Tumorigenicity of five dihydrodiols of benz(a)anthracene on mouse skin: exceptional activity of benz(a)anthracene 3,4-dihydrodiol.

Abstract

Benz[a]anthracene and the 5 metabolically possible vicinal trans dihydrodiols of benz[a]anthracene were tested for ability to initiate skin tumors in CD-1 female mice. A single topical application of 0.4-2.0 .mu.mol of hydrocarbon was followed 18 days later by twice weekly applications of the skin promoter 12-O-tetradecanoylphorbol-13-acetate. Comparisons of latency period, percent of mice with tumors and number of papillomas observed per mouse indicated that benz[a]anthracene 3,4-dihydrodiol was 10- to 20-fold more tumorigenic than the parent hydrocarbon, benz[a]anthracene. The benz[a]anthracene 1,2-, 5,6-, 8,9- and 10,11-dihydrodiols were less active tumor initiators than benz[a]anthracene. The high tumorigenicity of benz[a]anthracene 3,4-dihydrodiol, presumably the result of metabolism to either or both of the diastereomeric benz[a]anthracene 3,4-diol-1,2-epoxides, supports the bay region theory of polycyclic hydrocarbon carcinogenicity and provides the 1st example of a proximate carcinogenic metabolite that is much more active than the parent hydrocarbon on mouse skin.