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 Chinese hamster liver were characterized. The activity of benzo[a]pyrene hydroxylase in male hamster livers increased markedly by treatment with 3-methylcholanthrene (25 mg/kg per day, i.p., 3 days) and moderately with phenobarbital (60 mg/kg per day) and dexamethasone (100 mg/kg per day). In contrast, the ability for the mutagenic activation of benzo[a]pyrene determined by the mutagenicity test was increased most markedly by treatment with phenobarbital and significantly with 3-methylcholanthrene, but not with dexamethasone. These observations are similar to those in the rat rather than in the Syrian hamster. Western blot analysis and assay of the enzymes associated with cytochrome P450 isoforms showed that the 3-methylcholanthrene treatment elevated markedly the level of CYP1A2, but not that of CYP1A1, while the phenobarbital treatment elevated markedly the level of CYP2A and CYP3A, but not that of CYP2B. Further, immunoinhibition study demonstrated that, in Chinese hamster livers, CYP2A and CYP1A2 were mainly involved in the mutagenic activation of benzo[a]pyrene and CYP3A in the benzo[a]pyrene hydroxylase activity, respectively.
Fukuhara
M
M
Department of Pharmaceutical Sciences, National Institute of Public Health, Tokyo, Japan. fukuhara@iph.go.jp
Sun
B
B
Kato
K
K
Kimura
M
M
Yamazaki
S
S
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism*; D015153:Blotting, Western; D002273:Carcinogens / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000276:immunology / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D004790:Enzyme Induction; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology; D009152:Mutagenicity Tests; D010634:Phenobarbital / Q000494:pharmacology
D002273:Carcinogens; D065607:Cytochrome P-450 Enzyme Inhibitors; D007527:Isoenzymes; D001564:Benzo(a)pyrene; D008748:Methylcholanthrene; D003907:Dexamethasone; D003577:Cytochrome P-450 Enzyme System; D010634:Phenobarbital