Induction of monooxygenases in rhesus monkeys by 3-methylcholanthrene: metabolism and mutagenic activation of N-2-acetylaminofluorene and benzo(a)pyrene.
Induction of content and activity of hepatic and lung cytochrome P450-dependent monooxygenases by 3-methylcholanthrene (MCA) was studied in male rhesus monkeys. Hepatic microsomes were concomitantly studied for mutagenic activation of N-2-acetylaminofluorene (AAF) as well as with the use of sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Hepatic N-hydroxylation of AAF was increased sixfold to sevenfold after MCA treatment; aryl hydrocarbon hydroxylase was similarly increased in both liver and lung. The hepatic cytochrome P450 content was increased by 50%, and the Soret maximum in the CO-hemoprotein complex was shifted to the blue by 2 nm after MCA induction. Electrophoresis of hepatic microsomes from MCA-treated monkeys showed an increase in a polypeptide band of 54,000 molecular weight. Mutagenic activation of AAF by liver microsomes from untreated rhesus monkeys was low but was increased 40-fold after MCA treatment. No effect was observed on the mutagenic activation of N-hydroxy-2-acetylaminofluorene by liver microsomes after MCA treatment. Rhesus monkeys may provide a model for evaluation of the role of polycyclic hydrocarbon induction in chemically caused cancer and toxicity in primates.
D015073:2-Acetylaminofluorene / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis*; D001580:Benzopyrenes / Q000378:metabolism* / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D005449:Fluorenes / Q000378:metabolism*; D000882:Haplorhini; D008113:Liver Neoplasms / Q000139:chemically induced; D008168:Lung / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology*; D008861:Microsomes / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism; D009153:Mutagens / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000139:chemically induced; D012486:Salmonella typhimurium / Q000187:drug effects
D001580:Benzopyrenes; D005449:Fluorenes; D009153:Mutagens; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D015073:2-Acetylaminofluorene; D001189:Aryl Hydrocarbon Hydroxylases