Comparison of 7,12-dimethylbenz[a]anthracene metabolism and DNA binding in mammary epithelial cells from three rat strains with differing susceptibilities to mammary carcinogenesis.

The capacity of polycyclic aromatic hydrocarbons such as 7,12-dimethylbenz[a]anthracene (DMBA) to induce mammary carcinomas has been studied in three rat strains. Wistar/Furth (WF) rats are highly susceptible to DMBA-induced mammary carcinogenesis, Copenhagen (Cop) rats are completely resistant, and Fischer 344 (F344) rats have an intermediate susceptibility. We have previously shown that WF rats possess 'enhancer genes', which enhance susceptibility to induced mammary cancer. Cop rats, however, possess a single 'suppressor' gene which confers complete resistance to mammary cancer. Both gene types are apparently absent in F344 rats. In order to determine possible mechanisms of action of these enhancer and suppressor genes, we have examined DMBA metabolism and DNA binding in mammary epithelial cells isolated from each rat strain. Quantitative analyses of both metabolism and DNA binding indicate no significant differences among the strains. In addition, HPLC analyses of DMBA metabolites and DMBA-DNA adducts were essentially identical. These data suggest that the genes controlling susceptibility and resistance to mammary carcinogenesis in these rat strains are likely to be active at later stages of the carcinogenic process.