Involvement of non-oxidative enzymes in mutagenic activation of urine from rats, given benzidine and some other aromatic amines.
Urinary metabolites of rats treated with benzidine and some other genotoxic aromatic amines became mutagenic in the Ames assay after activation with liver cytosol from rat, mouse and guinea pig. Most of the mutagenic metabolites appeared in urine as glucuronides. Strong evidence was found that N,O-acyltransferase is responsible for the mutagenic activation by rat liver cytosol. The inhibitory effect of paraoxon and sodium fluoride indicates that the activation by mouse liver cytosol is due to the action of deacetylase. Mutagenic activation by guinea pig liver cytosol seemed to be mediated in part by deacetylase. The metabolite activated by these enzymes most likely is a glucuronidated, N-acetylated, N-hydroxylated product.
D000588:Amines / Q000494:pharmacology / Q000652:urine*; D000818:Animals; D001560:Benzidines / Q000378:metabolism / Q000494:pharmacology / Q000652:urine*; D001711:Biotransformation; D003600:Cytosol / Q000378:metabolism; D006168:Guinea Pigs; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism; D010261:Paraoxon / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects
D000588:Amines; D001560:Benzidines; D009153:Mutagens; D010261:Paraoxon