Metabolism of Tetrachlorobiphenyls by Chinese Hamster Liver Microsomes

Introduction The biotransformation of polychlorinated biphenyls, world-wide environmental pollutants, is initiated mainly by an oxygenation of aromatic ring catalyzed by liver cyochrome P450(P450) [1]. A series of our studies using some tetrachlorobiphenyls (TCBs), major components of Kanechlor 400 caused Yusho poisoning in Japan in 1968, demonstrated that the hydroxylating ability of liver microsomes from rats, guinea pigs and hamsters for some TCBs could be explained by the catalytic activity of each P450 isoform. Namely, phenobarbital (PB)-inducible P450 isoforms such as rat CYP2B1, Golden syrian (GS) hamster P450HPB-1 and guinea pig P450GP-1(CYP2B18) catalyze 3-hydroxylation for 2,2',5,5'and 2,3',4',5-TCB. Moreover, 3-methylchlanthrene (MC)inducible isoforms such as rat CYP1A1, GS hamster CYP2A8 and GS hamster CYP1A2 catalyze 4-hydroxylation for 2,2',5,5'or 2,3',4',5-TCB [2-7]. In addition, rat CYP1A1 shows the catalytic activity for 4-and 5-hydroxylation of 3,3',4,4'-TCB [2] and for 4-hydroxylation of 3,3',5,5'-TCB [8]. Recently, Fukuhara et al. have reported that Chinese (CH) hamsters differ from GS hamsters in terms of susceptibility of monooxygenase activities to P450 inducers, PB and MC [9]. For example, aflatoxin B1 activation and 7-ethoxycoumarin O-deethylase in CH hamsters are makedly accelerated by PB-treatment, whereas in GS hamsters by MC-treatment. Therefore, in this study we compared the metabolism of three TCBs, 2,2',5,5'-, 2,3',4',5and 3,3',4,4'-TCB, by liver microsomes of CH hamsters with those of GS hamsters.