N. Koga et al., METABOLISM OF 2,3',4',5-TETRACHLOROBIPHENYL BY CYTOCHROME-P450 FROM RATS, GUINEA-PIGS AND HAMSTERS, Chemosphere (Oxford), 37(9-12), 1998, pp. 1895-1904
The metabolism of 2,3',4',5-tetrachlorobiphenyl (TCB) was compared usi
ng liver microsomes and six isoforms of cytochrome P450 purified from
rats, guinea pigs and hamsters. In microsomal study, the following spe
cies differences were observed: 1) Untreated guinea pigs and hamsters
but not rats can metabolize this TCB to 3-hydroxy- or 4-hydroxy-2,3',4
',5-TCB, 2) Guinea pig microsomes showed only 3-hydroxylating activity
, whereas hamster microsomes showed higher activity of 4-hydroxylation
than that of 3-hydroxylation. In common with three species, the 3-hyd
roxylation was accelerated by phenobarbital. The 4-hydroxylation in ra
ts and hamsters was increased by pretreatment with 3-methylcholanthren
e and 3,3',4,4',5-pentachlorobiphenyl. The hydroxylation activities of
liver microsomes from the three species could be explained by an invo
lvement of different isoforms of cytochrome P450. In addition, it is a
pparent that hamster CYP1A2 as well as hamster CYP2A8 is involved in t
he 4-hydroxylation of 2,3',4',5-TCB although it has no activity for 2,
2',5,5'-TCB. (C) 1998 Elsevier Science Ltd. All rights reserved.