Induction of cytochrome P-450 and related drug-metabolizing activities in the livers of different rodent species by 2-acetylaminofluorene or by 3-methylcholanthrene.
In general, large differences in the control levels of different cytochrome P-450-catalyzed activities (aminopyrine N-demethylase, benzo(a)pyrene monooxygenase, ethoxyresorufin O-deethylase, ethoxycoumarin O-deethylase and total 2-acetylaminofluorene metabolism and metabolite pattern) and in the inducibility of these activities in different rodent species (rat, hamster, guinea pig and mouse) and sexes were observed. For all the activities measured the lowest levels were observed in untreated rats. With a few minor exceptions, the only species tested in which cytochrome P-450-catalyzed activities were induced by treatment with 2-acetylaminofluorene was the rat. A larger number of the species tested were susceptible to induction by 3-methylcholanthrene. However, this xenobiotic proved also to induce most potently in the rat. There are relatively large differences between the male and female rat both in terms of control cytochrome P-450-catalyzed activities and in the inducibility of these activities by 2-acetylaminofluorene and 3-methylcholanthrene. In general, both of these xenobiotics proved to be more potent inducers in the female than in the male. Thus, it is quite clear that in quantitative terms the hepatic microsomal cytochrome P-450-catalyzed activities and their inducibility by 2-acetylaminofluorene or 3-methylcholanthrene in the male Sprague-Dawley rat are not representative for other rodent species or even for the female of the same species.
D015073:2-Acetylaminofluorene / Q000494:pharmacology*; D015660:7-Alkoxycoumarin O-Dealkylase; D000633:Aminopyrine N-Demethylase / Q000096:biosynthesis; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000633:toxicity*; D001579:Benzopyrene Hydroxylase / Q000096:biosynthesis / Q000633:toxicity*; D006224:Cricetinae; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction; D005260:Female; D006168:Guinea Pigs; D007527:Isoenzymes / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D009929:Organ Size / Q000187:drug effects; D010088:Oxidoreductases / Q000378:metabolism; D010105:Oxygenases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012737:Sex Factors; D013045:Species Specificity
D007527:Isoenzymes; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D015073:2-Acetylaminofluorene; D010088:Oxidoreductases; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase; D001579:Benzopyrene Hydroxylase; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; D000633:Aminopyrine N-Demethylase