Tumorigenicity of 7,12-Dimethylbenz[a]anthracene, Some of Its Fluorinated Derivatives, and 1,2,3,4-Tetrahydro-7,12-dimethylbenz[a]anthracene in Mouse Skin and Rat Mammary Gland

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Abstract
Comparative studies of tumor-initiating activity in mouse skin and carcinogenicity in rat mammary gland were conducted with 7,12-dimethylbenz[a]anthracene (DMBA) and selected derivatives. Female SENCAR mice were initiated with DMBA, 1,2,3,4-tetrahydro-DMBA, 2-, 4-, 5-, 9-, and 10-fluoro DMBA, (FDMBA), and promoted with tetradecanoyl phorbol acetate. The same compounds were tested by intramammillary injection in female Sprague-Dawley rats. DMBA, 9-FDMBA, 10-FDMBA and 1,2,3,4-tetrahydr DMBA were strongly tumorigenic in both mouse skin and rat mammary gland, whereas 2-, 4- and 5-FDMBA were weakly active or inactive. In a third experiment DMBA, benzo[a]pyrene, 1,2,3,4-tetrahydro DMBA and 9,10-dimethylanthracene were tested by repeated application on the dorsal skin of Swiss mice. DMBA was the most carcinogenic, followed by benzo[a]pyrene and 1,2,3,4-tetrahydro DMBA, whereas 9,10-dimethylanthracene was inactive. The potent activity of 1,2,3,4-tetrahydro DMBA suggests that the bay-region diol epoxide pathway may not play a significant role in the activation of DMBA in these two target tissues. Some of these compounds can serve as useful models for elucidating the mechanism(s) of activation of DMBA.

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