Benzo(e)pyrene-induced alterations in the binding of benzo(a)pyrene and 7,12-dimethylbenz(a)anthracene to DNA in Sencar mouse epidermis.

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