Metabolism of 2,2ʼ,3,4,4ʼ,5,6ʼ-Heptachlorobiphenyl (CB182) by Rat, Guinea Pig and Human Liver Microsomes

Abstract

The in vitro metabolism of 2,2ʼ,3,4,4ʼ,5,6ʼ-heptachlorobiphenyl (CB182) by rat, guinea pig and human liver microsomes was compared and the effects of cytochrome P450 (CYP) inducers, phenobarbital (PB) and 3-methylcholanthrene (MC), on CB182 metabolism were examined. Only one metabolite was produced by rat, guinea pig and human liver microsomes and the order of the activity was rat (PB-treated)＞＞ guinea pig (PB-treated)＞ guinea pig (untreated, MC-treated)＞ human ＞ rat (untreated). Pretreatment of PB resulted in the remarkable increase of the metabolite in rats (1,370 pmol/hr/mg protein) and a slight increase in guinea pigs (27 pmol/hr/mg protein). In contrast, MC treatment to rats and guinea pigs decreased M-1. By comparison of GC-MS data of the methylated M-1 with a synthesized authentic sample, M-1 was determined to be 3ʼ-hydroxy (OH)-CB182. These results suggest that 3ʼ-OH-CB182 is a major metabolite formed by PB-inducible CYP2B enzymes in both animals and rat CYP2B enzymes possess much higher activity to hydroxylate CB182 than guinea pig and human CYP2B enzymes