[Comparative study on metabolism of three tetrachlorobiphenyls with animal liver microsomes]

In vitro metabolism of 3,5,3',4'-, 3,5,3',5'- and 2,4,3',4'-tetrachlorobiphenyls (TCBs) was studied using liver microsomes from rats, guinea pigs and hamsters. 3,5,3',4'-TCB was metabolized to 4-hydroxy-3,5,3',4'-TCB with liver microsomes of 3-methyl-cholanthrene (MC)- and 3,4,5,3',4'-pentachlorobiphenyl (PenCB)-treated rats but not of phenobarbital (PB)-treated ones. This result suggests that a MC-inducible cytochrome P450 isoform, probably CYP1A1, is more important in the in vitro metabolism of 3,5,3',4'-TCB in rat liver and that the isoform attacks the 3,5-dichloro-substituted phenyl ring more predominantly than 3,4-dichloro-substituted one. In 3,5,3',5'-TCB metabolism, liver microsomes from MC- and 3,4,5,3',4'-PenCB-treated hamsters formed 4-hydroxy-3,5,3',5'-TCB to a similar extent to rats reported previously. Guinea pig liver microsomes formed no metabolite. In 2,4,3',4'-TCB metabolism, PB accelerated 3-, 5- and 4-hydroxylations in guinea pigs and also 3- and 5-hydroxylations in hamsters, suggesting the involvement of a PB-inducible P450 isoform, presumably P450GP-1 and P450HPB-1, respectively. On the other hands, MC- and 3,4,5,3',4'-PenCB-treatment resulted in the marked increase of 4-hydroxylation in hamsters, but in the suppression of 4-hydroxylation in guinea pigs. From these results, it is suggested that the hydroxylation of coplanar TCBs such as 3,5,3',4'- and 3,5,3',5'-TCB is catalyzed by a MC-inducible P450 in rats and hamsters, whereas non-coplanar TCBs such as 2,4,3',4'-TCB which possesses both PB- and MC-like inducing ability of liver enzymes are metabolized by one or more kinds of P450 isoform induced by PB and MC.