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 Mu