Mutat Res, 1985 May, 149(3), 311 - 9 Genetic and quantum chemical basis of the mutagenicity of nitroarenes for adenine-thymine base pairs; McCoy EC et al.; The mutagenicity of nitroarenes for Salmonella typhimurium strains with adenine-thymine base pairs at the mutational site is dependent upon enzymic reduction of the nitro function . Although the electrophilic metabolites of nitroarenes are capable of mutating adenine-thymine base pairs, they show a marked preference for guanine-cytosine pairs when given a choice . Quantum chemical calculations indicate the reactivity order for nucleophilic sites in an AT run of base pairs to be the N-7 of adenine (N7(A)) first, followed by an approximately equal reactivity for C-8 of adenine (C8(A)) and O4 of thymine (O4(T)) . Given the low probability of reaction of electrophilic metabolites of nitroarenes with adenine-thymine base pairs, the mutagenic potency of nitroarenes for strains with adenine-thymine base pairs at the mutational site is remarkable. J Bacteriol, 1985 May, 162(2), 738 - 45 High-molecular-weight components in lipopolysaccharides of Salmonella typhimurium, Salmonella minnesota, and Escherichia coli; Peterson AA et al.; Lipopolysaccharide from smooth strains of Salmonella typhimurium, Salmonella minnesota, and Escherichia coli O111:B4, O55:B5, and O127:B8 was fractionated by gel filtration chromatography . All lipopolysaccharide samples separated into three major populations . Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the fractions from S . typhimurium and S . minnesota indicated that the three peaks were made up of molecules with average O-antigen lengths of (i) 70 or more repeat units, (ii) 30 and 20 repeats units in the samples from S . typhimurium and S . minnesota, respectively, and (iii) 1 repeat unit . In contrast to the Salmonella samples, peak 1 from the E . coli samples was not detected on polyacrylamide gels and lacked detectable phosphate . This high-molecular-weight material had a sugar composition similar to that of O-antigen and was tentatively identified as capsular polysaccharide . Peaks 2 and 3 of the E . coli samples were analogous to those of the Salmonella isolates, containing lipopolysaccharide molecules with averages of 18 and 1 O-antigen repeat units, respectively . These lipopolysaccharide molecules did not completely dissociate during electrophoresis, and multimers were detected as distinct, anomalous, slow-migrating bands . Increasing the concentration of sodium dodecyl sulfate in the gels resulted in the dissociation of these multimers. Carcinogenesis, 1985 May, 6(5), 727 - 32 Nitroreductase-dependent mutagenicity of p-nitrophenylhydroxylamine and its N-acetyl and N-formyl hydroxamic acids; Corbett MD et al.; p-Nitrophenylhydroxylamine (NPH) and two hydroxamic acids derived from it were synthesized and subjected to mutagenicity testing in Salmonella typhimurium strains TA98, TA98NR, TA1538 and TA1538NR . In addition, p-dinitrobenzene (DNB), p-nitroaniline (NA) and p-nitroacetanilide (AcNA) were simultaneously examined for mutagenic action against these four tester strains . NPH, its N-acetyl (AcNPH) and N-formyl (FoNPH) derivatives, and also DNB displayed strong mutagenic action to the nitroreductase-containing strains, TA98 and TA1538 . NPH was the most potent chemical in this series against both of these strains, while the two hydroxamic acids AcNPH and FoNPH, and also DNB displayed approximately the same degree of mutagenicity . In the nitroreductase-deficient strains, TA98NR and TA1538NR, the mutagenicity of these four compounds was markedly reduced . The necessity for nitroreduction in order to activate these promutagens is fairly certain; however, the lack of mutagenicity of NA and AcNA towards all four tester strains made the interpretation of these data somewhat more complicated . Several possible bioactivation pathways were presented, with one mechanism in particular being proposed . This mechanism requires only that the strong electron-withdrawing nitro group be converted to an electron-donating group by bacterial nitroreductase . Such a mechanism is unique for the bioactivation of nitro aromatics by nitroreductase, since the enzymatic reduction need not produce the intermediary hydroxylamine metabolite. J Bacteriol, 1985 May, 162(2), 810 - 6 Allosteric regulation of glycerol kinase by enzyme IIIglc of the phosphotransferase system in Escherichia coli and Salmonella typhimurium; Novotny MJ et al.; The mechanism by which enzyme IIIglc of the bacterial phosphotransferase system regulates the activity of crystalline glycerol kinase from Escherichia coli has been studied, and the inhibitory effects have been compared with those produced by fructose-1,6-diphosphate . It was shown that the free, but not the phosphorylated, form of enzyme IIIglc inhibits the kinase . Mutants of Salmonella typhimurium were isolated which were resistant to inhibition by either enzyme IIIglc (glpKr mutants) or fructose-1,6-diphosphate (glpKi mutants), and each mutant type was shown to retain full sensitivity to inhibition by the other regulatory agent . Other mutants were fully or partially resistant to regulation by both agents . The two regulatory sites on the kinase are evidently distinct but must overlap or interact functionally . Kinetic analyses have revealed several mechanistic features of the regulatory interactions . (i) Inhibition by both allosteric regulatory agents is strongly pH dependent, with maximal inhibition occurring at ca . pH 6.5 under the assay conditions employed . (ii) Binding of enzyme IIIglc to glycerol kinase is also pH dependent, the Ki being near 4 microM at pH 6.0 but near 10 microM at pH 7.0 . (iii) Whereas fructose-1,6-diphosphate inhibition apparently requires that the enzyme exist in a tetrameric state, both the dimer and the tetramer appear to be fully sensitive to enzyme IIIglc inhibition . (iv) Inhibition by enzyme IIIglc (like that by fructose-1,6-diphosphate) is noncompetitive with respect to both substrates . (v) The inhibitory responses of glycerol kinase to fructose-1, 6-diphosphate and enzyme IIIglc show features characteristic of positive cooperativity at low inhibitor concentration . (vi) Neither agent inhibits completely at high inhibitor concentration . (vii) Apparent negative cooperativity with respect to ATP binding is observed with purified E . coli glycerol kinase, with glycerol kinase in crude extracts of wild-type S . typhimurium cells, and with glpKr and glpKi mutant forms of glycerol kinase from S . typhimurium . These results serve to characterize the regulatory interactions which control the activity of glycerol kinase by fructose-1,6-diphosphate and by enzyme IIIglc of the phosphotransferase system. J Bacteriol, 1985 May, 162(2), 722 - 7 Ion selectivity of gram-negative bacterial porins; Benz R et al.; Twelve different porins from the gram-negative bacteria Escherichia coli, Salmonella typhimurium, Pseudomonas aeruginosa, and Yersinia pestis were reconstituted into lipid bilayer membranes . Most of the porins, except outer membrane protein P, formed large, water-filled, ion-permeable channels with a single-channel conductance between 1.5 and 6 nS in 1 M KCl . The ions used for probing the pore structure had the same relative mobilities while moving through the porin pore as they did while moving in free solution . Thus the single-channel conductances of the individual porins could be used to estimate the effective channel diameters of these porins, yielding values ranging from 1.0 to 2.0 nm . Zero-current potential measurements in the presence of salt gradients across lipid bilayer membranes containing individual porins gave results that were consistent with the conclusions drawn from the single-channel experiments . For all porins except protein P, the channels exhibited a greater cation selectivity for less mobile anions and a greater anion selectivity for less mobile cations, which again indicated that the ions were moving inside the pores in a fashion similar to their movement in the aqueous phase . Three porins, PhoE and NmpC of E . coli and protein P of P . aeruginosa, formed anion-selective pores . PhoE and NmpC were only weakly anion selective, and their selectivity was dependent on the mobility of the ions . In contrast, cations were unable to enter the selectivity filter of the protein P channel . This resulted in a high anion selectivity for all salts tested in this study . The other porins examined, including all of the known constitutive porins of the four gram-negative bacteria studied, were cation selective with a 3- to 40-fold preference for K+ ions over Cl- ions. Infect Immun, 1985 May, 48(2), 597 - 600 Binding activity of a murine anti-lipid A monoclonal antibody; Elkins K et al.; In this report we briefly describe an immunoglobulin G3 monoclonal antibody, 2G6/1H11, which binds purified lipid A from Salmonella minnesota and a lipid A precursor molecule derived from Salmonella typhimurium . 2G6/1H11 does not bind well to purified whole S . typhimurium lipopolysaccharide (LPS), S . minnesota LPS, LPS preparations from a series of S . minnesota rough mutants, or intact S . typhimurium bacteria . Thus, there are antigenic determinants in purified lipid A which are not exposed when lipid A is presented as part of the whole LPS molecule or intact bacteria. J Immunol, 1985 May, 134(5), 2872 - 8 Control of B cell proliferation: inhibition of responses to B cell mitogens induced by plasma cell tumors; Berman JE et al.; A multitude of factors has been described that positively and negatively regulate B cell proliferation . A model system for the study of negative control of B cell function is provided by mice bearing plasmacytomas (PC-mice) . In PC-mice, the primary immune response, as measured by development of antibody-forming cells (AFC), is severely suppressed . The present report specifically identifies a block in B cell proliferation as the apparent cause of this reduction in AFC production . Thus, the proliferative response of B cells from the spleens of PC-mice (PC-spleens) was significantly impaired when stimulated with four different B cell mitogens (lipopolysaccharide, Salmonella typhimurium mitogen, anti-mu conjugated to Sepharose, and 8-mercaptoguanosine) . Nevertheless, the mitogen-responsiveness of these B cells was recovered when they were segregated by various methods from macrophages . These data suggest that the proliferative ability of the B cells in PC-spleens is inherently normal . In concordance with this conclusion, it was shown that suppressor cells from PC-spleens can block the proliferation of normal B cells derived from nontumor-bearing mice . This inhibition does not require direct cell contact and is mediated via soluble factors . The relevance of these results to previous studies of PC-induced immunosuppression and to the control of normal B cell proliferation is discussed. Ann Inst Pasteur Microbiol, 1985 May-Jun, 136A(3), 289 - 301 Salmonella typhimurium strains carrying haemolysin plasmids and cloned haemolysin genes from Escherichia coli; Hacker J et al.; Like all other Salmonella typhimurium strains examined, the smooth variants SF1397 (LT2) and 1366 and also their semi-rough and rough derivatives are non-haemolytic . Nevertheless, two haemolysin (Hly) plasmids of E . coli belonging to the inc groups incFIII,IV (pSU316) and incI2 (pHly152) were able to be introduced into these strains by conjugation and stably maintained . A considerable percentage of the Hly+ transconjugants obtained had lost parts of their O-side chains, a result of selection for the better recipient capability of "semi-rough" variants rather than the direct influence of the Hly+ plasmids themselves . In contrast to the incFIII,IV plasmid pSU316, which exhibited higher conjugation rates with rough recipients, the incI2 plasmid pHly152 was accepted best by smooth strains . Transformation with cloned E . coli haemolysin (hly) determinant was inefficient (less than 10(-6)) for smooth strains, but 10(2) - 10(3) times higher for rough recipients, and was increased by the use of Salmonella-modified DNA . The transformants and transconjugants were relatively stable and showed the same haemolytic activity as the E . coli donor strains . The virulence of the Hly+ smooth, semi-rough and rough S . typhimurium strains was tested in two mouse models, and neither the mortality rate nor the ability to multiply within the mouse spleen was influenced by the hly determinants. Zentralbl Bakteriol Mikrobiol Hyg {B}, 1985 May, 180(5-6), 540 - 7 Determination of mutagenic activities in different fractions of automobile exhaust condensate by the Salmonella/oxygenase mutagenicity test system; Norpoth K et al.; Automobile exhaust condensate of a passenger car (gasoline engine) was separated into fractions of 2-3 rings containing -, 4-7 rings containing polycyclic aromatic hydrocarbons (PAHs) and PAH-free fractions . All fractions were tested for mutagenicity by the Ames system . The highest dose-dependent increase in revertant colonies was found for the 4-7 ring PAH-fraction when tested with Salmonella typhimurium TA 98 and TA 100 . These results are compatible with data obtained in in-vivo tests by previous investigations . The mutagenicity of these fractions in the absence of the oxygenase was negligible. J Biol Chem, 1985 Apr 25, 260(8), 4724 - 8 A single amino acid substitution in the enzyme 5-enolpyruvylshikimate-3-phosphate synthase confers resistance to the herbicide glyphosate; Stalker DM et al.; The enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EC 2.5.1.19), encoded by the aroA locus, is a target site of glyphosate inhibition in bacteria . A glyphosate-resistant aroA allele has been cloned in Escherichia coli from a mutagenized strain of Salmonella typhimurium . Subcloning of this mutant aroA allele shows the gene to reside on a 1.3-kilobase segment of S . typhimurium DNA . Nucleotide sequence analysis of this mutant gene indicates a protein-coding region 427 amino acids in length . Comparison of the mutant and wild type aroA gene sequences reveals a single base pair change resulting in a Pro to Ser amino acid substitution at the 101st codon of the protein . A hybrid gene fusion between mutant and wild type aroA gene sequences was constructed . 5-Enolpyruvylshikimate-3-phosphate synthase was prepared from E . coli cells harboring this construct . The glyphosate-resistant phenotype is shown to be associated with the single amino acid substitution described above. J Mol Biol, 1985 Apr 20, 182(4), 579 - 87 Two type I restriction enzymes from Salmonella species . Purification and DNA recognition sequences; Nagaraja V et al.; We have purified the type I restriction enzymes SB and SP from Salmonella typhimurium and S . potsdam, respectively, and determined the DNA sequences that they recognize . These sequences resemble those previously determined for the type I enzymes, EcoB, EcoK and EcoA, in that the specific part of the sequence is divided into two domains by a spacer of non-specific sequence that has a fixed length for each enzyme . Two main differences from the previously determined sequences are seen . Both of the new sequences are degenerate and one of them, SB, has one trinucleotide and one pentanucleotide-specific domain rather than the trinucleotide and tetranucleotide domains seen for all of the other enzymes . The only conserved features of the recognition sequences are the adenosyl residues that are methylated in the modification reaction . For all of the enzymes these are situated ten or 11 base-pairs apart, one on each strand of the DNA . This suggests that the enzymes bind to DNA along one face of the double helix making protein-DNA interaction in two successive major grooves with most of the non-specific spacer sequence in the intervening minor groove. JAMA, 1985 Apr 12, 253(14), 2058 - 60 An outbreak of multiple-drug-resistant Salmonella enteritis from raw milk; Tacket CO et al.; In early 1983, an outbreak of illness caused by raw milk contaminated with multiple-antimicrobial-resistant Salmonella typhimurium occurred in Arizona . One of the cases involved a 72-year-old woman who died with Salmonella enteritis and sepsis that had not responded to treatment with chloramphenicol . The S typhimurium isolates from this patient, from other ill persons, and from raw milk were resistant to ampicillin, chloramphenicol, kanamycin sulfate, streptomycin, sulfonamide, and tetracycline . These resistances were mediated by a 105-megadalton R plasmid . During the epidemic period, 43% of the S typhimurium isolates submitted to the Arizona Department of Health Services were resistant to chloramphenicol, and 80% of these possessed the same plasmid resistance . Although there was evidence of spread of the S typhimurium in the community, there was no evidence of spread of this Salmonella R plasmid to the normal flora of patients or their family members a median of 14 weeks after the infection . This outbreak demonstrates the ability of drug-resistant Salmonella to spread from the animal to the human reservoir and, in a suitable host, produce a fatal infection. Am Ind Hyg Assoc J, 1985 Apr, 46(4), 187 - 91 Destruction of aromatic amines in laboratory wastes through oxidation with potassium permanganate/sulfuric acid into non-mutagenic derivatives; Castegnaro M et al.; Nine aromatic amines, i.e., benzidine; o-tolidine; o-dianisidine; 3,3'-dichlorobenzidine; 4-aminobiphenyl; 1- and 2-naphthylamine; 4,4'-methylene bis(2-chloroaniline) and m-toluenediamine, were oxidized with potassium permanganate/sulfuric acid . Experimental conditions for complete degradation of these aromatic amines are described . The disappearance of the parent compound through oxidation was measured using HPLC coupled with UV spectrophotometry . The corresponding degradation products were found to be non-mutagenic to Salmonella typhimurium strains TA100, TA98 and TA97, both in the presence and absence of a rat liver S9 activation system . A collaborative study, involving 11 laboratories, has shown the applicability and the reproducibility of this degradation method. Cancer Lett, 1985 Apr, 26(3), 343 - 7 Mutagenicity and tumor initiating activity of methylated benzo{k} fluoranthenes; Amin S et al.; The mutagenic activities toward Salmonella typhimurium TA100 and tumor initiating activities on mouse skin of the polynuclear aromatic hydrocarbons benzo{k}fluoranthene (BkF),2-methylBkF,8-methylBkF,9-methyl-BkF and 7,12-dimethylBkF were compared . BkF and 2-methylBkF were the most mutagenic of the compounds tested and had comparable activity; they were more active than 7,12-dimethylBkF . 8-MethylBkF and 9-methylBkF were not mutagenic . BkF and the methylated BkFs had similar tumor initiating activities on mouse skin . The results suggest that 8,9-dihydro-8,9-epoxy-BkF might be involved in the metabolic activation of BkF to a mutagen, but do not indicate which metabolite may be involved in BkF tumorigenesis. Infect Immun, 1985 Apr, 48(1), 244 - 7 Immunomodulation of the antibody response to lipopolysaccharide in C3H/HeJ mice by complexing with heterologous ribosomes; Phillips M et al.; We show that formaldehyde fixation of Salmonella typhimurium lipopolysaccharide (LPS) to ribosomes purified from Brucella abortus induced a primary immunoglobulin M (IgM) response to LPS in C3H/HeJ mice and upon revaccination resulted in elevated titers of IgM and induction of IgG antibody to the O antigens of LPS, as measured by an enzyme-linked immunosorbent assay . A similar LPS-Aspergillus fumigatus ribosomal complex yielded IgM and IgG antibody to LPS only after secondary stimulation . These results demonstrate that the hyporesponsiveness of C3H/HeJ mice with respect to antibody formation to LPS can be overcome by complexing this molecule to ribosomal particles and provide a theoretical mechanism for the action of some "ribosomal" vaccines . The results are compatible with the hypothesis that LPS in complex with the ribosomes is converted to a T-dependent form of the antigen to which the C3H/HeJ mice can respond. Mutat Res, 1985 Apr-May, 156(1-2), 93 - 102 Differential mutagenic activity of IQ (2-amino-3-methylimidazo{4,5-f}quinoline) in Salmonella typhimurium strains in vitro and in vivo, in Drosophila, and in mice; Wild D et al.; IQ, a heterocyclic aromatic amine which is formed during the frying of meat, was prepared by chemical synthesis . Its genotoxic potential was studied in bacteria, Drosophila and in mice . A mutagenic effect of IQ (frameshift induction) was detected in Salmonella typhimurium in experiments without metabolic activation; this effect was several orders of magnitude lower than that observed in the presence of an activation system . Ames tests with liver-homogenate S9 fraction from PCB-induced mice and rats confirmed the high mutagenic potency of IQ metabolites (Kasai et al., 1980a) . Comparative studies on diagnostic Salmonella strains revealed that the high frameshift-inducing activity is independent of the plasmid pkM101; it is, however, greatly reduced by an intact excision-repair system for DNA lesions . The mutagenic activity of the metabolite(s) formed in vitro by S9 mix has a half-life of ca . 14 min . In the fruit fly, Drosophila melanogaster, IQ induced when used at sublethal concentrations, X-chromosomal recessive lethal mutations in male germ cells in a dose-dependent manner . In mice, tests were performed to detect somatic mutations: chromosomal anomalies (micronuclei) in bone marrow, and gene mutations (affecting coat pigmentation) in mice exposed to IQ in utero . No genotoxic effects were observed in these assays . However, the formation of mutagenic metabolites in the liver of IQ-treated mice was unequivocally demonstrated in host-mediated assays using Salmonella as mutagen probes in mice . The data demonstrate genotoxic activity of IQ in prokaryotic and eukaryotic organisms . The possible reasons for the different response of mammalian systems in vivo and the Salmonella system are discussed. Aust J Exp Biol Med Sci, 1985 Apr, 63 ( Pt 2), 177 - 82 The correlation between serum IgA antibody levels and resistance to infection with Salmonella typhimurium after oral immunization with various salmonellae; Srisart P et al.; Subsequent to oral feeding of various Salmonella strains to mice, the IgA antibodies directed against the O-somatic antigens of the immunising strain were measured in both serum and intestinal juice, using the ELISA technique . 21 days after oral immunization the IgA antibody levels were relatively high only in those mice which were resistant to challenge with a virulent strain of Salmonella typhimurium . Because there was no correlation between protection and the specificity of the 'O' somatic antigens of the immunising and challenge strains, the IgA antibodies measured were not responsible for protection . Nevertheless, the level of these antibodies affords a good index of the resistance of mice or immune status of mice to Salmonella infection. Eur J Clin Microbiol, 1985 Apr, 4(2), 129 - 31 Enterotoxigenicity among Salmonella typhimurium strains isolated in France; Baloda SB et al.; Twenty strains of Salmonella typhimurium isolated in France from patients with diarrhea were tested for enterotoxins and cytotoxic factors by conventional bioassays . Eighteen of the strains produced enterotoxins to varying degrees and did not react with antisera to Escherichia coli heat-labile enterotoxin . Cytotoxic factors were present in two strains . These findings suggest that efforts to elucidate the virulence mechanisms of Salmonella spp . isolated in different parts of the world should be renewed. Appl Environ Microbiol, 1985 Apr, 49(4), 822 - 7 Effects of dissolved organic carbon and second substrates on the biodegradation of organic compounds at low concentrations; Schmidt SK et al.; Pseudomonas acidovorans and Pseudomonas sp . strain ANL but not Salmonella typhimurium grew in an inorganic salts solution . The growth of P . acidovorans in this solution was not enhanced by the addition of 2.0 micrograms of phenol per liter, but the phenol was mineralized . Mineralization of 2.0 micrograms of phenol per liter by P . acidovorans was delayed 16 h by 70 micrograms of acetate per liter, and the delay was lengthened by increasing acetate concentrations, whereas phenol and acetate were utilized simultaneously at concentrations of 2.0 and 13 micrograms/liter, respectively . Growth of Pseudomonas sp . in the inorganic salts solution was not affected by the addition of 3.0 micrograms each of glucose and aniline per liter, nor was mineralization of the two compounds detected during the initial period of growth . However, mineralization of both substrates by this organism occurred simultaneously during the latter phases of growth and after growth had ended at the expense of the uncharacterized dissolved organic compounds in the salts solution . In contrast, when Pseudomonas sp . was grown in the salts solution supplemented with 300 micrograms each of glucose and aniline, the sugar was mineralized first, and aniline was mineralized only after much of the glucose carbon was converted to CO2 . S . typhimurium failed to multiply in the salts solution with 1.0 micrograms of glucose per liter . It grew slightly but mineralized little of the sugar at 5.0 micrograms/liter, but its population density rose at 10 micrograms of glucose per liter or higher . The hexose could be mineralized at 0.5 micrograms/liter, however, if the solution contained 5.0 mg of arabinose per liter.(ABSTRACT TRUNCATED AT 250 WORDS) Mutat Res, 1985 Apr-May, 156(1-2), 61 - 7 Mutagenicity of polycyclic aromatic hydrocarbons and quinones on Salmonella typhimurium TA97; Sakai M et al.; 18 polycyclic aromatic hydrocarbons (PAHs) and 7 quinones were tested for mutagenicity using Salmonella typhimurium TA97, TA98 and TA100 with or without metabolic activation . In the presence of metabolic activation, TA97 was more susceptible to mutation than either TA98 or TA100 by many of PAHs tested . PAHs such as 1-methylphenanthrene, fluoranthene, pyrene, benzo{a}pyrene, benzo{e}pyrene and perylene had high mutagenic effects on TA97 in the presence of metabolic activation . 1,6- and 1,8-pyrenequinones were also highly mutagenic on TA97 in the presence or absence of metabolic activation . It appears that pyrene is mutagenic through its metabolic conversion to pyrenequinones. Mutat Res, 1985 Apr-May, 156(1-2), 53 - 9 Mutagenicity of some derivatives of dipyrido{1,2-a:3',2'-d}imidazoles in Salmonella typhimurium with metabolic activation by rat liver and small intestine subcellular fractions; N'Goy K et al.; The mutagenic effect of 2-amino-dipyrido{1,2-a:3',2'-d}imidazole (Glu-P-2) was compared with that of the 3-amino, 3-nitro, or 3-N-hydroxylated derivatives of the same base ring with methyl groups at positions 4 and 6 of the molecule . The compounds were tested in Salmonella typhimurium strain TA98 without metabolic activation and in the presence of different concentrations of subcellular fractions from livers or small intestines of rats pretreated with different P448/P450 inducers . The 4,6-dimethyl compounds are always more mutagenic than Glu-P-2 . Pretreatment with Aroclor 1254 (ARO) is the most effective inducer in the activation of the 2- and 3-amino compounds by liver S9, whereas the same fraction decreases the mutagenicity of the 3-nitro derivative . S9 from small intestine increased the mutagenic effect of the 3-nitro and 3-N-hydroxylated compounds, but it was unable to activate the amino compounds. Mutat Res, 1985 Apr-May, 156(1-2), 39 - 52 Mutagenicity studies on coffee . The influence of different factors on the mutagenic activity in the Salmonella/mammalian microsome assay; Friederich U et al.; Recently, mutagenic activity on several strains of Salmonella typhimurium has been found in many heat-processed foodstuffs . The previously reported direct-acting mutagenic activity of coffee in Salmonella typhimurium TA100 (Ames assay) was confirmed in our study . In addition to TA100, a mutagenic effect of coffee was also found by using the newly developed strain TA102 . The mutagenic activity was abolished by the addition of rat-liver homogenate . 10% S9 mix completely eliminated the mutagenic activity of 30 mg of coffee per plate . The addition of reduced glutathione to active S9 further decreased the mutagenic activity and also reduced the mutagenicity together with inactivated S9 . The compound or compounds responsible for this inactivation are heat-labile and seem to be located in the cytosol fraction of the S9 . Part of the mutagenicity of coffee was also lost spontaneously upon incubation at temperatures between 0 degrees and 50 degrees C . The loss of activity was dependent on temperature, being more pronounced at 50 degrees C compared to 0 degrees C (at 50 degrees C approximately 50% of the mutagenic activity was lost after 6 h) . As anaerobic conditions prevented this loss of mutagenicity almost totally, oxidative processes are probably responsible for the inactivation . The stability of the mutagen was not influenced by incubation at low pH values (pH 1-3), with or without the addition of pepsinogen . The mutagenic properties of methylglyoxal, which to some extent could be responsible for the mutagenic activity of coffee, were compared with those of coffee . Methylglyoxal was strongly mutagenic towards Salmonella typhimurium TA100 and TA102 . Its mutagenic activity was partially inactivated by the addition of 10% S9 . Glyoxalase I and II together with reduced glutathione abolished the mutagenic activity of methylglyoxal but reduced the mutagenicity of coffee by only 80% . Since these enzymes occur in mammalian cells, the mutagenic compound(s) of coffee could also be degraded in vivo . This conclusion is supported by the fact that a long-term carcinogenicity study with rats was negative . These results clearly demonstrate that the effects observed in vitro do not necessarily also occur in vivo, but that in vitro experiments may contribute to the understanding of fundamental mechanisms of chemical carcinogenesis. J Environ Sci Health B, 1985 Apr, 20(2), 153 - 65 Mutagenicity tests with gallic and tannic acid in the Salmonella/mammalian microsome assay; Rashid KA et al.; Gallic acid, tannic acid mixture and a purified fraction of tannic acid were evaluated for possible mutagenic activity in three strains of Salmonella typhimurium, TA98, TA100, and TA1535 . These chemicals were not mutagenic either before or after activation with rat and woodchuck microsomal and cytosolic enzymes . However, tannic acid mixture and tannic acid fraction both gave a significantly (p = 0.05) dose-related reduction in the number of the revertant colonies, compared to the normal spontaneous revertants with no apparent toxic effects in the background lawn . With an agar diffusion assay, the chemicals exhibited toxic effects at 5000 micrograms/disc. Proc Natl Acad Sci U S A, 1985 Apr, 82(8), 2478 - 82 Metabolically activated steviol, the aglycone of stevioside, is mutagenic; Pezzuto JM et al.; Stevioside, a constituent of Stevia rebaudiana, is commonly used as a noncaloric sugar substitute in Japan . Consistent with reports in the literature, we have found that stevioside is not mutagenic as judged by utilization of Salmonella typhimurium strain TM677, either in the presence or in the absence of a metabolic activating system . Similar negative results were obtained with several structurally related sweet-tasting glycosides . However, steviol, the aglycone of stevioside, was found to be highly mutagenic when evaluated in the presence of a 9000 X g supernatant fraction derived from the livers of Aroclor 1254-pretreated rats . Expression of mutagenic activity was dependent on both pretreatment of the rats with Aroclor 1254 and addition of NADPH; unmetabolized steviol was not active . The structurally related species, isosteviol, was not active regardless of metabolic activation . Similarly, chemical reduction of the unsaturated bond linking the carbon-16 and -17 positions of steviol resulted in the generation of two isomeric products, dihydrosteviol A and B, that were not mutagenic . In addition, ent-kaurenoic acid was found to be inactive . It is therefore clear that a metabolite of an integral component of stevioside is mutagenic; structural features of requisite importance for the expression of mutagenic activity include a hydroxy group at position 13 and an unsaturated bond joining the carbon atoms at positions 16 and 17 . A potential metabolite of steviol, steviol-16 alpha,17-epoxide, was synthesized chemically and found to be ineffective as a direct-acting mutagen . Thus, although stevioside itself appears innocuous, it would seem prudent to expeditiously and unequivocally establish the human metabolic disposition of this substance. Fundam Appl Toxicol, 1985 Apr, 5(2), 382 - 90 Lack of concordance of the Salmonella/microsome assay with the mouse dermal carcinogenesis bioassay for complex petroleum hydrocarbon mixtures; Cragg ST et al.; Typical petroleum hydrocarbon mixtures were tested directly, without extraction, in the Salmonella/microsome mutagenesis assay in order to determine if the assay would be useful to predict their carcinogenic activity . The carcinogenic activity of each sample had been previously characterized in the in vivo mouse dermal carcinogenesis bioassay . The series of samples evaluated offered several advantages . They spanned a wide boiling point range, were well characterized chemically, had been tested for carcinogenic activity in a single laboratory, and varied in potency in vivo from inactive to highly active . Mutagenicity testing was performed in several well-established contract laboratories that routinely perform the assay . These laboratories were the main contracting laboratories for these assays at the time and had previously tested petroleum samples for clients . Initially, the first laboratory tested 13 samples in five strains of Salmonella typhimurium with and without rat liver S-9 (Arochlor 1254 induced), utilizing both plate and suspension techniques . None of the 13 samples exhibited a mutagenic response, even though 9 of the 13 were slightly to highly dermally carcinogenic in mice . Because of the unexpected results, it was decided to repeat the mutagenicity assays in two other laboratories . Six of the thirteen samples were selected, ranging in carcinogenic potency from negative to highly active . Again, none were mutagenic in the second contract laboratory . In a third facility, only one sample of the six exhibited a definite mutagenic response . However, the response was observed with a sample having only weak carcinogenic activity and, unusual for petroleum hydrocarbons, occurred without activation.(ABSTRACT TRUNCATED AT 250 WORDS) Mutat Res, 1985 Apr, 149(2), 265 - 9 Activation of N-acetoxy- and N-hydroxy-2-acetylaminofluorene to mutagenic and cytotoxic metabolites by V79 Chinese hamster cells; Glatt H et al.; N-Acetoxy-2-acetylaminofluorene (AAAF) and N-hydroxy-2-acetylaminofluorene (OH-AAF) are mutagenic to V79 cells, causing the induction of 6-thioguanine-resistant clones, and are cytotoxic . The presence of the deacetylase inhibitor, paraoxon, drastically reduces both the mutagenic and cytotoxic effects . This strongly suggests that deacetylated metabolites are the major active species . Furthermore, when Salmonella typhimurium TA98 is used as target organism, addition of homogenate of V79 cells strongly potentiates the mutagenicity of OH-AAF . To our knowledge, this is the first report demonstrating a significant biological effect due to the metabolism of a mutagen by V79 cells. Mutat Res, 1985 Apr, 142(4), 187 - 92 Activity of bromochlorodifluoromethane (BCF) in three mutation tests; Styles JA et al.; The halocarbon BCF was tested in 3 assays to assess its mutagenicity and clastogenicity . It produced a positive response in Salmonella typhimurium strain TA1535 but was negative in TA1537, TA1538, TA98 and TA100 . In an L5178Y mouse lymphoma microwell assay (TK locus), BCF was negative . BCF was administered at 5000 and 50 000 ppm in air for 6 h to groups of C57B1/6J mice of both sexes . Animals were killed at 24, 48 and 72 h after cessation of exposure and the incidence of bone marrow micronuclei per 1000 PCEs determined . There was no significant difference in the incidences of micronuclei between untreated animals and those exposed to either concentration of BCF at any of the sampling times . These results suggest that BCF is mutagenic in vitro in only one strain of Salmonella; in mammalian cells the compound induced no gene mutation in vitro nor clastogenic activity in vivo at doses that also produced clear evidence of toxicity. Mutat Res, 1985 Apr, 142(4), 153 - 8 Inhibitory effect of organic solvents on the mutagenicity of N-nitrosodialkylamines in Salmonella; Mori Y et al.; The influence of organic solvents on the mutagenicity of 11 N-nitrosamines was examined in Salmonella typhimurium TA100 using the Ames's liquid incubation assay in the presence of rat-liver S9 . The mutagenic activities of N-nitrosodimethylamine, N-nitrosodiethylamine, 6 oxidative derivatives of N-nitrosopropylamine and N-nitroso-2,6-dimethylmorpholine were considerably decreased by addition of dimethyl sulfoxide, dimethyl formamide, acetone, 95% ethanol or acetonitrile, which are recommended for use as solvents in the assay by Ames's group, to the incubation mixture . The mutagenic activities of N-nitrosodipropylamine and N-nitrosodibutylamine, which are barely soluble in water, were also suppressed by increasing concentrations of dimethyl sulfoxide . These organic solvents did not appear to exert their influence by desmutagenic and antimutagenic actions . In contrast, the recoveries of unmetabolized carcinogens from preincubation mixtures and from agar plates were significantly higher in the presence of organic solvents than in their absence . The results indicate that the inhibitory effect is a result of interference with the process of metabolic activation by liver S9. Mutat Res, 1985 Apr, 142(4), 149 - 52 Mutagenicity of pyrene in Salmonella; Matijasevic Z et al.; Pyrene was tested for mutagenicity in Salmonella typhimurium strains TA97, TA98, TA100 and TA1537 . Mutagenicity was seen in all strains when S9 was present. J Med Microbiol, 1985 Apr, 19(2), 159 - 67 Effect of a lysolecithin analogue on nonspecific resistance to infection of mice; Vassilev TL et al.; The effect of racemic 1-octadecyl-2-methoxy-sn-glycero-3 phosphorylcholine (ET-18-OCH3) on the nonspecific resistance of mice to infection with Salmonella typhimurium was investigated . Two S . typhimurium strains with different virulence were studied and no effect was observed in either case at concentrations of ET-18-OCH3 up to 100 micrograms/mouse . However, a concentration of 500 micrograms/mouse caused decreased resistance to S . typhimurium, correlating with a depression of carbon clearance . Treatment of macrophages with ET-18-OCH3 in vitro inhibited phagosome-lysosome fusion, but had no effect on zymosan-induced luminol-dependent chemiluminescence . The relationship between the adjuvant and nonspecific anti-infectious activity of ET-18-OCH3 and other compounds is discussed. J Bacteriol, 1985 Apr, 162(1), 183 - 9 Locations of hook-associated proteins in flagellar structures of Salmonella typhimurium; Homma M et al.; Hooks of the flagella of Salmonella typhimurium were purified from an flaL mutant . Hook-associated proteins, namely HAP1, HAP2, and HAP3, were separated from them, and the antibody against each HAP was prepared . By immunoelectron microscopic observation, these three kinds of antiHAP antibodies were found to bind on the distal ends of hooks of filamentless mutants consistently with their composition of HAPs . The antiHAP2 antibody bound to the very tops of the claw-shaped ends of the hooks which contain all three HAPS . The antibodies against HAP1 and HAP3 bound to the basal areas and the middle areas, respectively, of the claw-shaped ends . The order of disassembly of the component proteins by heat treatment of the hook structure from the filamentless mutants was (HAP2, HAP3) greater than HAP1 greater than hook protein . These observations were consistent with our layered structure model: HAP1, HAP3, and HAP2 are assembled at the distal end of the hook in this sequence . All three HAPs were detected in the hook-filament complexes prepared from a flagellate strain . When the hook-filament structure was treated with antibody against HAP1 and with the anti-rabbit immunoglobulin G antibody, the antibody aggregate was observed in the region corresponding to the boundary between filament and hook . This observation strongly suggests that HAP1 is the protein connecting filament with hook . The locations of HAP2 and HAP3 in the hook-filament structure were not clarified with the same procedure. Infect Immun, 1985 Apr, 48(1), 169 - 74 Effect of streptomycin administration on colonization resistance to Salmonella typhimurium in mice; Que JU et al.; The addition of 5 mg of streptomycin sulfate per ml to the drinking water of Swiss white mice resulted in a 100,000-fold reduction in the 50% implantation dose of streptomycin-resistant Salmonella typhimurium for the animals . When streptomycin-treated and untreated mice were challenged orogastrically with 10(3) viable S . typhimurium organisms, 100% of the treated and none of the untreated mice excreted the pathogen in their feces . Similarly, translocation of S . typhimurium from the intestinal tract to the liver, spleen, and mesentery occurred in 10 of 10 treated mice but in none of the untreated mice 7 days after challenge with 10(3) CFU . Studies of colonization dynamics showed that S . typhimurium was present at high population levels in the intestines of streptomycin-treated mice and in detectable levels in the liver, spleen, and mesentery within 72 h after challenge with 10(3), 10(5), or 10(8) organisms . In untreated mice challenged with either 10(3) or 10(5) S . typhimurium organisms, the organisms were isolated from ileal and cecal tissues but not from ileal or cecal contents or from extraintestinal tissue 72 h after challenge . When untreated mice were challenged with 10(8) organisms, however, S . typhimurium was present in all organs and in intestinal contents . Streptomycin treatment, therefore, facilitated colonization and development of streptomycin-resistant S . typhimurium populations in intestines of mice and the subsequent translocation of the organisms from the intestinal tract to other tissues. Am Rev Respir Dis, 1985 Apr, 131(4), 662 - 5 A case of invasive penicilliosis in Hong Kong with immunologic evaluation; So SY et al.; A 53-yr-old Chinese sailor developed prolonged pyrexia with unresolved lobar pneumonia, cervical lymphadenopathy, generalized subcutaneous abscesses, and pericardial effusion . Penicillium marneffei was isolated from pericardial fluid and subcutaneous pus and was demonstrated on histologic sections of lymph nodes and lung tissue . The penicilliosis was treated successfully with amphotericin B, ketoconazole, and 5-fluorocytosine . Subsequently, he also developed other T-lymphocyte-related opportunistic infections such as disseminated cutaneous herpes zoster and chronic osteomyelitis of sternum caused by Salmonella typhimurium . He was also a chronic carrier of cytomegalovirus . Further investigations showed that he had persistent depression of T-lymphocyte function and enhancement of B-lymphocyte activity, the cause of which was undetermined. Infect Immun, 1985 Apr, 48(1), 40 - 3 Adoptive transfer of murine host protection to salmonellosis with T-cell growth factor-dependent, Salmonella-specific T-cell lines; Paul C et al.; A spent medium antigen was prepared from the avirulent RIA strain of Salmonella typhimurium . Lymph node cells isolated from female BALB/c mice injected subcutaneously with the spent medium antigen exhibited antigen-specific proliferation . By using these cells and T-cell growth factor, continuous spent medium antigen-specific, Thy 1.2-sensitive lines were generated . These cells exhibited antigen-specific proliferation in vitro and were effective in inducing significant (P less than 0.01) host protection when adoptively transferred to naive syngeneic mice. Mutat Res, 1985 Apr-May, 156(1-2), 77 - 82 Mutagenicity and chemical reactivity of epoxidic intermediates of the isoprene metabolism and other structurally related compounds; Gervasi PG et al.; The mutagenic activities of the epoxidic intermediates of the isoprene biotransformation were investigated using Salmonella typhimurium and compared with those of other structurally related epoxides . The compound 2-methyl-1,2,3,4-diepoxybutane, chemically analogous to the well known carcinogenic 1,2,3,4-diepoxybutane, was found to be as mutagenic as the latter . Moreover, the mutagenic activities of oxiranes were correlated to their alkylating powers towards nicotinamide and to their half-lives for spontaneous hydrolysis . The relationship between alkylating power and mutagenicity was found to hold for the stable epoxides that react mainly by an SN2 substitution mechanism. Proc Natl Acad Sci U S A, 1985 Apr, 82(7), 2077 - 81 Mechanisms determining aerobic or anaerobic growth in the facultative anaerobe Salmonella typhimurium; Yamamoto N et al.; We isolated mutant strains of the facultative anaerobe Salmonella typhimurium that grow either aerobically or anaerobically . Strict anaerobic mutants contained a defective DNA topoisomerase I gene (topI), while strict aerobic mutants contained a defective DNA gyrase subunit A gene (gyrA, also nalA) . Topoisomerase I activity was detected in cell-free extracts of strict aerobic mutants but not of strict anaerobic mutant strains, whereas gyrase activity was detected in extracts of strict anaerobic mutants but not of strict aerobic mutants . Furthermore, extracts of wild-type cells, cultured under vigorous aerobic condition, contain topoisomerase I activity but no significant gyrase activity . In contrast, the extracts of anaerobically cultured wild-type cells contain gyrase activity but no significant topoisomerase I activity . Sucrose gradient centrifugation with ethidium bromide showed that chromosomal DNA in strict aerobic mutants and aerobically grown wild-type cells was relaxed, while the chromosomal DNA of strict anaerobic mutants and anaerobically grown wild-type cells was more supercoiled . Aerobic cultures of wild type and strict aerobic mutants produced both superoxide dismutase and catalase, whereas anaerobic cultures of wild type and strict anaerobic mutants did not . These results lead us to conclude that activity of topoisomerase I, associated with relaxation of chromosomal DNA, is necessary for expression of genes required for aerobic growth, whereas activity of gyrase, associated with supercoiling of chromosomal DNA, is necessary for expression of genes required for anaerobic growth. J Bacteriol, 1985 Apr, 162(1), 307 - 16 Composite IS1 elements encoding hydroxamate-mediated iron uptake in FIme plasmids from epidemic Salmonella spp; Colonna B et al.; Eleven FIme plasmids representative of those identified in epidemic strains of Salmonella wien and Salmonella typhimurium isolated in North Africa, Europe, and the Middle East have been examined for the presence of determinants of toxigenicity, adherence, and iron-sequestering mechanisms . Chemical and genetic data indicated that all plasmids code for a hydroxamate-mediated iron assimilation system . Detailed analysis of derivative plasmids and cloned fragments of FIme plasmid pZM61 demonstrated that the general genetic and structural organization of the DNA region containing the genes for hydroxamate biosynthesis and cloacin DF13 receptor was virtually identical to that described for the aerobactin-mediated iron uptake system of pColV-K30 . This DNA region is part of a composite element that is 16.7 kilobases long and carries its IS1 modules as inverted repeats . A very similar element is present in either orientation in all nine FIme plasmids analyzed. Acta Pathol Microbiol Immunol Scand {B}, 1985 Apr, 93(2), 125 - 31 Mannose-specific and hydrophobic interaction between Escherichia coli and polymorphonuclear leukocytes--influence of bacterial culture period; Ohman L et al.; The influence of culture period on mannose-specific and hydrophobic properties of the bacterial surface and on bacteria/polymorphonuclear leukocyte (PMNL) interaction was studied . Four E . coli strains, PN7 (01:K1), ABU2 (ON:K14), CU9 (06:K14) and CU13 (08:KN) and two Salmonella typhimurium strains 395 MR10 and 395 MS, well characterized according to physicochemical surface properties, presence of type 1 fimbriae and interaction with PMNL, were used in the study . The results show that with prolonged culture period, the liability to hydrophobic interaction increases, the agglutination-strength of mannose-specific maltobionamide liposomes increases, while the agglutination-titer with guinea-pig erythrocytes remains constant . Furthermore, the mannose-specific association with and metabolic activation of PMNL is augmented, while the ingestion is unchanged . In addition, our results demonstrate differences in sensitivity between the methods used to detect exposure of mannose-specific structures on the surface of bacteria, and that the culture condition is important for bacterial surface properties . It thus appears that the culture conditions have a great influence on the surface properties of E . coli bacteria and the interaction with phagocytic cells. J Biol Chem, 1985 Mar 25, 260(6), 3716 - 8 Crystallization and preliminary X-ray crystallographic data of the tryptophan synthase alpha 2 beta 2 complex from Salmonella typhimurium; Ahmed SA et al.; The tryptophan synthase alpha 2 beta 2 complex from Salmonella typhimurium can be crystallized by the method of vapor diffusion from solutions of polyethylene glycol 8000 and various salts . Thin needles are obtained in the presence of a monovalent cation (Na+), thicker crystals are obtained in the presence of divalent cations (Mg2+, Mn2+, Fe2+, Ca2+, Zn2+), and square-faced crystals are obtained in the presence of spermine . Although the spermine and Mg2+ crystals differ in morphology, they are both monoclinic and in space group C2 with a = 184.5 A, b = 62.4 A, c = 67.7 A, beta = 94 degrees 40', and one alpha beta pair of Mr = 71,700/asymmetric unit . The crystals appear reasonably resistant to radiation damage and should be suitable for a complete structure investigation . The separated S . typhimurium alpha, holo-beta 2, and apo-beta 2 subunits do not crystallize under these conditions nor do the alpha 2 beta 2 complex or the alpha- or holo-beta 2 subunits from Escherichia coli or from an interspecies hybrid. Nature, 1985 Mar 21-27, 314(6008), 257 - 60 Sulphate sequestered in the sulphate-binding protein of Salmonella typhimurium is bound solely by hydrogen bonds; Pflugrath JW et al.; An important question in understanding substrate binding by proteins is how charged groups are stabilized in the absence of their solvation shell . We have addressed this question here by solving the structure of the sulphate-binding protein of Salmonella typhimurium with bound substrate at 2.0 A resolution . The results are remarkable in that the charged oxygen atoms of the sulphate molecule, which is buried and completely inaccessible to the solvent, are not stabilized by the formation of salt-bridges but by hydrogen bonds donated by specific residues of the protein . These hydrogen bonds are in turn coupled via peptide units to several resonating hydrogen bonding systems . These findings may be of general significance for the role of electrostatic interactions in protein structure and function. Experientia, 1985 Mar 15, 41(3), 396 - 7 Lack of mutagenicity of irradiated glucose in Salmonella typhimurium using host-mediated assay; Varma MB et al.; Experiments were conducted to study the ability of irradiated glucose to induce reverse mutations in S . typhimurium by host-mediated assay . The results revealed no significant increase in the frequency of reverse mutations compared to controls. Biomaterials, 1985 Mar, 6(2), 129 - 32 Mutagenicity of endodontic sealers; Orstavik D et al.; Four endodontic sealer materials and some of their chemical constituents were subjected to Ames' test for mutagenicity with the Salmonella/microsome assay . Extracts of two zinc oxide-eugenol based materials and of one gutta-percha-zinc oxide-chloroform based sealer were negative in the test . Extracts of a synthetic polymer material, based on epoxy-bis-phenol A, induced mutations in Salmonella typhimurium TA 100 as did extracts of the epoxy-bis-phenol A resin alone . Formaldehyde, an active ingredient from one of the ZnO-based materials, induced mutations in both Salmonella typhimurium TA 98 and TA 100 . The mutagenic activity of formaldehyde as well as of the epoxy material was reduced in the presence of rat liver microsomes. J Pharmacobiodyn, 1985 Mar, 8(3), 199 - 205 Effect of liver S9 from 3,4,5,3',4'-pentachlorobiphenyl-pretreated rats on the mutagenic activity of the various carcinogens toward Salmonella typhimurium TA 98; Ozawa N et al.; Effects of liver 9000 X g supernatant fraction from 3,4,5,3',4'-pentachlorobiphenyl- and 2,4,5,2',4',5'-hexachlorobiphenyl-pretreated rats (PenCB-S9 and HexCB-S9, respectively) on the mutagenic activities of well-known carcinogens, benzo-{a}pyrene (BP), Glu-P-1 (2-amino-6-methyldipyrido {1,2-a:3',2'-d}imidazole), Trp-P-1 (3-amino-1,4-dimethyl-5H-pyrido{4,3-b}indole), and aflatoxin B1 (AFB), toward Salmonella typhimurium TA 98 have been described . Although the mutagenic activities of all of these carcinogens were enhanced by these S9, PenCB-S9 especially highly activated BP, Glu-P-1, and Trp-P-1 . The ability of PenCB-S9 to activate the carcinogens was much higher than that of liver 9000 X g supernatant fraction from 3-methylcholanthrene-pretreated rats (MC-S9) . PenCB-S9 enhanced the mutagenic activity of BP 8 times higher than MC-S9, while Glu-P-1 and Trp-P-1 were activated by PenCB-S9 twice as much as by MC-S9 . Effect of HexCB-S9 on the mutagenic activities of the above-mentioned three carcinogens was much less than those of PenCB- and MC-S9 and a little higher than that of 9000 X g supernatant fraction from rats pretreated with phenobarbital . As for AFB, phenobarbital was the most potent inducer, and HexCB and PenCB were next to this . Data suggest that PenCB is a strong inducer of P-448 species which activate environmental toxicants. Jpn J Cancer Res, 1985 Mar, 76(3), 184 - 91 Alpha-hydroxylation and mutagenicity of unsymmetrical N-nitrosodialkylamines with a butyl group; Suzuki E et al.; In order to compare the extents of metabolic alpha-hydroxylation of the two alkyl groups in unsymmetrical N-nitrosodialkylamines, N-nitroso-N-alkylbutylamines (alkyl = methyl, ethyl, propyl, butyl, and amyl) were incubated with liver microsomes prepared from phenobarbital- or polychlorinated biphenyl (PCB)-treated and untreated rats, and aldehydes produced by the alpha-hydroxylation were determined quantitatively . Although an increased production of aldehydes was observed with the induced microsomes compared with the non-induced microsomes, no marked differences were noted between the two alkyl groups of these unsymmetric nitrosodialkylamines in regard to the extent of alpha-hydroxylation with the exception of N-nitroso-N-methylbutylamine (NMBA) . The amount of aldehydes produced from these nitrosamines increased with elongation of the alkyl chain, amounting to 10-30% of the compounds incubated, and the recovery in the incubation (total aldehyde + nitrosamine recovered) was found to be more than 90%, indicating that alpha-hydroxylation is the principal oxidative metabolic pathway of the nitrosamines in vitro . The microsomal alpha-hydroxylation was inhibited by dimethyl sulfoxide and the extent of the hydroxylation was shown to be positively correlated with the mutagenic potency of the nitrosamines . Based on the mutagenic behavior of NMBA tested on Salmonella typhimurium TA1535 and Escherichia coli WP2 hcr- and the extent of the formation of formaldehyde and butyraldehyde from NMBA in the presence of the induced microsomes and S9 mix, it was concluded that NMBA acts as both a methylating and a butylating agent. Mutat Res, 1985 Mar, 142(3), 121 - 5 Weak mutagenicity to Salmonella of the formaldehyde-releasing anti-tumour agent hexamethylmelamine; Ashby J et al.; Hexamethylmelamine (HEMLA) is a metabolism-dependent formaldehyde-releasing agent related in structure to hexamethylphosphoramide (HMPA) . Both compounds are known to be mutagenic to Drosophila . HMPA, in common with the other formaldehyde-releasing agents studied, is non-mutagenic to Salmonella . The present paper describes the mutagenicity of HEMLA to strain TA100 of Salmonella typhimurium . Activity is dependent upon both the use of a pre-incubation assay protocol and on high concentrations of Aroclor-induced rat liver in the S9 mix . HMPA was inactive under similar conditions of test. Mutat Res, 1985 Mar, 142(3), 103 - 7 The effect of quercetin on the mutagenicity of 2-acetylaminofluorene and benzo{alpha}pyrene in Salmonella typhimurium strains; Ogawa S et al.; The comutagenic and desmutagenic effect of quercetin on the mutagenicity of typical mutagens e.g . 2-acetylaminofluorene (AAF), 4-nitroquinoline-1-oxide (4NQO) and benzo{alpha}pyrene (B{a}P), in Salmonella typhimurium TA98, TA100 and TA98/1,8 DNP6 were examined . In the mixed application of AAF with quercetin in the presence of mammalian metabolic activation system (S9 mix), the numbers of revertants in TA98 increased by as much 2.2-5.0-fold compared with the sum of those in the separate applications of AAF and quercetin . A 1.4-2.7-fold increase was observed in TA100 . Quercetin did not affect the mutagenicity of 4NQO, and depressed that of B{a}P . Dose-response curves for mutagenicity of quercetin with or without AAF (5 micrograms/plate) were examined . The results suggest that quercetin, present in a molarity of up to 1.5 times that of AAF, is apparently effective in enhancing the mutagenicity of AAF, because a linear dose-response curve was observed in the range of 0-5 micrograms/plate quercetin with AAF although quercetin alone was not mutagenic in the same range . Dose-response curves for mutagenicity of quercetin with or without 5 micrograms/plate B{a}P did not increase compared with that for quercetin alone . The mutagenicity of the mixed application of B{a}P with quercetin was reduced to about 60% of the sum of separate application at doses ranging from 25 to 100 micrograms/plate of quercetin . Since enhancement and depression of mutagenicity by quercetin were observed for indirect mutagens, AAF and B{a}P, respectively, in the presence of S9 mix, quercetin may affect the metabolic pathway of these mutagens. Biochimie, 1985 Mar-Apr, 67(3-4), 327 - 34 Use of a new DNA intercalating fluorescing probe for studies on the mechanism of frameshift mutagenesis in Salmonella typhimurium; Rene B et al.; As a general rule, ellipticine derivatives are mutagenic and intercalate into double-stranded nucleic acids . We have tested a new fluorescent ellipticine compound, 10{(1-carboxy-2-methylpropylidene)-amino}-9-hydroxy-2-methylell ipticinium (val-NMHE), for establishing the relationship between the amount of drug bound to nucleic acids in situ in Salmonella typhimurium and its biological effects: decrease of growth rate and mutagenesis . Val-NMHE is mutagenic only on Ames'strain TA 1977 which carries a + 1 frameshift mutation . On a per cell basis, the number of revertants is not linearly correlated to the amount of drug bound to nucleic acids: this number is relatively higher for increasing amounts of drug . This effect is not related to the mere probability of interaction between the drug molecule and its target, a GGGG/CCCC sequence . It might be explained by other hypotheses briefly discussed herein. Appl Environ Microbiol, 1985 Mar, 49(3), 505 - 8 Effect of pH, temperature, and potassium sorbate on amino acid uptake in Salmonella typhimurium 7136; Tuncan EU et al.; The effect of sorbate on L-serine and L-histidine uptake in Salmonella typhimurium was studied at various pH levels, temperatures, and amino acid and sorbate concentrations . Low pH had an apparent synergistic effect on amino acid uptake inhibition caused by sorbate . The relationship between sorbate concentration and the amount of amino acid uptake inhibition was not linear . Compared with L-histidine, L-serine uptake was more sensitive to changes in pH, temperature, and sorbate concentration . Various degrees of amino acid uptake inhibition by sorbate may be related to differences between amino acid transport systems . The results of this study suggest that sorbate acts as a noncompetitive inhibitor of amino acid uptake in S . typhimurium. J Appl Bacteriol, 1985 Mar, 58(3), 251 - 5 Protective effect of casein toward Salmonella typhimurium in acid-milk; Rubin HE; Lactic acid is the inhibitory agent in yoghurt responsible for the inhibition of Salmonella typhimurium . Casein, however, may exert a protective effect toward the survival of the salmonella in acid-milk products . Salmonella typhimurium was found to die-off 21.2% more rapidly in 18-h yoghurt-whey than in 18-h yoghurt at 37 degrees C with a pH of 3.85 and 1.42% lactic acid . When casein was added to yoghurt-whey, the die-off rate of the salmonellas was reduced to that found in yoghurt . The rate remained unchanged when 4.8% sodium caseinate was added to the whey . When 0 to 14% casein was added to the acid-whey the die-off rate changed from 9.7 to 24.0 min/log reduction of cells, respectively . There was a direct correlation between the increase in casein concentration and length of survival of the salmonellas . At a pH of 3.85, 4.2 or 4.5, the die-off rate was 6.5, 13.0 or 40 min/log reduction of cells in milk containing 1.42% lactic acid, and was 4.0, 10.0 or 33.3 min/log reduction, respectively, in whey with 1.42% lactic acid . Thus, the protective effect of casein toward Salm . typhimurium increased as the pH increased . This indicated that casein exerts a protective effect on Salm . typhimurium in acid dairy products and the degree of protection depends on the casein concentration, the form of the casein molecule and the pH. Carcinogenesis, 1985 Mar, 6(3), 441 - 4 Genotoxicity of the food mutagen 2-amino-3-methylimidazo-{4,5-f}quinoline (IQ) and analogs; Barnes WS et al.; The food mutagen 2-amino-3-methylimidazo{4,5-f}quinoline (IQ) is an analogue of quinoline, a hepatocarcinogen . 2-Aminofluorene, benzidine and 3,2'-dimethyl-4-aminobiphenyl (DMAB) are potent inducers of unscheduled DNA repair in primary culture rat liver hepatocytes, as was IQ (151 grains/nucleus at 1 X 10(-6) M) . Quinoline, on the other hand, is only weakly positive in this assay (15 grains/nucleus at 1 X 10(-3) M) . IQ, quinoline and DMAB were applied topically to shaved skin of Sencar mice with promotion by 12-O-tetradecanoylphorbol 13-acetate (TPA) for 20 weeks, when 14 of 20 mice in the quinoline group had 25 tumors, but only one of 30 animals in the IQ group and five of 30 in the DMAB group were tumor-bearing . Analogs of IQ synthesized by substitution at the 2- or 3-position with amino or methyl groups were assayed with the Ames Salmonella typhimurium tester strains TA98 and TA100 . Mutagenicity for TA98 is reduced in the absence of the 3-methyl group and is completely abolished with removal of the 2-amino moiety . None of these analogs are strong mutagens for TA100 . Exocyclic N-oxidation is a likely obligatory step in the activation of IQ to a mutagen. Arch Dermatol, 1985 Mar, 121(3), 348 - 9 The mutagenicity of dinitrochlorobenzene; Black HS et al.; A sample of dinitrochlorobenzene, determined by gas-liquid chromatography and mass spectrometry to be greater than 98% pure, was tested in the Salmonella typhimurium plate assay . The chemical evoked a marked mutagenic response at all concentrations tested (3 to 150 micrograms per plate) . These results confute the suitability of this agent for the treatment of benign skin disorders. Mutat Res, 1985 Mar, 149(1), 9 - 15 Relationship between mutagenic potency in Salmonella typhimurium and chemical structure of amino- and nitro-substituted biphenyls; Nohara M et al.; All positional isomers of mononitro- and monoaminobiphenyls and those of dinitro-, diamino- and aminonitrobiphenyls, which have one substituent on each benzene ring, were assayed for mutagenicity in Salmonella typhimurium by the Ames method . The results suggest that the structural requirements favoring mutagenic activity are the presence of substituents at the 4-position and their absence at the 2'-position . The introduction of an amino group to the 3'- or 4'-position of 4-nitrobiphenyl or a nitro group to 3'- or 4'-position of 4-aminobiphenyl enhanced the mutagenicity . Among the mutagenic compounds, 4-nitro analogues were mutagenic in strains TA98 and TA100 in the absence of a microsomal metabolic activation system . Strain TA98NR was not reverted by the direct-acting mutagens, whereas strain TA98/1,8-DNP6 was as revertible as strain TA98; these results suggest that the direct-acting mutagenicity involves the reduction of the nitro group by bacterial nitroreductase but does not involve specific esterification enzymes. Mutat Res, 1985 Mar, 149(1), 25 - 32 1-Nitrosopyrene: an intermediate in the metabolic activation of 1-nitropyrene to a mutagen in Salmonella typhimurium TA1538; Heflich RH et al.; Incubation of Salmonella typhimurium TA1538, in suspension culture, with 1.5 or 23 microM 1-nitropyrene resulted in a time-dependent increase in reversions for up to 7 h . In contrast, when the bacteria were exposed to 1.5 microM 1-nitrosopyrene, a reduction product of 1-nitropyrene, maximum reversion induction occurred after 1 h and a much higher mutation frequency was detected . Examination of DNA isolated from Salmonella typhimurium incubated with 4.1 microM {4,5,9,10-3H}1-nitrosopyrene indicated the presence of one major adduct, N-(deoxyguanosin-8-yl)-1-aminopyrene, the same adduct observed previously when the bacteria were exposed to 1-nitropyrene . When calf thymus DNA was treated with 1-nitrosopyrene in the presence of ascorbic acid, 1-aminopyrene was formed concomitant with the production of N-(deoxyguanosin-8-yl)-1-aminopyrene . In the absence of ascorbic acid, a 20-fold reduction in DNA binding was observed and 1-aminopyrene was not detected . The observations that 1-nitrosopyrene forms the same DNA adduct and is more mutagenic than 1-nitropyrene, suggest that 1-nitrosopyrene is an intermediate in the mutagenic activation of 1-nitropyrene in Salmonella typhimurium TA1538 . Since reduction of 1-nitrosopyrene was necessary to get appreciable DNA binding in vitro, further reduction of 1-nitrosopyrene to N-hydroxy-1-aminopyrene is probably required in the activation pathway. Mutat Res, 1985 Mar, 142(3), 99 - 102 Induction of umuC gene expression by nitrogen dioxide in Salmonella typhimurium; Kosaka H et al.; Gaseous nitrogen dioxide (NO2) was found to induce umuC gene expression in Salmonella typhimurium carrying the umuC-lacZ fusion plasmid . The induction level of the umu operon responsible for inducible mutagenesis was measured by the level of beta-galactosidase in the cell, encoded by the fusion gene . NO2 gas was bubbled into bacterial suspensions at 10, 30 and 90 microliters/l for 30 min at a flow rate of 100 ml/min . Expression of the umuC gene varied with the concentration, flow rate and bubbling time of the NO2 gas . Although NO2 gas induces SOS functions, mutagenesis due to it was not detectable in Salmonella typhimurium TA100 and TA102 . Nitric oxide gas (NO) did not induce any umuC gene expression. Mutat Res, 1985 Mar, 142(3), 87 - 91 Induction of the SOS response by ICR191 does not influence frameshift mutagenesis at the hisC3076 marker of Salmonella typhimurium; Podger DM et al.; Reversion of the Salmonella typhimurium frameshift marker hisC3076 by ICR191 and 9-aminoacridine in rec+ and recA1 backgrounds was examined using the standard plate-reversion assay . For both compounds, the level of reversion observed in the recA strain is significantly greater than in the rec+ strain . Thus reversion of hisC3076 is not recA-dependent, but is recA-modulated . The ability of a mutagen (or mutagenic treatment) to induce the recA lexA-dependent SOS response does not therefore imply that mutagenic effects will also be recA-dependent. Mutat Res, 1985 Mar, 142(3), 109 - 13 Effects of pH on weak and positive control mutagens in the Ames Salmonella plate assay; Popkin DJ et al.; The effects of pH on the mutagenic activity of several chemicals were evaluated in the standard Ames Salmonella typhimurium plate-incorporation assay . The pH of the base agar was varied between 6.0 and 8.0 . The positive control compounds routinely used in this laboratory, 2-aminoanthracene, 4-nitro-o-phenylenediamine, sodium azide and nitrofurantoin, showed increasing mutagenic activity as the pH was decreased to 6.0 . However, the activity of two weakly mutagenic cosmetic ingredients, 2,2',4,4'-tetrahydroxybenzophenone and trans-4-phenyl-3-buten-2-one, was completely eliminated at pH levels near 6.0 . It is concluded that plates poured with agar with pH levels below 7.0 can result in strong responses for the positive control chemicals but give negative results for some mutagens. J Bacteriol, 1985 Mar, 161(3), 1017 - 22 Identification of the phosphocarrier protein enzyme IIIgut: essential component of the glucitol phosphotransferase system in Salmonella typhimurium; Grenier FC et al.; The phosphoenolpyruvate-dependent phosphorylation of glucitol has been shown to require four distinct proteins in Salmonella typhimurium: two general energy-coupling proteins, enzyme I and HPr, and two glucitol-specific proteins, enzyme IIgut and enzyme IIIgut . The enzyme IIgut was solubilized from the membrane and purified about 100-fold, free of the other protein constituents of the phosphotransferase system . Enzyme IIIgut was found in both the soluble and the membrane fractions . The soluble enzyme IIIgut was purified to near homogeneity by gel filtration, hydroxylapatite chromatography, and hydrophobic chromatography on butylagarose . It was sensitive to parital inactivation by trypsin and N-ethylmaleimide, but was stable at 80 degrees C . The protein had an approximate molecular weight of 15,000 . It was phosphorylated in the presence of phosphoenolpyruvate, enzyme I, and HPr, and this phosphoprotein was dephosphorylated in the presence of enzyme IIgut and glucitol . Antibodies were raised against enzyme IIIgut . Enzyme IIIglc and enzyme IIIgut exhibited no enzymatic or immunological cross-reactivity . Enzyme IIgut, enzyme IIIgut, and glucitol phosphate dehydrogenase activities were specifically induced by growth in the presence of glucitol . These results serve to characterize the glucitol-specific proteins of the phosphotransferase system in S . typhimurium. Infect Immun, 1985 Mar, 47(3), 605 - 12 Immunity to Salmonella typhimurium infection in C3H/HeJ and C3H/HeNCrlBR mice: studies with an aromatic-dependent live S . typhimurium strain as a vaccine; Killar LM et al.; Immunization with avirulent Salmonella typhimurium strain SL3235, a smooth, aroA- derivative, was shown to induce high levels of resistance to challenge with virulent S . typhimurium in innately hypersusceptible C3H/HeJ mice and inherently resistant C3H/HeNCrlBR mice . Strain SL3235 is one of a class of avirulent aroA- derivatives made from various strains and species of Salmonella that are being considered as vaccine candidates for cattle and humans . This paper supports their efficacy and potential utility in this regard . In C3H/HeJ mice, immunity against over 1,000 50% lethal doses of virulent S . typhimurium was evident as early as 3 days after immunization and persisted for at least 7 months . Further, the vaccine was effective over a broad spectrum of doses, ranging from 10(4) to 10(6) organisms . Infection with SL3235 led to marked splenomegaly in both mouse strains . The relationship of splenomegaly to the growth kinetics and colonization by SL3235 in the spleens of infected C3H/HeJ and C3H/HeNCrlBR mice was followed . SL3235 initially multiplied slowly in the spleens of both mouse strains and then was rapidly cleared . Less multiplication was seen in the resistant C3H/HeNCrlBR mice than in C3H/HeJ mice . Maximum splenomegaly occurred after clearance of the organism had begun . Protection against virulent S . typhimurium persisted after virtually all of the SL3235 vaccine strain had been cleared from the spleen . Cross-protection against Listeria monocytogenes was evident, but had a later onset, waned by 21 days, and was not detectable by 1 month after vaccination . Demonstration of this cross-protection is consistent with the interpretation that SL3235 induces cellular immunity . One-week immune spleen cells adoptively transferred anti-S . typhimurium and anti-L . monocytogenes immunity . T cell-enriched fractions were ineffective in adoptive transfer, as were spleen cells taken 2 weeks or later after immunization . Protective capacity was in the adherent cell fraction and seemed to be associated with macrophages . Evidence for induction of a population of sensitized T cells was obtained by using a peritoneal exudate T-lymphocyte proliferation assay on peritoneal T lymphocytes collected 1 to 3 months after SL3235 infection. Cell Immunol, 1985 Mar, 91(1), 75 - 91 Macrophage-mediated mitogenic suppression induced in mice of the C3H lineage by a vaccine strain of Salmonella typhimurium; Lee JC et al.; Salmonella typhimurium, strain SL3235, an avirulent organism, has been used as a live vaccine in mice of the C3H lineage and has been found to confer high levels of protection . In the present study, it was found that intraperitoneal injection of approximately 5 X 10(5) live SL3235 induced potent suppression of spleen cell mitogenic responses to a panel of B- and T-cell mitogens in the Salmonella-hypersusceptible C3H/HeJ and C3HeB/FeJ, and the inherently resistant C3H/HeNCrlBR mice . Maximal suppression (greater than 99%) was seen at 1 week, and was still significant but waning (50%) at 3 weeks postimmunization . In contrast, cells of mice receiving acetone-killed cells were not suppressed . Removal of macrophages, but not T or B cells, restored responsiveness, indicating that suppression was macrophage mediated . Prostaglandins were not the major mediator of suppression, as in vitro administration of indomethacin failed to abrogate suppression . As mitogenic suppression occurred in mice with high levels of Salmonella immunity, the suppression is interpreted as a marker of a powerful immunomodulatory process induced by live cells, rather than as an indication of poor immune status of the host. J Bacteriol, 1985 Mar, 161(3), 836 - 49 Purification and characterization of the flagellar hook-basal body complex of Salmonella typhimurium; Aizawa SI et al.; The hook-basal body complex of Salmonella typhimurium, a major component of its flagellar apparatus, was subjected to detailed analysis by electron microscopy and gel electrophoresis . The study was facilitated by the development of an improved protocol for isolation of the complexes in high yield and purity . Nine proteins were identified with the structure . These proteins had apparent molecular weights of 65,000 (65K), 60K, 42K, 38K, 32K, 30K, 27K, 16K, and 14K . Small but reproducible shifts in the apparent molecular weights of specific proteins from conditionally nonflagellate mutants indicated the following gene-polypeptide correspondences: flaFV, 42K; flaFVI, 32K; flaFVII, 30K; flaFIX, 38K; flaAII.1, 65K . Several new morphological features of hook-basal body complexes were recognized, including a clawlike structure on the cytoplasm-proximal M ring and additional material at the cytoplasmic face of the M ring . Based on this study and the work of others, we suggest that the morphological features of the hook-basal body complex correspond to the following proteins: hook-filament junction, 60K; hook, 42K; rod, 30K and 32K; L ring and outer cylinder wall, 27K; P ring, 38K; S ring, unknown; M ring 65K. Ann Trop Paediatr, 1985 Mar, 5(1), 3 - 6 Use of non-carbonated soft drinks to provide safe drinking water; Gracey M et al.; Non-carbonated, low-calorie soft drink concentrates (cordials), when diluted according to manufacturers' instructions, had significant antibacterial effects in vitro . Bacteria affected include Vibrio cholerae, Aeromonas hydrophila, Shigella sonnei, Salmonella typhimurium and Escherichia coli . With vibrios, bacterial counts were reduced from 10(6)/ml to undetectable numbers in less than 10 min . Escherichia coli in an initial concentration of 10(6)/ml became undetectable after incubation for 1 h with one brand of cordial . Naturally contaminated water can be rendered potable by incubation with cordials at room temperature for 1 h . This may be a way to reduce the risk of water-borne diarrhoea, particularly where the cleanliness of drinking waters cannot be otherwise assured, for example when making up oral rehydration fluids and for travellers in high-risk areas. Nucleic Acids Res, 1985 Feb 11, 13(3), 673 - 85 Nucleotide sequence and biochemical characterization of the metJ gene from Salmonella typhimurium LT2; Urbanowski ML et al.; The nucleotide sequence of the Salmonella typhimurium metJ gene is presented along with the sequence of the promoter region for the closely linked metB gene . The two genes are transcribed in opposite directions, with transcription initiating from a single promoter for metB, and from two apparent promoters for metJ . RNA polymerase binding sites for metJ and metB, determined by in vitro protection studies, lie adjacent to each other and may overlap . The two metJ promoters, PJ1 and PJ2, are separated by approximately 65 base pairs . Binding of RNA polymerase in vitro could only be observed for PJ1, even though transcripts are initiated from both promoters in vivo . The metJ gene codes for a polypeptide of 105 amino acids with a calculated Mr of 12,110 . The translation start site was determined by N-terminal amino acid sequence analysis of a metJ-lacZ fusion protein. Arch Toxicol, 1985 Feb, 56(4), 267 - 71 In vitro mutagenicity of valepotriates; von der Hude W et al.; Valepotriates are epoxide-bearing triesters of the monoterpene alcohol 4,7-dimethylcyclopenta-(c)-pyrane isolated from the roots of several Valerianacae species . They are regarded as the main tranquilizing constituents of these drugs . Although the valepotriates valtrate/isovaltrate (VAL) and dihydrovaltrate (DH-VAL) showed a strong alkylating activity against the nucleophilic agent 4-(p-nitrobenzyl)-pyridine (NBP), they were not clearly mutagenic for the strains TA98, TA100, TA1535, and TA1537 of Salmonella typhimurium or for the strains WP2 and WP2 uvrA- of Escherichia coli in the absence of a metabolic activation system (S9-mix) . However, the valepotriates were mutagenic for TA100, WP2 and WP2 uvrA- at concentrations up to about 1.0 mumole/plate when S9-mix was added to the test system . With more than 1 mumole/plate the valepotriates were toxic in the presence of a metabolic activation system for all strains tested . The mutagenicity of the valepotriates was inversely related to the protein content of the S9-mix used . The mutagenicity and toxicity of the valepotriates could be inhibited when the S9-mix was preincubated with the esterase inhibitor paraoxon (1 mM) for 5 min before the test compounds and bacteria were added . Therefore, bioactivation of the valepotriates by an enzymatic hydrolysis of their ester groups is considered . This could be proven by activating the valepotriates with purified esterase. Sci Total Environ, 1985 Feb, 41(2), 173 - 86 Mutagenicity of three agricultural soils; Brown KW et al.; A chemical and biological testing protocol was employed to evaluate the mutagenic potential of the organic compounds extracted from three agricultural soils . The analytical procedures used included bioassays with Salmonella typhimurium and Aspergillus nidulans for the detection of point mutations and a gas chromatography/mass spectrometry/computer system to identify major organic constituents . The extracts of all three soils exhibited mutagenic response in the bioassays . At a dose level of 1000 micrograms per plate, the organic extract of the Bastrop clay induced 434 net revertants; while at the same dose level the Norwood sandy clay and the Sassafrass sandy loam induced 35 and 178 net revertants, respectively, in the Salmonella assay with metabolic activation . In the Aspergillus assay, the extract of the Norwood and Bastrop soils induced a positive response without metabolic activation; this effect was reduced or eliminated in the presence of metabolic activation . Chemical analysis identified a variety of initiators, promotors, inhibitors, and cocarcinogens; however, there were no mutagenic compounds identified in any of the soil extracts . The results of this combined testing protocol indicate that the agricultural soils tested had an inherent level of mutagenic activity, which was not detected by GC/MS analysis alone, and this activity may be related to the past history of agricultural practices, including biocide applications, fertilization, and cultivation. Mutat Res, 1985 Feb-Apr, 147(1-2), 37 - 43 Epidermal enzyme-mediated mutagenicity of the skin carcinogen, 2-aminoanthracene; Bickers DR et al.; Using four Salmonella typhimurium tester strains (TA1537, TA1538, TA98 and TA100) and the promutagen 2-aminoanthracene, an epidermal S9-mediated mutagenicity assay was developed . Using an activation mixture derived from whole skin of the rat, mutagenicity was observed in tester strain TA98 whereas an activation mixture derived from the dermis resulted in mutagenicity in tester strains TA1538, TA98 and TA100 . Activation mixtures from both the epidermis and the liver produced a positive response in all of the tester strains studied . Activation mixtures from liver were shown to have the highest specific activity followed in decreasing order of potency by epidermis, dermis and whole skin . These results indicate that the skin, a target tissue directly exposed to environmental chemicals, is capable of converting 2-aminoanthracene to mutagenic moieties . Since the skin of the rat is known to be susceptible to tumor induction by 2-aminoanthracene our findings re-emphasize that membrane-bound enzymes can influence toxic responses including mutagenicity to xenobiotics in cutaneous tissue. Infect Immun, 1985 Feb, 47(2), 534 - 9 Modulation of in vitro natural cell-mediated activity against enteropathogenic bacteria by simple sugars; Nencioni L et al.; Lymphoid cells from mouse Peyer's patches and spleens were tested in a 2-h in vitro assay for their natural activity against the enteropathogenic bacteria Salmonella typhimurium, Salmonella enteritidis, Salmonella tel aviv, and Shigella sp . X16 . The antibacterial activity expressed by normal cells was detected against all the bacterial strains tested with the exception of Peyer's patch lymphocytes against S . tel aviv and splenocytes against Shigella sp . X16 . To determine whether the different expression of natural antibacterial activity might be due to lectin-like proteins interacting with the saccharidic moieties of the bacterial wall, 11 simple sugars were preincubated with the effector cells before the in vitro assays . We found that some of them could block the natural antibacterial activity as well as induce antibacterial activity when this was not spontaneously expressed . Interestingly, a different panel of sugars among those employed was observed to affect the antibacterial activities for each of the above-mentioned bacterial targets and each effector cell . However, the same panel of sugars was able to block or stimulate the lymphocyte activity when bacteria with the same somatic antigens as two substrains of S . typhimurium and one strain of Salmonella schottmuelleri were employed . To further investigate the interaction between effector cells and bacteria, effector cells or Shigella sp . X16 targets were treated with proteolytic, glycolytic, and lipolytic enzymes before the in vitro assays . Furthermore, EDTA was used to analyze the role of divalent cations in this experimental system . The results obtained suggest that lectin-like proteins playing a role in this interaction are present not only on lymphocytes but also on bacteria and that divalent cations are essential for the expression of in vitro antibacterial activity. Ecotoxicol Environ Saf, 1985 Feb, 9(1), 84 - 91 Toxic impact of effluents from petrochemical industry; Nikunen E; The toxicity of effluents from a petrochemical industry center in southern Finland was tested by conducting bioassays on organisms from three different trophic levels . In fish tests, rainbow trout (Salmo gairdneri) were caged at the discharge site and simultaneously at a reference area . The only clear differences, among the measurements of 25 metabolic parameters, were observed in fish liver where activities of two detoxication enzymes were significantly increased in the exposed group . The water flea (Daphnia magna) was used both in acute (EC50) and long-term reproduction tests . No acute lethal toxicity was detected in any of the wastewater samples investigated . A combined effluent, however, caused a reduction in the reproduction rate with an EC50 of 3% . No mutagenic activity was observed with the Ames test (Salmonella typhimurium, strains TA 97, TA 98, and TA 100) in concentrated effluents, in sediment samples, or in liver samples from predator fish caught from the discharge site. Carcinogenesis, 1985 Feb, 6(2), 237 - 42 Inhibition of the mutagenicity of bay-region diol-epoxides of polycyclic aromatic hydrocarbons by tannic acid, hydroxylated anthraquinones and hydroxylated cinnamic acid derivatives; Huang MT et al.; Tannic acid and several hydroxylated anthraquinone and cinnamic acid derivatives inhibited the mutagenic activity of (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo {a}pyrene (B{a}P 7,8-diol-9,10-epoxide-2), an ultimate mutagenic and carcinogenic metabolite of benzo {a}pyrene . The mutagenic activity of 0.05 nmol of B{a}P 7,8-diol-9,10-epoxide-2 towards strain TA 100 of Salmonella typhimurium was inhibited 50% by incubation of the bacteria and the diol-epoxide with tannic acid (0.5 nmol), anthraflavic acid (7 nmol), rufigallol (7 nmol), quinalizarin (10 nmol), alizarin (30 nmol), purpurin (60 nmol), and danthron (88 nmol) . Dose-dependent, but weaker antimutagenic activity was observed for quinizarin, and a number of hydroxylated cinamic acid derivatives . Gallic acid and m-digallic acid, major components of tannic acid, possessed less than 1% of the anti-mutagenic activity of tannic acid, although m-digallic acid was over 3 times more active than gallic acid . The anti-mutagenic activity of tannic acid was a result of its interaction with B{a}P 7,8-diol-9,10-epoxide-2 since the rate of disappearance of the diol-epoxide from cell-free solutions in 1:9dioxane:water was markedly stimulated by the polyphenol . Tannic acid was a highly potent inhibitor of the mutagenic activity of the bay-region diol-epoxides of benzo{a}pyrene, dibenzo{a,h}pyrene and dibenzo{a,i}pyrene, but higher concentrations of tannic acid were needed to inhibit the mutagenicity of the chemically less reactive benzo{a}-pyrene 4,5-oxide and the bay-region diol-epoxides of benz{a}-anthracene, chrysene and benz{c}phenanthrene. J Bacteriol, 1985 Feb, 161(2), 673 - 80 Oxygen regulation in Salmonella typhimurium; Strauch KL et al.; Regulation by oxygen of the peptidase T (pepT) locus of Salmonella typhimurium was studied by measuring beta-galactosidase levels in strains containing a pepT::Mu d1(Apr lac) operon fusion . beta-Galactosidase was induced in anaerobic cultures and late-exponential and stationary-phase aerated cultures . Peptidase T activity also was induced under these growth conditions . pepT+ but not pepT strains will utilize as amino acid sources the tripeptides Leu-Leu-Leu and Leu-Gly-Gly only when grown anaerobically . Mutations at two loci, oxrA and oxrB (oxygen regulation) prevent induction of the pepT locus . The oxrA locus is homologous to the fnr locus of Escherichia coli . We have isolated 12 independent Mu d1 insertions (oxd::Mu d1, oxygen dependent) that show induction of beta-galactosidase in anaerobic cultures and stationary-phase aerated cultures . These insertions fall into nine classes based on map location . All of the oxd::Mu d1 insertions are regulated by oxrA and oxrB and therefore define a global regulon that responds to oxygen limitation. Chem Biol Interact, 1985 Feb-Apr, 53(1-2), 145 - 53 Structure-mutagenicity relationships of 5-nitro-2-furylethylenes in Salmonella typhimurium TA98; Sturdik E et al.; Mutagenicity of three selected series of 2-furylethylene was determined by the Ames test . These included: nine alkylesters and eleven N-alkylamides of 5-nitro-2-furylacrylic acid (NFAA) and ten derivatives differing not only at exocyclic double bond, but also in the position 5 of the furan ring . Mutagenicity of the derivatives depends on the presence of the 5-nitro-furan centre in the molecule; side chains in the position 2 modify the degree of mutagenicity . Among the derivatives of NFAA tested as changing the substituents virtually does not affect chemical properties of the 5-nitrofuran ring . Mutagenicity of the n-alkyl congeners decreases linearly with increasing lipophilicity . Mutagenicity of the derivatives with branched alkyl substituents is lower than expected from the behaviour of the n-alkyl homologues. Ecotoxicol Environ Saf, 1985 Feb, 9(1), 92 - 100 A comparison of the mutagenicity of soluble trivalent chromium compounds with that of potassium chromate; Langerwerf JS et al.; The mutagenic potential of water soluble complexes of trivalent chromium with five different amino acids in Salmonella typhimurium strains TA92, TA94, TA98, and TA100 was studied . All complexes were nonmutagenic at concentrations up to 50 mumol/plate in the strains used . In contrast, trivalent chromium chloride was slightly mutagenic in TA98 and a considerable increase in numbers of revertants was observed in TA94 . Hexavalent chromium was nonmutagenic in TA98 . Strong mutagenic effects were found in TA92, TA94, and TA100 . The large difference in mutagenicity between trivalent and hexavalent chromium is discussed with respect to affinity to extracellular phosphate, diffusability through membranes and reactivity with DNA . More definitive statements about the toxicological risks of the water soluble chromium complexes requires additional studies with well defined compounds in test systems specially suited to study metal complexes. Acta Pathol Microbiol Immunol Scand {B}, 1985 Feb, 93(1), 67 - 72 Invasiveness of Salmonella typhimurium in HEp-2 cell cultures pre-infected with Mycoplasma hominis and Mycoplasma orale; Bukholm G et al.; The influence of mycoplasma infection on the in vitro invasiveness of S . typhimurium in HEp-2 cell cultures has been tested . Two strains of arginine-utilizing mycoplasma species Mycoplasma hominis and M . orale both seemed to inhibit the bacterial in vitro invasiveness . Both the ratio of infected cells and the number of intracellular bacteria per cell were reduced in the mycoplasma-infected cultures. Eur J Biochem, 1985 Feb 1, 146(3), 597 - 603 Cloning and characterization of the pyrE gene and of PyrE::Mud1 (Ap lac) fusions from Salmonella typhimurium; Neuhard J et al.; A lambda-specialized transducing phage carrying the pyrE gene from Salmonella typhimurium LT2 was constructed and used as the source of DNA for subcloning the pyrE gene into pBR322 . The pyrE gene product was identified as a 23-kDa polypeptide using a minicell system for analysis of plasmid-encoded proteins . Studies utilizing a promoter-cloning vehicle provided evidence for the existence of two promoter regions, one located close to the start of the structural gene and the other positioned more than 300 base pairs upstream . Transcription from the more distal promotor was the only situation in which significant regulation by pyrimidines was observed . Additional studies served to localize sites involved in the regulation of pyrE expression and led to the inference that regulation does not occur at the level of initiation of transcription . A procedure was developed for the construction of plasmids through recombination in vivo, whereby pyrE::Mud1 (Ap lac) fusions were transferred to a recipient pyrE+ plasmid by bacteriophage P22-mediated transduction . This enabled the identification of the integration sites of Mud within pyrE and also verified the deduced orientation of the pyrE gene in the parental plasmid . The nucleotide sequence of the 5' end of the pyrE gene was determined, including 150 nucleotide residues encoding the first 50 N-terminal amino acids of orotate phosphoribosyltransferase, and 400 nucleotides upstream from the start of the coding region . The leader region contains sequences characteristic of a rho-independent transcriptional terminator preceded by a cluster of thymidylate residues . In addition, the leader RNA contains an open reading frame with a UGA stop codon immediately preceding the putative transcriptional terminator . The nucleotide sequence suggests that pyrE expression is regulated by modulated attenuation, as has been proposed to be the case for both pyrB and pyrE expression in Escherichia coli. Cancer Lett, 1985 Feb, 26(1), 113 - 9 Mutagenicity of flour from the palmyrah palm (Borassus flabellifer) in Salmonella typhimurium and Escherichia coli; Andersen PH et al.; Flour from the young shoots of the palmyrah palm (Borassus flabellifer) was tested in Salmonella typhimurium, strains TA98 and TA100 (Ames test) and Escherichia coli, strains WP2, WP2uvrA, CM881 and CM891 . The flour was tested in two forms: boiled and raw . Both forms showed dose related mutagenic responses in the basepair substitution sensitive strains TA100 and Escherichia coli WP2uvrA, CM881 and CM891 . The flour from boiled palmyrah shoots exerted a somewhat stronger mutagenic effect on TA100 than flour from the raw shoots . This investigation adds mutagenicity to the wide range of biological effects of palmyrah flour already described (induction of malignant lymphomas, immunosuppression, neurotoxicity and clastogenicity). Ann Intern Med, 1985 Feb, 102(2), 189 - 93 Recurrent Salmonella typhimurium bacteremia associated with the acquired immunodeficiency syndrome; Glaser JB et al.; Seven Haitian and one white patient with the acquired immunodeficiency syndrome and Salmonella typhimurium bacteremia were identified over a 28-month period . In three patients bacteremia developed concurrently with an opportunistic infection associated with the acquired immunodeficiency syndrome . The remaining five patients had their initial episodes of bacteremia 3 to 11 months before the diagnosis of the acquired immunodeficiency syndrome . These five patients had signs suggestive of the syndrome, plus evidence of disordered cellular immune function (lymphopenia, anergy, decreased T-helper cells, decreased proliferative responses, and a deficiency in mononuclear-cell alpha interferon production) . Salmonella typhimurium bacteremia in the appropriate clinical setting may be an opportunistic pathogen associated with the acquired immunodeficiency syndrome. Arch Ophthalmol, 1985 Feb, 103(2), 257 - 60 Lipopolysaccharide tolerance inhibits eye inflammation . I . Reduced immune complex or lipopolysaccharide effects; Howes EL Jr et al.; The effect of endotoxin tolerance on ocular inflammation was studied in rabbits . A single intravenous (IV) injection of endotoxin (bacterial lipopolysaccharide {LPS}) produced a mild acute iridocyclitis . Repeated daily (five to seven days) IV injections of LPS (5 micrograms extracted from Salmonella typhimurium) led to a state of refractoriness or LPS "tolerance," and ocular inflammation was no longer produced . In contrast to controls, in rabbits tolerant to LPS, IV LPS failed to elevate prostaglandin E2, thromboxane B2, or chemotactic factors in the aqueous humor . Rabbits tolerant to LPS also resisted the increase in vascular permeability normally induced by an ocular reversed passive Arthus reaction . These results demonstrated that LPS tolerance can induce anti-inflammatory effects in the eye. Anal Biochem, 1985 Feb 1, 144(2), 390 - 402 Quantitation of chemically induced DNA strand breaks in human cells via an alkaline unwinding assay; Daniel FB et al.; DNA strand breaks induced in human CCRF-CEM cells by electrophilic chemicals (carcinogens/mutagens) can be readily quantitated via a facile alkaline unwinding assay . This procedure estimates the number of chemically induced DNA strand breaks on the basis of the percentage DNA converted from double-stranded to single-stranded form during an exposure to the alkaline unwinding conditions . The assay is based on the assumption that each strand break serves as a strand unwinding point during the alkaline denaturation . The extent of strand separation can be standardized with respect to the initial level of induced strand breaks by the use of X-rays, which produce known levels of DNA strand breaks per rad in mammalian cells . Subsequent to the alkaline exposure, the single- and double-stranded DNA were separated by use of thermostated hydroxylapatite columns (60 degrees C), and the DNA was quantitated via a fluorescence assay (Hoechst 33258 compound) . A correlation was shown between mammalian DNA strand-breaking potential (as measured in this procedure) and the propensity of these chemicals to revert Salmonella typhimurium TA100. Acta Pathol Microbiol Immunol Scand {B}, 1985 Feb, 93(1), 61 - 5 Invasiveness of Salmonella typhimurium in HEp-2 cell cultures pretreated with UV-inactivated coxsackie virus; Bukholm G et al.; The invasiveness of Salmonella typhimurium was significantly enhanced in cell cultures pretreated with UV-inactivated virus . During the first 3 hours of virus infection there was no difference between the enhancement achieved with non-inactivated and that achieved with UV-inactivated virus . After 4 and 5 hours pretreatment the effect of non-inactivated virus was more pronounced than that of UV-inactivated virus . The results indicate that during the early period of virus infection the enhancement of bacterial invasiveness by pretreatment with virus is the result of a direct interaction between the virus and the cell membrane . During the later phase of viral reproduction, viral RNA induced alteration of the cell metabolism, and these altered products might be involved in the interaction. J Bacteriol, 1985 Feb, 161(2), 813 - 6 Salmonella typhimurium contains an anion-selective outer membrane porin induced by phosphate starvation; Bauer K et al.; A mutant of Salmonella typhimurium was selected that is constitutive for the pho regulon . It exhibited constitutive glycerol-3-phosphate transport activity and synthesized a new outer membrane porin . Upon measurement of porin activity in black lipid films, it exhibited anion selectivity . It therefore appears analogous to the Escherichia coli PhoE porin. J Bacteriol, 1985 Feb, 161(2), 641 - 9 Regulation of a cya-lac fusion by cyclic AMP in Salmonella typhimurium; Jovanovich SB; cya-lac and crp-lac operon fusions were isolated in Salmonella typhimurium by using the phage Mu d1(lac cts Apr) . Both transduction and reversion analyses have indicated that lac expression is controlled by the appropriate promoter, e.g., either crpp or cyap . By using chromosomal mobilization techniques, we found that cya had a clockwise direction of transcription on the standard S . typhimurium map . The cya-lac fusions could be complemented by Escherichia coli F'133, which covers cya, with a resultant 17 to 38% decrease in cya expression . Cyclic AMP was found to be able to repress the expression of the cya-lac fusion ninefold when present at 25 mM . This repression was not seen in crp backgrounds, and hence is mediated by the cAMP receptor protein . Repression of cya was also found upon growth on carbon sources known to elicit high cyclic AMP levels. J Bacteriol, 1985 Feb, 161(2), 484 - 92 Genetic analysis of Escherichia coli oligopeptide transport mutants; Andrews JC et al.; The composition of the outer membrane channels formed by the OmpF and OmpC porins is important in peptide permeation, and elimination of these proteins from the Escherichia coli outer membrane results in a cell in which the primary means for peptide permeation through this cell structure has been lost . E . coli peptide transport mutants which harbor defects in genes other than the ompF/ompC genes have been isolated on the basis of their resistance to toxic tripeptides . The genetic defects carried by these oligopeptide permease-negative (Opp-) strains were found to map in two distinct chromosomal locations . One opp locus was trp linked and mapped to the interval between att phi 80 and galU . Complementation studies with F'123 opp derivatives indicated that this peptide transport locus resembles that characterized in Salmonella typhimurium as a tetracistronic operon (B . G . Hogarth and C . F . Higgins, J . Bacteriol . 153:1548-1551, 1983) . The second opp locus, which we have designated oppE, was mapped to the interval between dnaC and hsd at 98.5 min on the E . coli chromosome . The differences in peptide utilization, sensitivity and resistance to toxic peptides, and the L-{U-14C}alanyl-L-alanyl-L-alanine transport properties observed with these Opp-E . coli strains demonstrated that the transport systems encoded by the trp-linked opp genes and by the oppE gene(s) have different substrate preferences . Mutants harboring defects in both peptide transport loci defined in this study would not grow on nutritional peptides except for tri-L-methionine, were totally resistant to toxic peptides, and would not actively transport L-{U-14C}alanyl-L-alanyl-L-alanine. EMBO J, 1985 Feb, 4(2), 539 - 47 Nitrogen regulation in Salmonella typhimurium . Identification of an ntrC protein-binding site and definition of a consensus binding sequence; Ferro-Luzzi Ames G et al.; We have investigated the DNA-binding ability of a nitrogen regulatory protein, the product of the ntrC gene, to several nitrogen-regulated promoters in Salmonella typhimurium . The ntrC protein is able to bind to the regulatory region (dhuA) of an operon coding for genes involved in the active transport of histidine, but not to another transport-related regulatory region, argTr . It bound to two different sites within the regulatory region of glnA (glutamine synthetase) and to one site in the regulatory region for the ntrBC operon . A consensus sequence has been derived from these four binding sites . The binding sequence displays dyad symmetry, as expected for the dimeric ntrC protein . The relationship of the binding sites to regulation of transcription initiation and termination, and to published homologies within the sequences of regulatory sites for nif genes is discussed. Infect Immun, 1985 Feb, 47(2), 434 - 40 Cloning and characterization of genes involved in production of mannose-resistant, neuraminidase-susceptible (X) fimbriae from a uropathogenic O6:K15:H31 Escherichia coli strain; Hacker J et al.; The uropathogenic Escherichia coli strain 536 (O6:K15:H31) exhibits a mannose-resistant hemagglutination phenotype (Mrh) with bovine erythrocytes and delayed Mrh with human and guinea pig erythrocytes . Neuraminidase treatment of the erythrocytes abolishes mannose resistant hemagglutination, which is typical for X fimbriae . E . coli strain 536 synthesizes two different fimbriae (Fim phenotype) protein subunits, 16.5 and 22 kilodaltons in size . In addition the strain shows mannose-sensitive hemagglutination and common type I (F1) fimbriae . The cosmid clone E . coli K-12(pANN801) and another nine independently isolated Mrh+ cosmid clones derived from a cosmid gene bank of strain 536 express the 16.5-kilodalton protein band, but not the 22-kilodalton protein, indicating an association of the Mrh+ property with the "16.5-kilodalton fimbriae." All cosmid clones were fimbriated, and they reacted with antiserum produced against Mrh+ fimbriae of the E . coli strain HB101(pANN801) and lacked mannose-sensitive hemagglutination (F1) fimbriae . From the Mrh fim cosmid DNA pANN801, several subclones coding for hemagglutination and X fimbriae were constructed . Subclones that express both hemagglutination and fimbriae and subclones that only code for the hemagglutination antigen were isolated; subclones that only produce fimbriae were not detected . By transposon Tn5 mutagenesis we demonstrated that about 6.5 kilobases of DNA is required for the Mrh+ Fim+ phenotype, and the 1.5- to 2-kilobase DNA region coding for the structural protein of the fimbriae has been mapped adjacent to the region responsible for the Mrh+ phenotype . Two different regions can thus be distinguished in the adhesion determinant, one coding for hemagglutination and the other coding for fimbria formation . Transformation of plasmid DNA from these subclones into a Mrh- Fim- mutant of E . coli 536 and into a galE (rough) strain of Salmonella typhimurium yielded transformants that expressed both hemagglutination and fimbria production. Zh Mikrobiol Epidemiol Immunobiol, 1985 Feb, (2), 34 - 8 {Mapping of the genetic determinant controlling Salmonella K-antigen synthesis . II . Nonmotile mutants of Salmonella typhimurium}; Romanova IuM et al.; According to the preliminary data, S . typhimurium K-antigen is located in the area of minutes 40-44 on the Salmonella chromosome map . The formation of nonmotile mutants from motile Salmonella strains was induced by the action of nitrosoguanidine . Two main groups of mutants differing in their reaction of agglutination with H- and K-antisera were obtained: Mot-H-K- (motA or motB mutants) and Mot-H-K- (H1- or fla- mutants) . The transduction transfer of the sign of motility by phage P22HT to H-K- mutants and to H1- and flaE- mutants led to the restoration of agglutination ability with respect to H- and K-antisera in all Mot+ transductants under study simultaneously . The restoration of H+K+ phenotype was also observed in spontaneous motile revertants obtained from H-K- mutants . Thus, the gene controlling the synthesis of K-antigen in Salmonellae was shown to be incorporated into the Fla operon, the regulatory system of the operon controlling the expression of this gene. J Gen Microbiol, 1985 Feb, 131 ( Pt 2), 245 - 52 Characterization of a Salmonella typhimurium mutant defective in phosphoribosylpyrophosphate synthetase; Jochimsen BU et al.; This study describes the isolation and characterization of a mutant (strain GP122) of Salmonella typhimurium with a partial deficiency of phosphoribosylpyrophosphate (PRPP) synthetase activity . This strain was isolated in a purE deoD gpt purin auxotroph by a procedure designed to select guanosine-utilizing mutants . Strain GP122 had roughly 15% of the PRPP synthetase activity and 25% of the PRPP pool of its parent strain . The mutant exhibited many of the predicted consequences of a decreased PRPP pool and a defective PRPP synthetase enzyme, including: poor growth on purine bases; decreased accumulation of 5-aminoimidazole ribonucleotide (the substrate of the blocked purE reaction) under conditions of purine starvation; excretion of anthranilic acid when grown in medium lacking tryptophan; increased resistance to inhibition by 5-fluorouracil; derepressed levels of aspartate transcarbamylase and orotate phosphoribosyltransferase, enzymes involved in the pyrimidine de novo biosynthetic pathway; growth stimulation by PRPP-sparing compounds (e.g . guanosine, histidine); poor growth in low phosphate medium; and increased heat lability of the defective enzyme . This mutant strain also had increased levels of guanosine 5'-monophosphate reductase . This genetic lesion, designated prs, was mapped by conjugation and phage P22-mediated transduction at 35 units on the Salmonella linkage map. Biochemistry, 1985 Jan 29, 24(3), 701 - 7 Accessibility to bacterial nucleic acids of the intercalating drug aliphatic amino acid ellipticinium derivatives in Escherichia coli and Salmonella typhimurium; Banoun H et al.; The fluorescence of the aliphatic (amino acido)-N2-methyl-9-hydroxyellipticinium (AA-NMHE) derivatives {Auclair, C., Voisin, E., Banoun, H., Bernardou, J., Meunier, B., & Paoletti, C . (1984) J . Med . Chem . 27, 1161-1166}, namely, dehydroglycino-NMHE, dehydroalanino-NMHE, dehydrovalino-NMHE, and dehydroleucino-NMHE, has been characterized . The changes in the fluorescence properties of the drugs, including increase in quantum yields, increase in fluorescence lifetimes, and occurrence of energy transfer upon binding to DNA in vitro, have been further investigated . The measurement of the fluorescence increment of AA-NMHE when bound to fluorescent sites inside intact bacteria has been found to be suitable for the determination of the accessibility of the drugs to bacterial nucleic acids according to the method of Lambert and Le Pecq {Lambert, B., & Le Pecq, J.B . (1984) Biochemistry 23, 166-176} . With this methodology, the kinetics of drug uptake, the ability of the drug to reach the bacterial nucleic acids at equilibrium, and the nature of the ligand binding model have been determined in two AA-NMHE-sensitive strains, Escherichia coli BL 101 (Lambert & Le Pecq, 1984) and Salmonella typhimurium TA 98 {Ames, B.N., Lee, F.D., & Durston, W.E . (1973) Proc . Natl . Acad . Sci . U.S.A . 70, 782-786} . The main results obtained are the following: At nonsaturating concentrations, each AA-NMHE exhibits a marked difference in its ability to reach the bacterial nucleic acids . This parameter seems to be correlated with the antibacterial efficiency of the drugs.(ABSTRACT TRUNCATED AT 250 WORDS) J Cancer Res Clin Oncol, 1985, 109(3), 203 - 7 Experimental studies on mutagenic and carcinogenic effects of tobacco chewing; Shah AS et al.; The alcoholic extract of the chewing (Pandharpuri) variety of tobacco (Nicotiana tabacum) was subjected to mutagenicity and tumorigenicity studies . The extract was found to be mutagenic in strain TA 98 of Salmonella typhimurium in the presence of S 9 mixture . It also induced 8 AZG-resistant mutation in V 79 Chinese hamster cells . Administration of tobacco extract to male Swiss mice by gavage or mixed with diet resulted in an increased incidence of lung/liver tumors . Further, an additive effect of tobacco extract and hexachlorocyclohexane on liver tumor induction was observed. Gene, 1985, 34(2-3), 137 - 45 High-level expression of M13 gene II protein from an inducible polycistronic messenger RNA; Johnston S et al.; Bacteriophage M13 gene II has been cloned in the plasmid expression vector pING1 and thereby placed under the control of the inducible araB promoter o