title: 3-Methoxy-4-aminoazobenzene, a unique carcinogenic aromatic amine as a substrate for cytochrome-P-450-mediated mutagenesis.
abstract: Rat liver microsomal enzyme(s) that catalyze mutagenic activation of a carcinogenic aminoazo dye, 3-methoxy-4-aminoazobenzene (3-MeO-AAB), was studied by virtue of the Salmonella typhimurium TA98 assay using o-aminoazotoluene (OAT) as the control. Male Wistar rats were pretreated with phenobarbital (PB), 3-methylcholanthrene (MC) or polychlorinated biphenyl (PCB), and the liver microsomal activities for mutagenic activation of 3-MeO-AAB and OAT were examined. In agreement with the reported results on several carcinogenic aromatic amines, MC pretreatment resulted in greater activation of microsomal activity in the OAT mutagenesis (about a 4-fold increase as compared to the untreated control) than did PB (1.5-fold increase). By contrast, the mutagenic activation of 3-MeO-AAB is found to be more efficiently catalyzed by those enzyme(s) that are induced by PB pretreatment (4-fold increase) than by those that are induced by MC (1.8-fold increase). The induced enzymes that principally mediate the mutagenic activation of these azo dyes are indicated to be cytochrome P-450s, because the mutagenic activation was strongly inhibited by addition of cytochrome P-450 inhibitors such as 2-diethylaminoethyl-2,2-diphenylvalerate (SKF 525A) and 7,8-benzoflavone. These data suggest that 3-MeO-AAB is a unique carcinogenic aromatic amine as a substrate for mutagenic activation via catalysis of those cytochrome P-450s that are induced by PB pretreatment.
mesh_terms: D000818:Animals; D001391:Azo Compounds / Q000494:pharmacology*; D001711:Biotransformation; D002273:Carcinogens / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009152:Mutagenicity Tests; D009154:Mutation; D010634:Phenobarbital / Q000494:pharmacology; D011078:Polychlorinated Biphenyls / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects; D010128:p-Aminoazobenzene / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D001391:Azo Compounds; D002273:Carcinogens; D008748:Methylcholanthrene; D010128:p-Aminoazobenzene; C044436:3-methoxy-4-aminoazobenzene; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; D010634:Phenobarbital