Human, rat and mouse liver-mediated mutagenicity of vinyl chloride in S. typhimurium strains.
Exposure of S. typhimurium strains TA 1530, TA 1535 and G-46 to vinyl chloride increased the number of His+ revertants/plate 16, 12 or 5 times over the spontaneous mutation rate. After 6 h of exposure to vinyl chloride, the mutagenic response for TA 1530 strain was enhanced 7-, 4- or 5-fold when fortified postmitochondrial liver fractions from humans, rats or mice were added. The enzyme-mediated vinyl chloride mutagenicity was dependent on an NADPH generating system and the enzyme activity was localized in a liver microsomal fraction; 9,000 times g liver supernatant was three times more active than microsomes, while liver cytosol or alcohol dehydrogenase did not affect the mutagenicity. Phenobarbitone pretreatment of rats and mice increased the mutagenic response by up to 15-40 percent as compared to untreated controls. The relative mutagenic activities of VCM, taking the value from mouse liver as 100, for TA 1530 strain mediated by 9,000 times g tissue fractions were: rat liver, 80; mouse and rat kidney, 20 and 16; mouse and rat lung, less than 7; human liver (from four biopsy specimens) 170, 64, 70 and 46. Chloroacetaldehyde and chloroacetic acid, a urinary metabolite of VCM, showed toxic effects, while chloroethanol was weakly mutagenic for TA 1530 strain.
D000079:Acetaldehyde / Q000031:analogs & derivatives / Q000494:pharmacology; D000085:Acetates / Q000494:pharmacology; D000818:Animals; D002273:Carcinogens; D002460:Cell Line; D003600:Cytosol; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism*; D009153:Mutagens; D009154:Mutation / Q000187:drug effects*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects*; D013268:Stimulation, Chemical; D013997:Time Factors; D014753:Vinyl Compounds / Q000008:administration & dosage / Q000494:pharmacology*
D000085:Acetates; D002273:Carcinogens; D009153:Mutagens; D014753:Vinyl Compounds; D000431:Ethanol; D000079:Acetaldehyde; D010634:Phenobarbital