Cytochrome P450 isoforms catalyzing benzo[a]pyrene metabolism in the Chinese hamster liver

Cytochrome P450 isoforms involved in the benzo[a]pyrene metabolism in the C hinese hamster liver were characterized. The activity of benzol[a]pyrene hy droxylase in male hamster livers increased markedly by treatment with 3-met hylcholanthrene (25 mg/kg per day, i.p., 3 days) and moderately with phenob arbital (60 mg/kg per day) and dexamethasone (100 mg/kg per day). In contra st, the ability for the mutagenic activation of benzo[a]pyrene determined b y the mutagenicity test was increased most markedly by treatment with pheno barbital and significantly with 3-methylcholanthrene, but not with dexameth asone. These observations are similar to those in the rat rather than in th e Syrian hamster. Western blot analysis and assay of the enzymes associated with cytochrome P450 isoforms showed that the 3-methylcholanthrene treatme nt elevated markedly the level of CYP1A2, but not that of CYP1A1, while the phenobarbital treatment elevated markedly the level of CYP2A and CYP3A, bu t not that of CYP2B. Further, immunoinhibition study demonstrated that, in Chinese hamster livers, CYP2A and CYP1A2 were mainly involved in the mutage nic activation of benzo[a]pyrene and CYP3A in the benzo[a]pyrene hydroxylas e activity, respectively. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.