Interspecies comparison of polycyclic aromatic hydrocarbon metabolism in human and rat mammary epithelial cells

Our laboratory has developed optimized and uniform methods for the isolation and culture of normal mammary epithelial cells from both rats and humans. We have reported that, in a cell-mediated mutagenesis assay, treatment of rat mammary epithelial cells with 7,12-dimethylbenz(a)anthracene, but not benzo(a)pyrene, resulted in significant rates of mutagenesis in cocultured V-79 cells. An opposite mutation pattern was found with human cells under identical conditions. To determine the mechanism of this species-specific difference in polycyclic aromatic hydrocarbon-induced mutagenesis patterns, we then studied the abilities of the human and rat mammary epithelial cells to metabolize benzo(a)pyrene and 7,12-dimethylbenz(a)anthracene. Quantitative levels of carcinogen metabolism were found to be highly dependent on the cell culture densities, although this factor appeared to have little qualitative effect. The most significant qualitative difference in polycyclic aromatic hydrocarbon metabolism between the two species was the ability of the rat, but not the human, mammary epithelial cells to conjugate significant amounts of either polycyclic aromatic hydrocarbon to glucuronic acid. Other aspects of carcinogen metabolism, including production of the precursors to known active metabolites of benzo(a)pyrene and 7,12-dimethylbenz(a)anthracene, were similar though not identical. These results, which address only primary metabolism of the polycyclic aromatic hydrocarbons, do not indicate a simple metabolic explanation for the species-specific pattern found in the mammary cell-mediated mutagenesis assay. They do suggest that the effects of cell culture density must be carefully considered in order to properly analyze either interindividual or species differences in carcinogen metabolism.