Abstract
1. The metabolism of 3,5,3′,5′-tetrachlorobiphenyl (TCB) was investigated with liver microsomes and purified P450 from the male Wistar rat.
2. One novel metabolite was produced after incubation with liver microsomes derived from the 3-methylcholanthrene (MC)- and 3,4,5,3′,4′-pentachlorobiphenyl-pretreated rat, but not after incubation with those from the untreated or phenobarbital (PB)-pretreated rat. These results suggest that P450 isozyme(s) induced by MC-type inducers is involved in 3,5,3′,5′-TCB metabolism.
3. The chemical structure of this metabolite was identified to be 4-hydroxy-3,5,3′,5′-TCB by comparison of its retention time in glc and the ms with those of a synthetic sample.
4. Purified rat P4501A1, a major MC-inducible P450 isozyme, catalyzed the 4-hydroxylation of 3,5,3′,5′-TCB, but P4502B1, a major PB-inducible isozyme, was inactive.
5. Reduced glutathione completely inhibited the formation of the hydroxylated metabolite, suggesting that 4-hydroxylation of 3,5,3′,5′-TCB proceeded via the 3,4-epoxide.