Activation of benzo(a)pyrene and 2-acetamidofluorene to mutagens by microsomal preparations from different animal species: role of cytochrome P-450 and P-448.
1. The metabolic activation of benzo(a)pyrene and 2-acetamidofluorene to mutagens was studied with liver microsomal preparations from rat, guinea-pig, hamster and mouse, untreated or pretreated with phenobarbitone or 3-methylcholanthrene. 2. Liver microsomal preparations from all animal species activated benzo(a)pyrene, that from mouse being the most efficient. Similarly, microsomal preparations from guinea-pig, hamster and mouse could activate 2-acetamidofluorene, but that from rat exhibited very weak activity. 3. Activation of benzo(a)pyrene into mutagenic intermediates by liver microsomal preparations was increased for all animals except mouse by pretreatment with 3-methylcholanthrene. In contrast, pretreatment with phenobarbitone decreased the activation by microsomal preparations from all species. 4. Activation of 2-acetamidofluorene by liver microsomal preparations from rat and guinea-pig, but not mouse and hamster, was increased by pretreatment of the animals with phenobarbitone. Pretreatment with 3-methylcholanthrene decreased the activation of this carcinogen by microsomal preparations from all species. 5. The metabolic activation of benzo(a)pyrene is catalysed by cytochrome P-448 but not cytochrome P-450. 6. The activation of 2-acetamidofluorene to mutagens may involve, in addition to the mixed-function oxidases, other microsomal enzyme systems.
D015073:2-Acetylaminofluorene / Q000378:metabolism*; D000818:Animals; D001564:Benzo(a)pyrene; D001580:Benzopyrenes / Q000378:metabolism*; D001711:Biotransformation; D006224:Cricetinae; D019388:Cytochrome P-450 CYP1A2; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003580:Cytochromes / Q000378:metabolism*; D005260:Female; D006168:Guinea Pigs; D008297:Male; D008647:Mesocricetus; D008748:Methylcholanthrene / Q000494:pharmacology; D051379:Mice; D008862:Microsomes, Liver / Q000201:enzymology*; D009153:Mutagens / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D001580:Benzopyrenes; D003580:Cytochromes; D009153:Mutagens; D001564:Benzo(a)pyrene; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D015073:2-Acetylaminofluorene; C017170:Cyp1a2 protein, rat; D019388:Cytochrome P-450 CYP1A2; D010634:Phenobarbital