Comparative Study on the in Vitro Metabolism of 2,2ʼ,3,4ʼ,5ʼ,6-Hexachlorobiphenyl (CB149) in Rats, Hamsters, Guinea Pigs and Humans

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  • OHTA Chiho
    Faculty of Nutritional Sciences, Nakamura Gakuen University
  • HARAGUCHI Koichi
    Faculty of Pharmaceutical Sciences, Daiichi University of Pharmacy
  • KATO Yoshihisa
    Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University
  • 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

Bibliographic Information

Other Title
  • 2,2ʼ,3,4ʼ,5ʼ,6-六塩素化ビフェニル（CB149）のラット，ハムスター，モルモットおよびヒトにおけるin vitro代謝の比較研究
  • 2,2',3,4',5',6-六塩素化ビフェニル(CB149)のラット,ハムスター,モルモットおよびヒトにおけるin vitro代謝の比較研究
  • 2,2',3,4',5',6-ロク エンソカ ビフェニル(CB149)ノ ラット,ハムスター,モルモット オヨビ ヒト ニ オケル in vitro タイシャ ノ ヒカク ケンキュウ

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Abstract

The in vitro metabolism of 2,2ʼ,3,4ʼ,5ʼ,6-hexachlorobiphenyl (CB149) was examined using liver microsomes of rats, hamsters, guinea pigs and humans. Three metabolites (M1, M2 and M3) were produced common to animals and humans and M1 was a major metabolite in all microsomes used in this study. Pretreatment of phenobarbital (PB) resulted in the marked increase of M1, M2 and M3 in all animals. In PB-treated animals, M1 production increased 253-, 11- and 2.4-fold of untreated in rats, hamsters and guinea pigs, respectively. Moreover, the order of M1 production was rats＞＞hamsters ＞ guinea pigs (46 : 5 : 1). In 3-methylcholanthrene-treated animals, M1 production was the same or less than that of untreated animals. GC-MS determinedM1, M2 andM3 to be 5-hydroxy (OH)-, 4-OHand 4,5-diOH-CB149, respectively. Human liver microsomes prepared individually from fifteen Caucasians exhibited quite similar metabolic patterns. However, there was about 6-fold inter-individual variation in the amounts of total metabolites. When the correlation coefficients between the amount of CB149 metabolites generated and the enzymatic activities of CYP isoforms were determined, the production of 5-OH- and 4,5-diOH-CB149 was significantly correlated with both activities of CYP2B6 and CYP3A4, and the production of 4-OH-CB149 was significantly correlated with CYP2A6 activity. So, when we actually investigated the metabolic activity using twelve CYP isoforms, CYP2B6 and CYP2A6 catalyzed the formation of 5-OH- and 4-OH-CB149, respectively. However, CYP3A4 showed no activity. From these findings, it was suggested that CYP2B and CYP2A enzymes play an important role in CB149 metabolism in animals and humans.

Journal

  • 福岡醫學雜誌

    福岡醫學雜誌 114 (1), 40-50, 2023-03-25

    Fukuoka Medical Association

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