Induction of mutations in DNA-repair deficient bacteria by a liver microsomal metabolite of aflatoxin B1.
Certain strains of Salmonella typhimurium and Escherichia coli, particularly those which are very sensitive to u.v. light, are killed when incubated with rat liver mixed function oxidases and aflatoxin B(1). UvrA or recA strains of E. coli are more susceptible than the wild-type strain, while the double mutant uvrA recA is the most sensitive strain yet tested. The aflatoxin B(1) metabolite is also able to induce reverse mutations in 2 histidine auxotrophic strains of S. typhimurium, one strain of which is reverted specifically by frame shift mutagens and the other by agents inducing base pair substitutions.Pretreatment of rats with either 3-methylcholanthrene or benzo(a)pyrene, both inducers of liver microsomal mixed function oxidases, did not alter the amount of lethal aflatoxin B(1) metabolite formed, whereas an increase was observed after phenobarbitone pretreatment. Addition of the nucleophiles methionine, cysteine, glutathione, sodium thiosulphate or sodium sulphide, or the epoxide hydrase inhibitor, cyclohexene oxide to the toxicity assay medium did not alter bacterial killing by the aflatoxin B(1) metabolite. 2,3-Dimercaptopropanol had some protective action.Toxic metabolites were also formed when 5-methoxysterigmatocystin, O-methylsterigmatocystin, parasiticol or versicolorin A, but not vericolorin B, were incubated with mixed function oxidases. The relationship between the metabolite of aflatoxin B(1) lethal to bacteria and that which initiates liver cancer is discussed.
D000348:Aflatoxins / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001580:Benzopyrenes / Q000494:pharmacology; D003545:Cysteine / Q000494:pharmacology; D004260:DNA Repair; D004269:DNA, Bacterial / Q000378:metabolism*; D004112:Dimercaprol / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects; D008099:Liver / Q000201:enzymology; D008297:Male; D008715:Methionine / Q000494:pharmacology; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000378:metabolism*; D009154:Mutation / Q000187:drug effects*; D010088:Oxidoreductases; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects; D014466:Ultraviolet Rays
D000348:Aflatoxins; D001580:Benzopyrenes; D004269:DNA, Bacterial; D004112:Dimercaprol; D008748:Methylcholanthrene; D008715:Methionine; D010088:Oxidoreductases; D003545:Cysteine; D010634:Phenobarbital