2,2ʼ,4,4ʼ,6,6ʼ-六塩素化ビフェニル（PCB155）のラット, モルモットおよびヒト肝ミクロゾーム, およびヒトチトクロムP450による代謝

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タイトル別名
  • Metabolism of 2,2ʼ,4,4ʼ,6,6ʼ-Hexachlorobiphenyl (PCB155) by Rat, Guinea Pig and Human Liver Microsomes and Human Cytochrome P450s
  • 2,2'4,4'6,6'-六塩素化ビフェニル(PCB155)のラット,モルモットおよびヒト肝ミクロゾーム,およびヒトチトクロムP450による代謝
  • 2,2'4,4'6,6'-ロク エンソカ ビフェニル(PCB155)ノ ラット,モルモット オヨビ ヒト カン ミクロゾーム,オヨビ ヒトチトクロム P450 ニ ヨル タイシャ

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The in vitro metabolism of a 2,4,6-trichloro-substituted PCB, 2,2ʼ,4,4ʼ,6,6ʼ-hexachlorobiphenyl (PCB155), was studied using rat, guinea pig and human liver microsomes, and human cytochrome P450 (CYP) isoforms. Three kinds of liver microsomes from untreated, phenobarbital (PB) -treated and 3-methylcholanthrene (MC) -treated rats and guinea pigs were also used. In rats, PCB155 was metabolized to M1 by PB-microsomes with a remarkable high rate of 4.554 nmol/hr/mg protein, but not by both untreated microsomes and MC-microsomes. In guinea pigs, both untreated microsomes and MC-microsomes showed the M1-producing activity with rates of 0.056 and 0.060 nmol/hr/mg protein, respectively, and the activity was increased to3 .5-fold of untreated microsomes by PB treatment. GC-MS analysis demonstrated that the methylatedM1 had the molecular weight of 388 and almost completely agreed with a synthesized authentic 3-methoxy-PCB155 with regard to the retention times and mass fragmentation. Of four human CYP isoforms, only CYP2B6 showed high activity to form M1 at a rate of 0.702 nmol/hr/nmo l CYP. These results suggest that the major metabolite formed by PB-inducible CYP2B enzymes in rats, guinea pigs and human is 3-hydroxy-PCB155, and that CYP2B6 plays the most important role in PCB155 metabolism in human liver.

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