Salmonella typhimurium

Mutat Res, 1979 Jan, 66(1), 25 - 32
Comutagenic effects exerted by N-nitroso compounds; Guttenplan JB; Mutagenesis induced by dimethylnitrosamine (DMN) and N-methyl-N-nitrosourea (NMU) in Salmonella typhimurium TA100 and TA1530 is characterized by biphasic dose and time response curves . At low doses or short incubation times mutagenic response is minimal, but increases rapidly when an apparent threshold dose or threshold incubation time is exceeded . Bacteria pretreated with subthreshold doses of DMN or NMU were many times more sensitive to the mutagenic effects of methylating and ethylating N-nitroso compounds than were untreated bacteria . The growth phase of the bacteria had little effect on the percentage enhancement of mutagenesis caused by pretreatment with NMU although exponentially growing cells were more sensitive to mutagenesis induced by NMU or diethylnitrosamine . Mutagenesis induced by methylmethanesulfonate and N-propyl-N'-nitro-N-nitrosoguanidine was not significantly enhanced by pretreatment of bacteria with NMU or NEU suggesting that the former mutagens act by different mechanisms than NMU or NEU.

Mutat Res, 1979 Jan, 66(1), 1 - 7
Mutagenicity of aliphatic nitrosamines in Salmonella typhimurium; Rao TK et al.; 25 aliphatic nitrosamines were examined in the Ames assay for bacterial mutagens, using rat liver "S-9" for activation . Of them, 8 carcinogens were mutagenic and 5 non-carcinogens were not mutagenic . However, 2 compounds not carcinogenic in rats were mutagenic and 9 carcinogens were not mutagenic, including 6 that are liver carcinogens in rats.

Infect Immun, 1979 Jan, 23(1), 140 - 5
Importance of the intestinal inflammatory reaction in salmonella-mediated intestinal secretion; Giannella RA; The ability of Salmonella typhimurium to invade the intestinal epithelium is essential to the pathogenesis of salmonella-induced intestinal secretion . This invasion is accompanied by an intense acute inflammatory reaction . The present study tests the hypothesis that the acute inflammatory reaction may have a role in the pathogenesis of salmonella-induced secretion . Two groups of rabbits infected with S . typhimurium were studied: normal animals and animals pretreated with nitrogen mustard . Nitrogen mustard depletes the polymorphonuclear leukocyte pool and thereby prevents the formation of an acute inflammatory reaction . In vivo ligated ileal loops were constructed and infected 72 h after nitrogen mustard administration when polymorphonuclear leukocytes were undetectable . Nitrogen mustard treatment markedly inhibited salmonella-induced secretion . Ileal histology in normal animals infected with S . typhimurium revealed an intense acute inflammatory reaction, while in animals pretreated with nitrogen mustard only a rare polymorphonuclear leukocyte was seen . The antisecretory effect of nitrogen mustard was not merely a nonspecific effect since nitrogen mustard treatment did not inhibit cholera toxin-induced secretion and did not alter either ileal morphology nor the activities of various intestinal enzymes in normal animals . Nitrogen mustard also did not alter the virulence of the inoculated S . typhimurium . These data suggest that the mucosal inflammatory reaction induced by salmonella invasion may be important to the pathogenesis of the salmonella secretory process . The mechanism by which the inflammatory reaction stimulates secretion is not known.

J Biochem (Tokyo), 1979 Jan, 85(1), 173 - 82
X-ray diffraction studies of outer membranes of Salmonella typhimurium; Ueki T et al.; X-ray diffraction studies were carried out on the outer membranes of various strains of Salmonella typhimurium . Ten distinct diffraction peaks which seem to be caused by protein assemblies were observed for most strains . Three small-angle reflections were used to determine an average structure of the protein assembly in the outer membrane of mutant HN202 . An electron density distribution of the averaged assembly was obtained by means of the Fourier-Bessel transform . It has a diameter of about 100A, in agreement with the results of electron microscope observations (Smit, Kamio, and Nikaido (1975) J . Bacteriol . 124, 942--958), and exhibits a low electron density region at its center, suggesting the presence of a pore, as predicted on the basis of transmembrane transport experiments (Nakae (1976) J . Biol . Chem . 251, 2176--2178).

J Bacteriol, 1979 Jan, 137(1), 433 - 9
Characterization of amber and ochre suppressors in Salmonella typhimurium; Winston F et al.; Amber and ochre suppressor mutations in Salmonella typhimurium were selected . The amino acid insertions directed by the suppressors were inferred from suppression patterns of Escherichia coli lacI amber mutations . These amber mutations only respond to nonsense suppressors that direct the insertion of particular amino acids . Four Salmonella amber suppressors characterized insert serine, glutamine, tyrosine, and (probably) leucine . Of the three ochre suppressors characterized, two direct the insertion of tyrosine and one directs that of lysine . Of the three amber and two ochre suppressors which have been mapped by phage P22 cotransduction, all are located in the same relative position on the Salmonella map as the analogous E . coli suppressors are on the E . coli map.

J Bacteriol, 1979 Jan, 137(1), 309 - 12
Incorporation of phosphatidylglycerol into murein lipoprotein in intact cells of Salmonella typhimurium by phospholipid vesicle fusion; Chattopadhyay PK et al.; The biosynthesis of the diglyceride moiety of murein lipoprotein was studied by fusion of labeled phospholipid vesicles with intact cells of Salmonella typhimurium . Phosphatidylglycerol was found to be an excellent donor for the glyceryl moiety in lipoprotein, whereas phosphatidylethanolamine and cardiolipin were not . The incorporation of radioactivity from monoacyl-phosphatidylglycerol into lipoprotein can be attributed to its conversion to phosphatidylglycerol . The results strongly support our hypothesis that the glyceryl residue covalently linked to murein lipoprotein is derived from the nonacylated glycerol moiety of phosphatidylglycerol.

Am J Clin Nutr, 1979 Jan, 32(1), 197 - 209
Evidence of a role for permeability factors in the pathogenesis of salmonellosis; Peterson JW et al.; Two clinical isolates of Salmonella typhimurium were shown to produce two skin permeability factors . One factor was heat stable and rapid in onset while the other was heat labile and elicited maximal induration by 18 to 24 hr . The rapid, erythematous permeability factor (PF) response could not be prevented by antisera to cholera toxin or Salmonella antisomatic serum, but it could be simulated by high concentrations of lipopolysaccharide from S . typhimurium . The appearance of the delayed PF reaction was indistinguishable from that of purified cholera toxin . Histological comparisons of rabbit skin injected with Salmonella-delayed PF and cholera toxin revealed that both toxins resulted in gross edema and infiltration of polymorphonuclear leukocytes after 18 hr . The Salmonella-delayed PF was shown to be resistant to a variety of enzymes, sensitive to extremes in pH, and had an isoelectric point of pH 4.8 . Unlike Salmonella lipopolysaccharide skin activity, the Salmonella-delayed PF was destroyed at 100 C and was neutralized by monospecific cholera antitoxin . The Salmonella-delayed PF, which shares antigenic determinants with cholera toxin, appears to be elaborated by living S . typhimurium cells in the rabbit ligated intestine, since rabbits immunized with procholeragenoid were protected against fluid loss from live cell challenge . Finally, production of the rapid PF is a stable genetic trait, while delayed PF production is apparently an unstable characteristic among the salmonellae.

J Natl Cancer Inst, 1979 Jan, 62(1), 71 - 7
Formation of methylnitrosocyanamide from methylguanidine and sodium nitrite in simulated gastric juice and in stomachs of rats: quantitative estimation by a mutagenicity assay; Ishizawa M et al.; The formation of methylnitrosocyanamide (MNC), a carcionogenic N-nitroso compound, from methylguanidine (MG) and NaNO2 in simulated gastric juice (SGJ) and in the stomachs of rats was quantitatively investigated . With a reverse mutation assay in which a tester strain of Salmonella typhimurium was used, MNC formation was shown to increase linearly for about 40--60 minutes after the incubation of MG with NaNO2 in SGJ . However, it decreased rapidly thereafter . The initial rate of MNC formation was directly proportional to the initial molar ratio of MG to NaNO2, but the yields of MNC depended only on the amount of MG added and were fairly constant (0.3--0.5% of the initial MG) . MNC did not form at a pH above 2.5 or in the presence of 2% casein in SGJ at pH 1.2 . It decomposed rapidly in SGJ at pH 1.2 with a half-life of approximately 2 minutes, whereas it was stable in phosphate buffer at pH 7.0 . Following concurrent administration of MG and NaNO2 via stomach tube, MNC formation was detected in the pylorus-ligated stomachs of rats preconditioned with a casein-free dextrin diet but not in those of rats preconditioned with a casein-containing or synthetic diet . The yields of MNC observed 40--60 minutes after administration of reactants ranged from 0.02 to 0.05% of the initial MG . The possible environment significance of MNC formation in vivo was considered.

J Natl Cancer Inst, 1979 Jan, 62(1), 153 - 6
Carcinogenicity and mutagenicity testing of three isomeric N-nitroso-N-methylaminopyridines in rats; Preussmann R et al.; Three isomeric N-nitroso-N-methylaminopyridines (NMPY's) were investigated for their carcinogenic activity in BD VI rats following chronic oral administration and for their mutagenic properties in the Ames assay . On the basis of postulated reaction mechanisms, it was expected that 3-NMPY would react differently than 2- and 4-NMPY, but the outcome of both carcinogenicity and mutagenicity assays did not show this . 2-NMPY induced tumors of the esophagus and possibly also of the liver; 3- and 4-NMPY had no activity as carcinogens under the experimental conditions used . Similarly, high concentrations of 2-NMPY showed mutagenic activity toward Salmonella typhimurium TA100, whereas 3- and 4-NMPY did not have such an effect.

J Neurosci Res, 1979, 4(2), 105 - 14
Bacterial lipopolysaccharide depresses spontaneous, evoked, and ionophore-induced transmitter release at the neuromuscular junction; Person RJ; The neurotoxocity of RNA-free lipopolysaccharide (LPS) extracted from Salmonella Typhimurium (SR-11) was tested at the frog neuromuscular junction using intracellular recording techniques . Spontaneous miniature endplate potential (MEPP) frequency was reduced to 45% of control after 60 minutes in the presence of 10 and 50 micrograms LPS/ml Ringer's solution . Elevation of extracellular {Ca} to 10 mM converted the MEPP frequency response to a biphasic pattern of early acceleration followed by late depression . Evoked endplate potentials (EEPs) were reduced in quantal content until phasic release of transmitter was abolished, while MEPP amplitude and endplate resting potential remained constant . Effects of the potent cation ionophore X537A on MEPP frequency were blocked by 45 minutes of pre-exposure to LPS . Because of its extremely lipophilic character, LPS apparently alters the physical structure of the presynaptic terminal membrane, eventually reducing resting and phasic Ca influx, and isolating the presynaptic terminal from ionophore action.

J Bacteriol, 1979 Jan, 137(1), 173 - 8
Utilization of D-xylose by wild-type strains of Salmonella typhimurium; Mortlock RP et al.; Enzyme studies of strains of Salmonella typhimurium representing biotypes that utilized D-xylose rapidly (xylose strong) or slowly (xylose weak) showed that they were different in the utilization of D-xylose because the xylose-weak strains were deficient in the transport of D-xylose . This observation is consistent with the idea that strains of the different xylose-weak biotypes, e.g . biotypes 17 to 32, were descended from strains of xylose-strong types, particularly from biotype 1.

Gerontology, 1979, 25(6), 327 - 36
Age-related defense against infection with intracellular pathogens; Emmerling P et al.; Young adult (6--12 weeks old) and aged (20--24 months old) NMRI mice were infected with various intracellular parasites . The following results were obtained: (1) After a sublethal infection with Listeria monocytogenes, aged mice were found to show a resistance similar to that of young adults . A challenge infection with this pathogen was followed by specific immunity of long duration in both age-groups . (2) On the other hand, young animals were significantly more resistant to Salmonella typhimurium than aged mice . It was concluded that this was due to the LD50 which was 14 times greater for 2-month-old than for 20-month-old mice . Furthermore, during 7 weeks after infection there were more S . typhimurium in the spleens of senescent mice than in those of young adult controls . (3) Aged mice showed highly increased susceptibility to the weakly virulent DX strain of Toxoplasma gondii . Almost all aged animals died whereas the control mice survived . When death of the aged mice was prevented by treatment with sulfadiazine after infection with the DX strain, the aged mice were found to be as well protected against subsequent infection with the strongly virulent BK strains as the young adult mice . These results suggest that the susceptibility of the aged animal to infectious agents may considerably vary from one pathogen to another.

Mutat Res, 1979 Jan, 66(1), 75 - 94
Comparison of the in vitro mutagenicity and metabolism of dimethylnitrosamine and benzo{a}pyrene in tissues from inbred mice treated with phenobarbital, 3-methylcholanthrene or polychlorinated biphenyls; Hutton JJ et al.; Homogenates of liver, lung, kidney, stomach, small intestine and colon from 8 strains of mice were compared for their ability to metabolize benzo{a}pyrene (BP) and dimethylnitrosamine (DMN) to mutagens . Females of strains CF1, AKR/J, AU/SsJ, DBA/2J, SWR/J, A/J, C3H/HeJ, and C57BL/6J were either untreated or received phenobarbital (PB), 3-methylcholanthrene (MC) or polychlorinated biphenyls (AR) to induce drug-metabolizing enzymes . The effects of these drugs on organ weight and on the amounts of DNA, S-10 protein, and microsomal protein per unit weight of tissue are reported . Salmonella typhimurium TA92 and TA98 were used as indicators of the formation of mutagens . For each organ there was an optimal balance between amount of tissue homogenate and concentration of test compound for maximal yield of revertants . A sensitive radiometric assay of DMN demethylase (DMND) is described which permits measurement of the enzyme in liver, lung and kidney . DMN at 1 mM is used as substrate . Aryl hydrocarbon hydroxylase (AHH) was measured in all tissue using BP as substrate . AR and MC are very good inducers of AHH activity in livers of mice classified as aromatic hydrocarbon responsive, but not in those classified as hydrocarbon nonresponsive . Responsiveness is strain-specific and genetically regulated . Metabolism of BP to mutagens by liver homogenates was correlated with extent of AHH induction . This dimorphism of response of AHH to inducers was present, but less pronounced, in non-hepatic tissues . Basal activities of AHH and DMND were correlated in livers and lungs from untreated mice . DMND activities were increased less than 2-fold by PB, MC or AR treatments . Metabolism of DMN to mutagens was not closely correlated with DMND activities . Strain of mouse, type of tissue and test substance are important variables in assessing the potential effect of microsomal enzyme-inducing agents on the metabolism of mutagenic substances.

Mutat Res, 1979 Jan, 66(1), 33 - 43
Mutagenicity studies with x-ray-contrast media, analgesics, antipyretics, antirheumatics and some other pharmaceutical drugs in bacterial, Drosophila and mammalian test systems; King MT et al.; As part of our investigation into mutagenic effects of environmental compounds, we studied 21 pharmaceuticals most frequently sold in West Germany: 6 X-ray-contrast media, 13 analgesics, antipyretics and antirheumatics, 1 central stimulant, and 1 antidepressant . They were studied in different bacterial, Drosophila and mammalian test systems . 4 of these 21 compounds could be detected as mutagens in one of the test systems . namely: 1,2-dichloroethane induced an increase in the frequency of recessive sex-linked lethal mutations in Drosophila melanogaster, quinine dihydrochloride and dimethylaminophenazone were mutagenic in the Salmonella typhimurium tester strain TA98 in the presence of S-9 liver fraction derived from Aroclor-induced rats, and trilithium citrate caused a significant effect in the micronucleus test on bone marrow of NMRI mice.

Proc Natl Acad Sci U S A, 1979 Jan, 76(1), 469 - 72
Photomutagenesis by chlorinated phenothiazine tranquilizers; Jose JG; Phenothiazine tranquilizers are widely used pharmaceuticals that have been associated with side effects, such as formation of cataracts, that seem related to light exposure . Because patients may use them over extensive time periods, it is important to determine what deleterious cellular effects these drugs may cause and, if possible, to select or design drugs that do not cause such effects . The results reported here demonstrate that chlorinated phenothiazine drugs can be photoactivated to mutagenic species, whereas the nonchlorinated analogues do not possess this characteristic . None of the phenothiazines tested is mutagenic in the dark . Mutagenicity was observed only in strains of Salmonella typhimurium that lacked excision repair of DNA, and the mutagenicity was elevated in strains that contained the plasmid pKM101, which may enhance error-prone repair.

Biochim Biophys Acta, 1978 Dec 4, 514(1), 69 - 82
Interactions between lipopolysaccharide and phosphatidylethanolamine in molecular monolayers; Fried VA et al.; Lipopolysaccharide and phosphatidylethanolamine are the two major lipid constituents of the membrane of Salmonella typhimurium . Interactions between the purified lipopolysaccharide and phosphatidylethanolamine were studied in molecular monolayers at air-water interfaces . The equilibrium surface pressures of mixed films of lipopolysaccharide and phosphatidylethanolamine were determined as a function of the film composition . The plot of the equilibrium surface pressrue vs . the area occupied by phosphatidylethanolamine molecules exhibited two distinct regions . Below a phosphatidylethanolamine surface concentration at which 55% of the surface was occupied by phosphatidylethanolamine molecules, the equilibrium pressure was invariant and had the value of a pure lipopolysaccharide monolayer at maximum compression . At phosphatidylethanolamine surface concentrations in excess of 55% surface area occupation (phosphatidylethanolamine/lipopolysaccharide (mol/mol) greater than 16), the equilibrium surface pressure was a function of the surface concentration of phosphatidylethanolamine . The results suggest a simple model in which lipopolysaccharide and phosphatidylethanolamine form a complex in which each lipopolysaccharide molecule is surrounded ("lipidated") by a shell of approx . 16 phosphatidylethanolamine molecules.

Zentralbl Bakteriol {B}, 1978 Dec, 167(5-6), 435 - 42
{The biochemical activity of the aflatoxins (author's transl)}; Reiss J; Results of experiments with the Salmonella typhimurium-liver microsome technique make it evident that the mutagenic and carcinogenic metabolite of aflatoxin B1 is aflatoxin B1-2,3-oxide . This compound forms adducts with guanine in DNA . There is a close relationship between the mutagenic activity and the hepatocarcinogenic property of the different aflatoxin derivatives.

Nucleic Acids Res, 1978 Dec, 5(12), 4523 - 36
Purification of pseudouridylate synthetase I from Salmonella typhimurium; Arena F et al.; Pseudouridylate synthetase from Salmonella typhimurium has been purified 1,000 fold and is about 90% pure . The enzyme has a molecular weight of 50,000 daltons . In the presence of tRNA there is a change in molecular weight from 50.000 to 100.000 . This change does not seem to be due to the formation of a tRNA-enzyme complex but rather to a tRNA induced dimerization . Other properties of the enzyme are described.

Mutat Res, 1978 Dec, 54(3), 311 - 21
Forward mutations to arabinose resistance in Salmonella typhimurium strains: a sensitive assay for mutagenicity testing; Pueyo C; The forward-mutation assay using the L-arabinose-sensitive strain SV3 of Salmonella typhimurium has been calibrated against a selected set of mutagens . Strain SV3 is sensitive to chemicals causing base-pair substitutions, frameshift mutations and deletions . New strains deficient for the excision-repair system or the lipopolysaccharide barrier or both have been selected from strain SV3 . The additional mutations do not affect the independence of the assay from experimental artifacts due to physiological or lethal damage or differences in plating density . The new strains are more sensitive than SV3 to certain mutagens . Techniques for using this set of strains are presented and their relative advantages discussed.

Mutat Res, 1978 Dec, 54(3), 297 - 309
Mutagenicity of plant flavonoids: structural requirements for mutagenic activity in Salmonella typhimurium; MacGregor JT et al.; 40 compounds structurally related to the plant flavonol quercetin were tested for mutagenic activity in Salmonella typhimurium strain TA98 . 10 flavonols, quercetin, myricetin, rhamnetin, galangin, kaempferol, tamarixetin, morin, 3'-O-methylquercetin, 7,4'-di-O-methylquercetin and 5,7-di-O-methyl-quercetin, exhibited unequivocal mutagenic activity . 4 compounds, quercetin, myricetin, rhamnetin and 5,7-di-O-methylquercetin, were active without metabolic activation, although metabolic activation markedly enhanced their activity . All 4 have free hydroxyl groups at the 3' and 4' positions of the B ring . The other active compounds required an in vitro rat-liver metabolizing system for significant activity . Structural features which appear essential for mutagenic activity in this strain are a basic flavanoid ring structure with (1) a free hydroxyl group at the 3 position, (2) a double bond at the 2, 3 position, (3) a keto group at the 4 position, and (4) a structure which permits the proton of the 3-hydroxyl group to tautomerise to a 3-keto compound . The data are consistent with the requirement for a B ring structure that permits oxidation to quininoid intermediates . Free hydroxyl groups in the B ring are not essential for activity if a rat-liver metabolic activating system is employed . Data from 12 compounds which differ only at the essential sites described above indicate that the structural requirements for mutagenicity in strain TA100 are the same as those for activity in strain TA98 . Based on the above structural requirements, a metabolic pathway for flavonol activation to DNA-reactive species is proposed.

J Infect Dis, 1978 Dec, 138(6), 820 - 8
Bone and joint infections due to Salmonella; Ortiz-Neu C et al.; A search of the records at the New York City Department of Health and the charts of patients at Columbia Presbyterian Hospital identified 37 cases of bone infection and nine cases of joint infection due to Salmonella between 1964 and 1978 . Factors that apparently contributed to the development of either osteomyelitis or septic arthritis in 23 of the patients included hemoglobinopathy, previous trauma or surgery, connective tissue disorder, and lymphoma . Salmonella typhimurium and Salmonella enteritidis were the most common serotypes involved with bone infections, whereas members of the C1 serogroup were the most common cause of septic joint infections . Isolates of C1 serogroup Salmonella were represented in both bone and joint infections with frequencies (24% and 67%, respectively) disproportionate to the numbers of Salmonella isolated from other sources during this period . Therapy for joint infections was usually successful, with minimal residual damage . Therapy for acute osteomyelitis was unaccountably inadequate, with many patients (47%) developing chronic infections . Use of inappropriate therapy or an insufficient period of therapy were the most important factors contributing to poor outcome.

J Virol, 1978 Dec, 28(3), 736 - 42
Effect of spermidine on bacteriophage P22 infection; Dasgupta B et al.; The effect of spermidine on phage P22 infection of Salmonella typhimurium has been found to depend on the time of addition of spermidine with respect to the time of addition of the phage and also on the composition of the growth medium . If spermidine was added prior to or within a short time after infection, the cells survived . Under this condition the invading DNA appeared to remain trapped in the cell membrane, and there was no expression of the phage genome . If spermidine was added after the initiation of the infective process, the replication of the phage was inhibited but the cells did not survive . If spermidine was added after DNA synthesis was over, there was no effect of spermidine on phage multiplication . Spermidine was found to affect phage DNA synthesis but not host DNA synthesis.

Infect Immun, 1978 Dec, 22(3), 804 - 9
Ultrastructural studies on the interaction between Salmonella typhimurium 395 M and HeLa cells; Kihlstrom E et al.; The interaction of Salmonella typhimurium 395 MS and its rough Rd-mutant 395 MR10 with HeLa cells was studied by transmission and scanning electron microscopy . The bacteria attached to central as well as more marginal positions of the HeLa cell surface . Bacteria associated preferentially to HeLa cells with a relatively low number of microvilli, in which they often were entangled . Bacteria attached to the cell border were sometimes surrounded by membrane folds, possibly as a response to their attachment . Infected cells had longer and more slender microvilli compared with noninfected cells . Some parts of the attached bacteria were in close contact with the HeLa cell membrane, whereas other parts were separated from the latter by a gap . Bacteria adhered preferentially to microvilli without obvious membrane damage . Most of the intracellular bacteria were surrounded by a membrane, often appearing as a vacuole, which sometimes contained more than one bacterium . Intracellular bacteria seemed to be morphologically intact . We propose that S . typhimurium enter HeLa cells by a process of phagocytosis.

J Immunol, 1978 Dec, 121(6), 2160 - 4
Stimulation of mitogenic responses in human peripheral blood lymphocytes by lipopolysaccharide: serum and T helper cell requirements; Miller RA et al.; Stimulation of human peripheral blood lymphocytes by lipopolysaccharide (LPS) was studied by the incorporation of 3H-thymidine . Peak stimulation occurred at 7 to 9 days over a broad range of LPS concentrations . Both Escherichia coli and Salmonella typhimurium LPS were effective mitogens with S . typhimurium having slightly higher activity . There was a strict serum requirement; pooled fresh frozen human serum was found to best support stimulation . In fetal calf serum, LPS caused a reduction in culture-induced stimulation . Cell separation procedures were employed in order to study the nature of the responding cell population . It was found that only non-T cells were stimulated by LPS, but in order for maximal stimulation to occur there was a requirement for helper T cells.

J Bacteriol, 1978 Dec, 136(3), 1094 - 108
Duplications of histidine transport genes in Salmonella typhimurium and their use for the selection of deletion mutants; Ames GF et al.; We demonstrate that tandem duplications of the histidine transport operon can be selected by requesting elevated levels of transport activity to be present . Several strains were constructed which contain duplications heterozygotic for either hisJ, hisQ, or hisP . The size of one duplication which was analyzed in detail is about 16 genes, with one end close to the promoter site (dhuA) of the histidine transport operon and, therefore, enclosing about 12 more genes counterclockwise to this operon . Duplication-carrying strains could be utilized for the selection of deletion mutations by requiring both copies of the operon to be rendered defective simultaneously and, therefore, unable to transport into the cell an inhibitory histidine analog, alpha-hydrazino imidazole propionic acid . Over 60% (probably as high as 100%) of the alpha-hydrazino imidazole propionic acid-resistant strains arising in the selection are deletion mutants . The principle of our selection method is generally applicable and will be useful in the accumulation of deletions for mapping and fusing of genes and other purposes.

Aust J Exp Biol Med Sci, 1978 Dec, 56(6), 727 - 35
Changes in the immunoglobulin levels of the mouse gut and serum during conventionalisation and following administration of Salmonella typhimurium; Horsfall DJ et al.; Increasess in all immunoglobulin classes, except IgM, were observed in the sera of specific pathogen-free (SPF) mice beginning 10 days after their removal from barrier conditions . Concentrations of serum immunoglobulins, comparable with those of conventional mice, were obtained in these animals between 21 and 35 days . Following the removal of germ-free mice from their sterile isolaters, their intestinal IgA levels increased over 35 days to attain levels found in conventional animals . A marked increase in serum immunoglobulin occurred within one day following intravenous administration of live Salmonella typhimurium organisms to SPF animals, and this persisted for longer than 7 weeks (the duration of the study), This rapid elevation in serum immunoglobulin was not elicited by nonbacterial antigens, killed Salmonellae, or viable Vibrio cholerae . Negligible amounts of this immunoglobulin increase could be attributed to specific antibody.

J Virol, 1978 Dec, 28(3), 865 - 76
DNA of Bacillus subtilis bacteriophage SPP1: physical mapping and localization of the origin of replication; McIntosh PK et al.; The genome of Bacillus subtilis bacteriophage SPP1, a linear, 28.5-megadalton DNA duplex, was mapped by analysis with the restriction endonucleases endo R.Sal I, Sma I, Xba I, Bgl I, Bgl II, and EcoRI . The SPP1 genome, like that of the Salmonella typhimurium phage, P22, was found to be a terminally repetitious, circularly permuted molecule . 6-(p-Hydroxyphenylazo)uracil, a selective, reversible inhibitor of SPP1 DNA synthesis, was exploited to synchronize the initiation of genome replication and to selectively label the site of its initiation with radioactive thymidine . Restriction endonuclease analysis of the distribution of the label located the origin of replicative synthesis at an area approximately 0.2 genome length from one molecular terminus.

Infect Immun, 1978 Dec, 22(3), 676 - 80
Heat-labile B-cell mitogen obtained from Listeria monocytogenes; Kearns RJ et al.; A water-soluble extract of Listeria monocytogenes strain 10403 acts as a mitogen on cultured mouse spleen lymphocytes . This mitogen induced a response six to nine times that of controls, as measured by {3H}thymidine incorporation . The mitogen extract was derived from washed bacterial cells which were mechanically disrupted with a French press . The extract was centrifuged at 105,000 X g and filtered through a 0.22-micrometer filter . Similar levels of lymphocyte stimulation were observed in lymphocyte cultures prepared from spleens of nude mice, indicating the effect of this mitogen on B-cells . The mitogenic property of this extract was destroyed by heating to 56 degrees C . This heat treatment does not destroy the antigens in the extract, which stimulate spleen cell cultures obtained from specifically immune mice . Similarly prepared extracts from Staphylococcus epidermidis and Salmonella typhimurium did not show similar levels of mitogenic activity . The mitogenic property of the L . monocytogenes extract was present in two strains of Listeria tested and was not associated with mouse virulence.

Jpn J Antibiot, 1978 Dec, 31(12), 859 - 71
{Safety evaluation of NK 631 . Antigenicity, effect on delated hypersensitivity, irritative effect on eye mucous membrane and mutangenicity of pepleomycin (NK 631) (author's transl)}; Abe F et al.; 1 . Whether NK 631 is antigenic to guinea pigs and rabbits was studied by the methods of active and passive anaphylactic shock tests, Schultz-Dale reaction, passive cutaneous anaphylaxis, Ouchterlony, tanned red cell haemagglutination test and test according to the U.S . Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics . However, none of the tests proved NK 631 to be antigenic . 2 . The immunosuppressive effect of NK 631 was studied by delayed hypersensitivity to picryl chloride in normal and L-1210 tumor bearing mice . Therapeutic dosis of NK 631 was no immunosuppressed but toxic dosis of NK 631 was slightly decreased in ear thickness of delayed hypersensitivity . 3 . The acute irritative effect of NK 631 and of bleomycin was studied by single instillation to the rabbit eye mucous membrane with 0.1 ml of either of 10, 33 and 100 mg/ml solution of the drugs in physiological saline . The irritative effect of NK 631 on the eye mucous membrane at each concentration was slightly severe than that of bleomycin at the same concentration . However, the manifestations were only mild to moderate dilatation of the conjunctival and nictating membrane blood vessels and eye mucous, and recovered or were mitigated 48 hours after the instillation . No severe changes such as corneal opacity, corneal desquamation, swelling and deaquamation of the conjunctival and nictating membrane were observed . The histopathological examination revealed no striking changes . 4 . Mutagenicity of NK 631 and of bleomycin on Salmonella typhimurium strain TA 100 and TA 98 was studied . It was definitely shown that neither NK 631 nor bleomycin exerted any mutagenic action on either test strains.

Biochim Biophys Acta, 1978 Nov 16, 513(3), 395 - 400
Na+-dependent methyl beta-thiogalactoside transport in Salmonella typhimurium; van Thienen GM et al.; We have studied the role of sodium ions in methyl beta-thiogalactoside (TMG) transport via the melibiose permease (TMG II) in Salmonella typhimurium . TMG uptake via TMG II in anaerobic, straved and metabolically poisoned cells is dependent on an inward-directed Na+ gradient . Cells which have been partially depleted of endogenous substrates show H+ extrusion upon sodium-stimulated TMG influx . Measurements of the electrochemical H+ gradient in cells, starved in different ways for endogenous substrates, suggest that this proton extrusion is probably not linked to the actual translocation mechanism but is the result of metabolism induced by TMG plug Na+ uptake.

J Biol Chem, 1978 Nov 10, 253(21), 7605 - 8
Evidence for protein kinase activities in the prokaryote Salmonella typhimurium; Wang JY et al.; Evidence for phosphorylation of proteins by protein kinases has been found in Salmonella typhimurium despite previous indications that protein kinase action is absent in prokaryotes . At least four proteins have been found to be phosphorylated . Serine and threonine phosphates have been isolated from acid hydrolysates of these proteins after in vivo and in vitro labeling . The kinases do not phosphorylate histones, casein, or phosvitin . It would appear that phosphorylation as a regulatory control exists in prokaryotes.

J Biol Chem, 1978 Nov 10, 253(21), 7595 - 7
Kinetic analyses of the sugar phosphate:sugar transphosphorylation reaction catalyzed by the glucose enzyme II complex of the bacterial phosphotransferase system; Rephaeli AW et al.; The sugar phosphate:sugar transphosphorylation reaction catalyzed by the glucose Enzyme II complex of the phosphotransferase system has been analyzed kinetically . Initial rates of phosphoryl transfer from glucose-6-P to methyl alpha-glucopyranoside were determined with butanol/urea-extracted membranes from Salmonella typhimurium strains . The kinetic mechanism was shown to be Bi-Bi Sequential, indicating that the Enzyme II possesses nonoverlapping binding sites for sugar and sugar phosphate . Binding of the two substrates appears to occur in a positively cooperative fashion . A mutant with a defective glucose Enzyme II was isolated which transported methyl alpha-glucoside and glucose with reduced maximal velocities and higher Km values . In vitro kinetic studies of the transphosphorylation reaction catalyzed by the mutant enzyme showed a decrease in maximal velocity and increases in the Km values for both the sugar and sugar phosphate substrates . These results are consistent with the conclusion that a single Enzyme II complex catalyzes both transport and transphosphorylation of its sugar substrates.

Can J Microbiol, 1978 Nov, 24(11), 1358 - 65
Antibiotic resistance among predominant Salmonella serovars and phagovars in Canada; Duck PD et al.; The antibiotic susceptibility of 2609 Salmonella isolates, collected during the period 1975-1976, was tested and the relationships between antibiotic-resistance pattern, source of isolation, and serovar and phagovar were determined . Of 95 serovars examined, 40 were sensitive to all of the antibiotics tested . Salmonella typhimurium was the major contributor to multiple resistance from both human and non-human sources . Multiply resistant strains were not found from animal feed sources and, in addition, S . typhimurium, one of the most predominant serovars, was found in every source but animal feeds . 90% of phagovar 10 was sensitive to all antibiotics tested whereas over 80% of phagovars 3-aerogenic, 92, and 123 were multiply resistant.

Mutat Res, 1978 Nov, 58(2-3), 225 - 9
Identification of a mutagenic substance in a spice, sumac, as quercetin; Seino Y et al.; The mutagenicity of a spice, sumac, was demonstrated on Salmonella typhimurium strain TA98 . The active principle was purified and characterized by thin-layer chromatography, UV-absorption spectroscopy and mass spectrometry . All the mutagenic activity of sumac was found to be due to quercetin.

Mutat Res, 1978 Nov, 58(2-3), 217 - 23
Mutagenicity of aliphatic epoxides; Wade DR et al.; The mutagenicity of 17 aliphatic epoxides was determined using the specially constructed mutants of Salmonella typhimurium developed by Ames . The activity of these epoxides together with those reported in the literature as mutagens in strains TA100 and TA1535 depended on the degree of substitution around the oxirane ring . Monosubstituted oxiranes were the most potent mutagens in both strains . 1,1-Disubstitution resulted in the complete loss or reduction of mutagenicity, trans-1,2-Disubstituted, and tetrasubstituted oxiranes all lacked mutagenicity, while the cis-1,2-disubstituted oxiranes tested were weakly mutagenic in strain TA100 only . For the monosubstituted compounds the presence of electron-withdrawing substituents increased mutagenicity.

Mutat Res, 1978 Nov, 58(2-3), 211 - 5
The lack of mutagenic properties of patulin and patulin adducts formed with cysteine in Salmonella test systems; von Wright A et al.; The mutagenic properties of patulin and the patulin adducts formed with cysteine were tested with histidine auxotroph Salmonella typhimurium strains as indicator organisms . The tests were performed by microsomal activation and host-mediated assay . Neither patulin nor patulin--cysteine reaction mixture was mutagenic in these test systems.

Mutat Res, 1978 Nov, 58(2-3), 205 - 9
Mutagenic activity of furfural in Salmonella typhimurium TA100; Zdzienicka M et al.; The mutagenic activity of furfural was tested in Salmonella typhimurium strains TA98 and TA100 . Furfural produced mutations in the TA100 strain, but not in the TA98 strain . A rat-liver microsomal fraction did not increase the mutagenic activity of furfural in either strain . Mutagenic activity of furfural in the TA100 strain was not increased by benzo{alpha}pyrene in the presence of metabolic activation.

Mutat Res, 1978 Nov, 58(2-3), 193 - 203
Mutagenicity to Salmonella typhimurium of some Aspergillus and Penicillium mycotoxins; Wehner FC et al.; 17 mycotoxins produced by various Aspergillus and Penicillium species were screened for their mutagenic activity to Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537, both with and without metabolic activation . Austdiol, austocystins A and D, kojic acid and viridicatumtoxin were found to be mutagenic after metabolic activation, while austdiol was also mutagenic per se . Aflatoxin B1, sterigmatocystin and versicolorin A, which were used as positive controls were also mutagenic . No mutagenic activity was evident in the case of citrinin, cyclopiazonic acid, fumitremorgen B, griseofulvin, luteoskyrin, O-methylsterigmatocystin, mycophenolic acid, ochratoxin A, patulin, penicillic acid, secalonic acid D and TR2-toxin . A good relationship was found between the mutagenic activity, or lack of it, of most of the mycotoxins with existing data on carcinogenicity . Inadequate information on the carcinogenicity of austdiol, austocystins A and D, kojic acid and viridicatumtoxin precluded correlations with mutagenicity to S . typhimurium . The relationship between chemical structure and mutagenicity of the mycotoxins is discussed.

Mutat Res, 1978 Nov, 58(2-3), 167 - 73
Oxidation of inactive trivalent chromium to the mutagenic hexavalent form; Petrilli FL et al.; Soluble trivalent chromium compounds (chromium potassium sulfate, chromium nitrate, chromium chloride, neochromium and chromium alum) were inactive for Salmonella typhimurium TA100, even at milligram amounts per plate . No effect could be detected either in the absence or in the presence of rat-liver, lung or muscle microsomal fractions, of rat-muscle mitochondria (with or without ATP), of oxidized glutathione (GSSG), or of human serum, plasma or erythrocyte lysates . Conversely, addition of a strongly oxidizing agent (potassium permanganate) resulted in toxic effects in plates incorporating more than 40--80 microgram of compounds and elicited a dose-effect mutagenic response at 10--40 microgram per plate . These effects could be ascribed to oxidation of chromium from the trivalent to the active hexavalent state . Insoluble chromite, as tested in the spot test, was spontaneously mutagenic, owing to contamination of the industrial product with hexavalent chromium . The results obtained may be useful to interpret the findings of carcinogenicity tests and to predict health hazards linked to chromium.

Mutat Res, 1978 Nov, 58(2-3), 159 - 65
Mutagenicities of styrene oxide derivatives on Salmonella typhimurium (TA 100): relationship between mutagenic potencies and chemical reactivity; Sugiura K et al.; The lethal and mutagenic effects of p-methyl-, m-chloro-, p-chloro- and unsubstituted styrene oxide on Salmonella typhimurium (TA 100) were investigated . At equal concentrations, p-chlorostyrene oxide was more lethal than p-methyl-, m-chloro- or unsubstituted styrene oxide . When the survival fraction was 0.8 or more, the mutagenicities of these compounds increased in the order: m-chlorostyrene oxide = p-chlorostyrene oxide less than styrene oxide less than p-methyl-styrene oxide . The mutagenicities of these compounds depended only on the reactivity of their benzylic site; the reactivity at their primary site and their partition coefficients appeared to have no effect.

Mutat Res, 1978 Nov, 58(2-3), 151 - 8
The effect of norharman on the metabolism of benzo{alpha}pyrene by rat-liver microsomes in vitro in relation to its enhancement of the mutagenicity of benzo{alpha}pyrene; Fujino T et al.; The effect of norharman on the metabolism of benzo{alpha}pyrene by rat-liver microsomes was studied . Separation of the metabolites into hydrophilic and hydrophobic fractions showed that norharman inhibited the conversion of hydrophobic metabolites to hydrophilic ones . Analysis of the hydrophobic metabolites by high-pressure liquid chromatography showed that norharman also inhibited the disappearance of benzo{alpha}pyrene itself . However, large amounts of hydrophobic metabolites, such as phenol, quinones and diols, were formed in the presence of norharman, and formation of the strong mutagen 7,8-dihydroxybenzo{alpha}pyrene was increased 10-fold by norharman . The increase in formation of this compound may be one of the chief reasons why norharman enhances the mutagenicity of benzo{alpha}pyrene on Salmonella typhimurium.

J Environ Pathol Toxicol, 1978 Nov-Dec, 2(2), 301 - 12
The influence of contaminants on the mutagenic activity of dibromochloropropane (DBCP); Biles RW et al.; This study investigates the possible role of impurities in dibromochloropropane in inducing mutations, and discusses the importance of contaminants in mutagenicity and carcinogenicity testing . A technical grade sample and a pure sample of DBCP (no epichlorohydrin added) were assayed in Salmonella typhimurium TA1535, with and without S-9 activation, using agar overlay procedures and dessicator procedures . Assays performed with both technical and pure DBCP without metabolic activation resulted respectively in an increase in revertants with increasing dose (0-1600 microgram/plate) when the technical grade was tested, and no substantial increase in revertants over the same dose range when the pure DBCP was tested . Distillation of technical grade DBCP yielded an initial fraction containing high amounts of epichlorohydrin (verified by GC-MS) which was highly mutagenic . The amount of epichlorohydrin in the technical DBCP sample was calculated for each dose level tested, and the number of revertants obtained in tests of the technical DBCP sample could be attributed solely to the calculated amount of epichlorohydrin in each test dose . Tests of pure and technical DBCP using a dessicator technique produced a similar differential between the technical and pure compounds in mutagenicity . Activation of both technical and pure DBCP with S-9 from Aroclor pre-treated rats resulted in high mutagenic responses, of equal magnitude, from both preparations.

J Gen Microbiol, 1978 Nov, 109(1), 97 - 112
Lipopolysaccharide core defects in Salmonella typhimurium mutants which are resistant to Felix O phage but retain smooth character; Hudson HP et al.; FOR mutants of Salmonella typhimurium are resistant to Felix O phage, whose receptor includes the N-acetylglucosamine branch of the lipopolysaccharide (LPS) core, but smooth in cultural properties, antigenic character and phage sensitivity pattern (MacPhee et al., 1975) . The rfa(FOR) genes determining the FOR character of nine mutants were transduced into a smooth cysE pyrE recipient: the nine FOR transductants (and a tenth FOR mutant) were then made rfb (i.e . unable to make O chains) by transduction or Hfr crosses . The rfb FOR strains were sensitive to FO phage but nearly all of them showed a somewhat reduced efficiency of plating and diminished rate of adsorption of the phage . This observation and the Ra (complete core) serological activity of their LPS (tested by haemagglutination inhibition) indicate the presence of some, but less than the normal number of, completed core chains in FOR rfb LPS . On the basis of the sensitivities of the FOR transductants and their rfb derivatives to various 'rough-specific' phages, their increased sensitivities to some antibiotics and to deoxycholate and the serological activity of the rfb FOR LPS in various incomplete core systems, the mutants were divided into three groups: (i) five mutants with probable defects in previously undetected rfa gene(s) concerned with formation of both the galactose I and the galactose II units of the LPS core; (ii) two mutants with defects inferred to affect the structure of the inner part of the core and also interfere with addition of the N-acetylglucosamine branch; (iii) three mutants in which no type of incomplete core could be detected, probably affected in formation of the inner part of the core chain . The mutation of one mutant of the last class, unlike those of the other nine mutants tested, lay outside the cysE-pyrE segment, in the 90 to 116 min region of the linkage map.

Genetics, 1978 Nov, 90(3), 427 - 61
Properties of the translocatable tetracycline-resistance element Tn10 in Escherichia coli and bacteriophage lambda; Kleckner N et al.; A number of independent insertions into bacteriophage lambda of the translocatable tetracycline-resistance element Tn10 have been isolated and characterized . The physical positions and relative orientations of several such insertions were determined . Two independent insertions appear to lie in the same orientation at or very near the same site in the cI gene, and two more lie in opposite orientations at or near the same position in or near the rex gene . Insertions in or near genes cI, rex, and cIII have been characterized genetically for their effects on expression of nearby genes . Tn10 appears to exert a polar effect on expression of distal genes when it is inserted within an operon, even when expression of that operon is under the influence of lambda N-function . In addition, Tn10 insertions in rex appear to influence in some way expression of an "upstream" gene, cI . Lambda derivatives carrying Tn10 give rise to spontaneously occurring, tetracycline-sensitive deletions at high frequencies . It is likely that formation of these deletions is promoted in some way by the Tn10 element . Lambda::Tn10 phages carrying a Tn10 element that has undergone several successive cycles of translocation since its first isolation and characterization have been analyzed . The results confirm that Tn10 often retains its physical and functional integrity during many cycles of translocation . Lambda derivatives carrying Tn10 have been used to generate insertions of Tn10 in the chromosome of Escherichia coli . This process is independent of recA function, and seems to be quite analogous to the translocation of Tn10 in Salmonella typhimurium as studied previously.

Proc Natl Acad Sci U S A, 1978 Nov, 75(11), 5447 - 51
Identification of a membrane protein as a histidine transport component in Salmonella typhimurium; Ames GF et al.; A component of high-affinity histidine transport in Salmonella typhimurium has been identified . It is a basic (pI about 9.0) membrane-bound protein, the P protein . It is shown to be coded for by the distal half of the previously described hisP gene by analysis of numerous hisP mutants, two of which exhibit P proteins with altered electrophoretic mobilities . Upon separation of the cytoplasmic (inner) from the outer membrane, it can be shown that the P protein is located in the cytoplasmic membrane . The P protein is under the same regulatory controls as histidine transport--i.e., transport operon promoter dhuA and nitrogen regulation . A wild-type cell contains about 200 molecules of P protein . As a result of this work we now divide the hisP gene into two genes: the hisP gene proper and the hisQ gene, which codes for another essential component of histidine transport, the Q protein . The P protein was shown previously by genetic analysis to interact with the periplasmic histidine-binding protein J, another essential component of histidine transport . Possible mechanism for the interaction of the J, P, and Q components in histidine transport, and of P and Q in lysine/arginine/ornithine transport, are discussed.

J Gen Virol, 1978 Nov, 41(2), 367 - 76
Somatic O-1 antigen conversion of Salmonella typhimurium by a type B phage P221dis, hybrid between P22 and Fels 1 phages; Yamamoto N; A type B Salmonella phage P221, derived from recombination between a type A phage P22 and a type B phage Fels 1, carries the protein coat of Fels 1 and the P22 early genes, at least the c to h21 genes . One of the P221 strains, P221dis, is dismune over P221 lysogens and co-immune with P22 . Thus it carries the Im gene (the second immunity region) of P22 to establish co-immunity with P22 . Since the att region and a1 gene for somatic 0--1 antigen conversion of P22 are located between the Im and c genes, the P221dis prophage attachment site and 0--1 antigen of P221dis lysogens were analysed . P221dis prophage is integrated at the attP22 site near the pro A region of the bacterial chromosomes and expresses the somatic 0--1 antigen.

J Bacteriol, 1978 Nov, 136(2), 714 - 22
Genetic mapping of tyramine oxidase and arylsulfatase genes and their regulation in intergeneric hybrids of enteric bacteria; Murooka Y et al.; The genes for arylsulfatase (atsA) and tyramine oxidase (tynA) have been mapped in Klebsiella aerogenes by P1 transduction . They are linked to gdhD and trp in the order atsA-tynA-gdhD-trp-pyrF . Complementation analysis using F' episomes from Escherichia coli suggested an analogous location of these genes in E . coli, although arylsulfatase activity was not detected in E . coli . P1 phage and F' episomes were used to create intergeneric hybrid strains of enteric bacteria by transfer of the ats and tyn genes between K . aerogenes, E . coli, and Salmonella typhimurium . Intergeneric transduction of the tynK gene from K . aerogenes to an E . coli restrictionless strain was one to two orders less frequent than that of the leuK gene . The tyramine oxidase of E . coli and S . typhimurium in regulatory activity resemble very closely the enzyme of K . aerogenes . The atsE gene from E . coli was expressed, and latent arylsulfatase protein was formed in K . aerogenes and S typhimurium . The results of tyramine oxidase and arylsulfatase synthesis in intergeneric hybrids of enteric bacteria suggest that the system for regulation of enzyme synthesis is conserved more than the structure or function of enzyme protein during evolution.

Cancer Res, 1978 Nov, 38(11 Pt 1), 3793 - 804
Vinyl carbamate as a promutagen and a more carcinogenic analog of ethyl carbamate; Dahl GA et al.; Vinyl carbamate was much more active (10 to 50 times) than ethyl carbamate for the initiation of skin tumors and for the induction of lung adenomas in mice . Vinyl carbamate was also mutagenic to Salmonella typhimurium TA 1535 and TA 100 in the presence of reduced nicotinamide adenine dinucleotide phosphate-fortified rat or mouse liver mitochondrial supernatant fractions . This mutagenic activity was inhibited strongly by cytochrome P-450 inhibitors . No mutagenic activity was observed for vinyl carbamate in the absence of added liver preparations or for ethyl carbamate in the presence or absence of liver fractions . Extensive tests with sensitive methods failed to detect vinyl carbamate as a metabolite of ethyl carbamate in the mouse in vivo . However, on administration of {ethyl-1-14C;1,2-3H}ethyl carbamate to adult mice the 3H/14C ratios of the hepatic DNA-, rRNA-, and protein-adducts were similar to each other and much lower than the ratio of the administered ethyl carbamate . These data are consistent with the presence of desaturated and/or oxidized ethyl groups in the macromolecular adducts . The qualitatively similar, but much stronger, carcinogenic activity of vinyl carbamate as compared to that of ethyl carbamate suggests that the metabolic pathways of these two carbamates may converge in the formation of similar or identical electrophilic reactants that bind covalently to macromolecules in vivo and initiate carcinogenesis.

Can J Microbiol, 1978 Nov, 24(11), 1339 - 45
5-Fluoroorotate-resistant mutants of Salmonella typhimurium; Zak VL et al.; Spontaneously occurring mutants of Salmonella typhimurium resistant to 5-fluoroorotate (5-FOA) were isolated . One class of mutant showed marked derepression of pyrimidine biosynthetic enzymes and had the unusual property of being unable to grow on nutrient agar . However, when the osmotic strength of nutrient agar was increased, the mutants were able to grow . The genetic basis for the osmotic fragility and elevated pyr enzyme synthesis was the result of mutations affecting pyrH, encoding the enzyme uridine 5'-monophosphate kinase.

J Histochem Cytochem, 1978 Nov, 26(11), 914 - 20
Masking of protein antigen by modification of amino groups with carbobenzoxychloride (benzyl chloroformate) and demasking by treatment with nonspecific protease; Takamiya H et al.; Cryostat sections of various substrates were treated with carbobenzoxychloride in acetone to modify antigens . By applying specific fluorescent antibodies, it could be shown that the antigenic determinants of rabbit gamma-globulin and bovine insulin were totally masked . The antigenicity of ACTH was markedly reduced, whereas the polysaccharide antigens of Salmonella typhimurium were only partially masked . After masking, antigenicity could be restored by treatment with nonspecific protease . The reversible protection of amino groups by carbobenzoxychloride may be a way to preserve protein antigens during embedding in plastics, as such materials also bind to amino groups, blocking the antigenicity of proteins.

J Bacteriol, 1978 Nov, 136(2), 588 - 96
Salmonella typhimurium LT-2 mutants with altered glutamine synthetase levels and amino acid uptake activities; Funanage VL et al.; To determine whether Salmonella typhimurium has a nitrogen control response, we have examined the regulation of nitrogen utilization in two mutants with fivefold and threefold elevations in their glutamine synthetase activities . The mutants do not require glutamine for growth on glucose--ammonia medium but do have altered growth on other nitrogen sources . They grow better than an isogenic control on media containing arginine or asparate, but more slowly with proline or alanine as nitrogen sources . This unusual growth pattern is not due to altered regulation of the ammonia assimilatory enzymes, glutamate dehydrogenase and glutamate synthase, or to changes in the enzymes for aspartate degradation . However, transport for several amino acids may be affected . Measurement of amino acid uptake show that the mutants with high glutamine synthetase levels have increased rates for glutamine, arginine, aspartate, and lysine, but a decreased rate for proline . The relationship between glutamine synthetase levels and uptake was examined in two mutants with reduced, rather than increased, glutamine synthetase production . The uptake rates for glutamine and lysine were lower in these two glutamine auxotrophs than in the Gln+ controls . These results show a correlation between the glutamine synthetase levels and the uptake rates for several amino acids . In addition, the pleiotropic growth of the mutants with elevated glutamine synthetase activities suggests that a nitrogen control response exists for S . typhimurium and that it can be altered by mutations affecting glutamine synthetase regulation.

Mol Gen Genet, 1978 Oct 30, 166(2), 217 - 23
Evidence for a common mechanism for the insertion of the Tn10 transposon and for the generation of Tn10-stimulated deletions; Noel KD et al.; Mutations in and near the Salmonella typhimurium histidine transport operon were generated by insertion of the translocatable tetracycline-resistance element Tn10 . Deletion mutants affecting histidine transport genes were subsequently isolated in several of the Tn10-containing strains . Tn10 insertions in hisJ occurred preferentially at one site, designated site A . This same site was also the preferential endpoint of deletions originating from Tn10 insertions at two neighboring sites . Thus, Tn10 insertion and Tn10-stimulated deletion formation appear to involve a common DNA-recogition step.

Mol Gen Genet, 1978 Oct 24, 165(3), 289 - 93
Method of isolation of cysteine constitutive mutants of the cysteine regulon in Salmonella typhimurium; Sledziewska E et al.; A method for selection of constitutive cysB mutation is described which takes advantage of the resistance of cysteine constitutive mutants to 1,2,4-triazole . Since cysM cysK double mutants are cysteine auxotrophs, by selecting for triazole resistance in cysM strains, mutants arising under this condition also should be constitutive for cysteine biosynthesis . Genetic analysis of mutants isolated by this technique showed that their mutational sites are located in the cysB region . Biochemical assays of cysteine enzymes, sulphite reductase and O-acetylserine sulfhydrylase of the mutants showed the derepressed level of these enzymes and the lack or slight repression by 1-cysteine.

JAMA, 1978 Oct 20, 240(17), 1885 - 6
Salmonellosis associated with homemade ice cream . An outbreak report and summary of outbreaks in the United States in 1966 to 1976; Gunn RA et al.; During the period 1966 to 1976, 22 outbreaks with 292 individual cases of salmonellosis associated with the consumption of homemade ice cream were reported to the Center for Disease Control . Salmonella typhimurium accounted for 45% of the outbreaks . The source of eggs used was known in 13 outbreaks, and all were ungraded farm- or home-produced eggs, a potential source of salmonellae . In 11 outbreaks, the method of preparation was known, and in all, the ice-cream custard had not been cooked before freezing.

Mol Gen Genet, 1978 Oct 4, 165(2), 129 - 43
A mutation to 5-methyltryptophan dependence in the tryptophan (trp) operon of Salmonella typhimurium . II . Studies of 5-methyltryptophan-dependent mutants and their revertants; Callahan R 3rd et al.; Mutants of S . typhimurium with a defect in the first structural gene of the trp operon can utilize anthranilic acid (AA) as a growth factor . Among a group of 5-methyltryptophan (MT) resistant derivatives of trpA mutants we encountered several with a novel phenotype: they actually grew better in the presence of MT than in its absence . Normally MT inhibits growth of S . typhimurium at the concentration we employed due to its ability to act as co-repressor of the trp operon and as a feedback inhibitor of anthranilate synthetase (AS) the first enzyme for tryptophan biosynthesis . Mutations to MT-dependence were only found in strains carrying extremely polar trpA mutations . In all cases analyzed, mutations causing MT-dependence mapped at the extreme operator distal end of trpA . The mutation trpA515 responsible for MT-dependence in strain SO61 (genotype trpA49trpA515) was recombined away from the polar mutation . The strain thus obtained, SO495 was totally dependent on MT for growth on AA supplement . Strain SO495 lacks AS and under repressing growth conditions synthesizes the trp enzymes constitutively at 2--3 times the basal level . Under derepression, while the levels of the distal enzymes, as represented by tryptophan synthetase--beta subunit (TSbeta), did not increase there was a marked drop in the activity of anthranilate-PRPP phosphoribosyltransferase, (PRT) the enzyme catalyzing the second step of tryptophan biosynthesis . trpA515 was found to revert to prototrophy at a low frequency (about 10(-8)) which was not increased by chemical mutagens or ultraviolet radiation . In contrast, it was found to revert to MT-independence (growth on AA in the absence of MT) at a fairly high spontaneous frequency (about 10(-6)) and this frequency could be increased approximately tenfold by mutagens causing base substitutions or deletions but not by frameshift mutagens . About one hundred MT-independent revertants of trpA515 were mapped and found to fall into three general classes: (A) mutations at or near the trpA515 site (B) secondary mutations located upstream from trpA515, (C) deletions of various sizes . Based on a detailed genetic and physiological study of twelve representative MT-independent revertants, it appears that trpA515 may be caused by the insertion of a piece of DNA with some of the properties described for the IS elements found in Escherichia coli . The trpA515 insertion should contain (in this order), a transcription terminator, a low efficiency promoter and, probably, a translation start signal.

Arch Microbiol, 1978 Oct 4, 119(1), 87 - 90
Detection of small cryptic plasmids in Salmonella typhimurium strain LT2; Derylo M et al.; Small cryptic plasmids of molecular weights ranging from 1 to 3 Mdal were detected by electron microscopy in Salmonella typhimurium strain LT2 (ColIb) . They were divided into different size classes . Two of the cryptic plasmids were transferred simultaneously with ColIb to Escherichia coli.

Immunology, 1978 Oct, 35(4), 651 - 61
Humoral immune responses in foetal sheep; Fahey KJ et al.; A total of fifty-two foetal sheep between 49 and 126 days gestation were injected with polymeric and monomeric flagellin, dinitrophenylated monomeric flagellin, chicken red blood cells, ovalbumin, ferritin, chicken gamma-globulin and the somatic antigens of Salmonella typhimurium in a variety of combinations . Immune responses were followed in these animals by taking serial blood samples from them through indwelling vascular cannulae and measuring the circulating titres of antibody . Of the antigens tested, ferritin induced immune responses in the youngest foetuses . A short time later in gestation, the majority of foetuses responded to chicken red blood cells, polymeric flagellin, monomeric flagellin and dinitrophenylated monomeric flagellin . Only older foetuses responded regularly to chicken gamma-globulin and ovalbumin . However, antibodies to all these antigens were first detected over the relatively short period of development between 64 and 82 days gestation and this made it difficult to define any precise order in the development of immune responsiveness . Of the antigens tested only the somatic antigens of S . typhimurium failed to induce a primary antibody response during foetal life . The character and magnitude of the antibody responses in foetuses changed throughout in utero development . Both the total amount of antibody produced and the duration of the response increased with foetal age . Foetuses younger than 87 days gestation did not synthesize 2-mercaptoethanol resistant antibodies or IgG1 immunoglobulin to any of the antigens tested, whereas most foetuses older than this regularly did so.

Arch Surg, 1978 Oct, 113(10), 1163 - 6
Salmonella arteritis: a precursor of aortic rupture and pseudoaneurysm formation; Wilson SE et al.; Salmonella arteritis developed in three patients with subsequent arterial rupture and pseudoaneurysm formation . They had a one- to two-week history of chills and fever, and blood cultures were positive for salmonella . Pulsatile, tender abdominal masses developed in two patients with aortic infection while they were hospitalized . The third patient's femoral artery infection presented as a painful swelling behind the knee . Arteriography demonstrated large vessel rupture with pseudoaneurysm formation and allowed a planned operation in each case . The infected aortic aneurysms were totally excised, the aortic stump oversewn, and the retroperitoneum drained through the flank . Axillobifemoral grafts were constructed to bypass the infection area . Antibiotics effective against salmonella (ampicillin sodium, amoxicillin trihydrate, or chloramphenicol) were given for six weeks postoperatively . Allthree patients are alive without evidence of furhter infection . Recognition that microbial arteritis may be a complication of salmonella infections, particularly when Salmonella choleraesuis and Salmonella typhimurium are cultured, will lead to earlier detection of vascular lesions.

Avian Dis, 1978 Oct-Dec, 22(4), 742 - 7
Survival of Salmonella typhimurium in poultry feed and litter at three temperatures; Williams JE et al.; Poultry feed and litter were contaminated with a large number of Salmonella typhimurium cells and then stored at 11, 25, or 38 C . Samples of feed and litter were cultured at daily or weekly intervals . The organisms survived best at the two lower temperatures . Persistence was as follows: at 11 C, at least 18 months in both feed and litter; at 25 C, 16 months in feed and 18 months in litter; and at 38 C, about 40 days in feed and only 13 days in litter . Hence, samples of feed and litter collected for bacteriologic examination should be stored at low temperatures.

J Wildl Dis, 1978 Oct, 14(4), 483 - 5
Osteomyelitis and arthritis caused by Salmonella typhimurium in a crow; Daoust PY; Salmonella typhimurium was isolated from an arthritic elbow joint of a crow (Corvus brachyrhynchos) which also had bilateral osteomyelitis of proximal tibias . The prevalence of Salmonella organisms in wild birds is reviewed briefly.

Mutat Res, 1978 Oct, 52(1), 81 - 6
Effects of chemical and physical mutagens on the frequency of a large genetic duplication in Salmonella typhimurium . II . Stimulation of duplication-loss from merodiploids; Hoffmann GR et al.; Strains of Salmonella typhimurium which contain a duplication of approximately 30% of the genome may be obtained by a simple selective procedure . These strains are highly unstable, losing the duplication when grown on non-selective medium . In this paper we report that treatment of merodiploid bacteria with mutagenic agents stimulates the rate at which haploid segregants are obtained from merodiploid strains . The mutagens which have been tested for this effect are X-rays, ultraviolet light (UV), ethyl methanesulfonate (EMS), and the azaacridine half-mustard ICR-372.

Mutat Res, 1978 Oct, 52(1), 73 - 80
Effects of chemical and physical mutagens on the frequency of a large genetic duplication in Salmonella typhimurium . I . Induction of duplications; Hoffmann GR et al.; In Salmonella typhimurium a simple selection has been described to detect bacteria that are merodiploid for almost one-third of the chromosome . The selective procedure is based upon improved utilization of L-malate as the sole carbon source in merodiploid strains . The spontaneous frequency of the duplication in haploid strains is approximately 10(-4) per cell plated . Following the exposure of a haploid strain to mutagenic agents, there is a dose-dependent increase in the duplication frequency above the spontaneous level . In this paper we describe the induction of genetic duplications in Salmonella typhimurium by X-rays, ultraviolet light (UV), ethyl methanesulfonate (EMS), nitrous acid, and the azaacridine half mustard, ICR-372.

Infect Immun, 1978 Oct, 22(1), 148 - 54
DNA release as a direct measure of microbial killing by phagocytes; Friedlander AM; A new assay for the precise measurement of microbial killing by leukocytes is presented . The method assumes that release of radioactively labeled DNA from the microbe is direct evidence of cell death . Human peripheral blood leukocytes incubated with {14C}thymidine-labeled Salmonella typhimurium released 32 to 59% of the radioactivity after 4 h and 63 to 75% after 18 h . Inactivated leukocytes released less than 5% of the radioactivity . None of the released radioactivity is retained within the leukocyte, and 60% remains precipitable with trichloroacetic acid . Leukocytes released substantial radioactivity from labeled Escherichia coli but only a slight amount from staphylococci . Mouse peritoneal macrophages were also shown to release radioactivity from Salmonella . The DNA release assay avoids the errors inherent in prior killing methods which measure viability by growth inhibition . It is rapid, reproducible, and highly specific.

Infect Immun, 1978 Oct, 22(1), 125 - 31
Protective effects of a supernatant factor from Salmonella typhimurium on Salmonella typhimurium infection of inbred mice; Plant J et al.; A supernatant factor prepared from 48-h cultures of Salmonella typhimurium has been used to immunize mice against subsequent challenge with normally lethal doses of S . typhimurium . The mouse strains used, C57BL and BALB/c, were sensitive to S . typhimurium with 50% lethal doses of less than 50 organisms . Two doses of supernatant factor, given intraperitoneally 20 days apart, protected mice against a subcutaneous challenge dose 10 days later of 100 50% lethal doses of S . typhimurium, resulting in 50 to 80% survival . The viable counts were reduced initially in organs of immunized mice compared with controls, and the multiplication of bacteria was delayed, although the final levels found in the organs would normally have been lethal . Protection obtained was specific for S . typhimurium in that no increased survival was shown after Salmonella enteritidis challenge of immunized mice . Although lipopolysaccharide was demonstrated in the supernatant factor, lipopolysaccharide alone did not protect challenged mice . Supernatant factor produced delayed-type hypersensitivity reactions in mice sensitized with nonlethal doses of Salmonella . The nature of the active factor, found to be partially protein, has yet to be elucidated.

Mutat Res, 1978 Oct, 54(2), 167 - 73
Mutagenic properties of ethylidene gyromitrin and its metabolites in microsomal activation tests and in the host-mediated assay; von Wright A et al.; Ethylidene gyromitrin (acetaldehyde-N-methyl-N-formylhydrazone) is the main poisonous hydrazine derivative in the edible mushroom false morel (Gyromitra esculenta Pers . Fr.) . The mutagenic properties of this compound, and of its metabolites N-methyl-N-formylhydrazine and N-methylhydrazine, were tested by microsomal activation and host-mediated assay . Histidine auxotroph strains of Salmonella typhimurium were used as indicator organisms . Microsomal preparations had no detectable effect on the biological activity of the compounds tested, but the results of host-mediated assay experiments suggested that a bacteriocidic metabolite is formed from ethylidene gyromitrin.

Mutat Res, 1978 Oct, 54(2), 121 - 9
A mutagen assay detecting forward mutations in an arabinose-sensitive strain of Salmonella typhimurium; Ruiz-Vazquez R et al.; Strain SV3 of Salmonella typhimurium is sensitive to arabinose, that is, unable to grow in a medium containing arabinose plus glycerol as carbon source . Arabinose resistance is the consequence of the mutational inactivation of one of at least three different genes . The selection of arabinose-resistant mutants provides a simple and sensitive assay for the detection of weak mutagens and for refined quantitative studies of strong ones . The assay is not influenced by experimental artifacts derived from physiological or lethal effects or from differences in plating density . Such artifacts are common with other bacterial mutagen assays, including those using strains analogous to SV3 . As practical examples, the assay was used with N-methyl-N'-nitro-N-nitrosoguanidine and the fungicide captafol.

J Bacteriol, 1978 Oct, 136(1), 286 - 94
Major outer membrane protein in Salmonella typhimurium induced by maltose; Palva ET; A maltose-induced major outer membrane protein (the 44K protein) is demonstrated in Salmonella typhimurium . This protein resembles the lambda receptor of Escherichia coli in its location, induction properties, apparent molecular weight, and association with the peptidoglycan layer of the cell wall . The 44K protein is missing in certain Salmonella Mal- mutants, which are also missing a protein analogous to the maltose-binding protein of E . coli . Thus, these mutants may be defective in the control of maltose genese in Salmonella . The proteins appear to be closely related, as indicated by cross-reaction of the Salmonella protein with the antiserum raised against the lambda receptor; however, they are not identical, since the peptide patterns obtained after limited proteolysis are completely different . Bacteriophage lambda does not use the 44K protein as a receptor.

J Bacteriol, 1978 Oct, 136(1), 191 - 200
Purification and characterization of a tRNA methylase from Salmonella typhimurium; Pope WT et al.; A tRNA methylase, in which supK strains of Salmonella typhimurium are deficient, was purified from strain LT2 and characterized . Column chromatography of protein extracts from wild-type cells on phosphocellulose, diethylaminoethyl-Sephadex A-50, and hydroxlapatite resulted in an enzyme that was estimated to be about 50% pure . tRNA from S . typhimurium which had been incubated at pH 9.0 served as a substrate for this methylase . The enzyme has a molecular weight of about 50,000 as estimated by gel chromatography and by electrophoresis on sodium dodecyl sulfate-polyacrylamide gels . The optimal assay conditions, as well as the kinetics and stability of the enzyme, were studied . As with other tRNA-methylating enzymes, S-adenosylhomocysteine is a potent inhibitor.

Appl Environ Microbiol, 1978 Oct, 36(4), 623 - 4
Toxicological model for a two-acid system; Rubin HE; Lactic and acetic acids were determined to be slightly synergistic in their inhibitory interrelationship against Salmonella typhimurium with the use of a modified toxicological model.

Lancet, 1978 Sep 2, 2(8088), 494 - 6
Ingested mutagens from opium and tobacco pyrolysis products and cancer of the oesophagus; Hewer T et al.; Substances which are commonly sucked or chewed in two areas where the incidence of oesophageal cancer is high, the Transkei and north-east Iran, were tested in bacterial mutagenicity assays . Pyrolysed substances, opium dross in north-east Iran and tobacco pipe residues in the Transkei, displayed mutagenic activity in Salmonella typhimurium strains TA98 and TA100 in the presence of rat liver microsomes.

Chem Biol Interact, 1978 Sep, 22(2-3), 297 - 308
Mutagenicity of dichlorvos and other structurally related pesticides in Salmonella and Streptomyces; Carere A et al.; The following pesticides: azinphosmethyl, diallate, dichlorvos, EPTC, fenchlorphos, mevinphos, monocrotophos, noruron, parathionmethyl, triallate, trichlorphon and vegadex were tested for the ability to induce his+ revertants in four histidines requiring strains of Salmonella typhimurium--TAI 535(missense), TAI 536, TAI 537 and TAI 538 (frame-shift)- and resistance to low levels of streptomycin in Streptomyces coelicolor . Dichlorvos, which is a phosphoric ester with a dichlorovinyl group as side chain, and trichlorphon, which is known for its spontaneous conversion in dichlorvos, are both mutagenic in Salmonella (strain TAI535) and Streptomyces . Five organophosphorus pesticides similar to dichlorvos but devoid of the vinyl group are not mutagenic . Three carbamates, diallate, triallate and vegadex, which contain a chloroallyl group similar to the vinyl group of dichlorvos are mutagenic in Streptomyes; triallate and vegadex are powerful mutagens also in Salmonella (strain TAI535); two other carbamates devoid of the chlorinated group are not mutagenic . The results suggest that the presence of a vinyl chloride or allyl chloride group in the molecule of these pesticides is responsible for the ability to induce point mutations in Salmonella and Streptomyces.

Appl Environ Microbiol, 1978 Sep, 36(3), 412 - 20
Mollicellins: mutagenic and antibacterial mycotoxins; Stark AA et al.; Eight mollicellins (depsidones) were assayed for mutagenicity and antibacterial activity in Salmonella/microsome tests involving histidine reversion and forward mutation to 8-azaguanine resistance . Two of them, mollicellins C and E, which contain a 3-methylbutenoic acid moiety, were mutagenic and bactericidal for Salmonella typhimurium in the absence of microsomes . Mollicellins D and F, each containing a chlorine atom, were bactericidal but not mutagenic . The mutagenic activity was completely abolished and the antibiotic activity was greatly reduced by coincubation with rat liver microsomes.

Res Vet Sci, 1978 Sep, 25(2), 139 - 43
Experimental Salmonella typhimurium infection in calves; Wray C et al.; The paper describes the clinical, bacteriological and pathological findings in experimental Salmonella typhimurium infection in calves . Oral doses of 10(8) and 10(9) organisms produced clinical disease and high mortality; doses ranging from 10(4)--10(7) organisms were less consistent in their action . Jersey calves appeared more susceptible to infection than Friesian calves . The clinical signs in most calves were pyrexia and a characteristic diarrhoea that lasted for up to 11 days; more severe symptoms were seen in the calves that received the higher doses . Following infection, all calves excreted S typhimurium in their faeces, the highest counts being observed in the calves that died . In the calves that survived, counts ranging from 10(2)--10(5)/g faeces occurred continuously for up to a maximum of 20 days and subsequent intermittent excretion occurred in a number of calves . In the calves that died, necrotic enteritis in the ileum and large intestine was the most striking lesion; lesions were uncommon in other organs . The findings are discussed in relation to the pathogenesis, diagnosis and control of the disease.

J Environ Pathol Toxicol, 1978 Sep-Oct, 1(1), 139 - 46
The mutagenicity of saccharin impurities . I . Detection of mutagenic activity; Stoltz DR et al.; Sodium saccharin, ortho-toluenesulfonamide and impurities extracted from commercially produced saccharin with water and organic solvents were tested for mutagenicity with strains of Salmonella typhimurium . The organic solvent soluble impurities exhibited strong mutagenic activity for TA98 and slight activity for TA100 . Mutagenic activity for S . typhimurium TA98 was demonstrated in extracts of some but not all lots of sodium saccharin produced by both Maumee and Remsen-Fahlberg processes . The significance of the mutagenic impurity to the carcinogenicity of saccharin is discussed.

Genetika, 1978 Sep, 14(9), 1564 - 70
{Study of metabolic activation of chemical compounds by using microorganisms . I . Effect of inducers of microsomal systems}; Fonshtein LM et al.; The effect of psychotropic drugs phenobarbital, benzonal, hexamidine and steroid hormone hydrocortizon acetate on the process of metabolic activation of mutagenicity of nitrosomorpholine, cyclophosphamide and benzidine was examines using tester strains TA 1950 and TA 1538 of Salmonella typhimurium (by B . N . Ames) . The listed above activators did not modify essentially the mutagenic effect of benzidine . The mutagenic action of nitrosomorpholine was increased by the presence of hydrocortizon acetate . Psychotropic drugs phenobarbital and its structural analogues increased the mutagenic effect of cyclophosphamide and nitrosomorpholine . Phenobarbital was the most potent as an inducer . Benzonal occupied the intermediate position according to the including activity of mutagens examined . Phenobarbital has shown to increase both the content of rat liver microsomal proteins and the specific activity of those . A possible role of microsomal enzymatic inducers as modifiers of the effects of environmental mutagens is discussed.

Mutat Res, 1978 Sep, 58(1), 35 - 40
Changes in mutagenicity of protein pyrolyzates by reaction with nitrite; Yoshida D et al.; Pyrolyzates of protein and related materials were treated with nitrite under acidic conditions, and the mutagenic activity toward Salmonella tester strains was determined . After treatment with nitrite in acidic solution, casein pyrolyzate, an extract of roasted chicken meat, tobacco-smoke condensate and some aromatic amines showed appreciable decreases in their mutagenic activities toward Salmonella typhimurium TA 98 . Aromatic amines in the pyrolyzates may be changed by nitrite treatment to other forms having no or lower mutagenic activity toward Salmonella typhimurium TA 98 . The contribution by aromatic amines to the total mutagenic activity of the pyrolyzates was as high as 80% in both casein pyrolyzate and extract of roasted chicken meat and 50% in tobacco-smoke condensate . Pyrolyzates of protein and related materials did not show a decrease in the mutagenic activity toward Salmonella typhimurium TA 100 with the same treatment.

Mutat Res, 1978 Sep, 58(1), 29 - 34
Suppression of mutation induction and failure to detect mutagenic activity with athabasca tar sand fractions; Shahin MM et al.; 5 different histidine-requiring strains of Salmonella typhimurium were used to test the mutagenic activity of 7 different fractions of Athabasca tar-sand . None of the 7 fractions (bitumen, maltenes, asphaltenes, saturated, monoaromatic, diaromatic and polyaromatic hydrocarbons), showed positive mutagenic response in any of the Salmonella typhimurium strains . We have tested a wide range of concentrations . The results obtained so far are consistent with the lack of mutagenic activity of all investigated fractions in the absence and in the presence of metabolic activation . Assuming that there might be an association between the absence of mutagenic activity and the complexity of the tar-sand fractions, we investigated the effect of the polyaromatic hydrocaron fraction on the mutagenicity of the carcinogenic agent 2-aminoanthracene . The data obtained indicate clearly that the polyaromatic hydrocarbon fraction suppresses the mutagenic activity of 2-aminoanthracene.

Mutat Res, 1978 Sep, 58(1), 11 - 22
Mutagenicity of some commercially available nitro compounds for Salmonella typhimurium; Chiu CW et al.; Benzoyl chloride and 53 commercially available aromatic heterocyclic and aliphatic nitro compounds were tested for mutagenicity in Salmonella typhimurium TA98 and TA100 . 34 of 53 nitro compounds (64%) were mutagenic, 4 in TA100 only, 15 in TA98 only, and 15 in both strains . 13 of the heterocyclic derivatives of pyridine, indole, indazole, quinoline, and benzimidazole were mutagenic . 21 of 34 mutagenic nitro compounds were bactericidal . Nitromethane was the only aliphatic tested and was not mutagenic . Benzoyl chloride, a human carcinogen, was mutagenic for TA98.

Mutat Res, 1978 Sep, 58(1), 1 - 10
Screening for the mutagenicity of nitro-group containing hypoxic cell radiosensitizers using Salmonella typhimurium strains TA 100 and TA98; Chin JB et al.; A series of sixteen 2-, 4- and 5-nitroimidazoles, four nitrobenzenes, five nitrofurans, and a nitropyrrole, most of which have been studied previously as hypoxic cell specific radiosensitizers, have been screened for their mutagenicity using the Salmonella typhimurium strains TA 100 and TA 98 developed by Ames and co-workers . Most of these compounds were mutagenic and had a one to two order of magnitude greater mutagenicity towards TA 100 (base-pair substitution sensitive) than TA 98 (frame-shift sensitive) . The spectrum of mutagenic efficiencies for the drugs which was observed could be correlated to some extent with the electron affinity of these compounds . Exceptions to this correlation may indicate drugs of interest for further studies both as mutagens and hypoxic cell radiosensitizers.

Toxicology, 1978 Sep, 11(1), 19 - 27
Mutagenicity of acrylonitrile; de Meester C et al.; Incubation of Salmonella typhimurium strains in an atmosphere of 0.2% gaseous acrylonitrile increased the numbers of his+ revertants/plate only in the presence of a fortified S9 liver fraction . The mutagenic effect was particularly pronounced with strains TA1530, TA1535 and TA1950 and much weaker with strains TA100, TA98 and TA1978 . The results of bacterial fluctuation tests confirmed the necessity of the presence of S9 mix and showed the particular sensitivity of TA1530 . The reversion rate varied with the S9 mix composition, the animal species utilized and the type of pretreatments applied to the animals . The mutagenicity of acrylonitrile in S . typhimurium is therefore microsome-mediated and is particularly discernable with strains sensitive to base-substitution mutagens.

Proc Natl Acad Sci U S A, 1978 Sep, 75(9), 4465 - 9
Relative sensitivities of forward and reverse mutation assays in Salmonella typhimurium; Skopek TR et al.; Forward mutation to 8-azaguanine resistance and reverse mutation to histidine prototrophy were measured in Salmonella typhimurium after treatment with 16 mutagens of both base-substitution and frameshift classes . The two approaches were found to be equisensitive for all 16 mutagens--i.e., induction of significant mutation occurred at similar concentrations in the forward mutation assay and in the most sensitive of the five Ames tester strains.

Proc Natl Acad Sci U S A, 1978 Sep, 75(9), 4281 - 5
DNA sequence from the histidine operon control region: seven histidine codons in a row; Barnes WM; The DNA sequence of 250 base pairs preceding the first structural gene of the histidine operon of Salmonella typhimurium was determined by the dideoxy chain-termination method . Single-stranded DNA template was provided by an M13-histidine transducing phage constructed for the purpose by in vitro recombination . The termination site for the histidine leader RNA is identified by analogy with the trp operon leader termination sequence, and is 47 nucleotides before the start codon of the first structural gene G . Beginning 150 nucleotides before the end of the presumed leader RNA is a possible short protein-coding region with seven histidine codons in a row . It is proposed that the major mechanism of histodine operon control must involve a ribosome arrested at this run of histidine codons when histidine is limiting.

J Virol, 1978 Sep, 27(3), 535 - 50
Bacteriophage P22-mediated specialized transduction in Salmonella typhimurium: identification of different types of specialized transducing particles; Kwoh DY et al.; The temperate bacteriophage P22 mediates both generalized and specialized transduction in Salmonella typhimurium . Specialized transduction by phage P22 is different from, and less restricted than, the well characterized specialized transduction by phage lambda, due to differences in the phage DNA packaging mechanism . Phage lysates produced by induction of lysogenic strains contain very high frequencies of supQ newD- and proA,B-specialized transducing particles (10(-2)/PFU and 10(-3)/PFU, respectively), most of which are produced by independent aberrant excision events of various types . In a model, 12 different modes of transduction mechanisms were characterized by: (i) the structure of the specialized transducing genomes after injection into a new host cell, i.e., linear or circular, and (ii) the requirements for the transduction process, i.e., host recombination functions, phage integration functions, or presence of a prophage . By using different recipient strains and phage helper strains, it was possible to show that most specialized transducing particles (ca . 99%) contain linear genomes that cannot circularize upon injection into a new host cell and that require the presence of an integrated prophage as a site for a recombinational event to give rise to a transductant . Only 0.1% of all specialized transducing particles were shown to transduce by integration, suggesting that transducing genomes containing terminally redundant ends represent only a minor fraction of all transducing particles that are produced . However, it should be pointed out that the frequency (approximately 10(-5)/PFU) of these specialized transducing genomes that can circularize upon injection into a new host cell is as high as or even higher than the frequency of specialized transducing particles of phage lambda . The remaining approximately 1% of all specialized transducing particles can transduce by any one of the other mechanisms described.

J Virol, 1978 Sep, 27(3), 519 - 34
Bacteriophage P22-mediated specialized transduction in Salmonella typhimurium: high frequency of aberrant prophage excision; Kwoh DY et al.; The temperate bacteriophage P22 mediates both generalized and specialized transduction in Salmonella typhimurium . Specialized transduction by phage P22 is different from, and less restricted than, the well characterized specialized transduction by phage lambda, due to differences in the phage DNA packaging mechanisms . Based on the properties of the DNA packaging mechanism of phage P22 a model for the generation of various types of specialized transducing particles is presented that suggests generation of substantial numbers of specialized transducing genomes which are heterogeneous but only some of which have terminally redundant ends . The primary attachment site, ataA, for phage P22 in S . typhimurium is located between the genes proA,B and supQ newD . (The newD gene is a substitute gene for the leuD gene, restoring leucine prototrophy of leuD mutant strains.) The proA,B and supQ newD genes are very closely linked and thus cotransducible by generalized transducing particles . Specialized transducing particles can carry either proA,B or supQ newD but not both simultaneously, and thus cannot give rise to cotransduction of the proA,B and supQ newD genes . This difference is used to calculate the frequency of generalized and specialized transducing particles from the observed cotransduction frequency in phage lysates . By this method, very high frequencies of supQ newD (10(-2)/PFU)- and proA,B (10(-3)/PFU)-specialized transducing particles were detected in lysates produced by induction of lysogenic strains . These transducing particles most of which would have been produced by independent aberrant excision events (which include in situ packaging), were of various types.

J Am Vet Med Assoc, 1978 Sep 1, 173(5 Pt 2), 610 - 3
Immunization of calves against salmonellosis; Bairey MH; Salmonella typhimurium bacterins, containing adequate antigenic mass, protected calves against clinical signs of salmonellosis and death . Protection against salmonellosis was correspondingly reduced when the bacterin was diluted 1:10 and 1:100 . A mouse protection test revealed that 17 of 18 (94%) of the S typhimurium-containing bacterin serials produced in 1977 stimulated adequate immunity.

J Gen Virol, 1978 Sep, 40(3), 669 - 73
A model for the adsorption of phage P22 to Salmonella typhimurium; Israel V; A new model for the adsorption of bacteriophage P22 to its host Salmonella typhimurium is proposed . The main feature of this model is that only three of the six tail proteins found on the mature phage function during adsorption . This model explains why there is a difference in the specific endoglycosidase activity of the tail protein of mature virions as opposed to unattached tail protein . It also accounts for the cubic relationship between p.f.u . and tail protein concentration in in vitro assembly experiments.

J Bacteriol, 1978 Sep, 135(3), 1151 - 3
Mapping of the hemE locus in Salmonella typhimurium; Desrochers M et al.; A new type of heme-deficient mutant was isolated in Salmonella typhimurium by neomycin selection . The mutant was deficient in uroporphyrinogen decarboxylase activity, coded by the hemE gene . The hemE gene was located between the genes rif and thi at 128 min on the chromosomal map of S . typhimurium.

Cancer Res, 1978 Sep, 38(9), 2939 - 44
Activation of carcinogens and mutagens by rat colon mucosa; Fang WF et al.; Colon mucosal cells can catalyze the activation of precarcinogens to mutagenic metabolites without the intermediacy of intestinal bacteria as shown in a mutagenesis assay system composed of Salmonella typhimurium strain TA100 and the 9000 X g supernatant fraction of rat colon mucosal cells . Pretreatment of rats with beta-naphtoflavone increased the activation of 2-aminoanthracene 10- to 20-fold and the activation of benzo(a)pyrene 4-fold . Pretreatment of rats with Aroclor 1254 doubled the activation of 2-aminoanthracene over control but had no effect on the activation of benzo(a)pyrene . The activation of 2-aminoanthracene and benzo(a)pyrene by liver was induced significantly by pretreatment with beta-naphthoflavone and Aroclor 1254 . Phenobarbital/hydrocortisone pretreatment did not increase the activation by the colon system of any precarcinogen tested but did increase the activation of 2-aminoanthracene, cyclophosphamide, and isophosphamide by the liver system . The activation of precarcinogens in the bacterial test system is directly correlated with the activities of the pretreated colon and liver preparations toward several drug and polycyclic hydrocarbon substrates assayed in vitro.

Cancer Res, 1978 Sep, 38(9), 2795 - 9
Mutagenic and recombinogenic effects of the antitumor antibiotic anthramycin; Hannan MA et al.; Anthramycin, one of the pyrrolo(1,4)benzodiazepine antibiotics with potent antitumor activity, was tested for its effects on a number of genetic parameters . The results show that this antibiotic is nonmutagenic in the Ames strains of Salmonella typhimurium while mutagenic in only one and antimutagenic in the rest of the genes tested in the eukaryotic organism Saccharomyces cerevisiae . The antibiotic is, however, a potent recombinogen inasmuch as it induced mitotic crossing over, mitotic gene conversion, and possibly other chromosomal alterations in a diploid strain of S . cerevisiae . These studies emphasize the need for a battery of test systems including eukaryotic organisms to detect the genetic activity of certain antitumor drugs . The importance of considering data distinguishing between highly mutagenic and poorly mutagenic cancer chemotherapeutic agents is also discussed.

J Bacteriol, 1978 Sep, 135(3), 928 - 34
Constitutive expression of the iron-enterochelin and ferrichrome uptake systems in a mutant strain of Salmonella typhimurium; Ernst JF et al.; Two high-affinity iron uptake systems are known in Salmonella typhimurium, one utilizing iron-enterochelin and the other utilizing ferrichrome . It has been shown previously that expression of several elements of the iron-enterochelin uptake system are regulated by the iron content of the medium, with growth in high-iron medium resulting in repression of enzymes of enterochelin synthesis and degradation and of the ability of whole cells to take up iron-enterochelin . In this study we describe a mutant strain in which growth in high-iron medium was associated with constitutive expression of: (i) iron-enterochelin uptake by whole cells; (ii) ferrichrome uptake by whole cells; (iii) synthesis of enterochelin; (iv) intracellular degradation of iron-enterochelin; and (v) synthesis of three major outer membrane proteins (OM1, OM2, and OM3) . In contrast, in the wild-type strain these properties were expressed only after growth in iron-deficient medium . It is proposed that the mutation affects a gene responsible for regulating expression of the structural genes for the components of the high-affinity iron uptake systems . The term fur, for iron (Fe) uptake regulation, is suggested for this new class of mutant.

Yale J Biol Med, 1978 Sep-Oct, 51(5), 527 - 38
Serum opsonic deficiency produced by Streptococcus pneumoniae and by capsular polysaccharide antigens; Giebink GS et al.; The opsonic requirements for phagocytosis of S . pneumoniae types 6, 7, 18, and 23 were determined in normal and C2 deficient serum, and in normal serum chelated with magnesium ethyleneglycoltetraacetic acid . All four strains were effectively opsonized via the alternative complement pathway, a finding suggesting that the capsular polysaccharides of these strains activated complement via the alternative pathway . Since bacteremic pneumococcal disease is often associated with circulating capsular polysaccharide, it was considered that this cellular component may activate complement in vivo and impair host defenses by producing an opsonic defect for pneumococci . To examine this hypothesis, serum was incubated with suspensions of whole S . pneumoniae types 6, 7, 18, or 23 or with purified capsular polysaccharide from each of these types, and residual complement activity and opsonic capacity were measured . Hemolytic C 3--9 complement activity and opsonic capacity for 3H-thymidine labeled Salmonella typhimurium, a species effectively opsonized via the alternative pathway, were reduced in serum following incubation . Polysaccharide concentrations as low as 1 microgram/ml inhibited serum opsonic capacity for salmonella . Whole pneumococci and pneumococcal capsular polysaccharide also inhibited the opsonic activity of human C2 deficient serum for salmonella, further evidence for activation of complement via the alternative pathway . Pneumococcal capsular polysaccharide markedly inhibited the opsonic capacity of normal serum for the homologous pneumoccal type . Thus, amounts of pneumococcal capsular polysaccharide, similar to those found in the serum of patients with pneumococcal disease, bring about decomplementation of serum via activation of the alternative pathway and inhibit pneumococcal opsonization.

Vet Rec, 1978 Aug 5, 103(6), 114 - 5
Eidemiological aspects of an outbreak of salmonellosis in sheep; Findlay CR; An outbreak of salmonellosis caused by Salmonella typhimurium occurred in a lambing flock where management factors and fostering movements were responsible for spread within the group and to farm personnel and their families . Possible sources of the infection are discussed.

Mol Gen Genet, 1978 Aug 4, 164(1), 57 - 62
Acylaminoacid esterase mutants of Salmonella typhimurium; Heiman C et al.; Salmonella typhimurium contains three electrophoretically separable enzyme activities that hydrolyze N-acetyl phenylalanine beta-naphthyl ester (NAPNE) . One of these enzymes is an endoprotease, protease I . Mutations at a locus apeA near purE lead to loss of this enzyme . We have found that N-acetyl leucine alpha-naphthyl ester (NALNE) is not hydrolyzed by protease I but is a good substrate for the other two activities . Using NALNE as a chromogenic substrate to screen colonies growing on agar, we have isolated mutants (apeB) that simultaneously lose both of the two other esterase activities . The chromosomal positions of apeB and nearby markers in the proC-purE region have been determined using both phage P1 and phage P22 mediated transduction . The observed order is proC thiC apeB apt apeA purE . Strains lacking all three activities (apeA apeB double mutants) have been constructed and have growth rates similar to wild-type strains.

J Antibiot (Tokyo), 1978 Aug, 31(8), 737 - 41
Antibiotics from Basidiomycetes . V merulidial, a new antibiotic from the Basidiomycete Merulius tremellosus Fr; Quack W et al.; Merulidial, a new antibiotic, was isolated from the culture fluid of the Basidiomycete Merulius tremellosus Fr., strain No . WQ 568 . Merulidial inhibits a variety of bacteria and fungi . In cells of the ascitic form of EHRLICH carcinoma, DNA synthesis is inhibited at lower concentration as compared to RNA and protein synthesis . Merulidial shows mutagenicity when incubated with the his-mutant TA 100 for Salmonella typhimurium (B.N.AMES) . The molecular formula as determined by high resolution mass spectrometry is C15H20O3.

Proc Natl Acad Sci U S A, 1978 Aug, 75(8), 3659 - 63
A protein methylesterase involved in bacterial sensing; Stock JB et al.; A protein methylesterase has been identified in soluble extracts of Salmonella typhimurium and Escherichia coli . This enzyme catalyzes the hydrolysis of gamma-glutamyl methyl ester residues from membrane-bound 60,000-molecular weight proteins that are essential for chemotaxis . Analyses of methylesterase activity in a variety of chemotactically defective strains suggest that the methylesterase is a product of the cheX gene in Salmonella and the cheB gene in E . coli . In addition, the cheT gene product in S . typhimurium seems to play a role in expression of methylesterase activity . Mutant strains lacking the protein methylesterase tumble incessantly in the absence of attractant gradients . This behavior is the converse of that shown by mutant strains defective in methyltransferase activity, which swim smoothly in the absence of repellent gradients . This finding indicates that reversible methylation acts as a control mechanism and that both a methyltransferase and a protein methylesterase are instrumental in bacterial sensing.

Infect Immun, 1978 Aug, 21(2), 349 - 53
Cellular response in Salmonella typhimurium-infected mice: evaluation of Salmonella receptors of B lymphocytes; Galdiero F et al.; The cellular response in the course of experimental infection with Salmonella typhimurium was studied in mice . T cells were detected by the presence of theta-antigen, B cells by the binding of fluorescent immunoglobulins, and cells with receptors by labeled Salmonella binding . Lymphocytes were from spleen and lymph nodes . Results have been divided into three groups: group A, including mice with slight symptomatology; group B, including those with serious infection symptomatology; and group C, including mice that died in the course of the experiment . In spleen and lymph nodes of group A mice, an increase in the percentage of T and B lymphocytes was observed . This increase reached a peak 10 days after experimental infection . In lymph nodes, the B-cell percentage was equal to the percentage of T cells, whereas in spleen lymphocytes the B-cell percentage was higher . In spleens of group B mice we observed the same response as in mice of group A, whereas in lymph nodes there was a low response of T and B lymphocytes . In group C mice, there was no significant response of T and B lymphocytes in either spleen or lymph nodes . In B lymphocytes prepared from spleens of surviving mice, a small number of Salmonella receptors was detected: 200 bacterial cells per 10(9) lymphocytes.

J Natl Cancer Inst, 1978 Aug, 61(2), 457 - 60
Detection of mutagenicity of the colon carcinogen 1,2-dimethylhydrazine by the host-mediated assay and its correlation to carcinogenicity; Moriya M et al.; Mutagenic potential of 1,2-dimethylhydrazine (DMH) was investigated in the host-mediated assay with mice used as hosts . This assay revealed potent mutagenicity of this colon carcinogen for Salmonella typhimurium G46 . The mutagenicity of DMH was inhibited by pretreatment of mice with disulfiram . In addition, mouse strain and sex differences influenced the mutation induction by DMH: Mutation induction was significantly lower in C57BL/6 mice than in outbred ICR mice of either sex and was generally higher in male than in females of either C57BL/6 or ICR mice.

J Bacteriol, 1978 Aug, 135(2), 687 - 702
Outer membrane of gram-negative bacteria . XVIII . Electron microscopic studies on porin insertion sites and growth of cell surface of Salmonella typhimurium; Smit J et al.; Salmonella typhimurium contains three "major proteins" or "porins" (34K, 35K, and 36K) in the outer membrane . A mutant strain producing only the 35K porin was first grown in media containing high concentrations of NaCl to "repress" the porin synthesis and then was shifted into a medium without NaCl . The newly made porin molecules were then labeled with the ferritin-coupled antibody at various times after the shift, and the samples were examined by whole-mount, freeze-etching, and thin-section electron microscopy . These experiments showed that newly inserted porins appeared as discrete patches uniformly distributed over the surface of the cell and, furthermore, that the sites of adhesion between the inner and outer membrane were most probably the pathway by which the newly made porin molecules appeared on cell surface . The 34K and 36K porins were also inserted in the same manner, since the appearance of new porins at discrete sites all over the cell surface was also observed when cells with wild-type porin phenotype were treated with unlabeled antibody to block existing antigenic sites, subsequently regrown, and labeled with the ferritin-coupled antibody . Since porins comprise a major portion of the densely packed, relatively immobile, "protein framework" of the outer membrane, these results lead us to conclude that the outer membrane grows predominantly by diffuse intercalation rather than by the zonal growth mechanism.

J Bacteriol, 1978 Aug, 135(2), 588 - 94
Salmonella typhimurium mutants lacking protease II; Heiman C et al.; Mutants of Salmonella typhimurium lacking protease II, an endoprotease with trypsin-like specificity, have been isolated . These mutants can be identified by using the chromogenic substrate N-methyl-N-p-toluenesulfonyl-L-lysine beta-naphthyl ester to screen colonies growing on agar for the presence of the enzyme . All of the mutations isolated map at locus tlp (typsin-like protease) which is cotransducible (approximately 1%) using phage P1 with tre (trehalose utilization) at approximately 58 min on the Salmonella map . Double mutants lacking both protease I and protease II have been constructed . These strains grew normally . They were able to degrade abnormal proteins and to carry out protein turnover during carbon starvation at the same rate as the wild type.

J Bacteriol, 1978 Aug, 135(2), 415 - 21
Inducible reactivation and mutagenesis of UV-irradiated bacteriophage P22 in Salmonella typhimurium LT2 containing the plasmid pKM101; Walker GC; The inducible (Weigle) reactivation of UV-irradiated bacteriophage P22 has been examined on strains of Salmonella typhimurium with and without the mutagenesis-enhancing plasmid pKM101 . A large inducible reactivation was observed in the plasmid-containing strain, but only a small response was observed in the strain lacking the plasmid . An increased frequency of clear-plaque mutants was detected among the survivors . The efficiencies of the plasmid-mediated and cellular repair processes have been determined . The kinetics of induction of the phage reactivation have been investigated . The relationship of the observed results to the inducible reactivation of UV-irradiated lambda in Escherichia coli and to error-prone repair is discussed.

Mutat Res, 1978 Aug, 54(1), 1 - 16
Microbial assays for mutagenicity: a modified liquid culture method compared with the agar plate system for precision and sensitivity; Mitchell I; A microbial assay system for mutagenicity was developed in which bacterial cells divided in liquid culture . The statistical and practical problems associated with dividing cells were avoided or reduced, whilst the advantages in precision and reliability resulting from the determination of mutation per colony-forming unit (survivor) and of separating the mutation and selection systems were retained . Seven mutagens, two of which required microsomal activation, were evaluated by this liquid-medium method and by the agar-plate method with two strains of Salmonella typhimurium to determine which assay system was the more sensitive . At highly mutagenic and/or very toxic concentrations of the test substance the liquid-medium assay was markedly more sensitive than the agar-plate assay, but at weakly mutagenic and less toxic concentrations the advantage of the liquid-medium test was reduced; however in only one case was the agar-plate assay obviously the more sensitive . There was a clear indication that the liquid-medium assay would be superior to the agar-plate assay for the detection of mutagenic agents active only at toxic concentrations, and also could be more easily and exactly quantified.

Mutat Res, 1978 Aug, 51(2), 151 - 64
Mutagenicity testing of benomyl, methyl-2-benzimidazole carbamate, streptozotocin and N-methyl-N'-nitro-N-nitrosoguanidine in Salmonella typhimurium in vitro and in rodent host-mediated assays; Ficsor G et al.; The fungicide benomyl and its commercial preparations Fundazol 50WP and Benlate 50WP and the benomyl metabolite methyl-2-benzimidazole carbamate and its commercial preparation MBC 50WP were tested for mutagenicity in in vitro spot tests, in microsomal plate assay, in liquid-culture treatments, or in rodent host-mediated assay . The base-pair substitution Salmonella typhimurium mutant hisG46 and the hisG46-bearing uvrB excision-repair-deficient mutants TA100, TA1530, TA1535 or TA1950 were used as test organisms . Complete genotypic information of these mutants is given in Ames et al . {2} . Captain 50WP, streptozotocin (SZN), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), 2-aminopurine and N-acetylaminofluorene were used as positive control compounds . In nonoverlay spot tests Benlate 50WP was not mutagenic over a dose range of 50-5000 microgram/spot in hisG46 and TA1535 . In overlay spot tests 50 or 100 microgram/spot Benomyl, MBC, Fundazol 50WP, Benlate 50WP and MBC 50WP were tested in hisG46, TA1530 or TA1950 . Only a non-commercial MBC sample at 100 microgram/spot showed weak mutagenic activity in hisG46 . In microsomal activation plate assay MBC, benomyl, Fundazol 50WP and Benlate 50WP were tested in TA100 over a dose range of 50-2000 microgram/plate . None of the compounds showed mutagenicity . In a 20-h liquid-culture treatment 10, 100, 1000 and 10 000 microgram/ml Fundazol 50WP were not mutagenic in TA 30 . In 1-h liquid-culture treatments benomyl, Benlate 50WP or Fundazol 50WP failed to induce mutations in hisG46, TA100 or TA1950 over a dose range of 0.25-1000 microgram/ml . Appropriate positive controls were mutagenic in each experiment . The consistently negative results in this study with commercial MBC and benomyl preparations are contrary to positive results reported earlier with similar methods and similar commercial preparations . Possible reasons to explain the different results are presented . The alkylating agents SZN and MNNG induced fewer mutations in TA1530 and TA1950 uvrB excision-repair-deficient strains than in the hisG46 excision-proficient strain, indicating that with these mutagens excision-repair is also a mutation-prone process . In rodent host-mediated assays with Fundazol 50WP in mice 3 consecutive subcutaneous hourly doses of 500 mg/kg in hisG46 and TA1950 and in rats or mice an oral dose of 4000 mg/kg in TA1950 were not mutagenic . The positive control SZN was mutagenic.

J Lab Clin Med, 1978 Aug, 92(2), 239 - 51
Model for disseminated intravascular coagulation: bacterial sepsis in rhesus monkeys; Wing DA et al.; DIC is a hemorrhagic syndrome frequently encountered as a complication in severe gram-negative bacterial sepsis . An animal model for sepsis-associated DIC was developed in order to permit study of the appearance and development of this syndrome in relation to the entire disease process . Rhesus monkeys (4 to 6 kg) were infected by intravenous injection of 10(9) Salmonella typhimurium organisms and studied for a period of 7 to 10 days following infection . Ten of 23 infected monkeys developed petechial rash characteristic of DIC, which appeared on days 1 to 2 infection and lasted 4 to 5 days . In the group of monkeys developing rash, activation of coagulation was suggested by an 80% decrease in platelet count and 20% to 30% increases in PT and APTT . Fibrinolytic system activation was indicated by the appearance of FDP . Kinin system activation was evidenced by decreases in both prekallikrein nad kininogen . Changes in laboratory tests suggestive of subclinical DIC were also noted in infected monkeys which did not develop a rash . Pathologic evidence of DIC was obtained through observation of numerous fibrin thrombi in the kidneys of the only monkey which died in the course of infection . Occurrence of DIC in association with this experimental infection in rhesus monkeys was established on the basis of clinical, laboratory, and pathologic criteria . Expression of the syndrome on days 1 to 2 following infection correlated with the period of increasing bacteremia.

J Infect Dis, 1978 Aug, 138(2), 134 - 42
Antibacterial functions of macrophages in experimental protein-calorie malnutrition . II . Cellular and humoral factors for chemotaxis, phagocytosis, and intracellular bactericidal activity; Keusch GT et al.; Cellular and humoral aspects of the antibacterial activity of macrophages during experimental protein-calorie malnutrition were studied . There were no defects in chemotaxis or bactericidal activity of cells from protein-deficient animals, although phagocytosis-associated oxygen consumption and hexose monophosphate shunt activity were depressed . However, marked impairment of humoral chemotactic factors generated in the peritoneal cavity by glycogen injection and of heatlabile serum opsonins for Staphylococcus aureus, Escherichia coli, Salmonella typhimurium, and Salmonella enteritidis was found . The studies suggested that some macrophage antibacterial functions measured in vitro are not altered in experimental acute protein-calorie malnutrition, but that serum factors, presumably complement-derived, would limit their in vivo function . Thymic involution and lymphocyte depletion would further impair in vivo cellular immune reactions affected by macrophages . This model may therefore prove useful for the study of specific aspects of cellular immunity in malnourished hosts and of specific rehabilitation strategies.

Immunology, 1978 Aug, 35(2), 307 - 15
Binding properties of goat IgM anti-dinitrophenyl antibodies; Congy N et al.; Goats immunized over 2 months with low doses of 1 mg/kg of dinitrophenylated Salmonella typhimurium responded with low levels of anti-DNP antibodies restricted to the IgM class . The purified antibodies show low association constants (Ka between 10(4) of 10(5) l/M), a high degree of homogeneity (heterogeneity indices alpha between 0.7 and 0.9) and ten combining sites when tested against dinitrophenyl-lysine as ligand by equilibrium dialysis . These binding properties remained unchanged during the whole immune response . When after 9 months the animals received the same immunogen and DNP-BGG, the anti-DNP antibody response included antibodies in the IgG class.

Biochim Biophys Acta, 1978 Jul 3, 541(3), 420 - 4
A mutant of Escherichia coli which accumulates large amounts of coproporphyrin; Kazmi SA et al.; A mutant of Escherichia coli which accumulates a large amount of coproporphyrin, presumably because of a block in heme biosynthesis, has been isolated after nitrosoguanidine mutagenesis . On rich media, the mutant forms colonies which give bright orange fluorescence when illuminated with ultraviolet light . The mutant appears to be similar to a Salmonella typhimurium mutant, deficient in uroporphyrinogen III cosynthase, described by Sasarman and Desrochers ((1976) J . Bacteriol . 128, 717--721) . A striking property of the mutant is that coproporphyrin is retained within the cells in rich media but is almost totally excreted out of cells in minimal glucose medium.

Proc Natl Acad Sci U S A, 1978 Jul, 75(7), 3104 - 8
Direct demonstration of duplicate tuf genes in enteric bacteria; Furano AV; Radioactive tuf mRNA was used to detect the tuf gene in bacterial DNA that had been digested by various restriction endonucleases . Both the K-12 and the B strains of Escherichia coli contain two tuf genes, but no more than two . Salmonella typhimurium also contains duplicate tuf genes.

Mutat Res, 1978 Jul, 57(3), 277 - 86
Microbiological mutagenicity studies of pesticides in vitro; Carere A et al.; 14 pesticides were tested as pure compounds for the induction of point mutations in four strains of Salmonella typhimurium--TA1535, TA1536, TA1537 and TA1538--in the presence and in the absence of rat-liver microsomal fractions and for the induction of resistance to low concentrations of streptomycin in the filamentous bacterium, Streptomyces coelicolor . The technique used was essentially the so-called "spot test" . The pesticides investigated were: aminotriazole, Benomyl, Captafol, Captan, Dichlorvos, Dalapon-Na, Dinobuton, Dodine, Ioxynil, Mecoprop, Neburon, Picloram, Triallate and Trichlorphon . In Salmonella, Captan and Triallate were mutagenic on the TA1535 strain; Dichlorvos and Trichlorphon were negative in the spot test but mutagenic after incubation in liquid cultures of strain TA1535 . By using the S . coelicolor forward-mutation test, aminotriazole, Dichlorvos, Picloram, Trichlorphon and Triallate were mutagenic with the "spot test" technique; Captan showed a weak mutagenic activity with a "plate-incorporated" technique.

Mutat Res, 1978 Jul, 57(3), 265 - 76
Analytical and biological analyses of test materials from the synthetic fuel technologies . I . Mutagenicity of crude oils determined by the Salmonella typhimurium/microsomal activation system; Epler JL et al.; We have assayed the mutagenicity of crude industrial products and effluents with the Salmonella/microsomal activation system . Test materials (crude products from coal-conversion processes and natural crude oils) were initially fractionated into primary classes by liquid--liquid extraction and then further fractionated by column chromatography . Prescreening was accomplished over a wide concentration range with the Ames tester strains . Active fractions (mainly the neutral fractions containing polycyclic aromatic hydrocarbons and certain basic fractions) can be identified, and dose--response relationships can be established . Standard values are expressed as revertants/mg of the test material assayed with frameshift strain TA98 including metabolic activation with rat-liver preparations . Total mutagenic activity of synthetic fuel samples was consistently higher than that of natural crude "controls." Activities of subfractions are roughly additive and presumably reflect the mutagenic potential of the whole test material . These results are being extended to other genetic assays . Chemical identification is carried out along with the bioassays.

J Bacteriol, 1978 Jul, 135(1), 259 - 69
Bacteriophage P22 is not a likely probe for zones of adhesion between the inner and outer membranes of Salmonella typhimurium; Crowlesmith I et al.; Thin-section electron micrographs of plasmolyzed Salmonella typhimurium infected with bacteriophage P22 demonstrated that phage adsorbed to cells over sites of inner- and outer-membrane contact . Efforts were made to isolate such adsorption sites by infection of cells with 35S- and 32P-labeled phage and by separation of the membranes on sucrose gradients . At 37 degrees C, about 75% of the 35S radioactivity could be recovered in a region of intermediate density between the inner and outer membranes . This region (phi band) did not contain 32P . The gradient profile was independent of the multiplicity of infection (between 0.2 and 50) and of the presence or absence of chloramphenicol, dinitrophenol, or cyanide . However, ethylenediaminetetraacetate, when present during the infection step, prevented the formation of phi band . The density of phi band was at least 1.30 g/cm3, as demonstrated by prolonged centrifugation on a D2O-sucrose gradient . phi Band was shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electron microscopy to contain empty phage heads and contaminating cellular debris . In purified preparations, phage heads were the only structures, visible by negative staining, and very little cellular phospholipid or protein was associated with the phage proteins (less than 2% and 30% by weight, respectively, as determined by using {3H}glycerol or {3H}leucine) . The residual cellular protein included all of the major outer-membrane proteins rather than any one specific protein . These results are interpreted as indicating that phi band probably does not contain adhesion site material stably associated with phage heads.

Genetics, 1978 Jul, 89(3), 439 - 51
The nature of genetic instability in auxotrophs of Salmonella typhimurium requiring cysteine or methionine and resistant to inhibition by 1,2,4-triazole; Kingsman AJ et al.; We tested the hypothesis that unstable suppression of auxotrophy in triazole-resistant derivatives of Cym- mutants of Salmonella typhimurium is due to reversible insertion at the Cym- site of genetic material originating in the cysALKptsHI region . We have shown that the unstable phenotype was co-transducible with markers in the cysCDHIJ region . The suppression of the Cym phenotype was recA dependent and frequencies of segregation were affected by UV irradiation . Restored enzyme activity in suppressed strains was determined by wild-type enzyme, suggesting that the unstable regions are located in cys gene regulatory regions . These results support the hypothesis . In contradiction, we found no evidence for a deletion in the cysALKptsHI region.

Cancer Res, 1978 Jul, 38(7), 2191 - 4
1,2-dihydro-1,2-dihydroxy-5-methylchrysene, a major activated metabolite of the environmental carcinogen 5-methylchrysene; Hecht SS et al.; The metabolic activation of the environmental carcinogen 5-methylchrysene was studied by combining high-pressure liquid chromatographic analysis of metabolites formed in vitro with assays of these metabolites for mutagenic activity toward Salmonella typhimurium . Metabolites were formed by incubation of 5-methylchrysene with the 9000 x g supernatant from Aroclor-treated rat livers . With the use of reverse-phase columns, the metabolites were resolved into nine peaks, A to I . Each peak was collected and tested for mutagenicity with activiation . Significant mutagenic activity was observed primarily in peak E and to a lesser extent in peak D . None of the other metabolites showed significant mutagenic activity . The major mutagenic metabolite (peak E) was identified as 1,2-dihydro-1,2-dihydroxy-5-methylchrysene (7.0% from 5-methylchrysene); Peak D was 7,8-dihydro-7,8-dihydroxy-5-methylchrysene (2.6% from 5-methylchrysene) . Other metabolites included 9,10-dihydro-9,10-dihydroxy-5-methylchrysene, 9-hydroxy-5-methylchrysene, 7-hydroxy-5-methylchrysene, 1-hydroxy-5-methylchrysene, and 5-hydroxymethylchrysene . These results indicate that 1,2-dihydro-1,2-dihydroxy-5-methylchrysene is a major proximate mutagen of 5-methylchrysene.

Cancer Res, 1978 Jul, 38(7), 2148 - 56
Mutagenicity of several classes of antitumor agents to Salmonella typhimurium TA98, TA100, and TA92; Seino Y et al.; The mutagenic activities of antitumor agents, including 5 antibiotics, 19 antimetabolites, 5 alkylating agents, 2 alkaloids, 1 enzyme, and 1 adrenal steroid hormone, were tested on Salmonella tyhimurium TA100, TA98, and TA92 . Four of these, busulfan, carbazilquinone, 1-(4-amino-2-methylpyrimidine-5-yl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride, and pipobroman were shown for the first time to be mutagenic . Further, the known mutagenicities of five others, daunomycin hydrochloride, Adriamycin hydrochloride, mitomycin C, 6-mercaptopurine, and cyclophosphamide, were confirmed.

Infect Immun, 1978 Jul, 21(1), 310 - 9
Strain-dependent cytotoxic effects of endotoxin for mouse peritoneal macrophages; Peavy DL et al.; The cytotoxic effects of bacterial lipopolysaccharides (LPS) on mouse leukocytes have been examined in vivo and in vitro . Intraperitoneal injection of LPS into C57BL/6 mice greatly reduced the recovery of mononuclear cells; LPS was cytotoxic for macrophages, but had a mitogenic effect on lymphocytes . Similar effects of LPS on peritoneal leukocytes were observed in vitro . When monolayers of adherent peritoneal cells were studied in vitro, cytotoxicity was also observed, suggesting that the effect of LPS on macrophages is direct and does not require participation by lymphocytes . Entirely different results were obtained when peritoneal macrophages from LPS-resistant C3H/HeJ mice were studied . LPS failed to activate lymphocytes and was not cytotoxic for macrophages in vitro or in vivo . The effect of LPS on polymorphonuclear leukocytes appeared to be the same in all mouse stains studied . Lipid A was shown to be the most biologically active portion of the LPS molecule . Whereas polysaccharide-deficient endotoxins extracted from rough mutants of Salmonella typhimurium were cytotoxic for macrophages in vitro, polysaccharides that lacked esterified fatty acids did not exhibit this activity . Since LPS may mediate its effects through affinity for mammalian cell membranes, the cellular unresponsiveness of C3H/H3J mice to LPS may reflect an inability of cells from LPS-resistant strains to interact with LPS at the membrane level.

Cancer Lett, 1978 Jul, 5(1), 1 - 6
Tissue-mediated mutagenicity of vinylidene chloride in Salmonella typhimurium TA1535; Jones BK et al.; Vinylidene chloride is weakly positive in the Salmonella typhimurium TA1535 test, mediated by kidney and liver post-mitochondrial supernatant (S-9 mix) from normal mice, but strongly positive with the S-9 mix from the induced animals . In the case of mediation by rat tissue, only liver S-9 mix from induced animals affords a significant positive response . These findings agree with the greater availability in treated mice than in rats of reactive vinylidene chloride metabolites, 1,1-dichloroethylene oxide and chloroacetyl chloride {5}, and with the vinylidene carcinogeneicity found in mice but not in rats {9} . Exploratory tissue-mediated testing of vinylidene chloride involving liver S-9 mix from marmosets and man suggests a trend in the generation of alkylating metabolites and their reactions with bacterial DNA for these primates which resembles rats more than mice.

Cancer Lett, 1978 Jul, 5(1), 39 - 47
Direct-acting mutagens in automobile exhaust; Wang YY et al.; Particulate matter in city air contains chemicals which are mutagenic in the Ames Salmonella typhimurium assay . In residential urban areas, the principal mutagens in air do not require liver enzymes to be activated . The source of these liver independent (direct-acting) mutagens may be automobile exhaust because (1) the mutagenic activities were correlated to the lead content or air, (2) the mutagens were found exhaust samples from automobiles and from an experimental CFR single-cylinder gasoline engine, and (3) these mutagens were not found in fuel or unused motor oil, but were found in used motor oil . The strain specificity and the fact that liver enzymes were not required for activation indicated that the exhaust and airborne mutagens were not unsubstituted polycyclic aromatic hydrocarbons (PAH), aromatic amines, alkylnitrosamines or aliphatic epoxides, peroxides and hydroepoxides . A number of nitro-substituted aromatic compounds are direct-acting mutagens in the Ames test, and it is possible that nitration of PAH in exhaust may form the compounds observed here . We synthesized 6-nitrobenzo {a} pyrene and found it to be a potent, direct-acting mutagen with activity comparable to that of benzo-{a} pyrene.

Infect Immun, 1978 Jul, 21(1), 286 - 91
Protective ability of Salmonella ribosomal protein and RNA in inbred mice; Misfeldt ML et al.; Ribosomal vaccines prepared from Salmonella typhimurium were effective immunogens in A/J, C3H/HeDub, and C3H/HeJ mice . Purified ribosomal components were also tested as immunogens in the inbred mice . Protein isolated from a Salmonella ribosomal fraction could protect all three mouse strains . Although purified RNA was shown to be protective for A/J and C3H/HeDub mice, it was not protective for C3H/HeJ mice . Protective immunity could be induced in A/J and C3H/HeDub mice by various immunostimulants . Immunity in C3H/HeJ mice, however, could only be induced by Salmonella ribosomes or protein isolated from the Salmonella ribosomal fraction.

Infect Immun, 1978 Jul, 21(1), 28 - 33
Effects of surface-active agents on neutrophil receptors; Boxer LA et al.; An easily performed assay to identify the C3b and Fc receptors on human neutrophils was developed . Salmonella typhimurium were treated with fluorescein and then incubated in nonimmune fresh human serum, which led to C3b fixation via activation of the alternative pathway . Similarly, type II pneumococci were treated with fluorescein and opsonized with type-specific rabbit antiserum . Neutrophils bearing C3b and Fc receptors formed rosettes with the respective bacteria, which were easily readable because of their bright fluorescence . Incubation of neutrophils at 37 degrees C with C3-coated bacteria generated 54 +/ 4% C3b rosettes, whereas neutrophils incubated with immunoglobulin G-coated bacteria yielded 75 +/ 7% rosettes . Incubation at 4 degrees C inhibited the formation of C3b rosettes but not Fc rosettes . Heat inactivation of the fresh human serum at 56 degrees C for 30 min completely inhibited the formation of the C3b rosettes, and addition of heat-aggregated immunoglobulin G to the polymorphonuclear leukocyte blocked the ability of the polymorphonuclear leukocyte to bind immunoglobulin G-coated bacteria . Addition of 1.0 mM N-ethylmaleimide, 0.1 mg of trypsin per ml, 10 mM H2O2, O2- generated by xanthine-xanthine oxidase, and 8 times 10(-4) M hydrocortisone inhibited the C3b receptor, but did not inhibit the Fc receptor . In neutrophils, the selective effect of the various inhibitors suggests that the Fc and C3b receptors are distinct entities.

Arch Microbiol, 1978 Jul, 118(1), 71 - 7
Utilization of D-amino acids by dadR mutants of Salmonella typhimurium; Wild J et al.; Utilization of D-amino acids being substrates of D-amino acid dehydrogenase of Salmonella typhimurium was examined . The experiments were done with wild type strains and the mutants dadA missing the enzyme activity and dadR in which its synthesis is released from catabolite repression . Growth on D-tryptophan, D-histidine and D-methionine used as precursors of the L-amino acids was faster when the respective auxotrophs carried dadR mutations . The dadR mutants grew faster when D-or L-alanine was present as a sole source of nitrogen . Experiments with D-amino acid dehydrogenase in vitro provided evidence that D-tryptophan is its substrate with a very low affinity to the dehydrogenase.

Mutat Res, 1978 Jul, 57(3), 287 - 96
Differential mutagenicity of reaction products of various pyrazolones with nitrite; Arisawa M et al.; Four pyrazolones in frequent use, i.e . antipyrine (AP), aminopyrine (AMP), sulpyrine (SP) and isopropylantipyrine (IPA), were compared for their reactivity with nitrite and for the in vitro mutagenicity of their reaction products by Ames' reversion tests . In various acidic solutions at 37 degrees C, AP, AMP and SP were found to react easily with nitrite and yield various products including dimethylnitrosamine (DMNA) and 4-nitrosoantipyrine (4-NAP) in the cases of AMP and AP, respectively . When tested with Salmonella typhimurium TA100 and TA98 after lyophilization, the reaction products of AP (AP-N) were found to be mutagenic in both strains, while products of AMP and SP (AMP-N and SP-N) were mutagenic only in TA100 . The presence of unknown ultimate mutagens, other than DMNA and 4-NAP, were evidenced in AP-N, AMP-N and SP-N . Incubation with S-9 mixture did not affect the mutagenicity of SP-N and decreased that of AP-N and AMP-N . In clear contrast to AP, AMP and SP, it was found that IPA remained essentially intact upon reaction with nitrite . No mutagenicity was detected with the reaction mixture (IPA-N) in either strain.

Nouv Presse Med, 1978 Jun 24, 7(25), 2239 - 40
{Post-salmonella rheumatism: case report}; Lemaire V et al.; A twenty seven year old man had polyarthritis following diarrhoea due to Salmonella typhimurium . The role of the salmonella infection in the pathogenesis of this joint problem would appear to be confirmed by the detection of the organism on stool culture and a positive reaction for specific antigens in the blood . The arthritis was cured in six weeks under the influence of non-steroid anti-inflammatory agents.

Br J Cancer, 1978 Jun, 37(6), 873 - 903
An evaluation of 6 short-term tests for detecting organic chemical carcinogens; Purchase IF et al.; A number of tests have been described which are thought to be capable of identifying carcinogens without using the actual induction of cancer as an endpoint . This study compared the performance of 6 such tests on a selection of 120 organic chemicals . The tests studies were: (1) mutation of Salmonella typhimurium; (2) cell transformation; (3) degranulation of endoplasmic reticulum; (4) sebaceous gland suppression; (5) tetrazolium reduction and (6) subcutaneous implant . A further 4 tests were examined briefly, but were not included in the complete evaluation . The chemicals were classified into carcinogens (58) and non-carcinogens (62) on the basis of published experimental data, and into 1 of 4 broad chemical classes . There was considerable variation between tests in their ability to predict carcinogenicity, with the cell-transformation test and the bacterial-mutation test being the most accurate (94% and 93% accurate respectively) . These 2 tests were considered to be of general use in screening, since they were clearly more accurate than the others . Statistical consideration of various combinations of these tests showed that the use of cell transformation and bacterial mutation together, provide an advantage over the use of either test alone . The inclusion of the other 4 tests in a screening battery predictably resulted in a great increase in overall inaccuracy and loss of discrimination, even though the detection of carcinogens is improved . All the tests were shown to generate both false positive and false negative results, a situation which may be controlled by the use, where possible, of appropriate chemical-class controls, to identify the test which is optimal for the class of chemical under test . Structural analogy may have a part to play in the rapid detection of environmental carcinogens, and some general guidelines for its use are given.

Appl Environ Microbiol, 1978 Jun, 35(6), 1160 - 5
Survival of a Salmonella typhimurium experimental contaminant during cooking of beef roasts; Blankenship LC; Twenty-one raw boneless beef roasts were experimentally injected with 2 X 10(7) cells of a nalidixic acid-resistant strain of Salmonella typhimurium per roast . Contaminated roasts were cooked to center internal temperatures of 137.0 to 147.5 degrees F (58.3 to 64.1 degrees C) in a gas-fired pilot plant food-processing oven . Viable experimental contaminants were recovered from two core samples of the 21 roasts (one cooked to 137.0 degrees F {58.3 degrees C} and one cooked to 141.5 degrees F {ca 60.8 degrees C}) . All of 17 cooking net samples taken from the contaminant injection side of roasts were salmonella positive, whereas 7 of 9 net samples from the side opposite injection were positive and all of 11 net samples from the bottom of roasts were positive . The implications of these results are discussed in relation to salmonella contamination of precooked beef roasts.

Appl Environ Microbiol, 1978 Jun, 35(6), 1150 - 4
Detection of mutagens produced by fungi with the Salmonella typhimurium assay; Bjeldanes LF et al.; Forty-one fungal isolates (one isolate per species) representing common plant pathogens and food crop contaminants were grown on sterile, polished rice and assayed for mutagenic activity in the Salmonella typhimurium-microsome system . Initially, single doses of aqueous and chloroform extracts of the moldy rice were assayed against the TA100 tester strain by incorporating extracts into the growth medium and by applying small quantities on disks placed on the agar surface . Suspected activity was examined further by analysis of several doses in the plate incorporation assay . Extracts of two aflatoxin-producing isolates (Aspergillus flavus and A . parasiticus) showed pronounced mutagenic activity, as did extracts of five other isolates (A . heterothallicus, A . nidulans, A . terricola, Alternaria tenuis, and Fusarium moniliforme) which did not contain detectable aflatoxins . Seven additional isolates (Botrytis cineria, Ceratocystis fimbriata, Cladosporium herbarum, Fusarium solani f . sp . pisi, Penicillium oxalicum, Thermomyces lanuginosus, and Verticilium albo-atrum) revealed activity which was possibly mutagenic; i.e., mutagenic responses were not observed in both the disk and incorporation assays, and clear dose-related activity was not observed in the incorporation assay . Extracts of the remaining fungi were not mutagenic in the bacterial assay.

Proc Natl Acad Sci U S A, 1978 Jun, 75(6), 2820 - 4
Potentiation, desensitization, and inversion of response in bacterial sensing of chemical stimuli; Rubik BA et al.; Behavior patterns of chemotactic mutants of Salmonella typhimurium were compared to those of the wild type by using the quantitative tumble frequency assay . Some cheU mutants were completely inverted in their responses--e.g., attractants produce responses expected for repellents and repellents produce responses expected for attractants . Still others swam smoothly and did not respond to any stimuli . Mutants of other complementation groups were found to exhibit exact additivity or potentiation in response to multiple stimuli whereas the wild type showed desensitization . The results suggest that the cheU gene product acts as a switch at the interface between the sensing system and the motor response . The system is finely tuned so that changes in individual proteins can produce potentiation, desensitization, exact additivity, or inversion of responses.

J Natl Cancer Inst, 1978 Jun, 60(6), 1495 - 7
Mutagenicity of nitrosourea compounds for Salmonella typhimurium; Auletta AE et al.; The nitrosourea derivatives 1,3-bis(2-chloroethyl)-1-nitrosourea (NSC-409962), 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU; NSC-79037), 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (Me-CCNU; NSC-95441), and 1-methyl-1-nitrosourea (MNU; NSC-23909) were screened for mutagenic potential with Salmonella typhimurium strains G46 and TA1530 in vitro and in vivo . Alu were also mutagenic in the host-mediated assay . Four additional chemotherapeutic nitrosoureas were tested in vitro, three of which were mutagenic . The lack of activity of the fourth agent was probably a reflection of its stability in solution rather than a true indication of mutagenic potential . All eight agents were tested in a repair test with S . typhimurium strains TA1978 and TA1538 . Results of this test were negative, reflecting the insensitivity of these strains to ethylating and methylating agents . The insensitivity of the host-mediated assay is also discussed.

J Bacteriol, 1978 Jun, 134(3), 751 - 6
Effect of substitution of monovalent anions in external medium on the swimming pattern of Salmonella typhimurium; Hosoi S et al.; The effect of replacement of ions in the extracellular medium on the swimming pattern of bacteria (Salmonella typhimurium) has been investigated . The replacement of chloride ion (Cl-) in the standard medium by methanesulfonate ion (MS-) or by propionate ion (Pr-) induced an increase in the tumbling frequency, or a decrease of the end-to-end distances of tracks . Replacement of MS- by Cl- resulted in transient depression of tumbling, and replacement of Pr- by Cl- resulted in immediate recovery of normal swimming . The replacement of cations was not very effective . The experimental data, including the dependence of the effect of replacement on the ion concentration, are consistent with the ideas that the tumbling frequency increases with depolarization of the bacterial membrane and that such anions as MS- and Pr- are more able to permeate the membrane than is Cl-.

Cancer Res, 1978 Jun, 38(6), 1595 - 600
Alkyl methane sulfonate mutation of diploid human lymphoblasts and Salmonella typhimurium; Hoppe H 4th et al.; Concentration dependence of mutation in equigenerational exposures to methyl, ethyl, propyl, and butyl methanesulfonates has been determined in diploid human lymphoblasts and Salmonella typhimurium . Forward mutation was measured at the hypoxanthine guanine phosphoribosyltransferase locus in human lymphoblasts and at the putative guanine phosphoribosyltransferase locus in S . typhimurium . Reverse mutation at the his G46 locus was also measured in S . typhimurium . This analysis and previous reports support the conclusion that S . typhimurium and mammalian cells are essentially equisensitive to the mutagenic effects of ethyl methanesulfonate when concentration and exposure time are taken into account . Comparison of forward and reverse mutation assays in S . typhimurium reveals no important differences in sensitivities for the four compounds studied.

C R Acad Sci Hebd Seances Acad Sci D, 1978 Jun, 286(22), 1633 - 5
{Protective action on mice of acellular extracts from Salmonella typhimurium}; Golebiowski TE et al.; Acellular fractions obtained by saline extraction at 60 or at 100 degree C of Salmonella typhimurium protect mice against an experimental infection with the homologous strain . After purification, these fractions which are complex, might be used for the development of a vaccine.

J Bacteriol, 1978 Jun, 134(3), 1046 - 55
Mutations that alter the covalent modification of glutamine synthetase in Salmonella typhimurium; Bancroft S et al.; glnD and glnE mutant strains of Salmonella typhimurium lack three of the four activities required for reversible covalent modification of glutamine synthetase (GS; EC 6.3.1.2) . The glnD strains, which are unable to deadenylylate GS and therefore accumulate the adenylylated or less active form of the enzyme, were isolated as glutamine bradytrophs . They lack the activity of PIIA uridylyl-transferase, one of the proteins required for deadenylylation of GS; in addition, they lack PIID uridylyl-removing activity . Mutations in glnD are suppressed by second-site mutations in glnE that eliminate the activity of GS adenylyltransferase (EC 2.7.7.42) and thus prevent adenylylation of GS . The glnD and glnE strains have one-third to one-half as much total GS as the wild-type strain when they are grown in a medium containing a high concentration of NH4+ . The wild-type strain derepresses synthesis of GS fourfold in response to nitrogen limitation; glnD and glnE strains derepress synthesis of the enzyme fourfold and sevenfold, respectively . Thus, mutations that alter covalent modification of GS in Salmonella do not significantly affect derepression of its synthesis . The glnD gene lies at 7 min on the Salmonella chromosome and is 50% linked to pyrH by P22-mediated transduction.

Mol Gen Genet, 1978 May 31, 161(3), 333 - 5
Arginine regulon control in a Salmonella typhimurium--Escherichia coli hybrid merodiploid; Kelln RA et al.; The regulation of synthesis of arg enzymes was studied in a hybrid merodiploid in which an episome of Escherichia coli carrying the argR+ allele was transfered to Salmonella typhimurium argR strain . The arg enzyme levels of the hybrid merodiploid were compared to that found in argR and argR+ haploids of S . typhimurium . The results showed that repression of synthesis of arg enzymes was effected through the introduction of the E . coli argR+ allele but significant quantitative differences of arg enzyme levels in the argR+ haploid and the hybrid merodiploid were observed.

Eur J Biochem, 1978 May 16, 86(2), 487 - 96
The acceptor for polar head groups of the lipid A component of Salmonella lipopolysaccharides; Lehmann V et al.; We describe here experiments which determine at which stage in the lipid A biosynthesis the polar head groups 4-aminoarabinose, phosphorylethanolamine and 3-deoxy-D-manno-octulosonic acid are transferred to the diphosphorylated glucosamine backbone of the lipid A structure . Use was made of a conditional lethal mutant of Salmonella typhimurium (Ts1) which is defective in the synthesis of 3-deoxy-D-manno-octulosonic acid 8-phosphate and accumulates under nonpermissive conditions an underacylated lipid A intermediate {Lehmann, Rupprecht and Osborn (1977) Eur . J . Biochem . 76, 41-49} . Pulse-chase experiments, including a detailed analysis of radioactive pulse and chase products, demonstrated that this underacylated compound is a key intermediate in the lipid A synthesis . It can serve as direct acceptor for the incorporation of the polar head groups 4-aminoarabinose, phosphorylethanolamine and 3-deoxy-D-manno-octulosonic acid . On the basis of these findings some steps in the sequence of reactions involved in the lipid A biosynthesis are proposed.

Infect Immun, 1978 May, 20(2), 375 - 80
Production and partial purification of Salmonella enterotoxin; Sedlock DM et al.; By using a strain of Salmonella typhimurium, we detected the presence of an enterotoxin, as determined by the rabbit ileal loop assay, in various complex and defined media . The enterotoxin was concentrated by ultrafiltration of culture supernatant fluids and eluted in and adjacent to the void volume of a Sephadex G-100 column . This suggested that the enterotoxic factor was of a relatively high molecular weight, and additional evidence indicated it was heterogeneous in size . Further chromatography, using a diethylaminoethyl-cellulose anion exchanger, facilitated at least a 50-fold purification of the Salmonella enterotoxin.

Genetika, 1978 May, 14(5), 900 - 8
{Mutagenic activity of dioxydine}; Fonshtein LM et al.; A previous evaluation of mutagenic activity of some drugs and perspective substances is carried out using indicator microorganisms . The mutagenicity of dioxydine, a drag with discovered antibacterial activity, is investigated . Dioxydine is shown to induce reversions in mutant of Salmonella typhimurium TA-1950, the indicator strain which demonstrates mutagenic activity of agents, producing mutations of base pair substitution type . Dioxydine proved to affect logariphmiically growing bacterial culture with great activity . Mutageni effect of dioxydine is not modified itself in microsomal oxidation system in vitro . Some data concerning participation of excision reparation enzyme (uvr-B+ gene product) in repair of lethal damages induced by dioxydine, have been obtained . The dioxydine ability to cause bacterial gene mutations in host mediated assay as well as dominant and recessive sex-linked lethal mutations in Drosophila is demonstrated . Dioxydine is capable of inducing chromosome aberrations in bone marrow cells and dominant lethal mutations in mouse germ cells.

Mutat Res, 1978 May, 57(2), 127 - 34
Mutagenicity of N-nitrosopiperazine derivatives in Salmonella typhimurium; Rao TK et al.; Mutagenicity of several nitroso derivatives of piperazine was assayed using histidine auxotrophic strains of Salmonella typhimurium . Nitroso derivatives of piperazine required metabolic activation with preference to phenobarbital induced rat-liver microsomal enzymes . We observed a good correlation between a positive effect in the mutation assay and the carcinogenic potency of the compound . Even though our results are not in complete agreement with earlier published work using several microbial mutation assay systems, the differences we observed demonstrate the predictive value of an in vitro activation system using S . typhimurium to detect carcinogenic compounds as mutagens.

J Immunol, 1978 May, 120(5), 1750 - 7
Immunochemistry of Salmonella O-antigens: preparation of an octasaccharide-bovine serum albumin immunogen representative of Salmonella serogroup B O-antigen and characterization of the antibody response; Svenson SB et al.; The O-antigenic polysaccharide of phenol-water extracted Salmonella typhimurium (O antigens 4, 12) lipopolysaccharide was enzymatically cleaved by phage P22 endorhamnosidase . An octasaccharide with the (formula: see text) structure Gal-Man-Rha-Gal-Man-Rha was isolated and shown to retain the O-antigen 4 specificity of the native polysaccharide . After oxidation of the terminal reducing rhamnose residue to the corresponding aldonic acid, the octasaccharide was covalently linked to bovine serum albumin (OLS-BSA) by use of a water-soluble carbodimide . The resulting conjugate showed O-antigen 4 specificity in enzyme-linked immunosorbent assay (ELISA) ans passive hemagglutination inhibition tests . Immunization of rabbits with the OLS-BSA conjugate gave rise to antibodies directed toward both the octasaccharide and the carrier protein . ELISA titration with synthetic disaccharide-protein conjugates as antigens revealed that the antibody titer against the mannose-rhamnose structure was higher than against the abequose-mannose structure . In rabbits immunized with heat-killed whole bacteria the titers against the two disaccharides were equal . The reason for this difference is not obvious . It is evident, however, that the OLS-BSA conjugate elicited in rabbits O-antibodies with the same specificity as whole bacteria.

J Bacteriol, 1978 May, 134(2), 612 - 20
Characterization of a Salmonella typhimurium hisU mutant defective in tRNA precursor processing; Bossi L et al.; The DA11 mutant of Salmonella typhimurium, originally isolated as derepressed for the histidine operon, carries a temperature-dependent alteration in a nucleolytic enzyme specifically involved in the maturation of tRNA . As a consequence of this alteration, no detectable synthesis of any mature tRNA species occurs in DA11 upon shift at 43 degrees C, whereas many tRNA precursors, whose sizes range between 80 and 750 nucleotides, do accumulate . Kinetic studies on the synthesis and processing of these maturation intermediates show that these molecules represent different stages in the maturation pathway, most of them being the products of previous nucleolytic events . These RNA molecules are in vivo substrates of methylation and thiolation enzymes and can be cleaved in vitro to 4S RNA by wild-type but not by DA11 cell-free extract . Evidence is presented that DA11 is very probably a ribonuclease P mutant.

Br Poult Sci, 1978 May, 19(3), 309 - 14
An epizootic of Salmonella typhimurium var . copenhagen in broilers and the use of cultured chicken interestinal flora for its control; Seuna E et al.; 1 . An epizootic caused by Salmonella typhimurium var . copenhagen and occurring on the farms of one company was examined with the following factors in mind: the spread of the epizootic, the infection rate of the flocks and the role of the food, hatchery and parent stock . 2 . A microbiological technique was used the aim of preventing infection on the farms . 3 . The method of control was not as effective the field as in the laboratory; the possible reasons for this are discussed.

Cancer Res, 1978 May, 38(5), 1307 - 10
Inhibitory effect of reducing agents on N-acetoxy- and N-hydroxy-2-acetylaminofluorene-induced mutagenesis; Rosin MP et al.; The effect of cysteine (alpha-amino-beta-mercaptopropionic acid) on the mutagenic activities of the proximate carcinogen, N-hydroxy-2-acetylaminofluorene, and the ultimate carcinogen, N-acetoxy-2-acetylaminofluorene, was examined by estimating the frequency of his+ revertants of Salmonella typhimurium . Nontoxic concentrations of cysteine significantly reduced the formation of revertants when it was applied concurrently with the two carcinogens . Cysteine showed no detectable effect on mutagenesis when added to bacteria before or after exposure to carcinogens . The magnitude of inhibition of mutagenesis depended on the dose of cysteine and the concentration of the carcinogens . Cysteine at equimolar concentrations inhibited to a larger degree the mutagenesis induced by N-hydroxy-2-acetylaminofluorene than it inhibited that elicited by N-acetoxy-2-acetylaminofluorene . The inhibitory action of cysteamine and glutathione was comparable to that of cysteine . The results appear to be consistent with the assumption that cysteine traps electrophiles prior to their action on DNA.

J Bacteriol, 1978 May, 134(2), 361 - 74
Salmonella typhimurium peptidase active on carnosine; Kirsh M et al.; Wild-type Salmonella typhimurium can use carnosine (beta-alanyl-L-histidine) as a source of histidine, but carnosine utilization is blocked in particular mutants defective in the constitutive enzyme peptidase D, the product of the pepD gene . Biochemical evidence for assigning carnosinase activity to peptidase D (a broad-specificity dipeptidase) includes: (i) coelution of carnosinase and dipeptidase activity from diethylaminoethyl-cellulose and Bio-Gel P-300 columns; (ii) coelectrophoresis of carnosinase and dipeptidase on polyacrylamide gels; and (iii) inactivation of carnosinase and dipeptidase activities at identical rates at both 4 and 42 degrees C . Genetic evidence indicates that mutations leading to loss of carnosinase activity map at pepD . Several independent pepD mutants have been isolated by different selection procedures, and the patterns of peptide utilization of strains carrying various pepD alleles have been studied . Many pepD mutations lead to the production of partially active peptidase D enzymes with substrate specificities that differ strikingly from those of the wild-type enzyme . The growth yields of carnosinase-deficient strains growing in Difco nutrient broth indicate that carnosine is the major utilizable source of histidine in this medium.

Vet Rec, 1978 Apr 22, 102(16), 354 - 6
Oral administration of neomycin to chickens experimentally infected with Salmonella typhimurium; Smith HW et al.; Groups of healthy chickens with a light experimental Salmonella typhimurium infection were fed on a diet containing 225 g per ton (1016 kg) of neomycin for two days . This brought about only a slight reduction in the incidence of chickens that were excreting S typhimurium in their faeces . Examination of caecal contents two days after the cessation of treatment revealed the neomycin had not had any effect in eliminating infection . In one experiment, the neomycin administration resulted in the emergence of enormous populations of Escherichia coli in the alimentary tract of treated chickens that possessed multiple antibiotic resistance of the transmissible type . For these reasons the practice of feeding broiler chickens on diets containing neomycin immediately before slaughter should be actively discouraged.

Science, 1978 Apr 21, 200(4339), 329 - 30
Crankcase oils: are they a major mutagenic burden in the aquatic environment?
Payne JF, Martins I, Rahimtula A.
Fractions from used crankcase oil enriched in polyaromatic hydrocarbons induced revertant colonies in Salmonella typhimurium strain TA 98 when activated by rat or trout liver extracts . The mutagenic activity was not due to benzopyrene or benzanthracene . Fractions from various crude and refined petroleums were nonmutagenic . Among various petroleum hydrocarbons entering inland and coastal waters, used crankcase oils may represent a major mutagenic burden.

Am J Physiol, 1978 Apr, 234(4), E399 - 406
Involvement of hepatic metallothioneins in hypozincemia associated with bacterial infection; Sobocinski PZ et al.; Hypozincemia was induced in rats by Salmonella typhimurium and live vaccine strain Francisella tularensis (LVS) infections . Hepatic synthesis of zinc-binding proteins (ZBP) was studied in order to elucidate the mechanisms involved in the redistribution of zinc from plasma to liver occurring during infectious illness . ZBP, labeled in vivo with 65Zn, were isolated and identified as metallothioneins based, in part, on their heat stability, dimorphism, and amino acid composition . Cysteine was the major amino acid found in both forms of metallothionein and constituted 28-31% of total residues . The apparent half-life of these proteins as measured by disappearance of 65Zn was determined to be 19 h in a relatively mild infection (LVS) and 38 h in a more severe S . typhimurium infection . Results provide evidence that metallothioneins not only have the previously postulated regulatory role in normal zinc homeostasis but are intimately involved in the zinc redistribution occurring during the acute stage of infectious illness.

Appl Environ Microbiol, 1978 Apr, 35(4), 659 - 62
Lack of mutagenicity to Salmonella typhimurium of some Fusarium mycotoxins; Wehner FC et al.; The mutagenicity of eight Fusarium toxins (mono-, di-, and triacetoxyscirpenol, T-2 toxin, deoxynivalenol, 3-acetyl-deoxynivalenol, zearalenone, and moniliformin) and of two positive controls (aflatoxin B1 and sterigmatocystin) to histidine-requiring strains TA 98, 100, 1535, and 1537 of Salmonella typhimurium was tested both with and without metabolic activation . Both aflatoxin B1 and sterigmatocystin, but none of the eight Fusarium toxins, were mutagenic to S . typhimurium . The lack of mutagenic activity of T-2 toxin and diacetoxyscirpenol supports the negative results that have been obtained with in vivo carcinogenicity tests . The negative mutagenicity of the four other 12,13-epoxytrichothecenes tested, and of zearalenone and moniliformin, could not be correlated with in vivo tests because published accounts of their chronic toxicity were not available.

Biophys J, 1978 Apr, 22(1), 79 - 96
The measurement of bacterial translation by photon correlation spectroscopy; Stock GB et al.; Photon correlation spectroscopy is shown to be a practical technique for the accurate determination of translational speeds of bacteria . Though other attempts have been made to use light scattering as a probe of various aspects of bacterial motility, no other comprehensive studies to establish firmly the basic capabilities and limitations of the technique have been published . The intrinsic accuracy of the assay of translational speeds by photon correlation spectroscopy is investigated by analysis of synthetic autocorrelation data; consistently accurate estimates of the mean and second moment of the speed distribution can be calculated . Extensive analyses of experimental preparations of Salmonella typhimurium examine the possible sources of experimental difficulty with the assay . Cinematography confirms the bacterial speed estimates obtained by photon correlation techniques.

J Bacteriol, 1978 Apr, 134(1), 356 - 8
Cyclic AMP-dependent synthesis of fimbriae in Salmonella typhimurium: effects of cya and pts mutations; Saier MH Jr et al.; Synthesis of bacterial fimbriae (group 1, subtype 1) was shown to be dependent on cyclic AMP and was subject to catabolite repression by many carbohydrates . Mutations in the genes coding for the energy-coupling protein constituents of the phosphoenolpyruvate:sugar phosphotransferase system prevented repression of fimbrial production by the sugar substrates of this enzyme system.

J Biol Chem, 1978 Mar 10, 253(5), 1503 - 11
Biosynthesis of lipid A . Enzymatic incorporation of 3-deoxy-D-mannooctulosonate into a precursor of lipid A in Salmonella typhimurium; Munson RS Jr et al.; The cell envelope fraction of Salmonella typhimurium contains an enzyme system which catalyzes transfer of 3-deoxyoctulosonate (KDO) from CMP-KDO to an incomplete, KDO-deficient precursor of lipid A . The enzyme system is firmly membrane-bound, but has been solubilized by treatment with nonionic detergent at alkaline pH and partially purified . Both the particulate and partially purified fractions catalyzed formation of a single reaction product containing 2 residues of KDO . Periodate oxidation of the purified product permitted tentative identification of the KDO disaccharide structure as KDO2-4KDO.

Nucleic Acids Res, 1978 Mar, 5(3), 1041 - 57
The identification of the tRNA substrates for the supK tRNA methylase; Pope WT et al.; Purified preparations of the tRNA methylase deficient in supK strains of Salmonella typhimurium transfer methyl groups from S-adenosylmethionine (SAM) to at least two tRNA species, an alanine tRNA and a serine tRNA . The identity of the tRNA substrates for this enzyme was determined by a change in the elution position of the methyl-labeled tRNA from BND-cellulose columns before and after aminoacylation with a specific amino acid followed by derivatization of the free primary amino group with phenoxy- or naphthoxyacetate . The radioactive methyl group enzymatically added to these tRNAs is both acid and base labile and can be hydrolyzed to a volatile product at pHs above 7.5 and also at pH 1 . The methylated 3'-nucleotide isolated from digested tRNA is a pyrimidine derivative and chromatographs like a modified uridylic acid . Its identity has not been established, but it is likely that it corresponds to the methyl ester of V, uridin-5-oxyacetic acid.

Mutat Res, 1978 Mar, 57(1), 11 - 5
Genetic activity of allyl chloride; McCoy EC et al.; Allyl chloride (3-chloroprene) is mutagenic for Salmonella typhimurium and it induces gene conversions in Saccharomyces cerevisiae . It also displays DNA-modifying activity for E . coli . This is in contrast to a recent study which reported its lack of genetic activity for Salmonella typhimurium.

Mutat Res, 1978 Mar, 57(1), 1 - 10
The mutagenicity of heterocyclic N-nitrosamines for Salmonella typhimurium; Zeiger E et al.; 14 carcinogenic and noncarcinogenic heterocyclic N-nitrosamines were evaluated for mutagenicity to Salmonella typhimurium TA-1535, which responds to mutagens inducing base-pair substitutions . Both suspension and plate tests were used, with mouse and rat liver in vitro metabolic activation systems . All carcinogenic nitrosamines showed a positive response in at least one test system, as did the noncarcinogens . In general, the mutagenic responses obtained with mouse liver were equal to, or greater than, the responses obtained with rat liver in both the suspension and plate tests . Although it is difficult to make quantitative comparisons between plate and suspension tests, both systems appeared to be responsive to the same dose ranges for the individual nitrosamines.

J Bacteriol, 1978 Mar, 133(3), 1467 - 71
Role of murein lipoprotein in morphogenesis of the bacterial division septum: phenotypic similarity of lkyD and lpo mutants; Fung J et al.; Phenotypes were compared in two different classes of mutants with defects in murein-lipoprotein (lkyD mutants of Salmonella typhimurium and an lpo mutant of Escherichia coli) . Both mutations are associated with the same triad of phenotypic abnormalities, consisting of defective formation of the division septum, leakage of periplasmic proteins during growth, and increased sensitivity to several unrelated external toxic agents . The abnormality in septum formation consists of a defect in invagination of the outer membrane during formation of the nascent septum . The results suggest that formation of the murein-lipoprotein link plays an important role in differentiation of the division septum and perhaps also in maintaining the normal barrier function of the outer membrane.

J Bacteriol, 1978 Mar, 133(3), 1412 - 8
Transmembrane permeability channels in vesicles reconstituted from single species of porins from Salmonella typhimurium; Nakae T et al.; Aggregates of the "major" outer membrane proteins, "porins," of Salmonella typhimurium form diffusion channels in reconstituted vesicle membranes . The aggregate consists of three species of porins with apparent molecular weights of 34,000, 35,000, and 36,000 when active aggregates are subjected to sodium dodecyl sulfate-acrylamide gel electrophoresis after heating in the presence of sodium dodecyl sulfate (Nakae, J . Biol . Chem . 251:2176-2178, 1976) . Single species of porins were isolated by solubilization of membranes and subsequent gel filtration in the presence of sodium dodecyl sulfate from the mutant strains of Salmonella typhimurium that produced only single species of porin . The single species of porins of either 34,000, 35,000, or 36,000 daltons formed diffusion channels when assayed for sucrose permeability in the vesicle membranes reconstituted from porins, phospholipids, and lipopolysaccharides . The exclusion limits of the pores made of single species of porins were not distinguishable from each other and from the exclusion limits of the pores made of the porin aggregates from the wild-type strain, when the permeability of vesicle membranes to radioactive di-, tri-, and tetrasaccharides and to various sizes of radioactive polyethylene glycol was determined . Porin-deficient mutants produced residual amounts of porin amounting to 1 to 5% that produced by the parent strain . This residual porin made diffusion channels when the isolated porins were incorporated into the vesicle membrane and assayed for permeability of saccharides.

J Bacteriol, 1978 Mar, 133(3), 1358 - 67
Permease-specific mutations in Salmonella typhimurium and Escherichia coli that release the glycerol, maltose, melibiose, and lactose transport systems from regulation by the phosphoenolpyruvate:sugar phosphotransferase system; Saier MH Jr et al.; Several carbohydrate permease systems in Salmonella typhimurium and Escherichia coli are sensitive to regulation by the phosphoenolpyruvate:sugar phosphotransferase system . Mutant Salmonella strains were isolated in which individual transport systems had been rendered insensitive to regulation by sugar substrates of the phosphotransferase system . In one such strain, glycerol uptake was insensitive to regulation; in another, the maltose transport system was resistant to inhibition; and in a third, the regulatory mutation specifically rendered the melibiose permease insensitive to regulation . An analogous mutation in E . coli abolished inhibition of the transport of beta-galactosides via the lactose permease system . The mutations were mapped near the genes which code for the affected transport proteins . The regulatory mutations rendered utilization of the particular carbohydrates resistant to inhibition and synthesis of the corresponding catabolic enzymes partially insensitive to repressive control by sugar substrates of the phosphotransferase system . Studies of repression of beta-galactosidase synthesis in E . coli were conducted with both lactose and isopropyl beta-thiogalactoside as exogenous sources of inducer . Employing high concentrations of isopropyl beta-thiogalactoside, repression of beta-galactosidase synthesis was not altered by the lactose-specific transport regulation-resistant mutation . By contrast, the more severe repression observed with lactose as the exogenous source of inducer was partially abolished by this regulatory mutation . The results support the conclusions that several transport systems, including the lactose permease system, are subject to allosteric regulation and that inhibition of inducer uptake is a primary cause of the repression of catabolic enzyme synthesis.

J Bacteriol, 1978 Mar, 133(3), 1203 - 11
Isolation and characterization of mutants of the plasmid pKM101 deficient in their ability to enhance mutagenesis and repair; Walker GC; A screening procedure was developed for identifying mutants of the plasmid pKM101 no longer capable of enhancing mutagenesis . The test was based on the large pKM101-mediated increase in the number of Gal+ papillae observed on colonies of Salmonella typhimurium gal mutants plated on tetrazolium-galactose plates in the presence of a mutagen . The pKM101 mutant plasmids transferred normally, were stably maintained in cells, caused normal levels of ampicillin resistance, and still imparted sensitivity to phage Ike to their hosts . However, the pKM101 mutants had lost the ability to (i) enhance the reversion of both point and frameshift mutations, (ii) protect the cells against killing by UV irradiation, (iii) increase the spontaneous reversion rates of point mutations, (iv) enhance plasmid-mediated reactivation of UV-irradiated phage P22, (v) enhance Weigle reactivation . One pKM101 mutant with different properties from the others was identified by its increased spontaneous mutator effect . It is suggested that pKM101 amplifies the activity of the inducible error-prone repair systems in bacteria and that this is the function of pKM101 in the Ames Salmonella tester strains used for detection of carcinogens as mutagens.

Appl Environ Microbiol, 1978 Mar, 35(3), 483 - 6
Recovery of sublethally heat-injured Salmonella typhimurium on supplemented plating media; D'Aoust JY; The efficacy of 32 additives to Levine eosin-methylene blue-salts agar medium (EMBS) for the recovery of sublethally heat-injured Salmonella typhimurium was evaluated . In order of decreasing effectiveness, lactate, mannitol, and alpha-glycerophosphate mediated 90% or more recovery of injured cells; similar levels of recovery were obtained on EMBS supplemented with 1% (wt/vol) tryptic soy broth, protease peptone, or plate count agar . Other additives showed little or no capacity for repair or strongly inhibited heated and nonheated cell suspensions . Conditions of growth and storage before heat treatment were also found to markedly affect susceptibility to heat injury.

Am Surg, 1978 Mar, 44(3), 174 - 6
Salmonella typhimurium pancreatic abscess: report of a case; Strand CL et al.; A case of pancreatic abscess from Salmonella typhimurium is reported . After surgical drainage of the abscess, positive stool cultures persisted . Finally, after intensive antimicrobial therapy with tetracycline and chloramphenicol, and cholecystectomy, stool cultures became negative . This is, to our knowledge, the first published case of S . typhimurium pancreative abscess.

Z Naturforsch {C}, 1978 Mar-Apr, 33(3-4), 235 - 44
On the evolution of an oligocephalic enzyme . glutamine-chorismate-amidotransferase-free anthranilate phosphoribosyltransferases from mutant strains of Salmonella typhimurium; Grieshaber M; (1) A procedure has been described for the purification of two glutamine-chorismate-amidotransferase-free anthranilate phosphoribosyltransferases from mutant strains TAX6trpR782 and trpAB1653trpR782 of Salmonella typhimurium . (2) The native enzymes tend to aggregate forming polymers of molecular weights 333,000 in the case of TAXtrpR782 and 220,000 and larger than 1X10(6) in the case of trpAB1653trpR782 . In the presence of sodium dodecyl sulfate the polymer of trpAB1653trpR782 dissociates into a single component with molecular weight of 72,000 . (3) In contrast to anthranilate phosphoribosyltransferase of the wild type component II, the glutamine-chorismate-amidotransferase-free proteins do not complex with component I . They do however show catalytical similarities with the wild type with respect to anthranilate phosphoribosyltransferase activity.

Mol Gen Genet, 1978 Feb 27, 159(3), 293 - 6
Superinfection exclusion and changes in cellular transport processes in phage infected Salmonella typhimurium; Taneja SK et al.; The changes induced by bacteriophage P22 in the cellular transport process(es) of the host Salmonella typhimurium (Taneja et al., 1975; Khandekar et al., 1975; Bandyopadhyay and Chakravorty, 1976) involve interactions between the superinfection exclusion system of the resident prophage and the C immunity region of the superinfecting phage . The sie A gene of the prophage interferes with the changes in the cellular transport process induced by the superinfecting phage . However, if the superinfecting phage carries active C1 and C2 genes there is no such interference . Thus the C1 and C2 genes of the superinfecting phage seem to be expressed in the sieA+ lysogen.

Vet Rec, 1978 Feb 18, 102(7), 143 - 5
Detection of Salmonella typhimurium infection of chickens; Thain JA; The serological response of two groups of chickens was followed by three techniques after experimental infection of one group with Salmonella typhimurium . Results obtained illustrate the greater sensitivity of the microantiglobulin (Coombs) test over more conventional methods for detecting salmonella agglutinins . The possibilities of the diagnostic use of the microantiglobulin test in the field are discussed.

Arch Toxicol, 1978 Feb 14, 39(4), 241 - 8
Mechanisms of bacterial mutagenesis and properties of mutagenesis tester strains; Green MH; Bacterial tester strains are available which can detect base pair substitution, frameshift and deletion mutations . I consider possible mechanisms for these types of event . I describe the four main types of DNA repair process operating in Escherichia coli and Salmonella typhimurium and how they may influence mutation: Means of modifying repair processes to increase the sensitivity of tester strains are discussed . The properties of some current strains are briefly described . I comment adversely on forward mutation systems and discuss aspects of the strategy and methodology of mutagenicity testing with bacteria.

Genetics, 1978 Feb, 88(2), 221 - 33
Selection of Salmonella typhimurium mutants with altered serine transhydroxymethylase regulation; Stauffer GV et al.; In Salmonella typhimurium the glyA gene product, serine transhydroxymethylase (E.C . 2.1.2.1.; L-serine:tetrahydrofolate-5,10-hydroxymethyltransferase) is responsible for the interconversion of serine and glycine . This reaction also provides the cell with one-carbon units from the 5,10-methylene-tetrahydrofolate formed during glycine synthesis . Despite the importance of this enzyme, however, no mutants in which its regulation has been specificially altered have been isolated . To isolate such mutants, we have devised a selection procedure using a strain (glyA951) in which the serine transhydroxymethylase activity is reduced . When this enzyme is completely repressed, the mutant requires gylcine for growth . Revertants which retain the glyA951 lesion, but no longer require glycine, have been isolated and the serine transhydroxymethylase regulation examined . One revertant has a 7-fold elevated serine transhydroxymethylase level, which can be repressed the normal amount (about 5-fold) when the cells are grown in supplemented media . Another revertant has only a 2-fold higher serine transhydroxymethylase level; however, the amount of repression is reduced . The new lesions in both mutants cotransduce with the glyA gene and are distinct from other mutations that alter the regulation of both serine transhydroxymethylase and the methionine biosyntheitc enzymes.

Infect Immun, 1978 Feb, 19(2), 575 - 82
Comparative efficacy and toxicity of a ribosomal vaccine, acetone-killed cells, lipopolysaccharide, and a live cell vaccine prepared from Salmonella typhhimurium; Angerman CR et al.; The protective and toxic properties of a ribosomal vaccine prepared from Salmonella typhimurium W118-2 were systematicaly compared with those of an acetone-killed whole cell vaccine, purified lipopolysaccharide, and living cells in CD-1 mice . Tests of graded immunizing doses of each vaccine against several challenge doses of live strain W118-2 showed that, although the protection given by ribosomes approached the levels of protection conferred by living organisms, acetone-killed cells administered in appropriate dosages provided levels of protection comparable to that of ribosomes . Lipopolysaccharide was found to be significantly less protective than the other vaccines . On a dry-weight basis, ribosomes were the least toxic with a 50% toxic dose (TD50) of 5,000 microgram; acetone-killed cells had an intermediate TD50 of 1,400 microgram; and lipolysaccharide was the most toxic, with a TD50 of 320 microgram . The dose of each vaccine that protected 50% of the mice against a challenge of 1,00 times the 50% lethal dose was determined and divided by the TD50 to give the therapeutic index . This ratio also indicated that the ribosomes and acetone-killed cells were equally effective, whereas lipopolysaccharide was markedly inferior.

Mutat Res, 1978 Feb, 53(1), 11 - 20
Evaluation of the mutagenic potential of mycotoxins using Salmonella typhimurium and Saccharomyces cerevisiae; Kuczuk MH et al.; The mutagenic effects of fiteen mycotoxins on Salmonella typhimurium strains TA1535, TA1537 and TA1538 and Saccharomyces cerevisiae strain D-3 were tested . Only aflatoxin B1 and sterigmatocystin were mutagenic . Both were active against S . typhimurium strain TA1538 and S . cerevisiae strain D-3; however, both required activation by the hepatic S-9 enzyme preparation . A positive correlation between the other mycotoxins reported to be carcinogenic and the two in vitro test systems employed was not demonstrated in our hands.

Mutat Res, 1978 Feb, 49(2), 187 - 94
High mutagenicity of N-(alpha-acyloxy)alkyl-N-alkylnitrosamines in S . typhimurium: model compounds for metabolically activated N,N-dialkylnitrosamines; Camus AM et al.; A series of N,N-dialkylnitrosamines (alkyl means methyl, ethyl, n-propyl, n-butyl or tert-butyl group) mono-substituted at the alpha-carbon with an acetoxy group, were tested for their mutagenic action in Salmonella typhimurium TA1530 in the presence or absence of a rat-liver supernatant from 9000 X g . The presumed released of methyl, ethyl, n-butyl and n-propyl carbonium ions from the corresponding alpha-acetoxy derivatives, either by enzymic cleavage or by non-enzymic hydrolysis of the ester group, caused high mutagenicity in the bacteria . As has been demonstrated for certain alpha-acetoxy compounds, the mutagenicity of these compounds was inversely related to their half-lives in aqueous media . N-(Acetoxy)methyl-N-tert-butylnitrosamine and a beta-acetoxy derivative of N,N-diethylnitrosamine were not mutagenic either in the presence or in the absence of hydrolysing rat-liver enzymes . These results support the hypothesis that alpha-carbon hydroxylation is one mechanism involved in the metabolic activation of N,N-dialkylnitrosamines.

J Bacteriol, 1978 Feb, 133(2), 904 - 15
Incomplete flagellar structures in nonflagellate mutants of Salmonella typhimurium; Suzuki T et al.; Incomplete flagellar structures were detected in osmotically shocked cells or membrane-associated fraction of many nonflagellate mutants of Salmonella typhimurium by electron microscopy . The predominant types of these structures in the mutants were cistron specific . The incomplete basal bodies were detected in flaFI, flaFIV, flaFVIII, and flaFIX mutants, the structure homologous to a basal body in flaFV mutants, the polyhook-basal body complex in flaR mutants, and the hook-basal body complex in flaL and flaU mutants . No structures homologous to flagellar bases or their parts were detected in the early-fla group nonflagellate mutants of flaAI, flaAII, flaAIII, flaB, flaC, flaD, flaE, flaFII, flaFIII, flaFVI, flaFVII, flaFX, flaK, and flaM . From these observations, a process of flagellar morphogenesis was postulated . The functions of the early-fla group are essential to the formation of S ring-M ring-rod complexes bound to the membrane . The completion of basal bodies requires succeeding functions of flaFI, flaFIV, flaFVIII, and flaFIX . Next, the formation of hooks attached to basal bodies proceeds by the function of flaFV and by flaR, which controls the hook length . Flagellar filaments appear at the tips of hooks because of the functions of flaL, flaU, and flagellin genes.

J Bacteriol, 1978 Feb, 133(2), 830 - 43
Promoter- and attenuator-related metabolic regulation of the Salmonella typhimurium histidine operon; Winkler ME et al.; Expression of the histidine (his) operon in Salmonella typhimurium was found to be positively correlated with the intracellular level of guanosine tetraphosphate (ppGpp) . Limitation for amino acids other than histidine elicited a histidine-independent metabolic regulation of the operon . In bacteria grown at decreased growth rates, his operon expression was metabolically regulated up to a point, after which further decreases in growth rate no longer resulted in further enhancement of operon expression . Studies using strains carrying various regulatory and deletion mutations indicated that metabolic regulation is achieved predominantly by increased RNA chain initiations at the primary (P1) and internal (P2) promoters . Metabolic regulation ordinarly did not involve changes in RNA chain terminations at the attenuator site of the his operon . A model is proposed that involves ppGpp-induced changes in RNA polymerase initiation specificity at particular promoters . A second, special form of metabolic regulation may operate which also is histidine independent, but does involve relief of attenuation.

J Bacteriol, 1978 Feb, 133(2), 744 - 54
Cluster of genes controlling proline degradation in Salmonella typhimurium; Ratzkin B et al.; A cluster of genes essential for degradation of proline to glutamate (put) is located between the pyrC and pyrD loci at min 22 of the Salmonella chromosome . A series of 25 deletion mutants of this region have been isolated and used to construct a fine-structure map of the put genes . The map includes mutations affecting the proline degradative activities, proline oxidase and pyrroline-5-carboxylic dehydrogenase . Also included are mutations affecting the major proline permease and a regulatory mutation that affects both enzyme and permease production . The two enzymatic activities appear to be encoded by a single gene (putA) . The regulatory mutation maps between the putA gene and the proline permease gene (putP).

J Bacteriol, 1978 Feb, 133(2), 737 - 43
Regulation of the major proline permease gene of Salmonella typhimurium; Ratzkin B et al.; The structural gene for the major proline permease is located in a tight cluster with genes coding for the proline degradative enzymes, proline oxidase and pyrroline-5-carboxylic acid dehydrogenase . Expression of the permease is regulated in parallel with the two degradative enzymes, and all three functions are subject to catabolite repression . Regulatory mutants (putC) have constitutively high levels of all three activities, suggesting that all are regulated by a single mechanism.

J Bacteriol, 1978 Feb, 133(2), 1032 - 3
Expression of Escherichia coli fol alleles in Salmonella typhimurium; Goff CG et al.; Studies of the expression of Escherichia coli fol alleles in Salmonella typhimurium indicated that fol regulatory functions are highly conserved between these bacterial species.

J Natl Cancer Inst, 1978 Feb, 60(2), 405 - 10
Quinoline: conversion to a mutagen by human and rodent liver; Hollstein M et al.; Quinoline, a hepatocarcinogen in rats, and 23 quinoline derivatives were tested for mutagenic activity with the Ames Salmonella typhimurium assay . Quinoline, 5-hydroxyquinoline, and 8-hydroxyquinoline were mutagenic in strain TA 100 when Aroclor 1254-induced rat (male outbred Sprague-Dawley) liver homogenate was present in the incubation mixture . Enzyme preparations from rats pretreated with P-448-dependent aryl hydrocarbon hydroxylase inducers {3-methylcholanthrene (MCA) and beta-naphthoflavone} and MCA-treated "responsive" C57BL mice also metabolized quinoline to a mutagen, but phenobarbital and pregnenolone-16alpha-carbonitrile pretreatment did not yield active preparations . The mutagenicity of quinoline was blocked by the in vitro addition of menadione, butylated hydroxytoluene, alpha-naphthoflavone, vitamin A acetate, and glutathione to the test system . Depletion of glutathione by diethyl maleate pretreatment in vivo enhanced the mutagenic potential of the liver enzyme preparation . Mutagenic activity was correlated to the formation of water-soluble quinoline metabolites, and we suggested that the reactive quinoline intermediate is quinoline-2,3-epoxide . Microsomal enzymes isolated from human liver tissue, but not lung tissue, also converted quinoline to a mutagen.

Res Commun Chem Pathol Pharmacol, 1978 Feb, 19(2), 225 - 32
Effect of endotoxin on uterine cycle AMP in pregnant mice; Shaw R Jr et al.; The effect of endotoxin (LPS) on uterine cAMP was determined by measuring the levels of cAMP and cAMP phosphodiesterase after challenge . Two LPS preparations, isolated from wild type (WT) and Re chemotype mutant cells of Salmonella typhimurium were used . The pattern of termination differed with WT LPS resulting in expulsion of the fetuses, and Re LPS primarily causing the resorption of the fetuses . The animals challenged with WT LPS showed a decrease in uterine cAMP when the mice were starting to expel the fetuses while the Re LPS treated group maintained control levels of cAMP . Cyclic AMP phosphodiesterase also decreased in WT LPS and not the Re LPS group . These results suggest the possibility that uterine cAMP is involved in the expulsion of the fetuses.

J Bacteriol, 1978 Feb, 133(2), 775 - 9
Mapping and characterization of the nad genes in Salmonella typhimurium LT-2; Foster JW et al.; An ampicillin enrichment technique was used to isolate 39 nicotinic acid-requiring mutants of Salmonella typhimurium LT-2 . Using interrupted-mating and transductional mapping procedures, three loci, designated nadA, nadB, and nadC, were identified . These loci mapped at 33, 82, and 6 min, respectively, on the S . typhimurium linkage map . The arrangement of the loci on the Salmonella linkage map corresponded closely to the nadA, nadB, and nadC loci on the Escherichia coli K-12 linkage map, indicating that the de novo pathway to nicotinamide adenine dinucleotide and the genes governing the enzymes involved in this pathway in S . typhimurium are very similar to those in E . coli . Evidence is also presented which indicates that the product of the nadC locus in S . typhimurium LT-2 is the enzyme quinolinic acid phosphoribosyltransferase . All nadC mutants of S . typhimurium secreted between 2 and 8 mumol of quinolinic acid per 100 ml of secretion medium . In addition, none of the nadC mutants isolated were able to grow in 10(-3) M quinolinic acid, whereas all nadA and nadB mutants of S . typhimurium grew well in the presence of quinolinic acid . Transductional crosses between nadB mutants provided evidence suggestive of more than one locus in the nadB region.

Mol Gen Genet, 1978 Jan 17, 158(3), 239 - 50
Re-initiation of tryptophan operon expression in a promoter deletion strain of Salmonella typhimurium; Fulcher CA et al.; A genetic and enzymological study was made of five spontaneous prototrophic revertants of a tryptophan auxotroph of Salmonella typhimurium which carries a deletion extending from the closely linked supX locus into the trp operator-promoter region . The revertants were found to have regained initiation of expression of all five trp genes . Recombinational tests showed that in each case the genetic change responsible for re-initiation is cotransducible with the trp-cysB region of the chromosome . Two different mechanisms leading to re-initiation of trp gene expression were established: (a) an extension of the limits of the original deletion resulting in the fusion of the trp structural genes with a nearby gene or gene set located outside the operator end of trp, and (b) translocation of a duplicate set of the trp structural genes to other chromosomal sites, located operator-distal to the normal trp operon, in such a manner that they are functionally fused to foreign genetic units . One revertant which arose by mechanism (a) was shown to have an extended deletion with one new terminus in trp and the other in the nearby cysB locus . All the revertants exhibit constitutive expression of the trp enzymes, with activities varying among strains from five to forty five times greater than the fully repressed wild type level . The protein product of trpA, the first structural gene of the operon, appears to have been partially damaged by the re-initiation event in at least two strains, while in the other strains, the enzyme appears in preliminary tests to be indistinguishable from that of wild type.

Experientia, 1978 Jan 15, 34(1), 118 - 9
Increased susceptibility of Trypanosoma lewisi infected, or decomplemented rats to Salmonella typhimurium; Nielsen K et al.; Rats infected with Trypanosoma lewisi or decomplemented by injection of cobra venom factor or complement activating factor of trypanosomes were found to be more susceptible to infection with Salmonella typhimurium . Decomplemented rats subsequently infected with T . lewisi developed higher blood parasitemia than did normal T . lewisi infected rats.

Vet Med Nauki, 1978, 15(9), 67 - 73
{Effect of protein in the feed on the resistance of poultry artificially infected with Salmonella galinarum pullorum and Salmonella typhimurium}; Ganovska M; Studied is the effect of the low protein level in rations of birds, experimentally infected with Salmonella gallinarum-pullorum and Salmonella typhimurium . Birds of different ages of the Leghorn and Cornish breeds are included in the experiments . Results obtained from the experiments indicate that the lowered level of protein in rations to young birds at the age of five months makes them more resistant to salmonella infection . This dependence is markedly demonstrated in particular in the case of the Leghorn breed.

Scand J Work Environ Health, 1978, 4 Suppl 2, 169 - 78
Mutagenicity of industrial compounds . VII . Styrene and styrene oxide: II . Point mutations, chromosome aberrations and DNA repair induction analyses; Loprieno N et al.; The possible genetic effects produced by styrene have been investigated by means of different methodologies in several biological organisms: (a) the induction of point mutation has been investigated in Salmonella typhimurium (reverse mutation), in the yeast Schizosaccharomyces pombe (forward mutation), both in vitro and in vivo, in the host-mediated assay of mice, and in the Chinese hamster cell line grown in vitro (V-79) (forward mutation); (b) the induction of chromosome mutation has been investigated in vivo, in mice, through the analysis of the presence of chromosome aberrations in bone marrow cells of treated animals; (c) the production of DNA (deoxyribonucleic acid) damage and the stimulation of DNA repair synthesis have been evaluated from measurements of unscheduled DNA synthesis in a heteroploid human cell line (EUE) and gene-conversion produced in the yeast Saccharomyces cerevisiae treated in vitro and in vivo (host-mediated assay) . All the in vitro studies have been developed by the testing of the styrene in the presence of a metabolic activating system obtained with a mouse liver microsomal preparation . Styrene oxide, one of the in vivo metabolites of styrene with electrophilic properties towards DNA molecules, have also been tested in similar systems . Styrene was not mutagenic in all the systems tested; styrene oxide, on the contrary, was shown to be an active mutagen, independently of the genetic system under evaluation.

Vet Med Nauki, 1978, 15(1), 49 - 56
{Effect of low temperatures on the count and virulence of salmonellae in slaughtered poultry}; Georgiev L et al.; Studied was the effect of shock freezing at -34 degrees C and the storing of slaughtered birds at -18 degrees C up to six months on the survival and the change in the virulence of Salmonella typhimurium, S . meleagridis, and S . gallinarum-pullorum . It was established that the number of the tested Salmonella species decreased steadily, however, no complete devitalizing was attained . The Salmonella count was most intensely reduced in the first fifteen days of storing . Most resistant to the effect of low temperature were S . typhimurium organisms, and least resistant was S . meleagridis . It was found that the virulence of the tested Salmonella strains gradually dropped, the amount of disappearing organisms correlating with the drop of their virulence.

Vet Med Nauki, 1978, 15(1), 43 - 8
{Distribution and characteristics of the R factors in E . coli isolated from poultry}; Kokosharov T; It has been demonstrated that Escherichia coli organisms isolated from birds in the district of Haskovo are up to 65 per cent resistant to drugs . It has been experimentally shown that the genetic determinants of resistance to chemotherapeutics are transferred via conjugation . The possibility of transferring R-factors from Escherichia coli to Salmonella typhimurium points to one of the routes for the occurrence of drug resistance in Salmonella bacteria.

Pharmacology, 1978, 16(6), 333 - 43
Nonmutagenic action of cannabinoids in vitro; Zimmerman AM et al.; Under the specific conditions reported for the separate tests delta9-tetrahydrocannabinol (THC) did not elicit a mutagenic response in microbial and eukaryotic in vitro test systems . THC treatment to histidine auxotrophs of Salmonella typhimurium strains TA 98 (susceptible to frame shift mutation) and TA 100 (susceptible to base pair substitution) were investigated . Analysis for possible revertance in the presence and absence of S9 microsomal activation system indicated an absence of induction of gene mutation . Cultured fibroblasts from healthy individuals and DNA repair deficient Xeroderma pigmentosum patients display similar survival activity upon exposure to THC . There was no observable increase in the number of chromosome breaks or chromatid exchanges following exposure to THC or THC plus S9 microsomal fraction . THC, 11-OHdelta9-THC, cannabinol, and cannabidiol did not induce unscheduled DNA repair synthesis in cultured human fibroblasts . Moreover, THC did not suppress UV-induced DNA repair synthesis.

Am J Vet Res, 1978 Jan, 39(1), 151 - 3
Nematospiroides dubius as a vector for Salmonella typhimurium; Bottjer KP et al.; Salmonella typhimurium within the 3rd stage larvae of Nematospiroides dubius was shown to infect mice, evidenced by prolonged shedding of salmonellae in the feces . Numbers of S typhimurium needed to infect mice were approximately 1,000- fold less if incorporated within the 3rd-stage larvae of N dubius . Results of these experiments demonstrate that nematode parasites may act as a vector for pathogenic species of enteric bacteria.

Proc Natl Acad Sci U S A, 1978 Jan, 75(1), 410 - 4
Quantitative forward mutation assay in Salmonella typhimurium using 8-azaguanine resistance as a genetic marker; Skopek TR et al.; We have developed a quantitative forward mutation assay using Salmonella typhimurium, in which resistance to the purine analog 8-azaguanine is used as a genetic marker . We present the assay protocol, the concentration-dependent toxicity and mutagenicity of five known mutagens (N-methyl-N'-nitro-N-nitrosoguanidine, ICR-191, 9-aminoacridine, dimethylnitrosamine, and benzo{a}pyrene), and reconstruction experiments testing the assay for possible bias . The relative merits of forward versus reverse mutation assays are discussed.

Mutat Res, 1978 Jan, 56(3), 281 - 8
Mutagenicities of the pyrolyzates of peptides and proteins; Matsumoto T et al.; Pyrolyzates of 10 peptides, 10 proteins and 5 naturally-occurring materials were tested for mutagenicity in the histidine-requiring mutants Salmonella typhimurium TA98 and TA100 . Significant mutagenic activity was detected with pyrolyzates of most of these materials . The pyrolyzates requred a liver microsomal fraction, as representative of mammalian metabolism, for their detection as mutagens . Among the pyrolyzates tested, the highest mutagenic activity was observed with that of a tryptophan-containing peptide . The pyrolyzate of protein obtained from tobacco leaf also showed mutagenicity . The higher the protein content in the leaf the higher the mutagenic activity of the pyrolyzate . Protein in a tobacco leaf may be the principal precursor of mutagens in tobacco-smoke condensate.

Mutat Res, 1978 Jan, 56(3), 273 - 80
Mutagenicity in Salmonella typhimurium mutants of the benzene-soluble organic matter derived from air-borne particulate matter and its five fractions; Teranishi K et al.; Air-borne particulate matter was collected on a filter, then extracted with benzene . The benzene-soluble material was separated into 5 fractions, namely acidic, basic, alipathic, polyaromatic and oxygenated fractions . The mutagenic activities of these fractions were examined with a set of Salmonella typhimurium mutants . The 6 mutants were from the TA1535 series, deep rough strains without excision repair, namely TA100 and TA98 (having a resistance-transfer factor) and the standard strain TA1535, TA1536, TA1537 and TA1538 . Linear dose-response curves were obtained for the benzene-soluble organic matter, and its acidic, polyaromatic and oxygenated fractions with strain TA98 and a 9000 X g liver supernatant from both phenobarbital(PB)- and dibenz(a,h)anthracene(DBA)-treated rats . Among the 5 fractions tested, 3 fractions, namely the acidic, polyaromatic and oxygenated, played an important role in the mutagenicity of the benzene-soluble organic matter derived from air-borne particulate matter . The 9000 X g rat-liver supernatant was not required to make the acidic fraction mutagenic.

Mutat Res, 1978 Jan, 56(3), 245 - 8
Mutagenic effect of dichloromethane on Salmonella typhimurium; Jongen WM et al.; The possible mutagenicity of the organic solvent dichloromethane was investigated with the mutation test as described by Ames et al . The compound was mutagenic in both tester strains used, namely TA98 and TA100 . The administration of rat-liver homogenate did not appear to be essential though it slightly increased the number of mutations.

Mutat Res, 1978 Jan, 56(3), 219 - 23
Mutagenicity of alkyl-(omega-hydroxyalkyl) nitrosamines related to dibutylnitrosamine; Olajos EJ et al.; Various alkyl-(omega-hydroxyalkyl) derivatives related to dibutylnitrosamine (DBN) were investigated for mutagenicity in the absence of liver-activation system . Butyl-(4-hydroxybutyl)-, butyl-(3-hydroxypropyl)-, and butyl-(2-hydroxyethyl)-nitrosamines were so tested and found to be mutagenic for TA 1535 strain of Salmonella typhimurium . In all cases, a simple dose-response relationship was observed . Furthermore, no significant (p less than 0.05) differences in the mutagenicity of the various test compounds were observed as the alkyl sidechain possessing the OH group increased in length . From these results it is siggested that mutagenesis in S . typhimurium by the higher dialkylnitrosamines is partially due to the formation of omega-hydroxylated derivatives in addition to the major mutagenic metabolite derived from alpha-carbon dealkylation.

J Infect Dis, 1978 Jan, 137(1), 67 - 73
The epidemiology and genetics of antibiotic resistance of Salmonella typhimurium isolated from diseases animals in New York; Timoney JF; Only 12% of 249 strains of Salmonella typhimurium isolated during the period 1973-1976 from diseased animals were sensitive to six commonly used antibiotics . Isolates from calves exhibited the highest frequency of resistance as well as a steadily increasing frequency of resistance to ampicillin and chloramphenicol . The majority of strains from horses, dogs, and cats were also resistant to more than one antibiotic, a finding which was interpreted as primarily an effect of therapeutic rather than of growth-promoting use of antibiotics in these species . Ninety-one percent of resistant strains possessed transferable resistance . In 31% of these strains, the transfer factors were heat-sensitive and did not function at 37 C . The determinant of resistance to ampicillin was usually associated with a non-heat-sensitive transfer factor, whereas resistance to chloramphenicol, kanamycin, and tetracycline was more commonly associated with heat-sensitive transfer factors . Strains of S . typhimurium with similar patterns of resistance often contained different plasmids . There was more genetic homogeneity among determinants of resistance to tetracycline than among other determinants.

Infect Immun, 1978 Jan, 19(1), 26 - 8
O antigen as virulence factor in mouse typhoid: effect of B-cell suppression; Valtonen MV et al.; Immunosuppression by cyclophosphamide was used to make mice incapable of B-lymphocyte responses; they could not make an antibody response to NIP-Ficoll . These mice, as well as untreated mice, were challenged intraperitoneally with graded doses of isogenic O-4,12 or O-6,7 Salmonella typhimurium derivatives . The 50% lethal dose of the O-6,7 strains was 35- to 70-fold higher than that of the O-4,12 strains, both in the normal and the immunosuppressed animals, although the latter were approximately 1,000-fold more susceptible to the infection by either challenge organism . We conclude that the O-antigen-dependent difference in the mouse virulence of these sister strains is not mediated through differences in their capacity to evoke B-lymphocyte-mediated immune responses.

Folia Microbiol (Praha), 1978, 23(1), 45 - 54
Antimutagenic effects of caffeine during nitrosoguanidine-induced mutagenesis of Salmonella typhimurium cells and phages; Hava P et al.; The effect of caffeine on nitrosoguanidine-induced mutagenesis of Salmonella typhimurium and its P22 and L phages was studied . The detected mutations included phage "clear" mutations, reversions of phage "amber" mutation, and prototrophic reversions of the his- auxotroph of Salmonella typhimurium . Neither the recA mutation of the host nor the erf mutation of the phage genome were found to affect the nitrosoguanidine-induced mutagenesis of the phage during vegetative growth . Beginning with a concentration of 0.2 mg/ml, caffeine decreased the frequency of mutants by 30--60%, attaining a maximum effect at 1.5 mg/ml and retaining this effect even at higher concentrations . A similar antimutagenic effect was observed with the mutagenesis of the host cells . The nitrosoguanidine-induced mutagenesis does not seem to be related to the function of the recA cell gene or the erf phage gene . The mechanism of mutagenesis by nitrosoguanidine probably has two components, one of them caffeine sensitive, the other caffeine-resistant.

Cancer Lett, 1978 Jan, 4(1), 21 - 5
Mutagenicity of some congeners of benzidine in the Salmonella typhimurium assay system; Lazear EJ et al.; The analogs of benzidine were assay for mutagenicity using Salmonella typhimurium TA-98 and TA-100 and a mouse liver enzyme preparation . Only 4-aminobiphenyl produced both frameshift and base pair substitution mutations and 3,3'-dichlorobenzidine was the only compound which was mutagenic without the mammalian enzyme factor . When hydrochloride salts of the parent compounds were made to improve their stability for animal feeding experiments, the mutagenicity for the Salmonella tester strains was reduced except for 3,3'-dimethylbenzidine . Animal feeding trials in mice are underway to determine the dose response relationship of tumor incidence and molecular configuration.

Antibiotiki, 1978 Jan, 23(1), 70 - 4
{Physiological characteristics of Salmonella typhimurium treated with penicillin}; Sakanian VA et al.; Growing bacteria of the two strains of Salmonella typhimurium differing in the sensitivity levels to UV-light formed multinuclear non-septal filaments in the penicillin-containing nutrient medium . The maximum number of the lifefull filaments was formed by the 4th hour of incubation in the beaf-peptone broth at a temperature of 37 degrees C in the presence of 5 gamma/ml of penicillin . The strains exposed to penicillin were less sensitive to UV-light . Exclusion of penicillin from the nutrient medium resulted in a new division of the filamentous cells and reduction of the initial UV-light sensitivity level . It was concluded that the low UV-light sensitivity level of the filaments induced by penicillin was associated with their multinuclear state.

Chemotherapy, 1978, 24(2), 87 - 91
Silver sulfadiazine: lack of mutagenic activity; McCoy EC et al.; Silver sulfadiazine was found to be devoid of mutagenic potential in a sensitive mutagenicity assay using Salmonella typhimurium . In view of the close relationship between mutagenicity in this system and carcinogenicity in animals, these findings suggest that silver sulfadiazine is apparently also devoid of carcinogenic properties.

J Bacteriol, 1978 Jan, 133(1), 149 - 57
Transport of antibiotics and metabolite analogs by systems under cyclic AMP control: positive selection of Salmonella typhimurium cya and crp mutants; Alper MD et al.; Mutants in the cyclic AMP (cAMP) control system in Salmonella typhimurium (cya = adenyl cyclase, crp = cAMP receptor protein) were partially resistant to growth inhibition by 22 antibiotics (including fosfomycin, nalidixic acid, and streptomycin) and 29 inhibitory analogs of normal bacterial fuel/carbon sources . This resistance was used as the basis for an efficient positive selection of cya and crp mutants . We propose that these antibiotics and analogs enter the bacteria through transport systems normally used for transporting fuel/carbon sources and that this is accomplished because of a structural similarity between the antibiotic and the natural substrate of the particular transport system involved . We propose that these transport systems are all under positive control by cAMP and that cAMP acts as a signal molecule (alarmone) for fuel/carbon deprivation . Evidence is provided for a hierarchy within operons controlled by cAMP . The methodology is shown to be useful for analyzing both antibiotic transport systems and the cAMP super-control system.

Microbios, 1978, 23(92), 73 - 81
Induction of bacteriolytic enzyme from pyocinogenic Pseudomonas aeruginosa and its enzymatic properties; Azegami M et al.; Mitomycin C induced a pyocinogenic Pseudomonas aeruginosa P15 to produce a bacteriolytic enzyme, PR1-lysozyme, together with pyocin R1 . No significant accumulation of the enzyme was observed inside the induced cells . The enzyme was partially purified by acrinol treatment and Amberlie CG-50 column chromatography . The mode of action of the enzyme on the host bacterial cells as well as on Micrococcus lysodeikticus cells or peptidoglycan isolated from Salmonella typhimurium, was compared with that of hen egg-white lysozyme or phage lambda-lysozyme . It is suggested that PR1-lysozyme should be classified as a glycosidase, rather than an amidase or an endopeptidase.

Z Allg Mikrobiol, 1978, 18(7), 471 - 8
An alteration in outer membrane permeability associated with a division lesion in a strain of Salmonella typhimurium; Ahmed N et al.; Salmonella typhimurium strain 4a is a temperature sensitive mutant with defects in both septation and separation . The separation lesion was reversed by phenethylalcohol but this agent failed to allow septation or growth at restrictive temperature . Organisms of strain 4a grown at 42 degrees C were, unlike the parental strain, resistant to lysis by lysozyme plus EDTA and lipopolysaccharide was poorly extracted by EDTA from cultures of strain 4a grown at 42 degrees C . Such cultures may, therefore, be resistant to lysis with lysozyme plus EDTA not because the murein is altered but because the EDTA fails to permeabilize the outer membrane to lysozyme . In confirmation of this, murein isolated from strain 4a after growth at 42 degrees C showed the same sensitivity to lysozyme as murein from the parental strain . In spite of the altered envelope properties of strain 4a after growth at 42 degrees C, no major changes in protein or phospholipid composition have so far been demonstrated.

Chem Biol Interact, 1978 Jan, 20(1), 1 - 16
The mutagenic effect of 1,2-dichloroethane on Salmonella typhimurium I . Activation through conjugation with glutathion in vitro; Rannug U et al.; One of the main components in the waste products from vinyl chloride industries (EDC-tar), is ethylene dichloride (1,2-dichloroethane) . This compound has been tested for mutagenicity on Salmonella typhimurium TA 1535 . It is concluded that 1,2-dichloroethane gives a weak direct mutagenic effect, which is enhanced by addition of the postmitochondrial liver fraction (S-9) . This activation is NADPH-independent and non microsomal . It is caused by a factor in the soluble fraction (115 000 g supernatant) . This activation was further enhanced by the addition of glutathione but not by the addition of L-cysteine, N-acetyl-L-cysteine or 2-mercaptoethanol . No activation was observed when glutathione was added in the presence of a totally denaturated S-9 fraction or in the absence of this fraction . Activation of 1,2-dichloroethane was also found in the presence of glutathione and glutathione S-transferase A and C but not with glutathione S-tranferase B . A synthetic conjugate S-(2-chloroethyl)-L-cysteine gave a strong direct mutagenic effect at concentrations where no effects were seen with 1,2-dichloroethane . It is thus concluded that 1,2-dichloroethane is activated by conjugation to glutathione . Another main component in EDC-tar, 1,1,2-trichloroethane, was not mutagenic under any of our experimental conditions . For comparison 1,2-dibromoethane was also tested and gave a stronger direct mutagenic effect than 1,2-dichloroethane . Like the latter 1,2-dibromoethane was also activated by a NADPH-independent process.

J Bacteriol, 1978 Jan, 133(1), 114 - 21
Biochemical-genetic study of the first enzyme of histidine biosynthesis in Salmonella typhimurium: substrate and feedback binding regions; Wainscott VJ et al.; Twenty-five strains of Salmonella typhimurium containing different mutations in the first gene of histidine biosynthesis were studied to correlate regions of the genetic map with biochemical functions . These strains contained either missense, double-frameshift, or suppressed nonsense mutations, all of which resulted in altered, though active, enzymes . Each mutant enzyme was assayed for activity in the presence of varying concentrations of the feedback inhibitor L-histidine or the substrates ATP and 5-phosphoribosyl-1-pyrophosphate . The feedback properties and substrate kinetics of each mutant enzyme were compared to wild-type values, and these results indicated that the following functions were correlated with regions of the hisG gene: feedback inhibition in two general areas, including regions IA and IB and regions V, VI, and VII; ATP binding in two general areas, including regions IA, IB, and II and regions V, VI, and VII; and 5-phosphoribosyl-1-pyrophosphate binding in two general areas, including regions IB, II, and III and regions V and VI.

Experientia, 1977 Dec 15, 33(12), 1590 - 2
A mutant of the antibiotic resistance factor R124 with altered copy number; Pritchard JJ et al.; A mutation conferring increased antibiotic resistance on Salmonella typhimurium strain 11G carrying R124 was plasmid determined; strains harbouring the mutant plasmid contained more DNA as ccc plasmid than those harbouring R124 . The increased copy number was manifested at all growth rates tested.

Schweiz Med Wochenschr, 1977 Dec 3, 107(48), 1774 - 6
{Iron overload: effect on specific and nonspecific immunity}; Puschmann M et al.; Acute overload with an iron salt in mice enhanced the virulence of a relatively avirulent type of Salmonella typhimurium in a dose-dependent fashion . Iron administration also partly abolished specific immunity . Ferritin iron did not display the virulence-enhancing effect.

Science, 1977 Dec 2, 198(4320), 944 - 6
Saccharin and other sweeteners: mutagenic properties; Batzinger RP et al.; Saccharin preparations commonly distributed as artificial sweeteners exhibited mutagenic activity in bacterial tests . When administered orally to mice, mutagenic activity was demonstrable in the urines of these animals as well as in a host-mediated assay . Highly purified saccharin was not mutagenic in the direct assay, but the urines of mice to which this material had been administered exhibited mutagenic effects on one tester strain (Salmonella typhimurium TA100) . Two other sweeteners, neohesperidin dihydrochalcone and xylitol, had no detectable mutagenic activity in any of these assays using his- Salmonella typhimurium strains TA100 or TA98.

Environ Health Perspect, 1977 Dec, 21, 65 - 9
Mutagenicity of the halogenated olefin, 2-bromo-2-chloro-1,1-difluoroethylene, a presumed metabolite of the inhalation anesthetic halothane; Garro AJ et al.; The presumed halothane metabolite, 2-bromo-1,1-difluoroethylene, produces both base substitution and frameshift mutations in Salmonella typhimurium . Direct mutagenesis of isolated DNA also was observed by using a Bacillus subtils transformation assay to score the production of mutagenic lesions in transforming DNA.

Infect Immun, 1977 Dec, 18(3), 673 - 9
Hyperthermia and human leukocyte functions: effects on response of lymphocytes to mitogen and antigen and bactericidal capacity of monocytes and neutrophils; Roberts NJ Jr et al.; It has recently been demonstrated that fever, or hyperthermia, results in enhanced survival of lizards infected by Aeromonas hydrophila . In the present study, the effects of hyperthermia on certain immune functions were assayed in vitro with purified human leukocytes . Lymphocyte transformation responses to the mitogen phytohemagglutinin and the common antigen streptokinase-streptodornase were enhanced at 38.5 degrees C relative to 37 degrees C whether analyzed according to absolute counts per minute of incorporated tritiated thymidine or according to stimulation indexes . Enhancement of response was not accompanied by acceleration of response . Augmentation of transformation response was generally not seen at 40 degrees C; incubation at that temperature was associated with decreased cellular viability . Significant, though small, increases of the bactericidal capacity of polymorphonuclear leukocytes at 40 degrees C relative to 37 degrees C were shown at 1 h with Escherichia coli, Salmonella typhimurium, and Listeria monocytogenes, but not with Staphylococcus aureus . Mononuclear phagocytes did not show enhanced bactericidal capacity at the elevated temperature with any of these organisms in this in vitro system . Hyperthermia may enhance certain host defense mechanisms and warrants further study.

J Pharm Sci, 1977 Dec, 66(12), 1781 - 3
Absence of mutagenicity of coralyne and related antileukemic agents: structural comparison with the potent carcinogen 7,12-dimethylbenz{a}anthracene; Cheng CC et al.; The structural similarity between antileukemic alkaloid coralyne and the carcinogenic and antineoplastic hydrocarbon 7, 12-dimethylbenz{a}anthracene, as well as the similarity between the antileukemic alkaloid nitidine and the carcinogenic hydrocarbon 5-methylchrysene, prompted a mutagenicity evaluation of coralyne sulfoacetate, nitidine chloride, the 8-ethyl homolog of coralyne, nitidine methosulfate, and the tetramethoxy analog of nitidine by the Ames method against the histidine-auxotroph strains of Salmonella typhimurium TA-1537, TA-1538, TA-98, and TA-100; 7,12-dimethylbenz{a}anthracene was used as a reference standard . The mutagenicity of these antileukemic compounds was either completely eliminated or drastically reduced, but the mutagenic response was generally high for 7,12-dimethylbenz{a}anthracene . The results suggest that the presence of a quaternary nitrogen atom and alkoxy groups could be important in alleviating the mutagenicity of the parent mutagenic and carcinogenic hydrocarbons.

Scand J Work Environ Health, 1977 Dec, 3(4), 203 - 11
Mutagenicity of fume particles from stainless steel welding; Hedenstedt A et al.; Welding fume particles collected from different welding procedures were tested for mutagenicity in Escherichia coli, with the inhibition zone in pol A- as compared to pol A+, and in Salmonella typhimurium, TA 100 strain . While no mutagenicity was found with mild steel welding, a mutagenic effect was established with samples from stainless steel welding . This mutagenicity was particularly associated with manual metal arc (MMA) welding, and less so with metal inert-gas welding . A decrease in or an elimination of the effect occurred with a liver microsomal metabolizing system (S-9 mix) . The MMA samples produced the strongest mutagenic effect . More-detailed investigations on these samples showed that the mutagenic agent(s) is water soluble . An increased mutagenicity, which also revealed the induction of frame shift mutations, was found with TA 98 . The same welding fume sample was used for a mutagenicity test (resistance to 6-thioguanine) with V 79 hamster cells . Because of the high toxicity of these welding fume particles on the cells, only very low concentrations could be tested, but the increase of mutations, when compared to the negative control, was significant . It is suggested that hexavalent chromium may be involved in the mutagenic effect of the welding fumes.

Mutat Res, 1977 Dec, 46(6), 387 - 94
Carcinogen activation by human liver enzymes in the Ames mutagenicity test; Tang T et al.; Liver post-mitochondrial supernatants derived from 10 individuals were used as the source of metabolic activation for carcinogens in the Ames quantitative mutagenicity test using Salmonella typhimurium TA 100 . The liver samples were obtained from brain-dead donors and autopsy cases . The ability of human enzymes to activate aromatic amines ranged from the undetectable to highly active for 2-acetylaminofluorene . None of the samples exhibited any ability to activate benzidine . A generally low activity was observed in the capability of human enzymes to activate the polynuclear aromatic hydrocarbons, 3-methylcholanthrene and benzo(a)pyrene . Most samples were positive for activating 4-nitrobiphenyl . However, the highest mutagenic activity in the presence of human enzymes was consistently observed for aflatoxin B1 and sterigmatocystin . These results indicated that (a) human enzyme systems, like rodent systems, are more effective in inducing mutagenic activity from mycotoxins than aromatic amines and polynuclear aromatic hydrocarbons, and (b) samples derived from different individuals exhibited considerable variation in the ability to activate carcinogens belonging to a same class of compound.

J Med Chem, 1977 Dec, 20(12), 1588 - 91
Nitramino acids . Synthesis and biological evaluation of 1-nitroproline, 1-nitropipecolic acid, and N-nitrosarcosine; Nagasawa HT et al.; The N-nitro derivatives of secondary alpha-amino acids, viz., 1-nitroproline (1a) (L and D), 1-nitro-DL-pipecolic acid (2a), and N-nitrosarcosine (3a), were prepared by the oxidation of the corresponding nitrosamino acids with peroxytrifluoroacetic acid . These nitramino acids (1a-3a) were not active against Escherichia coli, Candida albicans, Pseudomonas aeruginosa, or Mycobacterium smegmatis, and 1a and 2a did not show mutagenic activity in a Salmonella typhimurium TA-100 system, with or without added rat liver 9000g supernatant fraction . The marginal mutagenicity of 3a in this system suggests that additional work should be done to assess its carcinogenic-mutagenic potential.

Infect Immun, 1977 Dec, 18(3), 574 - 82
Role of phagocytosis in mouse virulence of Salmonella typhimurium recombinants with O antigen 6,7 or 4,12; Valtonen MV; The quality of lipopolysaccharide has previously been shown to influence the mouse virulence of Salmonella so that strains with O antigen 4,12 were more virulent than their O-9,12 sister strains . Immunosuppression did not alter this O-antigen-dependent difference in virulence . I have now constructed smooth O-4,12 and O-6,7 sister hybrid strains of Salmonella typhimurium . No other phenotypic differences were found between these strains; they were all "common antigen" positive . In intraperitoneal infection, the O-4,12 strains were more mouse virulent than their O-6,7 sisters . The difference in virulence correlated with a difference in clearance rates; the O-6,7 hybrids were removed from the blood more rapidly than their O-4,12 sisters . No natural bactericidal antibodies were found in the sera of the mice.

J Immunol, 1977 Dec, 119(6), 2157 - 62
Mechanism for induction of anti-DNA antibodies by bacterial lipopolysaccharides in mice; II . Correlation between anti-DNA induction and polyclonal antibody formation by various polyclonal B lymphocyte activators; Izui S et al.; The capacity of various polyclonal B lymphocyte activators (PBA) to induce, in mice, the formation of anti-DNA antibodies was compared with their ability to mediate the release of DNA in circulating blood and to stimulate polyclonal antibody synthesis in vivo . Anti-DNA antibodies or polyclonal antibody synthesis were induced in mice after the injection of at least 10 microgram lipopolysaccaride (LPS) from Salmonella typhimurium, 1 mg dextran sulfate (DS), or 2 mg purified protein derivative of tubercle bacteria RT32 (PPD) . Smaller quantities of LPS (0.1 microgram) or DS (500 microgram) were sufficient to cause the release of DNA in circulating blood, whereas PPD was not able to provoke such a release at any concentration used . The association of anti-DNA antibodies with polyclonal antibody synthesis in mice injected with various PBA contrasts with the lack of correlation between the formation of anti-DNA antibodies and the release of measurable amounts of DNA in circulating blood . These results strongly suggest that the induction of anti-DNA antibodies by PBA is a consequence of the polyclonal B lymphocyte activation.

Acta Med Okayama, 1977 Dec, 31(6), 343 - 9
The immunological relationship between filtrable agent, Salmonella and murine leukosis; Hamazaki Y; Salmonella typhimurium was invariably isolated from our J strain murine leukosis . Immunization of D103 mice with either inactivated Salmonella typhimurium or the cell-free extract of leukosis inhibited the transplantation of leukosis . The adoptive immunization of D103 mice with spleen cells of Strong A mice immunized with either Salmonella or the cell-free extract of leukosis inhibited the transplantation of leukosis . The addition of either Salmonella or the cell-free extract of leukosis inhibited the migration of macrophages of leukosis spleen in tissue culture . Strong A mice is non-susceptible to J strain leukosis . However, inoculation of neonatal Strong A mice with the cell-free extract of leukosis produced a susceptibility to the transplantation of leukosis . These results suggest that both a filtrable agent and Salmonella typhimurium are present in cells of this leukosis and might be etiologically related to the leukosis.

Mol Gen Genet, 1977 Nov 18, 156(3), 327 - 32
The structure of the cysCDHIJ region in unstable cysteine or methionine requiring mutants of Salmonella typhimurium; Kingsman AJ; A genetic method was devised to test the hypothesis that in some cysteine or methionine requiring (cym) mutants of Salmonella typhimurium suppression of auxotrophy is due to an insertion at the site of the cym mutation . It was found that suppressed strains have an insertion of about 9kb in the cysCDHIJ region and that in unstable suppressed strains it is the instability of this insertion which results in the segregation of cym auxotrophs.

Mol Gen Genet, 1977 Nov 18, 156(3), 313 - 8
An effect of F-like plasmids on the maintenance of Flac in a dnaC mutant of Salmonella typhimurium; Lemoine VR et al.; Flac maintenance was aberrant at permissive temperature in a temperature-sensitive dnaC mutant of Salmonella typhimurium when the normally resident pLT2 plasmid was present . Flac was, however, efficiently transferred into the dnaC pLT2+ strain and the resulting Flac derivative was almost as efficient in transferring Flac as was dnaC+ pLT2+ Flac strains indicating that aberrant Flac maintenance was not associated with appreciable inhibition of transfer replication . A range of F-like plasmids behaved like pLT2 in causing aberrant Flac maintenance when present in the dnaC pLT2- strain . Flac was, however, stably maintained in the dnaC strain in the absence of other plasmids . Although the F-like plasmids destabilized Flac, each was stably maintained when introduced into strain 11G dnaC pLT2+ and pLT2 was also apparently stable under these conditions . The destabilizing effect of pLT2 and other fi+ plasmids was not consequent upon their inhibiting the formation of a repressible F transfer component needed for Flac replication in the dnaC strain . Incompatibility between Flac and the other plasmids induced by the dnaC lesion also appeared unlikely to be a cause of the aberrant Flac maintenance . The possibility is discussed that the initiation of Flac replication differs from that of pLT2 and the F-like plasmids with F competing less effectively than the others for the DnaC gene product.

Biochim Biophys Acta, 1977 Nov 15, 471(1), 135 - 44
Transport of {14C}Gly-Pro in a proline peptidase mutant of Salmonella typhimurium; Yang SL et al.; The transport of {14C}Gly-Pro was examined using a mutant of Salmonella typhimurium (strain TN87) deficient in an X-Pro dipeptidase and an X-Pro-Y iminopeptidase . The dipeptide was taken up by one saturable transport system having a Km of 5.3-10(-7)M and a V of 1.4 nmol/mg dry wt cell per min . The uptake of Gly-Pro was not inhibited by amino acids or tripeptides and the transport system exhibited a rather broad side chain specificity for dipeptides . Dipeptides containing hydrophobic residues were the most potent inhibitors of this dipeptide transport system exhibiting Ki values between 10(-8) and 10(-7) M . In contrast, dipeptides containing glycine residues were particularly weak inhibitors . Finally, Gly-Pro was found to be in the intact form inside the cell and was concentrated more than 1000-fold.

Science, 1977 Nov 11, 198(4317), 625 - 7
Mandelonitrile beta-glucuronide: synthesis and characterization; Fenselau C et al.; Mandelonitrile beta-glucuronide, the compound patented as Laetrile, has been synthesized from rabbit liver uridine diphosphate-glucuronosyl transferase immobilized on beaded sepharose, has been analyzed by thin-layer chromatography, nuclear magnetic resonance, and gas chromatography-mass spectrometry, and has been tested for cytotoxicity and mutagenic activity with Salmonella typhimurium strains TA 98 and TA 100 . Several commercial laetrile preparations contained no glucuronide; they contained amygdalin and neoamygdalin instead . Mandelonitrile, mandelonitrile glucuronide, and a mixture of amygdalin and neoamygdalin were each found to be mutagenic.

J Biol Chem, 1977 Nov 10, 252(21), 7850 - 61
Periplasmic space in Salmonella typhimurium and Escherichia coli; Stock JB et al.; The volume of the periplasmic space in Escherichia coli and Salmonella typhimurium cells was measured . This space, in cells grown and collected under conditions routinely used in work with these bacteria, was shown to comprise from 20 to 40% of the total cell volume . Further studies were conducted to determine the osmotic relationships between the periplasm, the external milieu, and the cytoplasm . Results showed that there is a Donnan equilibrium between the periplasm and the extracellular fluid, and that the periplasm and cytoplasm are isoosmotic . In minimal salts medium, the osmotic strength of the cell interior was estimated to be approximately 300 mosM, with a net pressure of approximately 3.5 atm being applied to the cell wall . A corollary of these findings was that an electrical potential exists across the outer membrane . This potential was measured by determining the distributions of Na+ and Cl- between the periplasm and the cell exterior . The potential varied with the ionic strength of the medium; for cells in minimal salts medium it was approximately 30 mV, negative inside.

Microbiol Immunol, 1977 Nov, 21(11), 611 - 9
Immunological properties of Vibrio cholerae lipopolysaccharides; Nakano M et al.; Immunological effects of wall lipopolysaccharide (LPS) preparations obtained from Vibrio cholerae Inaba 569B, Ogawa NIH 41 and NAG 4715 strains by the hot phenol-water procedure were examined in mice . Although these LPS lack KDO, which are basic components of the core region of most gram-negative LPS, they still have potencies as B-cell mitogens, adjuvants, immunosuppressants, polyclonal B-cell activators and phagocytic stimulants for macrophages . The activities of these V . cholerae LPS on murine immune system seemed to be weaker than those of Salmonella typhimurium LT2-LPS . Among these V . cholerae LPS, NAG 4715-LPS showed the strongest mitogenic activity and phagocytic stimulation, while the potencies of this NAG 4715-LPS for the induction of polyclonal B cell activation, adjuvant effects and immunosuppression did not seem to be greater to those of the other LPS.

Clin Exp Immunol, 1977 Nov, 30(2), 262 - 70
Deficiency of serum bactericidal activity against Salmonella typhimurium in sickle cell anaemia; Hand WL et al.; Systemic salmonellosis is a recognized complication of sickle cell anemia (SCA) . In our initial study of SCA host defences against salmonella, we evaluated the bactericidal activity of serum against Salmonella typhimurium . When compared to controls, sera from eight out of nineteen SCA patients were deficient in bactericidal function . Levels of factor B, haemolytic complement and agglutinating antibody were similar in SCA and control sera . However, abnormalities that might theoretically account for the decreased antibacterial activity were observed in many SCA sera . These abnormal findings included: (a) defective function of the alternative complement pathway (decreased bacterial killing in the presence of Mg EGTA); (b) low serum C3 concentration; and (c) decreased total iron-binding capacity (TIBC), with a resultant increase in per cent saturation of iron-binding capacity . Of these deficiencies only the abnormal alternative pathway function was significantly associated with decreased serum bactericidal activity . A suggested function of serum bactericidal activity is prevention of bacteraemia by susceptible organisms . Thus diminished serum bactericidal capacity may increase the risk of Salmonella bacteraemia in some individuals with sickle cell disease.

Br J Cancer, 1977 Nov, 36(5), 564 - 71
Selection of an in vitro carcinogenicity test for derivatives of the carcinogen hexamethylphosphoramide; Ashby J et al.; The demonstration that hexamethylphosphoramide (HMPA) possesses potent carcinogenic properties has raised doubts about the safety of exposure to other phosphoric amides . In order to define a suitable short-term test with which to evaluate such analogues, the response of the Salmonella typhimurium mutation assay of Ames and cell transformation assay of Styles to HMPA and 3 selected analogues has been studied . These analogues were the related leukaemogen phosphoramide, the putative non-carcinogen, phosphoric trianilide and N.N'N''-trimethylphosphorothioic triamide, a compound of unknown and hitherto unpredictable properties . While both tests found the trianilide negative, the Ames test failed to detect phosphoramide as positive and gave an erratic and predominantly negative response to HMPA . In contrast, the transformation assay found both phosphoramide and HMPA positive . This test response profile indicates that the transformation assay is the preferred test with which to evaluate analogues of HMPA for potential carcinogenicity . Some structural requirements for potential carcinogenicity within this class of compounds are tentatively deduced.

Infect Immun, 1977 Nov, 18(2), 454 - 8
Mouse virulence of Salmonella typhimurium mutants deficient in two major outer membrane proteins; Valtonen MV et al.; The role of several outer membrane components as virulence factors is well established . We have now isolated spontaneous mutants and conjugational hybrids of smooth mouse virulent Salmonella typhimurium deficient in two major outer-membrane proteins . The lack of the 34,000- and/or 36,000-dalton proteins was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis . Mutants and recombinants were then tested for their mouse virulence by intraperitoneal inoculation and were found to be as virulent as the parent strain.

Infect Immun, 1977 Nov, 18(2), 261 - 5
Liability to hydrophobic and charge interaction of smooth Salmonella typhimurium 395 MS sensitized with anti-MS immunoglobulin G and complement; Stjernstrom I et al.; Sensitization of smooth Salmonella typhimurium 395 MS bacteria with hyper-immune anti-MS immunoglobulin G (IgG) antibodies increased the liability to hydrophobic interaction as assessed by the affinity for a column of Octyl-Sepharose . After sensitization, the material originally eluted with 1 M (NH4)SO4 in a 0.01 M phosphate buffer (pH 6.8) was not desorbed until the ionic strength was reduced to nil, and 0.1% (vol/vol) Triton X-100 in the 0.01 M phosphate buffer was used as eluant . Furthermore, by including positively charged bis-trimethylamino-polyethylene glycol (PEG) or negatively charged bis-sulfoamino-PEG in an aqueous two-phase system of dextran T500 and PEG 6000, the partition of the IgG-sensitized bacteria was affected by either of the polymers, whereas that of the parent bacteria was not . The hydrophobic effect of IgG binding was enhanced by complement . With heat-inactivated complement, the effect of IgG was diminished . The F(ab')2 fragment showed a much lower capacity to promote a hydrophobic interaction than the complete IgG molecule.

Cancer, 1977 Nov, 40(5 Suppl), 2557 - 64
Inhibitory effects of selenium on 1,2-dimethylhydrazine and methylazoxymethanol colon carcinogenesis: correlative studies on selenium effects on the mutagenicity and sister chromatid exchange rates of selected carcinogens; Jacobs MM; Selenium (Se) inhibition of either the activation of test compounds and/or mutagenic events elicited by activated compounds is suggested by experimental rat assays, mutagenesis assays, and assays with human lymphocytes in culture . The colon tumor incidence in 1,2-dimethylhydrazine (DMH)-treated rats was reduced from 87% to 40% by 4 ppm Se supplements in the drinking water . Supplemental Se decreased the total number of colon tumors induced by DMH more than three-fold and by methylazoxymethanol (MAM) almost two-fold . Coexposure of Salmonella typhimurium TA 1538 to an effective molar ratio of Se/2-acetylaminofluorene=10, Se/N-OH-acetylaminofluorene=10 and SE/N-OH-aminofluorene=300 reduced the mutagenicity to 65, 68, and 61% of their respective controls with mutagen alone . With a molar ratio of Se/N-OH-AAF=100, Se reduced the activity to 28% of the mutagenicity of N-OH-AAF alone . Preliminary data indicating MAM is mutagenic in S . typhimurium TA 1535 and His G 46(6837) are presented . In toxicity studies exposure of human lymphocyte cultures to 1.3 X 10(-9) to 1.6 X 10(-5) M Se yielded sister chromatid exchange (SCE) rates equivalent to background levels of 6--7 SCE per cell . The SCE frequencies of lymphocytes cultured with Se and selected carcinogens are discussed.

Infect Immun, 1977 Nov, 18(2), 439 - 45
Use of transferrin-iron enterobactin complexes as the source of iron by serum-exposed bacteria; Kvach JT et al.; Two smooth and six rough strains of Salmonella typhimurium with progressively smaller amounts of sugar and protein in their outer membrane were tested for degree of virulence in normal and iron-injected mice and for ability to acquire iron in mammalian sera . The rate of mortality showed that bacterial virulence for mice was lowered with progressive decrease of outer-membrane sugar and protein . Iron injections increased the rate of mortality in mice infected either with smooth strains or with superficially rough strains but were without effect in mice infected with deep rough strains . In in vitro experiments, iron promoted with equal effectiveness the growth of all serum-exposed bacterial strains, whereas enterobactin (E) was much more effective in promoting the growth of smooth and superficial rough than in promoting that of deep rough strains . Various experiments showed that deep rough strains cannot grow in E-supplemented serum because they are not able to use the transferrin-iron-E complexes that E forms with transferrin-iron . This failure to use transferrin-iron-E complexes by deep rough strains was found to be due to the inability of these strains to absorb iron containing complexes to their outer membrane . Adsorption studies with chemically treated bacteria showed that the receptor of transferrin-iron-E or E-iron complexes is a protein of the outer membrane of bacterial cells.

J Biol Chem, 1977 Oct 25, 252(20), 7405 - 12
Translocation of phospholipids between the outer and inner membranes of Salmonella typhimurium; Jones NC et al.; The reversibility and specificity of phospholipid translocation between the inner and outer membrane of Salmonella typhimurium has been investigated by incorporating exogenous lipids from phospholipid vesicles into the outer membrane of intact cells . Translocation of newly incorporated phospholipids to the inner membrane was demonstrated by decarboxylation of vesicle-derived phosphatidylserine and by recovery of vesicle constituents in both inner and outer membrane fractions . All Salmonella phospholipids tested, as well as phosphatidylcholine and cholesteryl oleate were effectively translocated to the inner membrane . However, no translocation of vesicle-derived lipopolysaccharide or an incomplete biosynthetic precursor of lipid A could be detected . Translocation of phospholipids and cholesteryl ester was rapid and extensive, and appeared to lead to equilibration of the lipids between the two membranes . The mechanism of intermembrane translocation has not been established, but the results are suggestive of diffusional flow across zones of adhesion between the inner and outer membranes.

J Biol Chem, 1977 Oct 25, 252(20), 7398 - 404
Interaction of Salmonella typhimurium with phospholipid vesicles . Incorporation of exogenous lipids into intact cells; Jones NC et al.; Incubation of intact cells of Salmonella typhimurium with bilayer phospholipid vesicles results in significant transfer of vesicle lipids to the cells . The transfer requires Ca2+ or spermine, and is dependent on time, temperature, the concentration and composition of the vesicles, and the nature of the cellular lipopolysaccharide . The process results in bulk transfer of vesicle lipids to the cells rather than reciprocal molecular exchange between vesicles and the outer membrane . All components of mixed lipid vesicles, including cholesteryl oleate and lipopolysaccharide, are transferred to the cells in a ratio similar to that of the donor vesicles . The properties of the transfer process are consistent with direct fusion of vesicles with the outer membrane of the cell.

Arch Microbiol, 1977 Oct 24, 115(1), 37 - 43
Properties of the cell envelope and a cell-envelope protein of Pseudomonas facilis; Jones RC et al.; The molecular weight of the protein moiety of a phospholipoprotein complex isolated from Pseudomonas facilis has been examined with a variety of sodium dodecylsulfate-polyacrylamide gel electrophoretic systems . A molecular weight of 35 000 was determined for the protein in all analyses . A 35 000-dalton protein was present in the EDTA extract of P . facilis and in the cytoplasmic and outer membrane fractions, but not in the lipopolysaccharide and peptidoglycan . Prior inoculation of mice with the phospholipoprotein complex led to a 7.5- to 15-fold increase in the LD50 when mice were subsequently inoculated with Salmonella typhimurium; this pathogen has a cell-surface protein which cross-reacts immunologically with antibody to the P . facilis phospholipoprotein complex.

Mol Gen Genet, 1977 Oct 20, 155(2), 227 - 9
Identification of the sid outer membrane receptor protein in Salmonella typhimurium SL1027; Braun V et al.; A protein of molecular weight 78,000 daltons, missing in albomycin and phage ES18 resistant mutants, has been identified in the outer membrane of Salmonella typhimurium SL1027 . Mutants with a tonB like resistance and over production of outer membrane proteins due to iron shortage were also isolated . The mutation which leads to the protein deficiency maps in the sid gene region, the mutation related to overproduction of proteins maps near trp . Although the S . typhimurium and the E . coli protein mediate translocation of the iron complex ferrichrome and the structurally analogous antibiotic albomycin through the outer membrane no cross-reactivity exists in binding the phages T5, T1 and ES18 or colicin M.

Mol Gen Genet, 1977 Oct 20, 155(2), 117 - 21
Genetic studies of hybrids between coliphage lambda and salmonella phage P22: genetic analysis of the P22-lambda hybrid class; Yamamoto N et al.; P22-lambda hybrids which retain the protein coat of P22 have been isolated and characterized into two types . Type 1 hybrids which have the c through O-P genes of lambda are unable to grow lytically on Salmonella typhimurium . On the other hand, type 2 hybrids which contain only the c region of lambda, plated on S . typhimurium . Both hybrid types retained the generalized transducing and antigenic conversion capabilities of P22.

Aust J Exp Biol Med Sci, 1977 Oct, 55(5), 523 - 37
The response of foetal sheep to the somatic and flagellar antigens of Salmonella typhimurium; Fahey KJ; Following the injection of polymeric flagellin (POL), foetal sheep older than 70 days gestation produced haemagglutinating antibody and synthesized IgM . The maximum titre of antibody in the blood increased with the age at which the foetus was injected . All foetuses synthesized 2-mercapto-ethanol-sensitive antibodies, while older foetuses (approximately 120 days gestation) also produced 2-mercaptoethanol-resistant antibodies and synthesized IgG1 . During the primary immune response, there was a poor correlation between the antibody titre and the amount of immunoglobulin synthesized . The majority of IgM synthesized and almost all IgG1 had no demonstrable specificity for POL . During the secondary response to POL, the majority of IgG1 synthesized was specific and in one case appeared to be monoclona . There was no detectable primary antibody response in foetal sheep to the somatic antigens of Salmonella typhimurium, although all foetuses synthesized IgM . Only one of six foetuses receiving a second injection of antigen produced antibody . There was an increase in the numbers of blood lymphocytes following the injection of both POL and S . typhimurium, but only POL induced a rapid increase in the numbers of neutrophils in the blood and produced histological changes in the draining lymph nodes and spleen.

Acta Pathol Microbiol Scand {B}, 1977 Oct, 85B(5), 322 - 28
Endocytosis of Salmonella typhimurium 395 MS and MR10 by HeLa cells; Kihlstrom E et al.; Monolayer of HeLa cells were examined for their ability to endocytose Salmonella typhimurium 395 MS (wild) and MR10 (chemotype RD) . Monolayers treated with the glycolytic inhibitors iodoacetic acid (IAA) or N-ethylmaleimide (NEM) or the respiratory inhibitor sodium azide (NaN3) or cytochalasin B (CB) were incubated with S . typhimurium . The numbers of cell-associated (intracellular plus cell-membrane attached extracellular) and intracellular bacteria were determined by viable counts, together with the HeLa cell ATP levels . IAA and NEM at concentrations 10(-4)M and 10(-3)M decreased significantly the number of intracellular MR10 and the cellular ATP levels, but did not influence significantly the total number of cell-associated bacteria except for 10(-3)M IAA which slightly increased the association . On the other hand, NaN3 at concentrations 10(-4)M and 10(-3)M did not affect the number of associated or intracellular bacteria, or the cellular ATP levels . CB at concentrations of 5, 10 and 20 microgram/ml increased the number of associated bacteria, decreased the number of intracellular bacteria and caused a small decrease in cellular ATP levels . Thus, HeLa cells may internalize S . typhimurium by an energy-requiring, glycolysis-dependent process . CB had a dose-dependent inhibitory effect on the internalization without influencing significantly the HeLa cell ATP levels . This indicates that CB might affect the internalization process by some means other than decreasing the ATP content.

Proc Natl Acad Sci U S A, 1977 Oct, 74(10), 4365 - 9
Transcription termination at the trp operon attenuators of Escherichia coli and Salmonella typhimurium: RNA secondary structure and regulation of termination; Lee F et al.; Transcription termination at the attenuators of the trp operons of Escherichia coli and Salmonella typhimurium was studied in vitro using DNA restriction fragments as templates . Readthrough transcription beyond the terminators occurred with 5 and 30% efficiency, respectively, in E . coli and S . typhimurium . This difference is correlated with the stability of proposed secondary structures of the respective trp leader transcripts . Secondary structure analyses of the two leader transcripts revealed a well-conserved pattern of RNA base paring . This and the possibility that trp leader RNA is translated suggest a model for regulation of transcription termination that is based on ribosome movement along the RNA and a shift between alternative RNA base-pairing configuration.

Chem Biol Interact, 1977 Oct, 19(1), 77 - 90
Mutagenesis by 4-nitrobenzofurazans and furoxans; Macphee DG et al.; 15 nitrobenzofurazans and 10 nitrobenzofuroxans synthesized primarily for testing as potential anti-rheumatic drugs were also tested for mutagenicity in Salmonella typhimurium strains TA98 and TA100 . The method used involved placing each compound in a "well" cut out of a plate of selective medium previously seeded with the appropriate tester strain, and then adding a rat liver microsome/cofactor mixture to one of the two wells on each plate . This method is considerably cheaper and more convenient than the conventional agar overlay technique, but in the present series of experiments failed to detect 4 compounds which could be detected by the overlay technique . Using a combination of the two techniques, 21 of the 25 compounds tested were found to be mutagenic . All 10 benzofuroxans and 9 of the 15 benzofurazans were detected as direct-acting mutagens with at least one of the two tester strains . Two of the benzofurazans gave positive results only in the presence of rat liver microsomes, and hence are pro-mutagens . One of the 4 benzofurazans which gave negative results for mutagenicity in these tests was found to be an efficient inhibitor of a neutral protease activity found in rheumatic synovial fluid, and may therefore have some potential as an anti-rheumatic drug.

Can J Microbiol, 1977 Oct, 23(10), 1494 - 6
Complex medium toxicity to some DNA repair-deficient strains of Salmonella typhimurium; Amsden AB et al.; The recovery of several strains of Salmonella typhimurium LT-2 which had first been grown in minimal medium varies when the organisms are grown on minimal medium agar and complex medium agar . The strains tested included mutants with deficiencies in DNA-repair systems (uvrB-and rec-), a deep rough (rfa-) mutant, and a double mutant carrying both the uvrB- and the rfa-mutation . The uvrB- and rec-mutations imparted sensitivity to complex medium agar . The rfa-mutation suppressed the sensitivity of the uvrB-mutant to complex medium agar . Differences in colony-forming ability were not observed when the bacteria were first grown in the complex medium broth.

Mutat Res, 1977 Oct, 45(1), 1 - 6
Spontaneous, ultraviolet and ionizing radiation mutagenesis in two auxotrophic strains of Salmonella typhimurium carrying an R plasmid; MacPhee DG; Ultraviolet-induced, gamma-induced and spontaneous mutation yields were studied in two different auxotrophic strains of Salmonella typhimurium in the presence and absence of the UV-protecting drug resistance transfer factor R-Utrecht . One strain, carrying the hisC527 (amber) mutation, showed significantly increased spontaneous, UV- and gamma-induced mutability in the presence of the R-Utrecht plasmid . The other strain, carrying the trpD1 mutation (thought to be a missense mutation), also showed significantly increased UV mutability in the presence of the R-Utrecht plasmid . The other strain, carrying the trpD1 mutation (thought to be a missense mutation), also showed significantly increased UV mutability in the presence of the R factor, but appeared to show no significant increase in spontaneous mutability and only a very slight increase in gamma-mutability when carrying the R factor . These results demonstrate that the R-Utrecht plasmid, known to enhance UV-induced mutation yields in S . typhimurium, can also significantly enhance both spontaneous and gamma-induced mutation yields in this species . The latter effects are not so discernible with all markers, however, as shown by the results with strains carrying the trpD1 mutation . Enhancement of spontaneous mutability thus appears to be correlated with enhancement of gamma-mutability rather than UV mutability.

Acta Pathol Microbiol Scand {B}, 1977 Oct, 85B(5), 334 - 40
Surface-charge characteristics of smooth and rough Salmonella typhimurium bacteria determined by aqueous two-phase partitioning and free zones electrophoresis; Stendahl O et al.; Aqueous biphasic partitioning of Salmonella typhimurium S and R bacteria in a system containing 6.2 per cent (w/w) dextran 500 and 4.4 per cent (w/w) poly(ethyleneglycol) 6000 (PEG) was similar to the partition of the corresponding surface lipopolysaccharide (LPS) . Further partition analysis with charged PEG showed that S bacteria and their LPS exposed very little charge, whereas R bacteria and their LPS showed a conspicuous negative charge at neutral pH . Free zone electrophoresis also indicated that the S bacteria have a much lower surface charge density than the R bacteria and accordingly a different surface structure . Thus, the physico-chemical properties of the bacterial surface seem to be determined to a great extent by the characteristics of the cell surface LPS.

Appl Environ Microbiol, 1977 Sep, 34(3), 285 - 91
Effects of enrichment media and incubation conditions on isolating salmonellae from ground-meat filtrate; Kafel S et al.; Forty-eight combinations of enrichment media, secondary enrichment, incubation times and temperatures, and atmospheres were examined for their efficacy in recovering different serovars of Salmonella that had been inoculated into ground-meat extract . Variations included three selective-enrichment media, two (37 and 43 degrees C) incubation temperatures, two (24 and 48 h) incubation times, two (aerobic and anaerobic) incubation atmospheres, and secondary enrichment to two of the selective-enrichment media . The ratio of Salmonella to other microorganisms was 10: greater than 1,000,000 . One-hundred and twenty-four tests were conducted for each enrichment under each condition of incubation . None of the methods recovered Salmonella in more than 60% of the trials . Salmonella typhimurium was recovered most frequently of the serovars tested; S . abortusovis was recovered least frequently . There was considerable variation in the results obtained by the different methods, but there was a statistically significant advantage in the 43 degrees C incubation temperature . Secondary enrichment in tetrathionate broth showed a statistically significant advantage over secondary enrichment in selenite broth . Secondary enrichment into a different medium from the primary enrichment also was advantageous.

Am J Clin Nutr, 1977 Sep, 30(9), 1439 - 46
Sequential changes in body composition during infection: electron probe study IV; Nichols BL et al.; Alterations occur in human muscle electrolyte and water composition in response to infection . There appear to be at least two basic mechanisms; the first is an exchange of sodium for potassium without alteration in water content of muscle . The second is an increase in cellular Na and water without a loss of K on a dry weight basis . In a series of studies in monkeys, Salmonella typhimurium sepsis was induced as an experimental model . Both patterns of muscle response to infection were detected . Electron probe microanalysis revealed that the loss of K concentration was due to an accumulation of intracellular saline which dilute the K content . The mechanism of this is unclear; however, a concomitant increase in undertermined osmoles in the serum suggests that there may be an increase in organic osmoles within the cell which leads to the dilution of intracellular K concentration.

Poult Sci, 1977 Sep, 56(5), 1674 - 5
Effect of low level feeding chlortetracycline on subsequent therapy of chicks infected with Salmonella typhimurium; Quarles CL et al.; A six-week trial was conducted to determine if therapeutic use of chlortetracycline (CTC) would be affected by previous use of the same antibiotics at subtherapeutic levels in the feed . Results indicated therapeutic effect of CTC on mortality was not compromised by the previous use of the low level antibiotic.

Mutat Res, 1977 Sep, 56(1), 7 - 12
Mutagenicity of hydroxamic acids for Salmonella typhimurium; Wang CY; P-Butoxyphenylacethydroxamic acid, benzohydroxamic acid, salicylhydroxamic acid, 2-naphthohydroxamic acid, indole-2-carbohydroxamic acid and benzoylaminoacethydroxamic acid were synthesized, and their mutagenicity for Salmonella typhimurium strains TA98 and TA100 were determined . Except for p-butoxyphenylacethydroxamic acid, all the hydroxamic acids were mutagenic for both strains . The mutagenicity progressed in the following order: 2-naphthohydroxamic acid greater than benzohydroxamic acid and salicylhydroxamic acid greater than benzoylaminoacethydroxamic acid and indole-2-carbohydroxamic acid . The starting materials for the synthesis of these acids including hydroxylamine were not in themselves mutagenic for TA98 and TA100 . Thus, while the mutagenicity may require the hydroxamic acid as a whole, the acyl group may determine the mutagenic potency.

Mutat Res, 1977 Sep, 56(1), 1 - 6
Mutagenicity screening of five methyl carbamate insecticides and their nitroso derivatives using mutants of Salmonella typhimurium LT2; Blecvins RD et al.; The mutagenic activity of five methyl carbamate insecticides-carbaryl, baygon, BUX-Ten, landrin and methomyl-and their nitroso derivatives were investigated using histidine auxotrophs-his TA98, his TA100, his TA1535, his TA1537 and his TA1538--of Salmonella typhimurium LT2 derived by Ames . The methyl carbamate insecticides did not cause a signficant increase in the number of revertant colonies in any of the strains used . In contrast, the nitroso derivatives of the carbamate insecticides greatly increased the number of colonies on plates inoculated with strains his TA100 and his TA1535 . We conclude that the nitroso derivatives of the tested methyl carbamate insecticides are potent mutagens; whereas, the parent insecticides are non-mutagenic.

Mutat Res, 1977 Sep, 44(3), 447 - 50
Mutagenicity of fungal metabolites related to aflatoxin biosynthesis; Wong JJ et al.; Fungal metabolites identified as the intermediates in aflatoxin biosynthetic pathway were screened for their mutagenic activity to Salmonella typhimurium TA98 . Norsolorinic acid, averufin, and versiconal acetate were found to possess questionable mutagenic activity, but versicolorin A, and sterigmatocystin were significant mutagens relative to aflatoxin B1 . The mutagenic activity appears to be related to the bisfuran and not the anthraquinone moiety of the molecule, even though the latter is a key structure of such potent carcinogenic mycotoxin as luteoskyrin.

Mutat Res, 1977 Sep, 44(3), 313 - 26
Mutagenicity of isomeric diol-epoxides of benzo{a}pyrene and benz{a}anthracene in S . typhimurium TA98 and TA100 and in V79 Chinese hamster cells; Malaveille C et al.; Pairs of isomeric vicinal diol-epoxides derived from benzo{a}pyrene 7,8- and 9,10-dihydrodiols and from benz{a}anthracene 8,9-dihydrodiol were tested for their abilities to revert salmonella typhimurium strains TA98 and TA100 to histidine prototrophy and to induce the formation of 8-azaguanine- or of ouabain-resistant V79 Chinese hamster cells . All six diol-epoxides were active in both bacterial strains, but 7beta,8alpha-dihydroxy-9beta,10beta-epoxy-7,8,9,10-tetrahydrobenzo{a}pyrene (the syn isomer) was considerably more mutagenic than the other diol-epoxides . Within the three pairs of stereo-isomeric diol-epoxides, the ratio of the mutagenic potencies of the syn over the related anti isomers varied bothwith the chemical structure and the bacterial strain . The half lives of hydration of these diol-epoxides at pH 7.4 were inversely related to their mutagenic potencies in bacteria . In V79 cells, the two benzo{a}pyrene 7,8-diol 9,10-oxides were mutagenic and the anti isomer was more active than the syn isomer; a reversed order of mutagenic potency with these stereo isomers was observed in S . typhimurium . The other four diol-epoxides were non-mutagenic in V79 cells at the concentrations tested.

Mutat Res, 1977 Sep, 44(3), 305 - 12
Frameshift mutagenesis in bacteria by 8-methoxypsoralen (methoxalen) in the dark; Bridges BA et al.; We confirm that 8-methoxypsoralen (8-MOP) in the dark induces frameshift mutations in both Escherichia coli and Salmonella typhimurium when present in adequate concentration under growth conditions . The dose response is sigmoidal with a threshold or quasi-threshold at concentrations below about 10 microgram/ml . Frameshift mutagenesis by 8-MOP in the dark is unaffected by mutations at the uvrA or uvrB genes, in contrast to base pair substitution mutagenesis by 8-MOP plus near UV light . RecA (but not recB) bacteria are hypersensitive to the growth-inhibiting action of 8-MOP in the dark and are not detectably mutagenized . The characteristics of 8-MOP dark mutagenesis are consistent with the chemical interacting in a non-covalent manner with DNA and affecting the rate of occurrence of base deletions or insertions during DNA replication . The question of extrapolation of the genetic effect of 8-MOP to man is discussed.

Infect Immun, 1977 Sep, 17(3), 663 - 4
Increased resistance of iron-deficient mice to salmonella infection; Puschmann M et al.; Nutritional iron deficiency in mice attenuated Salmonella typhimurium infection compared with both iron-substituted littermates and normal diet control animals.

Biochim Biophys Acta, 1977 Aug 23, 493(2), 429 - 40
Histidinol dehydrogenase from salmonella typhimurium and Escherichia coli . Purification, some characteristics and the amino acid sequence around a reactive thiol group; Bitar KG et al.; The purification and some physical properties of histidinol dehydrogenase, L-histidinol-nicotinamide adenine dinucleotide oxido-reductase (EC 1.1.1.23) from either Salmonella typhimurium or Escherichia coli are reported in this paper . Modification of histidinol dehydrogenase with one equivalent of N-(4-dimethylamino-3,5-dinitrophenyl)maleimide at pH 6.8 yields an enzyme that is inactive toward the oxidation of L-histidinol . The modified cysteine residue was located in an acid insoluble tryptic core . The amino acid sequence around the reactive thiol group in S . typhimurium is: Leu-Cys-Gly-Val-Glu-Glu-Ile-Phe, and in E . coli is: Leu-Cys-Gly-Val-Glu-Asp-Val-Phe . These unique sequences show no homology to the reactive thiol groups from some other dehydrogenases.

Experientia, 1977 Aug 15, 33(8), 1084 - 5
In vitro mutagenicity of the soil nematicide 1,3-dichloropropene; Neudecker T et al.; The cis- and trans-isomers of 1,3-dichloropropene have been tested in the Ames mutagenicity assay system on Salmonella typhimurium tester strain TA 1535 . Both isomers have been found to be mutagenic even without microsomal activation.

Science, 1977 Aug 5, 197(4303), 577 - 8
Mutagenic activity of quercetin and related compounds; Bjeldanes LF et al.; The mutagenic activities of several flavonoids and flavonoid metabolites were examined by means of Salmonella typhimurium mutants that reveal base-pair substitution and frameshift mutagens . Of the compounds tested (naringin, rutin, neohesperetin, hesperetin, dihydroquercetin, quercetin, quercetin pentaacetate, permethylquercetin, m-hydroxyphenylacetic acid, and m,p-dihydroxyphenylacetic acid), only quercetin was mutagenic without microsomal activation . With activation, however, the mutagenic activity of quercetin was increased significantly and that of quercetin pentaacetate was revealed . The health implications of these findings and aspects of flavonoid structural requirements for mutagenic activity are discussed.

J Gen Microbiol, 1977 Aug, 101(2), 319 - 25
A Salmonella typhimurium endonuclease that converts native DNA to fragments of about 8 X 10(5) daltons; Schumann W et al.; Crude extracts of Salmonella typhimurium were found to contain an endonuclease that degraded double-stranded linear DNA from bacteria and phages to fragments with a molecular weight of about 8 X 10(5) . The nuclease did not have an absolute requirement for Mg2+ . One discrete intermediate product had a molecular weight of 6-6 X 10(6) . Extracts from two different mutants were tested: one completely lacked the endonuclease activity (strain DB5575), and the other showed an absolute requirement for Mg2+ (strain 4543) . No biological role has yet been found for this endonuclease of S . typhimurium.

Rheumatol Rehabil, 1977 Aug, 16(3), 150 - 1
Salmonella typhimurium arthritis in rheumatoid disease; Rae S et al.; Septic arthritis is a well recognized complication of rheumatoid arthritis (British Medical Journal, 1976; Mitchell et al., 1976), particularly after joint replacement (Freeman, 1976) . We report here infection with an unusual organism--Salmonella typhimurium.

Mutat Res, 1977 Aug, 44(2), 177 - 82
A study of the photoinduced mutagenicity of methylene blue; Gutter B et al.; Illumination of Salmonella typhimurium strains in the presence of methylene blue resulted in the production of mutations of the base-substitution type . This photodynamic effect mediated by the dye was separable from the genetic event seen when bacteria are illuminated in the absence of added photosensitizers.

Am J Clin Nutr, 1977 Aug, 30(8), 1289 - 93
Nutritional effects of salmonellosis in mice; Moore RN et al.; Mice infected with a standard challenge of Salmonella typhimurium manifest a number of changes associated with endotoxemia . These changes result in profound alterations in the nutritional and metabolic status of the host . Food and water intake approaches levels of total inanition, blood glucose declines more rapidly than in fasted controls, hepatic phosphoenolpyruvate carboxykinase (the enzyme that is rate limiting in gluconeogenesis) shows diminished activity and loss of cortisol inducibility, and hypothermia, rather than hyperthermia, becomes acute . These changes occur at a time when bacteremia is first demonstrable . This occurs on the 3rd day after infection under the conditions employed . Death occurs in most mice within the next 24 to 48 hr . Mice vaccinated with a highly immunogenic ribosomal preparation and subsequently infected with the standard number of organisms did not manifest the above changes . Other work from this laboratory has established that effects of the type described are elicited by bacterial endotoxin as a result of mediating substances released into the blood by cells of the reticuloendothelial system . Presumably these substances appear in blood of infected mice as well.

J Immunol, 1977 Aug, 119(2), 609 - 13
Physicochemical consequences of opsonization: perturbation of liposomal membranes by Salmonella typhimurium 395 MS opsonized with IgG antibodies; Tagesson C et al.; When phagocytosis-resistant Salmonella typhimurium 395 MS bacteria sensitized with anti-MS IgG antibodies were incubated with liposomes composed of phosphatidylcholine, cholesterol, and dicetylphosphate, a previously sequestered liposomal marker (4-methylumbelliferylphosphate) was released . Unsensitized or F(ab')2-sensitized bacteria had no such effect . This perturbation was neither dependent upon negatively charged dicetylphosphate nor upon cholesterol . It was further evident that palmitoyl-poly(ethyleneglycol) caused release of the trapped marker in a similar way as sensitized bacteria . These findings demonstrate a similarity between sensitized bacteria and a hydrophobic probe and lend support to the hypothesis that the perturbation was brought about by hydrophobic interaction . The observations indicate that liposomes, like phagocytes, possess "receptor sites" for the activated part of IgG and raise the possibility that phagocytic effectors can operate in a relatively nonspecific manner.

J Hyg (Lond), 1977 Aug, 79(1), 17 - 24
The immunization of mice and calves with gal E mutants of Salmonella typhimurium; Wray C et al.; A galactose epimeraseless (gal E) mutant of Salmonella typhimurium was investigated in mice and calves for its suitability as a live vaccine . In mice, a very highly significant difference in the mortality rates was observed when vaccinated and non-vaccinated animals were challenged with virulent strains of S . typhimurium and S . dublin . In calves, doses of 10(6) and above of gal E mutant injected subcutaneously provided highly significant protection both in terms of mortality and prevalence of symptoms when calves were challenged orally with S . typhimurium . However, there appeared to be a relation between the vaccine and the presence of renal lesions and before gal E mutants can be recommended, further work is necessary to determine the pathogenesis of these lesions.

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