Benzo[e]pyrene-induced alterations in the binding of benzo[a]pyrene to DNA in hamster embryo cell cultures.

Benzo[e]pyrene (B[e]P), a weakly carcinogenic polycyclic aromatic hydrocarbon (PAH) modifies tumor induction in mouse skin and the induction of mutation in mammalian cells by carcinogenic PAH. To determine how B[e]P alters the metabolic activation of the carcinogen benzo[a]pyrene (B[a]P), early passage Syrian hamster embryo cell cultures were exposed to [3H]B[a]P or [3H]trans-7,8-dihydro-7,8-dihydroxyB[a]P (B[a]P-7,8-diol) in the presence of various concentrations of B[e]P for 24 h. The DNA was isolated, degraded to deoxyribonucleosides and the B[a]P-deoxyribonucleoside adducts were analyzed by h.p.l.c. As the dose of B[e]P increased, the amount of B[a]P bound to DNA decreased and the ratio of anti-B[a]P-7,8-diol-9,10-epoxide (B[a]PDE)-deoxyguanosine adduct to syn-B[a]PDE-deoxyguanosine adduct decreased. B[e]P treatment inhibited the binding of B[a]P-7,8-diol to DNA to a greater extent than it inhibited the binding of B[a]P and decreased the ratio of anti- to syn-B[a]PDE-deoxyguanosine adducts formed from the 7,8-diol. These results indicate that B[e]P decreases the activation of B[a]P to DNA-binding intermediates in these cells; especially the oxidation of B[a]P-7,8-diol to a diol-epoxide. The B[e]P-induced alterations in the ratio of DNA adducts formed from the syn- and anti-isomers of B[a]PDE suggest that B[e]P selectively inhibited certain pathways of metabolic activation of B[a]P. Thus, B[e]P-induced modifications in the biological activity of PAH may result from alteration in both the amounts and the relative proportions of various isomeric forms of the ultimate carcinogenic metabolites formed from PAH.