Benzo(e)pyrene [B(e)P] cotreatment slightly increases the
tumor-initiating activity of
benzo(a)pyrene [B(a)P] and greatly decreases the
tumor-initiating activity of
7,12-dimethylbenz(a)anthracene (DMBA) in Sencar mice (DiGiovanni et al.,
Carcinogenesis 3: 371-375, 1982). The effects of B(e)P on the binding of B(a)P and DMBA to Sencar mouse epidermis were investigated using a protocol similar to the mouse skin tumorigenicity studies. After 12 h of exposure to 50 nmol [3H]B(a)P and low or high doses of B(e)P, the level of [3H]B(a)P bound to mouse epidermal
DNA increased by 30%. However, after 24 h exposure to 50 nmol [3H]B(a)P and after 12 or 24 h of exposure to 200 nmol [3H]B(a)P, B(e)P had no effect on the amount of [3H]B(a)P bound to
DNA. The ration of anti-(the isomer with the
epoxide and benzylic
hydroxyl on opposite faces of the molecule) B(a)P-7,8-diol-9,10-epoxide [B(a)PDE]-deoxyribonucleoside adducts to syn- (the isomer with the
epoxide and benzylic
hydroxyl on the same face of the molecule) B(a)PDE-deoxyribonucleoside adducts did not change at either initiating dose of B(a)P or at any time regardless of the dose of B(e)P. After 12 h of exposure to high doses of B(e)P and a 50-nmol initiating dose of B(a)P the level of [3H]B(a)P bound to
DNA increased but there was no change in the proportion of particular B(a)PDE-deoxyribonucleoside adducts present. In contrast, B(e)P inhibited the binding of initiating doses of DMBA (5 and 20 nmol) to
DNA after 12 and 48 h of exposure to all dose ratios of B(e)P:DMBA tested. The three major adducts, tentatively identified as anti-DMBA-3,4-diol-1,2-epoxide (DMBADE):
deoxyguanosine, syn-DMBADE:
deoxyadenosine and anti-DMBADE:
deoxyadenosine, decreased to the same relative extent as the dose of B(e)P increased. Thus, the effects of B(e)P on the total binding of these
hydrocarbons to
DNA in epidermis correlate with the cocarcinogenic and
anticarcinogenic effects of B(e)P on B(a)P and DMBA, respectively, in a mouse skin initiation-promotion assay. These results indicate that the mechanism of the co- or anticarcinogenic action of
hydrocarbons such as B(e)P involves alteration of the binding of carcinogenic
hydrocarbons to
DNA. They also suggest that measurement of carcinogenic
hydrocarbon-
DNA adducts formed during cotreatment with other
hydrocarbons will provide a rapid method for predicting the co- or
anticarcinogenic effect of the other
hydrocarbons.