HAMSTER LIVER CYTOCHROME-P450 (CYP2A8) AS A 4-HYDROXYLASE FOR 2,5,2',5'-TETRACHLORABIPHENYL

Metabolism of 2,5,2',5'-tetrachlorobiphenyl (TCB) was studied using li ver microsomes of hamsters and two hamster P450 isoforms, CYP1A2 and 2 A8. CYP2A8 catalyzed selectively 4-hydroxylation of 2,5,2',5-TCB at a rate of 21.7 pmol/min/nmol P450. In contrast, CYP1A2 showed no activit y for hydroxylation of 2,5,2',5'-TCB. Immunological study revealed tha t rabbit antiserum against CYP2A8 almost completely inhibited the micr osomal 4-hydroxylation but that against CYP1A2 did not. It was also sh own that the induction pattern of CYP2A8 protein by P450 inducer was s imilar to that of the 4-hydroxylase activity in hamster liver microsom es. These results suggest that CYP2A8 plays a major role in the 4-hydr oxylation of 2,5,2',5'-TCB in hamster liver. (C) 1996 Academic Press, Inc.