title: [Species difference in the metabolism of 2, 2', 3, 4', 5, 5'-hexachlorobiphenyl (CB146) by animal and human liver microsomes].
abstract: The in vitro metabolism of 2, 2', 3, 4', 5, 5'-hexachlorobiphenyl (hexaCB) (CB146) was examined using liver microsomes of rats, guinea pigs, hamsters and human. Untreated animal livers produced one metabolite (M-2) in rats, three metabolites (M-l, M-2and M-3) in guinea pigs and no metabolite in hamsters. Pretreatment of phenobarbital (PB) resulted in a marked increase of M-1 in three animals and of M-2in guinea pigs. In contrast, pretreatment of 3-methylcholanthrene showed a significant increase of M-3 in guinea pigs and a decrease of M-2in rats. Human liver microsomes prepared from nine Caucasians mainly formed M-2and M-3 at a ratio of 2: 1 and two individuals also formed one more metabolite M-1. The formation of M-1 was significantly correlated with CYP2B6 activity. By comparison of the GC-MS data of three metabolites with synthesized authentic samples, M-1 and M-2were determined to be 3'-hydroxy (OH)-CB146 and 4-OH-CB146, respectively. However, M-3 is unclear at present except the fact that it is OH-hexaCB. These results suggest that 3'-OH-CB146 is formed by PB-inducible cytochrome P450 (CYP2B enzymes) in animal and human livers and 4-OH-CB146 is a major metabolite in rat and human liver.
authors.affiliation: Faculty of Nutritional Sciences, Nakamura Gakuen University, 5-7-1, Befu, Johnan-ku, Fukuoka 814-0198, Japan.
authors.forename: Chiho
authors.initials: C
authors.lastname: Ohta
authors.forename: Koichi
authors.initials: K
authors.lastname: Haraguchi
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kato
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Endo
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Koga
mesh_terms: D000818:Animals; D006224:Cricetinae; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008862:Microsomes, Liver / Q000378:metabolism*; D011078:Polychlorinated Biphenyls / Q000378:metabolism*; D051381:Rats; D013045:Species Specificity
chemical_list: D011078:Polychlorinated Biphenyls