The role of highly purified cytochrome P-450 isozymes in the activation of 4-aminobiphenyl to mutagenic products in the Ames test.
The role of cytochromes P-450 and P-447 in the activation of 4-aminobiphenyl to mutagens in the Ames test was studied using S9 preparations and highly purified isozymes. S9 preparations from beta-naphthoflavone-pretreated rats were more efficient in converting 4-aminobiphenyl to mutagens than the corresponding preparations from phenobarbitone-pretreated animals. Similarly, reconstituted systems comprising purified cytochrome P-447 were twice as efficient as cytochrome P-450 in activating the carcinogen. Of all the known Phase I metabolites of 4-aminobiphenyl, only the N-hydroxy-derivative was mutagenic in the Ames test. These findings indicate that arylamine N-hydroxylase is a cytochrome P-450 dependent enzyme, and the nature of the isozyme of the cytochrome is an important determinant of its mutagenicity.
D000611:Aminobiphenyl Compounds / Q000378:metabolism* / Q000633:toxicity; D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism*; D009152:Mutagenicity Tests; D009153:Mutagens; D009154:Mutation; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D012486:Salmonella typhimurium / Q000187:drug effects; D013329:Structure-Activity Relationship
D000611:Aminobiphenyl Compounds; D002273:Carcinogens; D007527:Isoenzymes; D009153:Mutagens; C006757:4-biphenylamine; D003577:Cytochrome P-450 Enzyme System; D009251:NADPH-Ferrihemoprotein Reductase