Metabolism of 2,2ʼ,3,4,4ʼ,5,5ʼ-Heptachlorobiphenyl (CB180) by Animal Liver Microsomes

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  • Ohta Chiho
    Faculty of Nutritional Sciences, Nakamura Gakuen University
  • Haraguchi Koichi
    Daiichi College of Pharmaceutical Sciences
  • Kato Yoshihisa
    Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University
  • Endo Tetsuya
    Research and Clinical Center for Yusho and Dioxin, Kyushu University Hospital
  • Kimura Osamu
    Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido
  • Koga Nobuyuki
    Faculty of Nutritional Sciences, Nakamura Gakuen University

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Other Title
  • 2,2ʼ,3,4,4ʼ,5,5ʼ-七塩素化ビフェニル（CB180）の動物肝ミクロゾームによる代謝
  • 2,2',3,4,4',5,5'-七塩素化ビフェニル(CB180)の動物肝ミクロゾームによる代謝
  • 2,2',3,4,4',5,5'-ナナ エンソカ ビフェニル(CB180)ノ ドウブツ カン ミクロゾーム ニ ヨル タイシャ

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Abstract

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 guinea 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.

Journal

  • 福岡醫學雜誌

    福岡醫學雜誌 106 (5), 176-183, 2015-05-25

    Fukuoka Medical Association

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