Mammary gland cell-mediated mutagenesis of mammalian cells by organ-specific carcinogens.

Rat mammary gland cells have been used to activate chemical procarcinogens to mutagenic compounds in a culture system. Mutagenesis was tested in Chinese hamster V-79 cells that were cocultured with the mammary cells. The locus mutations tested for were resistance to ouabain and resistance to 6-thioguanine. Mammary cells were separated into several fractions. Fractions enriched in either epithelial or stromal cells could both mediate mutagenesis. The mutation frequency related to the density of the mammary cells. The mammary carcinogen 7, 12-dimethylbenz(a)anthracene exhibited a dose-dependent enhancement of mutation frequency and cytotoxicity when added to the cocultures, whereas the hepatocarcinogen aflatoxin B1 did not. This system may be useful in examining some of the mechanisms of organ-specific carcinogenesis and also may act as a screening system for carcinogenic environmental contaminants.