COMPARATIVE TUMOR-INITIATING ACTIVITY OF METHYLATED BENZO(A)PYRENE DERIVATIVES IN MOUSE SKIN

Abstract

The abilities of various mono and dimethyl derivatives of benzo(a)pyrene (BP) to initiate skin tumors in mice were determined by using a 2-stage system of tumorigenesis. 11-Methylbenzo(a)pyrene was approximately 3 times more active as a tumor initiator than was the parent hydrocarbon; 1-methyl benzo(a)pyrene was about twice as active as was BP. Substitution of a methyl group in positions 7, 8, 9 or 10 of BP, which would be involved in a bay-region diol-epoxide, completely counteracts the tumor-initiating ability of BP. 3-, 4-, and 12-Methyl-benzo(a)pyrenes had activity equivalent to that of BP, whereas 2-, 5-, and 6-methylbenzo(a)pyrenes, and 1,2-, 4,5-, 1,6- and 3,6-dimethylbenzo(a)pyrenes were less active than BP. The concepts of steric inhibition of metabolic activation and stereospecific activation may explain the tumor-initiating activities of various methylated derivatives.