In vitro metabolism of 7,12-dimethylbenz[a]anthracene in mammary epithelial cells from rats with different susceptibilities to carcinogenesis.

These in vitro metabolism studies of 7,12-dimethylbenz[a]anthracene (DMBA) by rat mammary epithelial cells were initiated to determine whether differences in the incidence of DMBA-induced mammary carcinomas observed between young virgin, old virgin and parous Sprague-Dawley rats can be explained through variations in their ability to metabolize DMBA. The results show that: (a) qualitatively, the metabolic profiles produced by epithelial cells from the 3 groups of rats were similar; (b) the level of metabolism with cells from young virgin and parous rats was similar but was 1.5-2.0 times higher than that obtained with cells from old virgin rats; c) the major ethyl acetate-soluble metabolite detected by h.p.l.c. from cells of old virgin and parous rats was the trans-8,9-dihydrodiol (50-65% of total metabolites), whereas the majority of the radioactivity following incubation with cells from young virgin rats co-eluted with very polar metabolites (65% of total metabolites); and (d) the amount of phenolic metabolites produced by young virgin rat cells was higher than in old virgin or parous rat cells. The data suggest that the susceptibility of young virgin rat mammary cells to DMBA may be due in part to the conversion of a greater percentage of DMBA to phenolic compounds and to water- and ethyl acetate-soluble polar metabolites, and event known to influence the susceptibility of cultured cells to the cytotoxic effects of DMBA.