Induction of rat hepatic mixed function oxidases by aromatic amines and its relationship to their bioactivation to mutagens.
Hepatic microsomal mixed-function oxidase activities were determined in rats pretreated with the aromatic amines 2-aminoanthracene, 2-naphthylamine or 4-aminobiphenyl. All three amines stimulated the O-deethylation of ethoxyresorufin (cytochromes P-448) but none had any effect on the p-hydroxylation of aniline. 2-Aminoanthracene and 4-aminobiphenyl also stimulated the NADPH-dependent reduction of cytochrome c and 2-naphthylamine inhibited the N-demethylation of benzphetamine. Hepatic preparations from animals pretreated with 2-aminoanthracene were more efficient in converting this carcinogen to mutagens while in contrast pretreatment with Aroclor 1254 caused a marked decrease in mutagenicity. 4-Aminobiphenyl also enhanced its own activation but Aroclor-pretreated preparations were the most effective. The latter preparations were also more efficient than controls in activating 2-naphthylamine to mutagens. It is concluded that 4-aminobiphenyl and 2-aminoanthracene enhance their own activation at least partly, by inducing the synthesis of cytochromes P-448.
D015081:2-Naphthylamine / Q000378:metabolism / Q000633:toxicity; D000588:Amines / Q000378:metabolism* / Q000633:toxicity; D000611:Aminobiphenyl Compounds / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D000873:Anthracenes / Q000378:metabolism / Q000633:toxicity; D001711:Biotransformation; D004790:Enzyme Induction / Q000187:drug effects; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000096:biosynthesis*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D000588:Amines; D000611:Aminobiphenyl Compounds; D000873:Anthracenes; D009153:Mutagens; C006757:4-biphenylamine; C006593:2-anthramine; D015081:2-Naphthylamine; D006899:Mixed Function Oxygenases