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.