The metabolic activation of 7-methylbenz(a)anthracene: the induction of malignant transformation and mutation in mammalian cells by non-K-region dihydrodiols.

Four different dihydrodiols derived from 7-methylbenz(a)anthracene have been tested, together with the parent hydrocarbon, for their ability to induce the in vitro malignant transformation of mouse M2 fibroblasts and mutations in V79 Chinese hamster cells. In the transformation tests withe the non-K-region dihydrodiols, the 3,4-diol was the most active dihydrodiol tested and the 8,9-diol was also more active than 7-methylbenz(a)anthracene itself; the 1,2-diol showed only slight activity. The K-region dihydrodiol, the 5,6-diol, which cannot be directly metabolized to a vicinal diol-epoxide, was inactive. These differences in biological activity were similar to those apparent in the results from the mutagenicity tests. The data support the general hypothesis that non-I-region dihydrodiols, which can be metabolized to vicinal diol-epoxides, are important in the metabolic activation of the carcinogenic polycyclic hydrocarbons and, when taken together with other results, indicate that 3,4-dihydro-3,4-dihydroxy-7-methylbenz(a)anthracene is most probably involved in the metabolic activation of 7-methylbenz(a)anthracene presumably following conversion into the related diol-epoxide, 3,4-dihydro-3,4-dihydroxy-7-methylbenz(a)anthracene 1,2,-oxide.