In Vitro Metabolism of Tetrachlorobiphenyls by Chinese Hamster Liver Microsomes

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  • OHTA Chiho
    Faculty of Nutritional Sciences, Nakamura Gakuen University
  • KATO Yoshihisa
    Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University
  • HARAGUCHI Koichi
    Faculty of Pharmaceutical Sciences, Daiichi University of Pharmacy
  • FUJII Yukiko
    Faculty of Pharmaceutical Sciences, Daiichi University of Pharmacy
  • 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
  • チャイニーズハムスター肝ミクロゾームによるTetrachlorobiphenylの代謝
  • チャイニーズハムスター カン ミクロゾーム ニ ヨル Tetrachlorobiphenyl ノ タイシャ

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Abstract

The in vitro metabolism of 2,2ʼ,5,5ʼ-tetrachlorobiphenyl (TCB) (CB52), 2,3ʼ,4ʼ,5-TCB (CB70) and 3,3ʼ,4,4ʼ-TCB (CB77) with liver microsomes of Chinese (CH) hamsters was studied and compared with those of Golden Syrian (GS) hamsters. It has been revealed that GS hamster liver microsomes produces two hydroxy (OH)-metabolites each from three TCB isomers and that phenobarbital (PB) pretreatment mainly increased 3-OH-metabolite of CB52 and CB70, whereas 3-methylcholanthrene pretreatment preferentially increased 4-OH-metabolite of CB52, CB70 and CB77. In this study, CH hamster liver microsomes produced only 4-OH-metabolite from both CB52 and CB70 and their metabolic activities were increased to about 4-fold of untreated microsomes by PB pretreatment. However, CH hamster liver microsomes had no activity for CB77. In addition, coumarin 7-hydroxylase activity, a characteristic activity of CYP2A enzymes, was also markedly induced by PB pretreatment. As with the report of Fukuhara and others, immunoblot analysis of CH hamster liver microsomes using anti-CYP2A14 antiserum confirmed that CYP2A14 was constitutive and PB-inducible. From these results, it was suggested that CH hamster is a unique animal different from GS hamster in terms of the mode of TCB metabolism and that CYP2A14 plays a major role as a 4-hydroxylase for CB52 and CB70 in CH hamster liver.

Journal

  • 福岡醫學雜誌

    福岡醫學雜誌 114 (1), 31-39, 2023-03-25

    Fukuoka Medical Association

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