Comparison of the morphological transforming activities of dibenzo[a,l]pyrene and benzo[a]pyrene in C3H10T1/2CL8 cells and characterization of the dibenzo[a,l]pyrene-DNA adducts

C3H10T1/2CL8 (C3H10T1/2) mouse embryo fibroblasts were used to study the invitro carcinogenic activities of dibenzo[a,l]pyrene (DB[a,l]P) andbenzo[a]pyrene (B[a]P). The morphological transforming activities of theserodent carcinogens were compared using replicate concentration- responsestudies. In concentration ranges where both polycyclic aromatichydrocarbons (PAHs) were active, DB[a,l]P proved to be four to 12 times aspotent as B[a]P based on concentration. At lower concentrations DB[a,l]Pwas active at 0.10 and 0.20 microM, concentrations where B[a]P wasinactive. This makes DB[a,l]P the most potent non-methylated PAH evaluatedto date in C3H10T1/2 cells. DNA adducts of DB[a,l]P in C3H10T1/2 cells wereanalyzed by both TLC and TLC/HPLC 32P-postlabeling methods usingmononucleotide 3'-phosphate adduct standards derived from the reactions ofanti-DB[a,l]P-11,12-diol- 13,14-epoxide (anti-DB[a,l]PDE) andsyn-DB[a,l]P-11,12-diol-13,14- epoxide (syn-DB[a,l]PDE) with deoxyadenosine3'-monophosphate and deoxyguanosine 3'-monophosphate. All of the DNAadducts observed in C3H10T1/2 cells treated with DB[a,l]P were identifiedas being derived from the metabolism of DB[a,l]P to its fjord region diolepoxides through DB[a,l]P-11,12-diol. The predominant adduct was identifiedas an anti-DB[a,l]PDE-deoxyadenosine adduct. Other major adducts were anti-DB[a,l]PDE-deoxyguanosine and syn-DB[a,l]PDE-deoxyadenosine adducts withminor amounts of syn-DB[a,l]PDE-deoxyguanosine adducts. These DNA adductdata are consistent with similar findings of DB[a,l]PDE- deoxyadenosineadducts in mouse skin studies and human mammary cells in culture.