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The in vitro metabolism of 2,2ʼ,3,4,4ʼ,5,5ʼ-heptachlorobiphenyl (CB180) was examined using liver microsomes of rats, guinea pigs and hamsters. Of liver microsomes from untreated animals, rats and guin...ea pigs produced one metabolite (M-1) with the activity of 1.2 and 18.1 pmol/hr/mg protein, respectively, but hamsters did not at all. Pretreatment of phenobarbital (PB) resulted in about 32-fold increase in rats, 4-fold increase in guinea pigs and an appearance of M-1 in hamsters (15 pmol/hr/mg protein). In addition, another metabolite (M-2) was formed only by liver microsomes of PB-treated guinea pigs. In contrast, pretreatment of 3-methylcholanthrene showed no metabolite in three animals. By comparison of the GC-MS data of the metabolites with synthesized authentic samples, M-1 and M-2 was determined to be 3ʼ-hydroxy (OH) -CB180 and 4’-OH-2,2ʼ,3,4,5,5ʼ-hexachlorobiphenyl (CB141), respectively. These results suggest that 3ʼ-OH-CB180 is a major metabolite and is formed by PB-inducible cytochrome P450 (CYP2B enzymes) in animals and also guinea pigs possess much higher activity to metabolize CB180 than rats and hamsters.続きを見る
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