The catalytic activity of four expressed human cytochrome P450s towards benzo[a]pyrene and the isomers of its proximate carcinogen.
The catalytic properties of expressed human cytochromes P4501A1, 1A2, 3A4 and 3A5 with respect to the metabolite distribution for the carcinogen benzo[a]pyrene (BP) and the proximate carcinogen (-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene ((-)-BP-7,8-DHD) were determined. P4501A1 formed a higher proportion of the proximate carcinogen from BP than the other isozymes. Both P4501A1 and 1A2 were more selective for oxidation at the benzo ring of BP and showed a greater production of dihydrodiol metabolites than either P4503A4 or 3A5. The formation of diolepoxides from the individual enantiomers of BP-7,8-DHD occurred in a highly stereoselective fashion.
Roberts-Thomson
S J
SJ
University of Sydney, Pharmacy Department, N.S.W., Australia.
McManus
M E
ME
Tukey
R H
RH
Gonzalez
F F
FF
Holder
G M
GM
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000378:metabolism*; D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism*; D002460:Cell Line; D003001:Cloning, Molecular; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D007536:Isomerism; D007700:Kinetics; D013379:Substrate Specificity; D014162:Transfection
D007527:Isoenzymes; D001564:Benzo(a)pyrene; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D003577:Cytochrome P-450 Enzyme System