Comparison of the tumor-initiating activities of benzo(a)pyrene arene oxides and diol-epoxides.

The ability of arene oxides, and diol epoxides of benzo(a)pyrene to initiate skin tumors in mice was determined by using a two-stage system of tumorigenesis. (+/-)-7beta,8alpha-Dihydroxy-9alpha, 10alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene was a more effective tumor initiator than was (+/-)-7beta,8alpha-dihydroxy-9beta,10beta-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene when applied topically to CD-1 mice and then followed by twice-weekly applications of the promotor 12-O-tetradecanoylphorbol-13-acetate. (+/-)-7beta,8alpha-Dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene was approximately 20 to 30% as active as benzo(a)pyrene was as a tumor initiator. (+/-)-7beta,8alpha-Dihydroxy-7beta,8beta-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene, benzo(a)pyrene, 9,10-oxide, and benzo(a)pyrene 11, 12-oxide, possessed about 1, 2, and 10%, respectively, of the tumor-initiating activity of benzo(a)pyrene.