J. Jacob et al., Species-dependent metabolism of benzo[c]chrysene mediated by C-DNA-expressed human, rodent and fish cytochrome P450 enzymes, POLYCYCL AR, 21(1-4), 2000, pp. 109-121
The metabolism of benzo[c]chrysene (B[c]Ch) with various cytochrome P350 (C
YP) enzymes including rat 1A1, 1A2, 2B1 and 2E1, human 1A1, 1A2, 2A6, 1B1,
3A4 and 2E1, mouse 1B1, and scup fish 1A1 expressed in Chinese hamster V79
cells has been investigated to clarify the role of individual enzymes in th
e regioselective oxidation of B [c]Ch and the species dependency. In six ce
ll lines expressing individual CYP enzymes from four different species B[c]
Ch was metabolized to several isomeric phenols and trans-dihydrodiols. Howe
ver, cell lines expressing human 3A4, 2A6 and 2E1 or rat 1A2, 2B1 and 2E1 w
ere metabolically in-competent towards B[c]Ch. Among the trans-dihydrodiols
the 9,10-isomer could be detected in cells expressing human, rat and fish
CYP 1A1 and to a minor extent in cells with human 1A2, but not in cells exp
ressing human and mouse CYP 1B1. The latter two cell lines produced high am
ounts of the bay region 3,4-dihydrodiol, whereas the K-region 7,8-dihydrodi
ol was a minor metabolite. Oxidation of B[c]Ch to the 1,2-dihydrodiol could
not be catalyzed by any of the CYP enzymes investigated except fish 1A1. O
ur results suggest that metabolic activation of B [c]Ch is initiated predom
inantly by CYP 1A1 to result selectively in the formation of fjord region 9
,10-dihydrodiol Il,12-epoxides regardless of the species involved. The acti
vation of B [c]Ch appears to be limited by a low regioselectivity for the 9
,10-oxidation.