Of the bacteria tested, only Streptococcus equi, Strep zooepidemicus and Staphylococcus aureus (non-beta lactamase producing) would have been treated effectively with the serum levels which persisted in these foals . It is concluded that amoxycillin cannot be considered for broad spectrum use against pathogens likely to be encountered in the foal, but, because of its ease of administration orally, has a useful role in treating streptococcal infections and staphylococcal infections not caused by beta lactamase producers . If sensitivity testing of isolates is made, the drug may be useful also for treatment of some infections caused by the Gram-negative organisms Actinobacillus equuli and Salmonella typhimurium.

Adv Exp Med Biol, 1981, 136 Pt B, 1389 - 98
Threshold levels in toxicology: significance of inactivation mechanisms; Greim H et al.; Metabolic inactivation of chemicals may prevent toxic effects of reactive intermediates when present at low levels whereas inactivation may be overcome at high levels changing dose-effect relation . This is demonstrated in various in vitro test systems: a) Monooxygenase-mediated metabolism causes formation of reactive oxygen species which induce DNA repair in lymphoblastoid cells . DNA damage is suppressed in the presence of glutathione (GSH), catalase or superoxide dismutase . b) Chloroprene is mutagenic in Salmonella typhimurium but not carcinogenic, possibly due to inactivation by GSH-conjugations . c) Chlorodinitrobenzene is not mutagenic is Salmonella typhimurium in the presence of GSH . However it is increasingly mutagenic at concentrations exceeding those of the GSH . d) Suppression of glucuronidation and sulfation in isolated hepatocytes highly increases irreversible binding of naphthalene . It is concluded that information on the metabolism of chemicals is essential for interpretation of toxicity studies in animals and their relevance to man.

Microbios, 1981, 31(125-126), 161 - 9
Effect of growth medium on the lipid composition of log and stationary phase cultures of Salmonella typhimurium; El-Khani MA et al.; The lipid content of Salmonella typhimurium was not significantly influenced by the carbon source present in the growth medium . The principal fatty acid was palmitic acid . Significant levels of palmitoleic acid were found in log phase cultures, and this was replaced by a C17 delta fatty acid in the stationary phase . The other fatty acids present in significant quantities were lauric, myristic, cis-vaccenic and linoleic acids . The phospholipids present were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidic acid and phosphatidylserine.

Mol Gen Genet, 1981, 184(3), 564 - 6
The relationship of two invertible segments in bacteriophage Mu and Salmonella typhimurium DNA; Kamp D et al.; A Mu gin- mutant which lacks the function required for inversion of the G segment can be complemented by hybrid plasmids and phages carrying the invertible segment that controls flagellar phase variation in Salmonella typhimurium . This suggests that the same kind of site-specific recombination mechanism is responsible for these inversions . Based on the different features of the two invertible segments we propose a model for their evolutionary relationship.

Microbiol Immunol, 1981, 25(11), 1163 - 72
Biological and biochemical characterization of macrophage activating factor (MAF) in murine lymphocytes: role of mannopyranosyl residue of the MAF molecule in macrophage activation; Fukazawa Y et al.; Activation of macrophages with macrophage activating factor (MAF) was evaluated by measuring the intracellular killing activity of murine macrophages against Salmonella typhimurium . Concanavalin A (Con A)-induced MAF-rich fraction was obtained by a Sephadex G-100 column, which contained molecules ranging from 25,000 to 67,000 daltons . The intracellular killing ability of mouse peritoneal macrophages against S . typhimurium was found to be increased by 0.1 M D-mannose as well as by Con A-induced MAF-rich fraction . Both 0.1 M D-mannose and MAF exhibited a similar timing pattern for macrophage activation . The same concentration of D-glucose or L-rhamnose did not change bacterial uptake and intracellular killing by macrophages . Moreover, when MAF-rich fraction was applied to a Con A-Sepharose column, a fraction that was adsorbed on Con A and eluted with 0.1 M alpha-methyl D-mannoside exhibited MAF activity . These results suggest the possibility that mannopyranosyl residues in the MAF molecules play an important role as a ligand in macrophage activation.

Carcinogenesis, 1981, 2(12), 1339 - 44
A correlation between mutagenic and carcinogenic potencies in a diverse group of N-nitrosamines: determination of mutagenic activities of weakly mutagenic N-nitrosamines; Lee SY et al.; The mutagenic activities of a diverse group of N-nitrosamines were measured in Salmonella typhimurium TA 100 under conditions designed to maximize metabolism of N-nitrosamines and enhance their mutagenic effects . These conditions were also chosen since some of the carcinogens were previously reported to be non-mutagenic or of questionable mutagenic activity and some only became mutagenic after the bacteria were exposed to a "threshold does" of metabolites . The mutagenic potencies spanned a range of 10(5)-fold and correlated well with semiquantitative carcinogenic potencies taken from the literature . This correlation appears to be the strongest yet reported for any particular class of compounds . In addition, the mutagenic activities of a number of carcinogens, previously reported to be non-mutagenic, were determined . Among the structural features necessary for high mutagenic activity in this group of compounds was a potential, unsubstituted methylating or ethylating group . Substitution of alkyl, hydroxyl, methoxyl, and cyano moieties at the alpha or beta carbon of these groups reduced mutagenic activity.

Vopr Onkol, 1981, 27(12), 47 - 51
{Metabolic activation and the mutagenic properties of carcinogenic N-nitramines in a liquid incubation test}; Khudolei VV et al.; The study established the mutagenicity of carcinogenic dimethylnitramine and nitromorpholine in a liquid-incubation system using Salmonella typhimurium TA 100 and TA 1530 as indicator, in the presence of hepatic postmitochondrial supernatant obtained from 1254 aroclor-treated rats, oxygen and NADP+--generating system . Synthesis of mutagenic metabolites of nitramines was in correlation with the level of N-dimethylase activity . Ascorbic acid and disulfiram efficiently inhibited intramune-induced mutagenesis . Metabolic activation of nitramines involves (a) conversion of nitramines to nitrosoamines due to reduction of a nitro group, (b) hydroxylation by means of multi-function oxydases, and (c) heterolysis resulting in the formation of an end metabolite which is actually responsible for carcinogenicity and mutagenicity.

Carcinogenesis, 1981, 2(11), 1147 - 9
Effect of methyl substitution on mutagenicity of 2-amino-3-methylimidazo{4,5-f}quinoline, isolated from broiled sardine; Nagao M et al.; 2-Amino-3-methylimidazo{4,5-f}quinoline {I} is a potent mutagen isolated from broiled sun-dried sardine . {I} and its seven of derivatives, (two isomers, one demethylated derivative and four methyl-substituted derivatives), were tested for mutagenicity on Salmonella typhimurium TA98 and TA100 in the presence of S9 mix . 2-Amino-1,4-dimethylimidazo{4,5-f}quinoline was the strongest mutagen of these 8 compounds on TA98, giving 159,000 revertants/nmol (750,000 revertants/micrograms) . The demethylated derivative, 2-aminoimidazo{4,5-f}-quinoline, had very weak mutagenicity, inducing only 55 revertants/nmol (200 revertants/micrograms) . Compounds having a methyl group at position N-1 or N-3 of 2-aminoimidazo{4,5}f}quinoline were strong mutagens . The 1,5-dimethy-derivative was more mutagenic than 3,5-dimethyl-derivative . Introduction of a methyl group at position 4 and position 5 enhanced and reduced the mutagenicity, respectively . All the compounds tested were more mutagenic to TA98 than to TA100, but their relative orders of mutgenicity with TA98 and TA100 were the same.

Arzneimittelforschung, 1981, 31(10a), 1838 - 40
Bacterial mutation test on plafibride; Richold M et al.; N-2-(p-Chlorophenoxy)-isobutyryl-N'-morpholinomethylurea (plafibride, ITA 104) was tested for mutagenic activity of the Ames Salmonella/mammalian microsome test . Salmonella typhimurium strains TA 1535, TA 1537, TA 1538, TA 98 and TA 100 were employed . Two of these strains (TA 1535 and TA 100) are sensitive to base pair substitution mutagens, whilst the remaining three are sensitive to frame-shift mutagens . No evidence of mutagenic activity of plafibride was observed either in the presence or absence of a liver microsomal supplement.

Acta Biol Med Ger, 1981, 40(3), 317 - 30
The primary immune response of brown trout (Salmo trutta) to cellular and soluble antigens: Enumeration of antibody-secreting and antigen-binding cells, and the production of antibody; Ingram GA et al.; Significantly increased numbers (P less than 0.01) of antigen-binding (ABC) and antibody-secreting cells (ASC) were stimulated, in the spleen and the anterior kidney (AK) of the brown trout (Salmo trutta), by a single intraperitoneal injection of Salmonella typhimurium lipopolysaccharide (LPS), keyhole limpet haemocyanin (KLH), sheep red blood cells (SRBC) or KLH- or LPS-coated SRBC . With the exception of the SRBC group, the spleens contained more AVC and ASC per 10(6) lymphoid cells than the AK . Fewer ASC were found when guinea pig complement was used than with salmon serum; with 3 exceptions the differences were significant . In both organs, ABC and ASC were detected between 2 and 4 days after injection and maxima were reached between day 14 and day 18 in most of the experimental groups . However, with fish immunised with SRBC, ABC and ASC first occurred on day 6 and peak counts were obtained on day 12 . In all groups the counts had returned to background levels by day 28 . The coupling of LPS or KLH tro SRBC, with one exception, significantly increased the numbers of ABC and ASC (p less than 0.02) compared to when uncoated SRBC, LPS or KLH were injected . There was no significant change when the ABC results for antigen-coated SRBC were compared to those obtained when LPS was injected by itself . Following antigenic stimulation there were significant increases (p less than 0.05) in most cases in both the spleen and the AK to body weight ratios . There were significant differences in both the spleen and the AK to bodyweight ratios . There were significant differences (p less than 0.001) between KLH and KLH-SRBC (spleen and AK), LPS and LPS-SRBC (spleen and AK) and SRBC and LPS-SRBC (AK alone) . Antibodies were detected 2 to 8 days after sensitised cells were first found and reached maxima 5 to 16 days after the cellular responses . The titres obtained with experimental sera were significantly different (p less than 0.001) compared to the appropriate control groups.

Mol Gen Genet, 1981, 182(3), 422 - 5
The muc+ gene of plasmid pKM101 prevents respiration shutoff in far ultraviolet-irradiated Salmonella typhimurium; Swenson PA; The plasmid PKM101 is known to protect Escherichia coli and Salmonella typhimurium against killing by far UV irradiation and to enhance UV-induced mutagenesis . The muc+ gene of the plasmid is responsible for both of these effects . This paper shows that respiration of S . typhimurium shuts off about an hour after UV irradiation and that pKM101 prevents the shutoff . Plasmids which contained Tn5 translocatable elements, either in (and having produced a muc mutation) or flanking the muc+ gene, have been introduced into S . typhimurium . The muc mutant plasmid, which does not protect its host against UV killing and does not enhance UV induced mutagenesis, also does not protect against UV induced respiration shutoff . Likewise, plasmids in which the Tn5 translocatable elements flank the muc+ gene protect against shutoff of respiration . Thus the muc+ gene of pKM101 is responsible for protection against UV induced shutoff of respiration in S . typhimurium.

Carcinogenesis, 1981, 2(10), 991 - 7
Investigations on the mutagenicity of primary and secondary alpha-acetoxynitrosamines with Salmonella typhimurium: activation and deactivation of structurally related compounds by S-9; Pool BL et al.; alpha-Acetoxynitrosamines may serve as model compounds to study mechanisms of action of N-nitrosamines . They are readily cleaved through hydrolysis, or by esterases, to yield the same ultimate, reactive species presumably also arising after metabolic activation of N-nitrosamines, Structure-activity investigations on alpha-acetoxynitrosamines promise to aid in elucidating mechanisms involved during the activation of N-nitrosamines . A series of alpha-acetoxyalkynitrosamines was therefore tested for mutagenicity with Salmonella typhimurium TA 1535 . The compounds were readily cleaved, by hydrolysis, to mutagenic intermediates . When comparing compounds according to their proposed alkylating properties, unstable secondary alpha-acetates were considerably more mutagenic than the corresponding relatively stable primary alpha-acetates . Addition of S-9 mix caused both activation as well as deactivation in an unexpected structure-related pattern . This was so because an exactly opposite influence of S-9 components on the mutagenicity was observed for each pair of primary and secondary compounds containing the same alkylating spices . Furthermore, pairs of compounds with both methylating and ethylating properties were differently influenced by S-9 addition than those with propylating or butylating effects . This clearly demonstrates how different chemical properties of intermediate forms may strongly influence the biological activity of otherwise quite similar compounds.

Carcinogenesis, 1981, 2(10), 1057 - 61
Ethanol- or acetone-pretreatment of mice strongly enhances the bacterial mutagenicity of dimethylnitrosamine in assays mediated by liver subcellular fraction, but not in host-mediated assays; Glatt H et al.; The activation of dimethylnitrosamine (DMN) to a bacterial mutagen in liver subcellular fraction and in intrasanguinous host-mediated assays was studied, in particular the effect of pretreatment of the animals with ethanol or acetone . Salmonella typhimurium TA 92 was much more sensitive to DMN mutagenicity than TA 100 and TA 1535 or Escherichia coli WP2uvrA and was used for the main part of the study . Noteworthy, in part already known, features of the in vitro activation are the relatively low pH optimum (pH 6-6.4), the non-linear dose-mutagenic response-relationship and the relatively high doses of DMN required for activation with control preparations . Pretreatment of mice with ethanol or acetone greatly reduced the minimal mutagenically effective concentration of DMN in the in vitro assay . Pretreatment with Aroclor 1254, an inducer frequently used in mutagenicity research, showed little effect when used alone, but reduced the potentiation by acetone . The results of the host-mediated assays substantially differed from those of the in vitro activation assays (a) in the relatively low dose of DMN required for mutagenicity to occur and (b) in the lack of potentiation by acetone-or ethanol-pretreatment . Acetone even led to a marginal decrease in mutagenicity . As a possible explantation for this apparent discrepancy were assume that with the in vitro system the activity of the dilute metabolizing system is limiting for the activation of DMN and induction therefore will increase the mutagenicity, whereas in vivo DMN is quantitatively metabolized in both induced and non-induced animals . The results show that caution has to be taken in the interpretation from in vitro results to the in vivo situation . In particular our in vivo experiments do not support the hypothesis that the induction by ethanol of an activating system with a low Km (which would strongly activate traces of DMN ingested with many foods) is one of the reasons for the increased risk of liver tumors in alcoholics.

Carcinogenesis, 1981, 2(10), 1007 - 11
Metabolism of 1-nitropyrene and formation of DNA adducts in Salmonella typhimurium; Messier F et al.; 1-Nitropyrene is slowly reduced by intact cells of Salmonella typhimurium to yield 1-aminopyrene and N-acetyl-1-aminopyrene plus six unidentified minor products . When the bacteria are exposed to tritiated 1-nitropyrene, increasing amounts of radioactivity become bound to DNA as the nitropyrene is metabolized . Enzymatic hydrolysis of the labelled DNA yields low molecular weight labelled compounds which probably represent nucleoside adducts formed by the reaction of nitropyrene metabolites with DNA . Results with appropriate mutant strains indicate that bacterial nitroreductases are involved in activating nitropyrene to a reactive intermediate that binds to DNA and that nitropyrene adducts in DNA are subject to excision repair.

Environ Mutagen, 1981, 3(5), 519 - 30
Mutagenicity of municipal water obtained from an agricultural area; Heartlein MW et al.; We have studied the mutagenicity of the water from Lake Bloomington and of the tap water that is made from the lake water . The lake, which is the source of drinking water for Bloomington, Illinois (pop . 44,000), is surrounded by land that is farmed intensively--being mainly in maize and soybeans . Samples were collected monthly from May through October 1979 and concentrated 3,000X with XAD-2 resin . Nearly all of the lake and tap water concentrates were mutagenic in Salmonella typhimurium TA98 and TA100 in the presence of S-9 mix, and the May tap water concentrate was highly mutagenic . In addition, many of the concentrates were toxic to the bacteria in the absence of S-9 mix . Chemical analysis of the highly mutagenic tap water concentrate from May revealed the presence of a number of organic contaminants that were absent from control concentrates prepared from deionized and distilled treated-well water . In addition, unconcentrated lake and tap water were tested in a reverse-mutation test in maize (Zea mays); no mutagenicity was detected . This study indicates that the contamination of drinking water with agricultural and/or industrial chemicals may result in a potential health hazard.

Environ Mutagen, 1981, 3(5), 499 - 511
Structural basis of the mutagenicity in bacteria of nitrated naphthalene and derivatives; McCoy EC et al.; While 2-nitronaphthalene was a weak direct-acting base-substitution mutagen (1.4 revertants/nanomole) for Salmonella typhimurium, the analogous nitronaphthalic acid anhydride and imides were moderate frameshift mutagens (approximately 20 rev/nanomole in strain TA98) . Although imide derivatives are efficient DNA intercalators, mutagenicity data indicate that the bulk of the frameshift activity is derived from adduct formation between hydroxylamine intermediates and DNA . The low level of frameshift activity (approximately 8% of total) resulting from simple intercalation (measured in strain TA 1537) is not dependent upon reduction of the nitro function . Evidence is presented that suggests that the reduction of the nitro function to the corresponding hydroxylamine might not involve a free nitroso intermediate . The introduction of a second nitrofunction into nitronaphthalenes results in great positional effects of the various isomers on mutagenic activity and specificity.

Carcinogenesis, 1981, 2(8), 753 - 6
Fluoro-substituted N-nitrosamines . 1 . Inactivity of N-nitrosobis(2,2,2-trifluoroethyl)amine in carcinogenicity and mutagenicity tests; Preussmann R et al.; N-Nitroso-bis(2,2,2-trifluoroethyl)amine (hexafluorodiethylnitrosamine, 6-F-DEN) was synthesized as a derivative of diethylnitrosamine (DEN) with blocked terminal C-atoms to avoid metabolic oxidation at this site . Chronic oral administration of 6-F-DEN in drinking water did not induce tumours in Sprague-Dawley and in Fischer 344 rats . On the other hand, equimolar doses of DEN or even much lower ones are clearly carcinogenic . Mutagenicity tests using Salmonella typhimurium strains TA 1535 and TA 100 and metabolic activation by rat liver S-9 fraction were equally negative with 6-F-DEn . The substitution of fluorine in the beta-position of DEn apparently inhibits the alpha-oxidation considered necessary for carcinogenesis and mutagenesis of dialkylnitrosamines.

Ann Acad Med Singapore, 1981 Jan, 10(1), 34 - 9
Salmonella infections in Singapore; Lam S et al.; The incidence of typhoid and paratyphoid in Singapore from 1976 to 1979 is reviewed . Common Vi-phage types were A, B1, B2, D1, D2 and E1 . Most of the paratyphoid cases were imported but an outbreak of paratyphoid A started in 1979 for the first time in Singapore with a predominance of untypable phage type strains . Most of the strains of Salmonella typi and Salmonella paratyphi A & B were susceptible to antibiotics, except for 4 strains of S typhi isolated from imported cases . Infections caused by Salmonella typhimurium were most common in children under five . The strains were initially multiple-resistant to antibiotics, but gradually became more susceptible with decline in the number of cases . Among the salmonella serotypes isolated from clinical materials, Salmonella oranienburg showed multiple-resistance to antibiotics and started an outbreak among children in October 1978 . A total of 55 serotypes other than salmonella typhimurium was isolated between 1976 and 1979, with most of them susceptible to the antibiotics except triple-sulpha.

Microbiol Immunol, 1981, 25(5), 467 - 77
Immunopotentiating activity of whole cells and mini-cells of Salmonella typhimurium; Kurashige S et al.; Salmonella typhimurium strain 9 produces mini-cells during cell proliferation . Mini-cells are viable but cannot proliferate since they do not contain chromosomal DNA . Effects of whole cells and mini-cells of S . typhimurium on the immune responses were investigated, with the following results . Phagocytosis of peritoneal macrophages was enhanced by in vivo stimulation of both whole cells and mini-cells . Cellular immunity against L1210 cells (mouse leukemia cells) and Sarcoma 180 cells was also enhanced by both whole cells and mini-cells . Mini-cells slightly stimulated in vitro blast cell transformation of normal mouse lymphocytes . Whole cells of S . typhimurium induced antibody-forming cells to produce IgG of higher affinity but mini-cells did not . Mini-cells were not directly cytotoxic for normal lymphocytes or L1210 cells.

Environ Mutagen, 1981, 3(3), 205 - 9
A rapid and simple scheme for confirmation of Salmonella tester strain phenotype; Zeiger E et al.; A simple scheme has been developed for confirming the phenotype of the standard set of Salmonella typhimurium tester strains . This scheme employs a series of filter paper discs impregnated with diagnostic mutagens or bacterial toxins . Up to 6 diagnostic discs can be placed on a petri dish to test a single Salmonella strain . The Salmonellae are distinguished by their responses to ampicillin, crystal violet, nitrofuratoin, 9-aminoacridine, 4-nitro-o-phenylenediamine and sodium azide.

Carcinogenesis, 1981, 2(6), 559 - 65
Nitrated polycyclic aromatic hydrocarbons: potent bacterial mutagens and stimulators of DNA repair synthesis in cultured human cells; Campbell J et al.; Ten polycyclic aromatic hydrocarbons (PAHs), viz . anthracene pyrene, chrysene, perylene, fluoranthene, benzo{a}pyrene, benzo{a}pyrene, benz{a}anthracene, benzo{ghi}perylene, benzo{k}fluoranthene, have been nitrated using concentrated nitric acid and the crude nitrated mixture examined for biological activity . All the nitro PAHs examined were mutagenic to Salmonella typhimurium in the absence of a rat liver preparation . Addition of Aroclor-1254 induced liver had little effect on mutagenicity . Mutagenic potency differed for the various nitrated mixtures with nitrated pyrene and nitrated fluoranthene the most potent and nitrated anthracene the least potent . Both frame-shift and base-substitution mutations were induced by the nitrated PAHs . The nitrated PAHs were also able to induce DNA repair synthesis in cultured HeLa cells in the absence of liver, indicating that these cells have the necessary enzymes to activate nitro PAHs . Potency again varied from compound to compound with nitrated pyrene appearing to be the most active . Isolation of individual components from the crude nitrated mixtures has not been carried out in this study . In view of the possible wide-spread distribution of nitrated PAHs in the environment further work is required to assess the carcinogenic potency of these compounds which possibly pose a risk to man.

Carcinogenesis, 1981, 2(4), 269 - 75
A quantitative structure-activity analysis of the mutagenic and carcinogenic action of 43 structurally related heterocyclic compounds; Niculescu-Duvaz I et al.; Quantitative structure-activity relationships for the carcinogenicity and mutagenicity (against Salmonella typhimurium his- TA98, TA100 and TA1537 strains) of 43 structurally related heterocyclic compounds were formulated . The compounds investigated belong to the following two series of congeners : (a) benzo(thio)-pyranoquinolines and (b) benzo(thio)pyranoindoles . Their biologic activities were correlated with the following parameters : (a) the minimal topological difference (describing the fit of the considered molecules with a possible receptor, enzyme or DNA) and (b) the lipophilicity constants . The computed regression equations suggest that the structural requirements for carcinogenicity are different from those responsible for mutagenicity in the Ames test.

Basic Life Sci, 1981, 18, 533 - 42
The role of proline in osmoregulation in Salmonella typhimurium and Escherichia coli; Csonka LN; Previously we demonstrated that high intracellular proline levels conferred enhanced osmotolerance on Salmonella typhimurium . Stimulation of growth rate under conditions of osmotic inhibition could be brought about either by the addition of proline to the culture media or by mutations which result in proline over-production . Here, we report that there is a novel proline transport system in S . typhimurium which is activated in media of elevated osmolarity . this conclusion is based on the observation that putP- proP- double mutants, which lack both of the known proline permeases are resistant in minimal medium to the toxic proline analogues 3,4-dehydro-D, L-proline and L-azetidine-2-carboxylate . However, they regain sensitivity to the analogues in media of elevated osmolarity . Selecting resistance to 3,4-dehydro-D, L-proline in media of elevated osmolarity, we obtained mutants of putP- proP- strains which lack the osmotically activated proline permease . In these strains, exogenous proline could no longer alleviate osmotic inhibition.

Mol Gen Genet, 1981, 182(1), 82 - 6
Proline over-production results in enhanced osmotolerance in Salmonella typhimurium; Csonka LN; Mutants of S . typhimurium with enhanced osmotolerance were isolated . These mutants were obtained as strains which over-produced proline due to regulatory mutations affecting proline biosynthesis . The mutations are located on F'proBa and upon transfer to other S . typhimurium strains, they confer enhanced osmotolerance on the recipients . The osmotolerant mutants not only have higher intracellular proline levels than the osmosensitive parental strain, but the proline levels in the osmotolerant mutants are regulated such that they increase in response to osmotic stress . Possibly reasons why elevated proline levels lead to enhanced osmotolerance are discussed.

Environ Mutagen, 1981, 3(4), 453 - 65
An examination of the quantitative suspension assay for mutagenesis with strains of Salmonella typhimurium; Thompson ED et al.; The effects of cell toxicity on the mutagenic response obtained in a quantitative suspension assay using the strains of Salmonella typhimurium developed by Ames et al {Mutat Res 31:347--364, 1975} were examined . Cell toxicity was shown to produce false-positive results when the cells were plated immediately with trace amounts of histidine in the overlay agar . Replacement of the overlay agar with one lacking histidine produced false-negative results when the cells were plated immediately after exposure to a frame-shift-type mutagen . The inclusion of an overnight growth period in brain-heart infusion broth before plating the cells on minimal medium permitted incorporation of mutations into the genome and also yielded constant titers . The addition of the regrowth period is shown to be necessary for obtaining valid results in a suspension assay.

Environ Mutagen, 1981, 3(4), 401 - 19
Mutagenicities of 61 flavonoids and 11 related compounds; Nagao M et al.; The mutagenicities of 61 flavonoids (naturally occurring flavonoid aglycones and flavonal glycosides and synthetic flavonoids) and those of 11 compounds structurally related to flavonoids were tested with Salmonella typhimurium strains TA100 and TA98 . Among the 22 flavone derivatives tested, only wogonin was strongly mutagenic, while five derivatives, apigenin triacetate, acacetin, chrysoeriol, pedalitin, and pedalitin tetraacetate, were only weakly mutagenic . Two bisflavonyl derivatives, neither of which has a 3-hydroxyl group, were not mutagenic . Of the 16 flavonol derivatives tested, all except 3-hydroxyflavone and the tetra- and penta-methyl ethers of quercetin were mutagenic . Of the five flavanone derivatives tested, only 7,4-dihydroxyflavanone was mutagenic, showing weak activity . Of the four flavanolol derivatives tested, hydrorobinetin and taxifolin were weakly mutagenic . Of the six isoflavone derivatives tested, tectorigenin was weakly mutagenic . Of the 11 compounds in the miscellaneous group structurally related to flavonoids, only isoliquiritigenin was mutagenic, showing weak activity . For the emergence of strong mutagenicity, the double bond between positions 2 and 3 and the hydroxyl group at position 3 are required, except in wogonin, which does not have a hydroxyl group at position 3 but is strongly mutagenic to TA100 . The 3-O-acetyl ester of flavonol, quercetin, was mutagenic with S9 mix, but 3-O-methyl ethers were not . Six flavonol glycosides, three quercetin glycosides and three kaempferol glycosides were mutagenic after preincubation with "hesperidinase," a crude extract of Aspergillus niger . Of 66 flavonoid agylcones and compounds structurally related to flavonoids, quercetin was the strongest mutagen . The carcinogenicity of this compound should be clarified because it is ubiquitously found in vegetables.

Environ Mutagen, 1981, 3(1), 1 - 9
Use of rat/hamster S-9 mixture in the Ames mutagenicity assay; Weinstein D et al.; Based on the findings of Nagao et al {1978} that phenacetin is negative in the standard Ames test with Aroclor induced rat S-9 and positive with hamster S-9, the test was performed with a mixture of rat/hamster S-9 . Phenacetin was mutagenic with the mixture . The activity of the mixture was compared to the rat S-9 alone with low concentrations of 2-aminoanthracene (a strong promutagen for Salmonella typhimurium TA 1535, TA 100, TA 1537, and TA 98), nitrosopiperidine (a weak promutagen), and 1,2 epoxybutane (a weak, direct-acting mutagen) . Except for an increased mutagenic activation by the mixture with nitrosopiperidine the mixture was comparable to the rat S-9 alone, indicating that replacing rat S-9 with a rat/hamster S9 mixture in the standard Ames test could increase the sensitivity of the test without interfering with rat S-9 activity.

Can J Genet Cytol, 1981, 23(1), 17 - 25
Mutagenic evaluation of 1,1,2,3-tetrachloro-2-propene, a contaminant in pulp mill effluents, using a battery of in vitro mammalian and microbial tests; Ellenton JA et al.; The mutagenicity of 1,1,2,3-tetrachloro-2-propene (TCP), a component of chlorinated pulp mill effluents, was investigated with a battery of in vitro mammalian and microbial assays . In fluctuation tests, TCP showed potent mutagenic activity with Salmonella typhimurium strain TA1535 but only very weak activity with Escherichia coli WP2 . In Chinese hamster ovary (CHO) cells, TCP without metabolic activation induced chromosome aberrations . This activity was enhanced by the addition of Aroclor 1254-induced rat liver preparation (S9) . Endoreduplication was also induced by TCP in the presence of S9 . Without activation, TCP caused an increase in the number of sister chromatid exchanges (SCEs), however this increase was eliminated by S9 . TCP did not cause DNA damage in CHO cells as measured by alkaline sucrose gradient sedimentation either with or without metabolic activation.

Genetika, 1981, 17(1), 60 - 5
{Lethal and mutagenic action of UV light on salmonellae carrying wild or mutant alleles of the Escherichia coli lexA-gene}; Andreeva IV et al.; To elucidate the reasons for the absence of UV-mutability in Salmonella typhimurium, the lexA gene of Escherichia coli has been transduced by phage P1 into S . typhimurium . The functioning of lexA+ allele of E . coli in the chromosome of Salmonella failed to cause UV-mutability of the hybrid . The transfer of pKM101 plasmid into the LexA+ hybrid mediates the expressed UV mutability and UV-protective plasmid effect . This plasmid harboured by the LexA hybrid fails to increase UV-resistance and mutability, thus showing the dependence of plasmid mediated effect on LexA+ phenotype.

Toxicol Lett, 1981 Jan, 7(3), 259 - 62
Mutagenicity and toxicity studies with high pressure nitrous oxide; Baden JM et al.; The mutagenic and toxic potential of nitrous oxide were assessed in vitro by microbial assay using two histidine dependent strains of Salmonella typhimurium, TA98 and TA100 . Bacteria on plates and in liquid suspension in the presence or absence of enzymes prepared from rat liver, were exposed in a pressure chamber to partial pressures of nitrous oxide ranging from 0.5 to 6 atmospheres . Nitrous oxide decreased viability of both strains of bacteria at 4 and 6 atmospheres but was not mutagenic at any pressure tested.

Toxicology, 1981, 19(1), 67 - 75
Metabolic activation of 2-aminofluorene by isolated rat liver cells through different pathways leading to hepatocellular DNA-repair and bacterial mutagenesis; Brouns RM et al.; The aromatic amine 2-aminofluorene (2-AF) is metabolised by isolated rat liver cells to reactive species, thereby causing mutagenic effects in Salmonella typhimurium TA 1538 and evoking DNA-excision repair within the liver cells . The pathway leading to the production of metabolites mutagenic in Salmonella is likely to proceed via direct N-hydroxylation of 2-AF to N-hydroxy-2-aminofluorene (N-OH-2-AF) . On the other hand, the formation of intermediates giving rise to hepatocellular DNA-repair is shown to depend upon N-acetylation of 2-AF to 2-acetylaminofluorene(2-AAF), whereas a subsequent conjugation reaction, most likely to be sulfate ester formation, is also essentially involved.

Mol Gen Genet, 1981, 181(1), 150 - 2
envB mutations confer UV-sensitivity to Salmonella typhimurium and UV-resistance to Escherichia coli; Anton DN; An envB mutation isolated in Salmonella typhimurium LT2 was transferred by conjugation to Escherichia coli K-12 . The mutation produced the same alterations in E . coli as in S . typhimurium concerning cell shape, sensitivity to drugs, autolysis, and fermentation of carbohydrates . However, although the mutation conferred sensitivity to UV irradiation in Salmonella, in E . coli it behaved as a genuine envB mutation producing resistance to UV inactivation . The fact that the mutation produced opposite effects in the survival of UV-irradiated S . typhimurium and E . coli discloses an intriguing difference between these closely related species.

J Clin Lab Immunol, 1981 Jan, 5(1), 37 - 40
Impaired bacterial binding to peritoneal exudate cells from mice with alloxan induced diabetes; Weir DM et al.; Mice made diabetic by treatment with alloxan showed increased susceptibility to intraperitoneal injection of a rough strain of Salmonella typhimurium (SL 1099) expressing glucose as the terminal sugar of its core lipopolysaccharide . Peritoneal exudate cells from mice with alloxan induced diabetes were compared with those from control mice for binding and uptake of S . typhimurium . Cells from the diabetic mice bound fewer bacteria than those of non-diabetic mice . The implications of these findings are considered in relation to bacterial pathogenicity in diabetes.

Int J Environ Anal Chem, 1981, 9(2), 93 - 144
The identification of polynuclear aromatic hydrocarbon (PAH) derivatives in mutagenic fractions of diesel particulate extracts; Schuetzle D et al.; The soluble organic fraction (SOF) of particulate matter from diesel exhaust (from point sources, ambient air, etc.) contains hundreds of organic constituents . Norman-phase high pressure liquid chromatography (HPLC) has been used to separate the SOF into subfractions suitable for subsequent chemical analysis and bioassays . These fractions consist of non-polar(PAH), moderately polar (transition) and highly polar constituents . The non-polar fractions have been well characterized and consist of PAH and aliphatic hydrocarbons . The specific compounds present in the transition and polar fractions are for the most part unknown . This analytical information has been difficult to obtain since these compounds are highly labile, polar, of low volatility and in very low concentrations when compared to the bulk of material found in the SOF . Mutagenicity tests using the Ames Salmonella typhimurium assay indicate that the transition fraction accounts for most of the mutagenicity when compared to the non-polar (PAH) and polar fractions . A variety of chromatographic and mass spectrometric techniques are described that have been used to determine the composition of the HPLC fractions . More than one hundred species have been identified in the transition fraction of diesel particulate matter using high resolution gas chromatography (HRGC)/high resolution mass spectrometry (HRMS), HPLC and direct-probe high resolution mass spectrometry . It has been found that the transition fraction contains mostly PAH derivatives consisting of hydroxy, ketone, quinone, carboxaldehyde, acid anhydride and dihydroxy derivatives of PAH . Three nitro-PAH species have been tentatively identified and 1-nitropyrene positively identified in the transition fraction . The 1-nitropyrene was found to account for approximately 45% and 30% of the direct-acting mutagenicity observed for the transition fraction and total extract, respectively . The HPLC separation procedure was shown to give better than 95% recovery of the mass and mutagenic activity . The problem of PAH oxidation during the analytical procedures and possible effect on bioassay results are discussed.

Infect Immun, 1981 Jan, 31(1), 33 - 41
Characterization of murine antibody response to Salmonella typhimurium by a class-specific solid-phase radioimmunoassay; Metcalf ES et al.; A heavy-chain class-specific, solid-phase radioimmunoassay was developed to characterize the murine antibody response to Salmonella typhimurium . The specificity of the assay was verified by quantitation of the extent of binding of anti-S . typhimurium antibodies to other bacterial genera and species and by cross-adsorption studies . The sensitivity of the procedure was also examined, and it was determined to be substantially more sensitive than either the passive hemagglutination or the whole-cell agglutination technique . The method was subsequently used to analyze th murine antibody response to S . typhimurium . Groups of mice were prebled and then immunized with live S . typhimurium via different routes . The animals were bled weekly for 12 weeks, and then sera were assayed for antibodies directed against whole bacteria or purified lipopolysaccharide . Anti-Salmonella antibodies of the immunoglobulin M class appeared in the serum approximately 2 to 3 weeks after immunization, and then immunoglobulin G anti-Salmonella antibodies appeared which constituted the major part of the long-term response . Immunoglobulin A was not a major component of the serum antibody response . The antibodies were primarily directed against the lipopolysaccharide determinants, but a small percentage of the response was directed against other cell surface components . Qualitatively and quantitatively similar anti-Salmonella antibody responses were observed in sera of outbred and inbred strains of mice.

Eur J Biochem, 1981, 114(1), 51 - 8
Competition between two pathways for sugar uptake by the phosphoenolpyruvate-dependent sugar phosphotransferase system in Salmonella typhimurium; Scholte BJ et al.; The interaction between the two pathways for glucose entry via the phosphoenolpyruvate:sugar phosphotransferase system, i.e . via enzyme II-A/II-B and enzymes II-BGlc/IIIGlc, was studied in Salmonella typhimurium . Thio-beta-D-glucoside and 5-thio-D-glucose were shown to be substrates of P-pyruvate:sugar phosphotransferase specific for enzyme II-BGlc both in intact cells and in toluene-treated cells of S . typhimurium . The activity of the II-A/II-B pathway was strongly inhibited by the presence of II-BGlc substrates . It is concluded that the two pathways compete for phosphoryl groups provided by P-pyruvate, and that under the conditions tested the flow of phosphoryl groups through enzyme I/HPr is the rate-limiting step in vivo of activity of the pathways studied . The results corroborate the proposed mechanism of the regulatory function of the P-pyruvate:sugar phosphotransferase system which predicts a net dephosphorylation of components of the P-pyruvate:sugar phosphotransferase in the presence of a substrate of P-pyruvate:sugar phosphotransferase.

Mutat Res, 1981 Jan, 88(1), 17 - 22
Mutagenicity in Salmonella typhimurium of some angelicin derivatives proposed as new monofunctional agents for the photochemotherapy of psoriasis; Venturini S et al.; A series of angelicin derivatives were tested for their mutagenic activity with and without near-ultraviolet irradiation (NUV) in Salmonella typhimurium strains . After irradiation with NUV, the tested compounds induced different numbers of revertants in strain TA100, indicating that the mutational events involved are base substitutions . In the dark, 3 chemicals behaved as frame-shift mutagens causing reversion in strain TA98.

Mutat Res, 1981 Jan, 80(1), 99 - 104
Effects of L-cysteine and O-acetyl-L-serine in the synthesis and mutagenicity of azide metabolite; Owais WM et al.; The ability of L-cysteine to inhibit azide-metabolite synthesis and mutagenicity is investigated in Salmonella typhimurium TA1530 and cys E6 strains . L-cysteine specifically inhibits the synthesis of the mutagenic azide metabolite as other compounds containing SH group did not affect the production of this metabolite . Azide mutagenicity is completely inhibited by L-cysteine at a concentration (5 mumoles/plate) where the metabolite mutagenicity was not affected . O-Acetyl-L-serine can reverse the L-cysteine mediated inhibition of the metabolite synthesis and thus mutagenicity in the same strains . These results suggest that O-acetyl-L-serine may be required to synthesize the azide metabolite or its precursor.

Mutat Res, 1981 Jan, 80(1), 9 - 14
Frameshift mutagenesis by ultraviolet light effects of broth and caffeine in the post-irradiation plating medium; MacPhee DG et al.; Ultraviolet-induced back mutation yields were studied in the frameshift strain of Salmonella typhimurium, LT2 hisC3076 . The numbers and frequencies per 10(8) survivors of small and large revertant colonies were found to be affected significantly by plating density, but it was possible to detect a considerable enhancement of mutation frequency when broth (2.5%, v/v) was present in the post-irradiation plating medium . Caffeine also significantly enhanced the yields of UV-induced frameshift mutations, but not of gamma-induced frameshifts, indicating that the UV-induced pre-mutational lesions which lead to frameshift mutations may be treated in a similar way by the excision-repair system to those which lead to base-pair substitutions.

Mutat Res, 1981 Jan, 80(1), 1 - 7
Co-mutagenic effect of norharman with N-nitrosamine derivatives; Wakabayashi K et al.; The mutagenicities of 14 nitrosamine compounds were tested on Salmonella typhimurium TA98 and TA100 in the presence of the co-mutagen norharman . N-Nitrosophenyl compounds, such as N,N-diphenylnitrosamine, N-methyl-N-phenylnitrosamine, N-ethyl-N-phenylnitrosamine and N-phenyl-N-benzylnitrosamine, were mutagenic when norharman was added to the incubation mixture, but not mutagenic in its absence . Norharman did not enhance the mutagenic activities of N-nitrosoaliphatic compounds.

J Bacteriol, 1981 Jan, 145(1), 657 - 60
Globomycin sensitivity of Escherichia coli and Salmonella typhimurium: effects of mutations affecting structures of murein lipoprotein; Lai JS et al.; The sensitivity of strains of Escherichia coli and Salmonella typhimurium to globomycin is increased in mutants defective in the lipopolysaccharide structure . E . coli mutants altered in the structures or biosynthesis of murein lipoprotein are more resistant to globomycin than the parental strains.

J Bacteriol, 1981 Jan, 145(1), 156 - 63
Ferric citrate transport in Escherichia coli requires outer membrane receptor protein fecA; Wagegg W et al.; Mutants of Escherichia coli K-12 AB2847 and of E . coli K-12 AN92 were isolated which were unable to grow on ferric citrate as the sole iron source . Of 22 mutants, 6 lacked an outer membrane protein, designated FecA protein, which was expressed by growing cells in the presence of 1 mM citrate . Outer membranes showed an enhanced binding of radioactive iron, supplied as a citrate complex, depending on the amount of FecA protein . The FecA protein was the most resistant of the proteins involved in ferric irion iron translocation across the outer membrane (FhuA = TonA, FepA, Cir, or 83K proteins) to the action of pronase P . It is also shown that previously isolated fec mutants (G . C . Woodrow et al., J . Bacteriol . 133:1524-1526, 1978) which are cotransducible with argF all lack the FecA protein . They were termed fecA to distinguish them from the other ferric citrate transport mutants, now designated fecB, which mapped in the same gene region at 7 min but were not cotransducible with ArgF . E . coli W83-24 and Salmonella typhimurium, which are devoid of a citrate-dependent iron transport system, lacked the FecA protein . It is proposed that the FecA protein participates in the transport of ferric citrate.

J Natl Cancer Inst, 1981 Jan, 66(1), 33 - 6
Mutagenicity of extracts of pickled vegetables collected in Linhsien County, a high-incidence area for esophageal cancer in Northern China; Lu SH et al.; Extracts of pickled vegetables commonly consumed in Linhsien County, a high-incidence area for esophageal cancer in Northern China, were studied for mutagenicity . The liquid residue from ethereal extracts produced a dose-dependent increase of mutants in Salmonella typhimurium TA98 and TA100 strains; mutagenicity required the presence of a fortified liver microsomal activation system induced by Aroclor 1254 in adult male BD VI inbred rats . An amount of extract equivalent to 2.8 g fresh pickled vegetables produced sixfold (75 revertants/g) and twofold (45 revertants/g) increases in revertant frequencies in strains TA98 and TA100, respectively . Roussin's red methyl ester, a tetranitroso compound, {(NO)2Fe(CH3S)}2, not previously reported to occur in nature, was isolated and identified from the ethereal extracts . The synthetic compound was mutagenic in strain TA100 in the presence of a liver activation system, producing 25 revertants/mumol . Findings on the presence of mutagenic compounds in pickled vegetables were discussed in relation to their possible etiologic role in cancer of the esophagus in Linhsien County.

Arzneimittelforschung, 1981, 31(5a), 882 - 92
Toxicological evaluation of fluproquazone; Ruttimann G et al.; The toxicological characteristics of 4-(p-fluorophenyl-1-isopropyl-7-methyl-2-(1H)quinazolinone (fluproquazone), an analgesic with distinct antiinflammatory properties, were evaluated in acute and chronic toxicity studies as well as in reproduction toxicity, carcinogenicity and mutagenicity studies . The following overall results were obtained: The acute oral toxicity in mice, rats, and rabbits is of low order . In the chronic oral studies fluproquazone was generally well tolerated when given to rats and dogs for 13 weeks, to dogs and monkeys for 52 weeks, to mice for 78 weeks and to rats for 104 weeks . In particular, there was no indication of gastrointestinal irritations or lesions in any of these studies . The results of the studies in dogs and rats showed the major target organs for the toxicity of fluproquazone to be the liver and kidney, where mild, reversible changes were observed . These findings were considerably less severe than those found with several other antiphlogistic-analgesic compounds . In the reproduction toxicity studies, the only drug-related effects seen in experiments on female fertility or peri- and postnatal development in rats were a prolongation of pregnancy and an impairment of delivery leading to an increased perinatal mortality . These findings may be related to an inhibition of prostaglandin synthesis by fluproquazone . Similar effects are known to occur after administration of other inhibitors of prostaglandin synthesis . The oral teratological studies in rats and rabbits did not reveal any embryolethal or teratogenic effects . The drug had no mutagenic effects in either the micronucleus test and the dominant-lethal test using mice, or in the Ames-Test using Salmonella typhimurium . The carcinogenicity studies showed that fluproquazone has no carcinogenic potential in rats and mice.

Environ Mutagen, 1981, 3(5), 565 - 73
Radiosterilization of rat liver microsome containing postmitochondrial supernatant for mutation assays; Barfknecht TR et al.; Gamma-irradiation was effectively employed to sterilize rat liver postmitochondrial supernatant (PMS), which is required for the metabolic activation of soots and soot-derived polycyclic aromatic hydrocarbons to mutagens . When a known number of Bacillus subtilis spores were added to the PMS and gamma-irradiated at -80 degrees C, a 2-Mrad dose resulted in a 7.5 log kill of the spores . A dose of 3 Mrads was selected as a sufficient effective sterilizing dose and had no significant effect upon the ability of gamma-irradiated PMS to metabolically activate diesel soot and two diesel soot components, benzo(a)pyrene and fluoranthene to mutagens in a Salmonella typhimurium 8-azaguanine resistance forward mutation assay . Three Mrads of gamma-irradiation also had no effect upon the ability of PMS to activate benzo{a}pyrene to a mutagen for the human lymphoblasts . However, gamma-irradiation did reduce the ability of PMS to activate dimethylnitrosamine to a mutagen for S typhimurium.

Tsitol Genet, 1981, 15(3), 68 - 72
{Comparative study of the mutagenic activity of organophosphate insecticides on bacteria}; Shigaeva MKh et al.; Mutagenic activity of the organo-phosphorus insecticides, metaphos, phosphamide and carbophos, on indicator Salmonella typhimurium TA-1535 strain is shown which is determined without metabolic activation . It is established that all the three preparations induce direct mutations in Pseudomonas aeruginosa . The quantity of visible mutations increases with the prolongation of exposure time and the insecticide concentration . Metaphos and phosphamide induced auxotrophic mutations . Phosphamide has the highest mutagenic activity in the assays with bacterial systems.

Environ Mutagen, 1981, 3(2), 167 - 79
Stability of activating systems for in vitro mutagenesis assays: enzyme activity and activating ability following long-term storage at - 85 degrees C; Dent JG et al.; Activating systems for in vitro mutagenesis assays are commonly prepared and stored at low temperature until required . The objective of the studies reported here was to determine the long-term stability of activating systems stored at - 85 degrees C . A broad range of microsomal enzymes in the postmitochondrial supernatant (PMS) and the microsomal fraction of livers from Aroclor 1254 treated rats were studied in conjunction with the ability of these fractions to catalyse the conversion of dimethylnitrosamine (DMN) and benzo(a)pyrene (B(a)P) to products mutagenic to Chinese hamster ovary (CHO) cells and Salmonella typhimurium TM677 . Biphenyl-2- and biphenyl-4-hydroxylase showed a rapid decline in activity on storage, epoxide hydratase activity increased with storage and other enzyme activities studied were relatively stable for up to 32 weeks . No consistent trends in the ability of either the microsomes or the PMS to catalyze DMN or B(a)P induced mutation were observed for up to 12 weeks with CHO cells and 24 weeks with bacteria . It is concluded that low temperature storage of activating systems is an acceptable procedure . However, the results also indicate that certain enzyme activities change during storage, suggesting that aberrant results may be obtained when stored activating systems are used in in vitro tests to screen for mutagens.

Mol Gen Genet, 1981, 181(2), 268 - 72
Transfer of Salmonella typhimurium and Klebsiella pneumoniae genes in E . coli K12 by mini-muduction; Lefebvre N et al.; Using Mu/mini-Mu mixed lysates prepared by induction of Salmonella typhimurium and Klebsiella pneumoniae lysogenic for Mucts62 or the Mu-P1 hybrid, MPh1, and mini-Mu, Mu18A-1, we were able to transfer Arg and His genes from Klebsiella and Salmonella into E . coli K12.

J Bacteriol, 1981 Jan, 145(1), 299 - 305
Infection of Salmonella typhimurium with coliphage Mu d1 (Apr lac): construction of pyr::lac gene fusions; Csonka LN et al.; A procedure was developed for introducing the coliphage Mu d1 (Apr lac) into Salmonella typhimurium in order to construct gene fusions that place the structural genes of the lac operon under the control of the promoter-regulatory region of other genes . To introduce Mu d1 from Escherichia coli K-12 into S . typhimurium, which is normally not a host for Mu, we first constructed an E . coli double lysogen carrying the defective Mu d1 phage and a Mu-P1 hybrid helper phage (MuhP1) that confers the P1 host range . A lysate prepared from this strain was used to infect a P1-sensitive (i.e., galE), restriction-deficient, modification-proficient strain of S . typhimurium, and a double lysogen carrying Mu d1 and MuhP1 was isolated . Induction of the latter strain produced lysates capable of infecting and generating gene fusions in P1-sensitive strains of S . typhimurium . In this paper we describe the construction of pyr::lac fusions by this technique.

Mol Gen Genet, 1981, 181(2), 153 - 7
Cosmid cloning and transposon mutagenesis in Salmonella typhimurium using phage lambda vehicles; Palva ET et al.; We have constructed a strain of Salmonella typhimurium which contains the malB region from Escherichia coli and carries the bacteriophage lambda receptor protein in its outer membrane . Phage lambda adsorbs to this strain but cannot grow, thus providing a very useful system for transposon mutagenesis of S . typhimurium using lambda vehicles carrying transposons . This system can also be used for cosmid cloning.

Mol Gen Genet, 1981, 181(4), 448 - 53
Regulation of methyl beta-galactoside permease activity in pts and crr mutants of Salmonella typhimurium; Postma PW et al.; We have studied the regulation of the synthesis and activity of a major galactose transport system, that of methyl beta-galactoside (MglP), in mutants of Salmonella typhimurium . Two classes of mutation that result in a (partially) defective phosphoenolpyruvate: sugar phosphotransferase system (PTS) interfere with MglP synthesis . pts mutations, which eliminate the general proteins of the PTS Enzyme I and/or HPr and crr mutations, which result in a defective glucose-specific factor IIIGlc of the PTS, lead to a low MglP activity, as measured by methyl beta-galactoside transport . In both ptsH,I, and crr mutants the amount of galactose binding protein, one of the components of MglP, is only 5%-20% of that in wild-type cells, as measured with a specific antibody . We conclude that synthesis of MGlP is inhibited in pts and crr mutants . Once the transport system is synthesized, its transport activity is not sensitive to PTS sugars (i.e., no inducer exclusion occurs) . The defect in pts and crr mutants with respect to MGlP synthesis can be relieved in two ways: by externally added cyclic adenosine 3',5-monophosphate (cAMP) or by a mutation in the cAMP binding protein . The conclusion that MglP synthesis is dependent on cAMP is supported by the finding that its synthesis is also defective in mutants that lack adenylate cyclase . pts and crr mutations do not affect growth of S . typhimurium on galactose, however, since the synthesis and activity of the other major galactose transport system, the galactose permease (GalP), is not sensitive to these mutations . If the galactose permease is eliminated by mutation, growth of pts and crr mutants on low concentrations of galactose becomes very slow due to inhibited MglP synthesis . Residual growth observed at high galactose concentrations is the result of yet another transport system with low affinity for galactose.

Environ Mutagen, 1981, 3(2), 159 - 66
Synergistic, additive, and antagonistic mutagenic responses to binary mixtures of benzo(a)pyrene and benzo(e)pyrene as detected by strains TA98 and TA100 in the Salmonella/microsome assay; Hass BS et al.; Binary mixtures of benzo(a)pyrene (B(a)P) and benzo(e)pyrene (B(e)P) produce synergistic mutagenic (comutagenic) responses in Salmonella typhimurium strain TA98 (a frameshift detector) . The optimum enhancement (25 X) was found at B(a)P concentration of 0.3 microgram/plate and B(e)P concentration of 1.5 microgram/plate . The response of strain TA100 (mostly a base-substitution detector) is opposite that of TA98, showing antagonism and additivity in similar concentration ranges.

Zh Mikrobiol Epidemiol Immunobiol, 1981 Jan, (1), 40 - 3
{Behavior of cAMP-deficient mutants of Salmonella typhimurium in macrophage cultures}; Boichenko MN et al.; The behavior of c-AMP-deficient S . typhimurium mutants in the culture of peritoneal macrophages of white mice and the antibacterial activity of immune macrophages obtained from mice previously immunized with c-AMP-deficient S . typhimurium mutants were studied; c-AMP-deficient mutants were shown to have a lesser cytotoxic effect on macrophages than the initial virulent strain, while retaining their capacity for intracellular proliferation . Immune macrophages acquired the ability to withstand the cytotoxic action of the virulent strain.

J Bacteriol, 1981 Jan, 145(1), 664 - 7
Physical maps of Klebsiella aerogenes and Salmonella typhimurium hut genes; Blumenberg M et al.; The recognition sites for several restriction endonucleases were mapped within deoxyribonucleic acid coding for histidine utilization (hut) genes of Salmonella typhimurium and Klebsiella aerogenes . Deoxyribonucleic acid fragments containing the two hut promoters were identified by ribonucleic acid polymerase binding.

Z Allg Mikrobiol, 1981, 21(10), 715 - 28
A mutant of Salmonella typhimurium with an abnormal septation pattern associated with an inhibition of RNA synthesis; Herrero E et al.; A mutant strain of S . typhimurium that is disturbed in the regulation of cell division and macromolecular synthesis is described . The life cycle of the mutant can be divided into two discrete stages . When growing in rich medium at a low cell density, cell division is inhibited and the cells filament at the same time as the relative amount of RNA shows a continuous increase . However, at a certain stage, RNA synthesis stops and the filaments start to septate resulting in chain-formation . These chains can thereafter segregate into individual cells of unit cell length . The accumulation of RNA is rather due to a regulatory defect in th synthesis of ths stable RNA species than to a unusual stability of messenger RNA (mRNA) as the half life of mRNA was estimated to 2.3 minutes during the period of RNA accumulation . Latter inhibition of RNA synthesis affects only stable species of RNA . The ppGpp pools of the strain did not fluctuate during growth, showing that inhibition of RNA . The ppGpp pools of the strain did not fluctuate during growth, showing that inhibition of RNA synthesis is not correlated to changes in the level of ppGpp . Different treatments that reduce the level of transcription such as sublethal concentrations of rifampicin, shift-down or high concentrations of nalidixic acid, all induced cell division of filamentous cells, suggesting that there exists an intimate relationship between macromolecular synthesis and cell division . The behavior of this mutant its best with the proposed hypothesis that the biomass to volume ratio is of importance in the regulation of cell division in bacteria.

Arzneimittelforschung, 1981, 31(9), 1453 - 6
{Studies on the effects of a modified immunoglobulin and beta-lactam antibiotics in the experimental mouse septicemia (author's transl)}; Klesel N et al.; A new gamma-globulin preparation obtained by partial enzymatic cleavage of Fc-regions (Gamma-Venin), was effective in i.v . monotherapy in mice, infected with Streptococcus Aronson B, Pneumococcus mucosus and Salmonella typhimurium . These septicemias are characterized by protracted mortality . There was no measurable effect of the gamma-globulin preparation monotherapy in infections with acute course (Staphylococcus aureus 108, E . coli 078) . But in all five experimental septicemias the additional administration of the gamma-globulin formulation enhanced the effectivity of cefotaxime or ampicillin . In those animals both antibiotics were effective in lower doses than in animals having obtained only chemotherapy.

Environ Mutagen, 1981, 3(4), 421 - 7
Evidence for the existence of a family of bacterial nitroreductases capable of activating nitrated polycyclics to mutagens; McCoy EC et al.; A derivative of Salmonella typhimurium TA98 which does not respond to the potent mutagenicity of 1,8-dinitropyrene is described . This novel strain also shows a lack of response to the mutagenic action of 1,3-dinitropyrene and a greatly reduced response to 1,6-dinitropyrene and 1-nitropyrene . The responses to 1,3,6-trinitropyrene and 1,3,6,8-tetranitropyrene are affected to a much lesser extent . This strain (TA98/1,8DNP6) is fully sensitive to the mutagenicity of 4-nitroquinoline-1-oxide, niridazole, nitroacridine, and nonnitrated frameshift mutagens . This strain appears to be deficient in a nitroreductase which reduces nitrated pyrenes and possibly other nitrated polycyclic aromatic hydrocarbons to corresponding hydroxylamines, the penultimate mutagens.

J Cancer Res Clin Oncol, 1981, 99(1-2), 153 - 66
Metabolic studies on the possible mode of action of isoniazid tumorigenicity; Bhide SV et al.; Data on tumorigenicity and mutagenicity of INH show that INH is tumorigenic in mice but not in rats . The metabolic studies on the two species denote that rats are rapid inactivators whereas mice are slow inactivators of INH . Rats are also resistant to the immediate inhibitory effect of INH on DNA biosynthesis . Using Ames test it was observed that INH is mutagenic to salmonella typhimurium strains TA 100 and 1535 and this effect is abolished in presence off 59 mixture . In vivo and in vitro studies on INH interaction with macromolecules reveal that there is a greater interaction with RNA than with DNA and the site of interaction is the cytidine and deoxycytidine, respectively . A preliminary study is undertaken to see if healed TB cases have a higher risk for cancer . It is found that cancer incidence in this group is higher as compared to noncancer patients.

Environ Mutagen, 1981, 3(2), 109 - 21
Evaluation of the release of mutagens from diesel particles in the presence of physiological fluids; King LC et al.; The Ames Salmonella typhimurium plate incorporation assay was used to evaluate the mutagenicity of organics extracted from diesel exhaust particles . Organic solvents were more efficient than physiological fluids in removing mutagens from diesel particles, with dichloromethane extracts having the greatest mutagenic activity of the solvents examined . Serum and lung cytosol were more effective than acellular lung lavage fluid in releasing mutagenic activity from diesel particles . The mutagenic activity of diesel particle organics preextracted with dichloromethane is greatly reduced upon the addition of serum and lung cytosol to organics . Subsequently, incubation of protease with serum and lung cytosol-bound diesel organics increases the mutagenic activity . Fluorescence intensity was quantitated and found to correlate with mutagenic activity in the organic and serum extracts, but not the lung cytosol extracts . These studies suggest that substantial mutagenic activity is released from diesel particles upon incubation with serum and lung cytosol.

Mol Gen Genet, 1981, 184(2), 213 - 7
Complementation analysis of glnA-linked mutations which affect nitrogen fixation in Klebsiella pneumoniae; Espin G et al.; A number of mutants have been isolated which affect regulation of the nitrogen fixation (nif) gene cluster in Klebsiella pneumoniae and all of which are linked to glnA, the structural gene for glutamine synthetase (G.S.) . These mutants were classified on the basis of their G.S . and nitrogenase activities in conditions of nitrogen limitation and excess . The plasmid R68.45 was then used to generate a number of R-primes carrying the glnA region of the K . pneumoniae chromosome . One of these R-primes (pGE10) was subsequently used in complementation analysis and by isolation of transposon-induced insertion mutations in pGE10 we have demonstrated the existence of a gene, glnG, closely linked to glnA . Mutations in glnG have a similar phenotype to glnG mutants described in Escherichia coli (Pahel and Tyler 1979) and Salmonella typhimurium (Kustu et al . 1979) in that substantially reduce G.S . activity but are not glutamine auxotrophs . GlnG mutants have very low nitrogenase activity indicating that the glnG product may be involved regulation of the nif gene cluster in K . pneumoniae.

Mol Gen Genet, 1981, 181(3), 373 - 8
D-Amino acid dehydrogenase of Escherichia coli K12: positive selection of mutants defective in enzyme activity and localization of the structural gene; Wild J et al.; A method for the positive selection of dadA mutants defective in D-amino acid dehydrogenase has been devised . It consists in isolating mutants resistant to beta-chloro-D-alanine and screening for mutant colony color on a special agar medium . All 70 Escherichia coli K12 dadA mutants isolated either by this method or by other selection procedures map at a locus which is near to hemA and closely linked with dadR . Since some of the dadA mutants are thermosensitive in D-methionine utilization in vivo and have thermolabile D-amino acid dehydrogenase in vitro, it is proposed that the dadA gene codes for the enzyme structure . The broad substrate specificity, apparent membrane localization, inducibility by alanine, and repressibility by glucose strongly suggest that the D-amino acid dehydrogenase coded by the dadA gene is a species variant of the enzyme described under the same name in Salmonella typhimurium . It may be identical or homologous with the enzymes described under the names alaninase, D-alanine oxidase or D-alanine dehydrogenase in E . coli K12 or B.

Mol Gen Genet, 1981, 181(3), 338 - 45
Flurorcitrate resistant tricarboxylate transport mutants of Salmonella typhimurium; Somers JM et al.; Spontaneous and Tn10 induced fluorocitrate resistant mutants were isolated and characterized . These mutants were unable to grow on either cis-aconitate or DL-isocitrate but were still able to grow slowly on sodium citrate and normally on potassium or potassium-plus-sodium citrate . These mutants were defective in both citrate transport and citrate binding to priplasmic proteins . Tn10 insertion mutants were unable to produce immunologically detectable amounts of the citrate inducible periplasmic C protein previously shown to bind tricarboxylates . Using a series of tct::Tn10 directed Hfrs the tct locus was accurately positioned at 59 units between srlA and pheA, but was not cotransducible with either gene . In the absence of P22 mediated cotransduction with 16 adjacent chromosomal markers the srlA and tct loci were bridged by using a series of tct flanking Tn10 insertions, and by newly isolated and characterized nalB mutants . In addition the hyd and recA loci were located establishing the gene order in this region of the chromosome as: pheA tct nalB recA srlA hyd cys . Nitrosoguanidine derived tricarboxylate mutations (Imai 1975) were also mapped within the tct locus.

Med J Aust, 1980 Dec 13, 2(12), 674 - 5
Chronic pulmonary infection with Salmonella typhimurium; Reiss-Levy E et al.; The first report of a case of chronic sputum carriage of salmonella is presented . The patient was a 51-year-old male with pulmonary cavitation and mycetoma, who developed pulmonary infection with Salmonella typhimurium after rectal surgery, and subsequently has carried the salmonella in his sputum for 18 months to date.

Appl Environ Microbiol, 1980 Dec, 40(6), 1039 - 43
Effect of phenolic antioxidants on the mutagenicity of aflatoxin B1; Shelef LA et al.; The Ames assay employing Salmonella typhimurium TA100 and TA98 was used to investigate potential interactions between aflatoxin B1 (AFB1) and the phenolic antioxidants butylated hydroxytoluene, butylated hydroxyanisole, and propyl gallate . AFB1 doses were within the linear response range, and the antioxidants were used at levels of 0 to 50 micrograms per plate . All three antioxidants were nonmutagenic in either bacterial tester strain, with or without the hepatic S-9 enzyme preparation; toxic effects were observed at doses higher than 20 micrograms per plate . Butylated hydroxytoluene and butylated hydroxyanisole substantially increased AFB1-induced mutagenesis in the two tester strains with microsomal activation . The addition of 5 to 20 micrograms of butylated hydroxytoluene or hydroxyanisole to 5 to 20 ng of AFB1 per plate caused more than a twofold increase in the number of His+ revertants . Addition of propyl gallate resulted in only a moderate increase in the number of revertants . Whereas several anticarcinogenic and antimutagenic effects by phenolic antioxidants have been reported, particularly in studies with polycyclic aromatic hydrocarbons, the enhancement of mutagenic potency of AFB1 by these compounds suggests a specificity with respect to the chemical nature of AFB1.

Q Rev Biol, 1980 Dec, 55(4), 369 - 93
Scaffolding proteins and the genetic control of virus shell assembly; King J et al.; Historically a gap has existed between the study of the one-dimensional organization of hereditary information in genes, and of the three-dimensional organization of macromolecules in biological structures . In this article we describe progress in closing this gap through the genetic and biochemical analysis of the assembly of the icosahedral shells of spherical viruses, a class of subcellular structures whose subunit organization is relatively well understood . The genes specifying the proteins required for capsid assembly have been identified for many bacterial viruses . By using mutants defective in these genes, it has been possible to identify intermediates in shell morphogenesis and DNA condensation, and to unravel the different levels of the genetic control of macromolecular assembly processes . In general, a precursor shell or procapsid is first constructed, and the DNA is subsequently coiled within it . The construction of a closed shell poses as difficult a problem for a virus as for an architect . In the well-studied bacteriophage P22 of Salmonella typhimurium, the construction of the procapsid requires the interaction of about 200 molecules of the gene-8 scaffolding protein with 420 molecules of the gene-5 coat protein, forming a double-shelled structure with the scaffolding protein on the inside . Once completed, procapsids undergo substantial alteration in the course of encapsulating the viral DNA . In P22, the initiation of DNA packaging triggers the exit of all of the scaffolding molecules from within the capsid, probably through the coat-protein lattice . These released molecules are re-utilized, interacting with newly synthesized coat subunits to form further procapsids . Thus, the scaffolding protein functions catalytically in capsid assembly . All of the well-studied DNA phages require a scaffolding protein species for procapsid assembly, though their properties vary . Purified coat and scaffolding subunits by themselves show little tendency to polymerize, and are stable as monomers in solution . Upon mixing together under the appropriate conditions, however, the proteins copolymerize into double shells . Their interaction with each other appears to be critical for efficient assembly; this interaction probably occurs on the edges of growing shells, and not among subunits in solution . We have termed this kind of process, which we previously described in T4 tail morphogenesis, self-regulated assembly . The subunits are synthesized in a nonreactive form and are activated, not in solution, but upon incorporation into the growing substrate structure . A number of further transformations of the capsid subunits occur only within the organized structure and not as free subunits . Thus, aspects of the genetic information controlling the assembly process are not fully expressed at the level of the properties of protein subunits, but become manifest only through interactions with other proteins, or at a higher level, after completion of the correct organized structure.

J Gen Microbiol, 1980 Dec, 121(Pt . 2), 357 - 64
Genetic separation of purine transport from phosphoribosyltransferase activity in Salmonella typhimurium; Benson CE et al.; Two mutants of Salmonella typhimurium were isolated which differ from their respective parental strains in their growth responses to guanine and xanthine . Both mutants had purine phosphoribosyltransferase activities similar to their parental strains . One mutant, CB-3, had a lower guanine uptake rate apparently caused by a genetic lesion in a specific gene (designated guaP) responsible for facilitating the transport of guanine . This gene mapped at 3.5 min in the sequence azi-guaP-nadC . The second mutant, GP103, had a purine carrier molecule with altered specificity, as demonstrated by a competition between hypoxanthine and xanthine for uptake.

Can J Microbiol, 1980 Dec, 26(12), 1438 - 42
The role of delayed hypersensitivity in the enhancement of host resistance to infection; Hsu HS et al.; Swiss-Webster mice were vaccinated by the intraperitoneal route (i.p.) with Mycobacterium tuberculosis BCG and challenged i.p . 4-10 weeks later with 10(4) virulent Salmonella typhimurium in the presence or absence of purified derivative (PPD) of tuberculin . Normal control mice were similarly challenged . Such an infection was fatal to the normal mice within 12 days . BCG vaccination prolonged the survival time and protected about 36% of the salmonella-infected mice from death . In contrast, tuberculin sensitivity, elicited in the BCG-vaccinated mice, significantly increased the survival time and protected about 70% of the mice against an otherwise fatal challenge . When these experiments were repeated using an infective dose of 10(6) organisms, the protective effect of the tuberculin reaction became substantially reduced, but there remained a statistically significant improvement in the survival distribution of the challenged mice as compared with that among the BCG-vaccinated mice . The examination of peritoneal washings obtained from BCG-vaccinated mice stimulated with PPD showed that the enhanced resistance to salmonella infection was directly associated with a quantitatively increased influx of phagocytic leukocytes accumulating at the site of infection as a result of the elicitation of tuberculin sensitivity.

Mutat Res, 1980 Dec, 73(2), 227 - 35
Mutagenicity of trialkyltriazenes: mutagenic potency of alkyldiazonium ions, the putative ultimate carcinogens from dialkylnitrosamines; Sieh DH et al.; Although aryldialkyltriazenes have been known for many years and their mutagenic, carcinogenic and carcinostatic properties have been investigated, almost nothing is known of the related trialkyltriazenes . Our recently developed general preparative route to these substances has allowed the examination of the mutagenic properties of several representative examples of this class of compounds . This, 1-benzyl-3,3-dimethyl-, 3-benzyl-1,3-dimethyl, 3-benzyl-3-methyl-1-n-butyl- and 1,3-di-n-butyl-3-methyltriazenes are direct acting mutagens in the TA1535 strain of Salmonella typhimurium . The respective mutagenic potencies of these substances can be accounted for by the in situ generation of alkyldiazonium ions . These ions are considered to be strong candidates for the ultimate mutagens/carcinogens derived from some dialkylnitrosamines.

Mutat Res, 1980 Dec, 79(4), 345 - 50
Enhancement of sister-chromatid exchange in Chinese hamster ovary cells by nitrofurans; Shirai T et al.; The nitrofurans, N-{4-(5-nitro-2-furyl)-2-thiazolyl}formamide (FANFT), N-{4-(5-nitro-2-furyl)-2-thiazolyl}acetamide (NFTA), 2-amino-4-(5-nitro-2-furyl)thiazole (ANFT), 2-methyl-4-(5-nitro-2-furyl)thiazole (MNFT), 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (AF-2), nitrofurantoin, 5-nitro-2-furfurylidene diacetate and 5-nitro-2-furamidoxime were assayed for the enhancement of sister-chromatid exchange (SCE) in Chinese hamster ovary (CHO) cells and for the mutagenic activity in Salmonella typhimurium strain TA100 . All of the nitrofurans significantly increased the frequency of SCE in CHO cells, and they were mutagenic for Salmonella . The increases in the frequencies of SCE were well correlated with the mutagenic activities in Salmonella.

J Bacteriol, 1980 Dec, 144(3), 1068 - 75
Histidine starvation and adenosine 5'-triphosphate depletion in chemotaxis of Salmonella typhimurium; Galloway RJ et al.; Starvation for histidine prevented tumbling in Salmonella typhimurium hisF auxotrophs, including constantly tumbling strains with an additional mutation in cheB or cheZ . However, histidine-starved cheZs hisF strains were not defective in flagellar function or the tumbling mechanism since freshly starved auxotrophs tumbled in response to a variety of repellents . Tumbling in histidine-starved S . typhimurium could be restored in 13 s by addition of adenine or in 4 min by addition of histidine . Chloramphenicol did not prevent restoration of tumbling by these substances . Assays of adenosine 5'-triphosphate were performed based upon previous demonstration of adenine depletion in hisF auxotrophs starved for histidine . The adenosine 5'-triphosphate concentration dropped rapidly during the course of starvation, falling to less than 5% of the initial level as the cells ceased tumbling entirely . The change to smooth motility was prevented by 2-thiazolealanine, which inhibits phosphoribosyltransferase, thereby preventing adenine depletion during histidine starvation . These results suggest that an adenosine 5'-triphosphate deficiency was responsible for the change in tumbling frequency.

J Bacteriol, 1980 Dec, 144(3), 1043 - 7
Temperature-sensitive glutamate dehydrogenase mutants of Salmonella typhimurium; Dendinger SM et al.; Mutants of Salmonella typhimurium defective in glutamate dehydrogenase activity were isolated in parent strains lacking glutamate synthase activity by localizcd mutagenesis or by a general mutagenesis combined with a cycloserine enrichment for glutamate auxotrophs . Two mutants with temperature-sensitive phenotypes had glutamate dehydrogenase activities that were more thermolabile than that of an isogenic control strain . Eight other mutants had less than 10% of the wild-type glutamate dehydrogenase activity . All the mutations were cotransducible with a Tn10 element (zed-2:Tn10) located at approximately 23 U on the S . typhimurium linkage map . These data strongly indicate that this region contains the structural gene (gdhA) for glutamate dehydrogenase.

Cancer Res, 1980 Dec, 40(12), 4704 - 8
Mutagenicity of hydroxamic acids and the probable involvement of carbamoylation; Skipper PL et al.; A series of hydroxamic acids (aceto-, propiono-, benzo-, and p-nitrobenzo-) and seven derivatives of these were examined for biological activity using Salmonella typhimurium . Acylation to yield O-acetyl and O-benzoyl derivatives markedly enhanced toxic properties and was necessary for mutagenic activity for all but p-nitrobenzohydroxamic acid . The dose necessary to produce a minimum significant mutagenic response varied from 21 microM for O-benzoyl benzohydroxamate to 430 microM for O-acetyl acetohydroxamate . These two compounds were also tested with human lymphoblasts to which they were toxic at 100 microM but not mutagenic . O-Acetyl benzohydroxamate, a mutagen, was prepared wih a 14C label in the carbonyl carbon atom of the benzoyl group and was shown to form an adduct in vitro with DNA and polyguanylic acid . The level of binding was 1 mol of 14C per 5 X 10(4) mol of DNA phosphate and 1 mol of 14C per 10(5) mol of polyguanylic acid phosphate.

Cancer Res, 1980 Dec, 40(12), 4528 - 32
Identification of mutagenic dihydrodiols as metabolites of benzo(j)fluoranthene and benzo(k)fluoranthene; LaVoie EJ et al.; The metabolism of the environmental agents benzo(j)-fluoranthene and benzo(k)fluoranthene was investigated using supernatants from the livers of Aroclor 1254-pretreated rats, which are effective in activating benzo(j)fluoranthene and benzo(k)fluoranthene to metabolites mutagenic toward Salmonella typhimurium TA 100 . Six bands of metabolites of benzo(j)fluoranthene were separated by high-pressure liquid chromatography, and each band was tested for mutagenicity toward S . typhimurium TA 100 with activation . The major mutagenic band contained two dihydrodiols, one of which was identified as 9,10-dihydro-9, 10-dihydroxybenzo(j)fluoranthene by comparison to a synthetic reference standard . 9,10-Dihydro-9,10-dihydroxybenzo(j)fluoranthene was mutagenic toward S . typhimurium TA 100 with activation, presumably as a result of conversion to the corresponding dihydrodiol-epoxide . The major dihydrodiol metabolite of benzo(k)fluoranthene was identified, by comparison to a synthetic standard, as 8,9-dihydro-8,9-dihydroxybenzo(k)fluoranthene . This dihydrodiol, which could also be converted to a dihydrodiol-epoxide, was mutagenic toward S . typhimurium TA 100 with activation . The results of this study indicate that metabolism to dihydrodiols is one pathway in the activation of benzo(j)fluoranthene and benzo(k)fluoranthene to ultimate mutagens for S . typhimurium TA 100.

Methods Find Exp Clin Pharmacol, 1980 Dec, 2(6), 313 - 7
Recent advances in salmonellosis treatment based on in vitro susceptibilities; Paradelis AG et al.; Chloramphenicol-resistant strains of Salmonella typhi (MIC 60 micrograms/ml), chloramphenicol and ampicillin-resistant strains of Salmonella typhimurium as well as multiresistant strains of various salmonella serotypes were found to be very sensitive to cephradine (MIC 0.078-0.625 micrograms/ml) . Ten patients with Salmonella typhi bacteremia were successfully treated with cephradine; all the patients' strains were chloramphenicol-resistant . Cephradine appears to warrant further clinical trial for the treatment of salmonellosis.

Cancer Lett, 1980 Nov, 11(1), 51 - 6
Mutagenicity of some fluoro-derivatives of benzo{alpha}pyrene; Gairola C et al.; Benzo{alpha}pyrene (BP) and its 4 fluoroderivatives substituted at positions 7(BP-7F), 8(BP-8F), 9(BP-9F) and 10 (BP-10F) were mutagenic in strains TA98 and TA1538 of Salmonella typhimurium, when tested in the presence of liver S-9 or microsomes from Aroclor or 3MC-treated rats . While the presence of fluorine at position 10 resulted in some reduction in mutagenicity, several-fold increase in mutagenicity occurred when fluorine was substituted at position 8 . Our data suggests additional involvement of other metabolites in the mutagenicity of BP.

Mutat Res, 1980 Nov, 79(3), 223 - 30
The pH-dependent response of Salmonella typhimurium TA100 to mutagenic N-nitrosamines; Negishi T et al.; The mutagenicity of some N-nitrosodialkylamines, i.e . N-nitrosodimethylamine, N-nitrosodiethylamine, N-nitrosodi-n-butylamine, N-nitrosomorpholine and N-nitrosopyrrolidine, was assayed on Salmonella typhimurium TA100 by the pre-incubation method, and the effect of changing the pH of the pre-incubation mixture was examined . Markedly higher mutagenicities were observed when the pre-incubation of bacteria with nitrosamine and S9 mix was done at pH 5.2, compared with mutagenicities observable after the pre-incubations at conventional pH 7 . Pre-incubations at pH 6.2 resulted in responses of intermediate strength . With phenobarbital-induced rat S9, the ratios of mutagenic potency found by the pH 5.2 pre-incubation to that found by the pH 7.2 preincubation were 15-30 for N-nitrosodimethylamine, 5-10 for N-nitrosodiethylamine, 10-20 for N-nitrosodi-n-butylamine, 2-3 for N-nitrosomorpholine and 4-6 for N-nitrosopyrrolidine . The mutagenic potency of each nitrosamine varied with the change of S9 source . The S9 sources examined were PCB-induced rat and mouse livers, and uninduced rat and mouse livers . No exceptions were observed for these S9 preparations regarding the higher mutagenicity at pH 5 than at pH 7 . It is speculated that the higher mutagenicity observed by the pH 5 pre-incubation was due to the stability of the active intermediate, alpha-hydroxynitrosodialkylamines, in weakly acidic media.

Forensic Sci Int, 1980 Nov-Dec, 16(3), 283 - 7
A case of sudden cardiac death in connection with Salmonella typhimurium infection; Simonsen J et al.; A case of fatal myocarditis in a 24-year-old otherwise healthy man is described . It was possible to cultivate Salmonella typhimurium from the alimentary tract, the blood, the liver and skeletal muscles . The possibility of a solitary myocarditis with fatal outcome due to Salmonella typhimurium infection is discussed . Such a case seems not to have been mentioned previously in the literature . The problems concerning the statistical registration of such a death are briefly discussed.

Cancer Res, 1980 Nov, 40(11), 3940 - 4
Metabolic activation of cyclopenta(cd)pyrene to 3,4-epoxycyclopenta(cd)pyrene by rat liver microsomes; Gold A et al.; Cyclopenta(cd)pyrene (CPP), a polycyclic aromatic hydrocarbon without a bay region, is a potent bacterial mutagen . The experiments reported in this paper demonstrate that the major CPP metabolite generated by liver microsomes prepared from either phenobarbital or 3-methylcholanthrene pretreated rats is the optically active trans-3,4-dihydroxy-3,4-dihydrocyclopenta(cd)pyrene . Other experiments indicate that formation of the trans-3,4-dihydrodiol of CPP probably proceeds via enzymatic hydrolysis of 3,4-epoxycyclopenta(cd)pyrene by opening of the O--C(3) bond . (a) The racemic 3,4-epoxycyclopenta(cd)pyrene has been synthesized via the bromohydrin of CPP and shown to hydrolyze primarily to 3,4-dihydrocyclopenta(cd)pyrene-4-one and to mixtures of the trans- and cis-3,4-dihydrodiols . Detection of 3,4-dihydrocyclopenta(cd)pyrene-4-one as the major acid catalyzed rearrangement product indicates the opening of the epoxide at the C(3) position to yield a carbonium ion followed by an NIH shift . (b) The synthetic epoxide is potently mutagenic to bacteria with a similar spectrum of mutagenicity against Salmonella typhimurium strains carrying base-pair substitution or frameshift mutations as was seen with CPP in the presence of liver enzymes . These results indicate that 3,4-epoxycyclopenta(cd)pyrene is the major microsomal and mutagenic metabolite of CPP.

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