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The in vitro metabolism of 2, 2', 3, 4', 5, 5'-hexachlorobiphenyl (hexaCB) (CB146) was examined using liver microsomes of rats, guinea pigs, hamsters and human. Untreated animal livers produced one me...tabolite (M-2) in rats, three metabolites (M-1, M-2 and M-3) in guinea pigs and no metabolite in hamsters. Pretreatment of phenobarbital (PB) resulted in a marked increase of M-1 in three animals and of M-2 in guinea pigs. In contrast, pretreatment of 3-methylcholanthrene showed a significant increase of M-3 in guinea pigs and a decrease of M-2 in rats. Human liver microsomes prepared from nine Caucasians mainly formed M-2 and M-3 at a ratio of 2 : 1 and two individuals also formed one more metabolite M-1. The formation of M-1 was significantly correlated with CYP2B6 activity. By comparison of the GC-MS data of three metabolites with synthesized authentic samples, M-1 and M-2 were determined to be 3'-hydroxy (OH) -CB146 and 4-OH-CB146, respectively. However, M-3 is unclear at present except the fact that it is OH-hexaCB. These results suggest that 3'-OH-CB146 is formed by PB-inducible cytochrome P450 (CYP2B enzymes) in animal and human livers and 4-OH-CB146 is a major metabolite in rat and human liver.続きを見る
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