Separation of initiating and promoting effects of the skin carcinogen 7-bromomethylbenz(a)anthracene.

Dibenz(a,c)anthracene and 7-bromomethylbenz(a)-anthracene are hydrocarbons with comparable tumor initiating potencies, although they differ about 100-fold in the amount of hydrocarbon bound to mouse skin DNA. We have found that they are comparably mutagenic in Salmonella typhimurium strain TA 100, but that 7-bromomethylbenz(a)anthracene is additionally mutagenic in strains TA 1538 and TA 98. The bromo-compound is also a powerful promoter of tumors initiated in mouse skin with 7,12-dimethylbenz(a)anthracene, whereas dibenz-(a,c)anthracene is inactive as a promoter. Accordingly, 7-bromomethylbenz(a)anthracene is an effective complete carcinogen in mouse skin, while dibenz(a,c)anthracene is not. These results suggest that certain types of chemical damage are far more effective than others for initiation, but that extensive non-initiating damage may be effective for promotion. This has previously been proposed for different alkylating agents, which differ in their abilities to attack DNA and protein, but has not been demonstrated in a single compound. 7-Bromomethylbenz(a)anthracene is found in this experiment to be the most powerful skin tumor promoter known outside of the phorbol ester series. It may be concluded from these results and others that total binding of carcinogen to DNA is not quantitatively related to mutagenic events or tumor initiation, but may be an index of overall risk of tumor development.