Skin carcinogenesis tests in mice of derivatives of 7,12-dimethylbenz[a]anthracene substituted in the 'A' ring.

Seven derivatives of 7,12-dimethylbenz[a]anthracene (DMBA) having substituents in the 'A' ring have been tested for carcinogenic activity by chronic application to the skin of female Swiss mice. Saturation of the A ring, as in 1,2,3,4-tetrahydro-DMBA, resulted in a very potent skin carcinogen which induced almost 100% of skin carcinomas within 26 weeks. The 2-bromo-derivative was apparently not carcinogenic. Respectively, 35% and 40% of the mice treated with 2-methoxy and 4-bromo-DMBA developed skin tumors, mainly squamous cell carcinomas with the former and mainly neurosarcomas for the latter. The remaining compounds, 3-methoxy-, 4-methoxy- and 3-bromo-DMBA each induced skin tumors on 3-5 animals. There were no quantitative correlations between bacterial mutagenicity of the substituted DMBA's and their carcinogenic potencies in mouse skin painting. The reasons for the differences in carcinogenic activity are not clear, but the effects, particularly the strong carcinogenicity of the tetrahydro-derivative, suggest the possibility that mechanisms other than formation of a dihydrodiol expoxide in the A ring might be involved.