Differences in mediated mutagenesis and polycyclic aromatic hydrocarbon metabolism in mammary cells from pregnant and virgin rats.

Abstract

The physiological state of pregnancy confers significant resistance to polycyclic aromatic hydrocarbon (PAH)-induced mammary tumorigenesis. We have tested the abilities of primary mammary cells from pregnant and virgin rats cultured on collagen-coated plates to metabolize PAHs and convert these carcinogens to mutagenic derivatives. Using a cell-mediated mutagenesis assay, we found that mammary epithelial cells from pregnant rats produced half the levels of mutagenic 7,12-dimethylbenz[a]anthracene (DMBA) metabolites formed by cells from virgin rats. Pregnant-derived mammary cells also showed consistently lower levels of metabolism of DMBA and benzo[a]pyrene (B[a]P) than cells from virgin rats. H.p.l.c. analysis of B[a]P metabolism by these cell populations indicated no significant qualitative differences in the extracellular and intracellular metabolites formed. We have previously shown that mammary cells from rat strains exhibiting significant differences in susceptibility to PAH-induced tumors have equivalent qualitative and quantitative abilities to metabolize PAH carcinogens. Our current data suggest that modifications in mammary tumor susceptibility found in various physiological states, unlike genetically determined differences, may be related in part to an altered ability to activate chemical carcinogens within the mammary gland.