2,2',5,5'-四塩素化ビフェニル（CB52）のウサギ肝ミクロゾームによる代謝

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特集号油症とPCB及びダイオキシン関連化合物研究報告第22集責任編集者古江増隆The Twenty-second Reports of the Study on Yusho―PCBs and Dioxin-Related Compounds―Guest Editor Masutaka FurueOur preceding studies have reported that 2,2',5,5'-tetrachlorobiphenyl (tetraCB)(CB52) is mainly metabolized to 3-hydroxy (OH)-metabolite by phenobarbital (PB)-inducible cytochrome P450 (P450) isoforms such as CYP2B1 and CYP2B18. In this study, the metabolism of CB52 by liver microsomes of untreated and PB-treated rabbits was investigated. Rabbit liver microsomes produced mainly 3-OH- and 4-OH-metabolites (M-1 and M-2) at an equal extent and two other metabolites (M-3 and M-4) and also that phenobarbital (PB) treatment accelerated the formation of all these metabolites. M-3 was assumed to OH-tetraCB by GC-MS. Another metabolite, M-4, was determined to 3,4-diOH-CB52 by GC-MS and 1H-NMR. Addition of antiserum against CYP2B4, a constitutive and PB-inducible rabbit P450 isoform, to a microsomal incubation system resulted in almost complete inhibition of the formation of 3-OH-, 4-OH- and 3, 4-diOH-metabolites. These results suggest that CYP2B4 plays an important role in CB52 metabolism in rabbit liver.
2009-05-25