Fatty acid-induced modifications of mouse mammary epithelium as studied in an organ and cell culture system.

The results obtained from the experiments described in this article may be summarized as follows: Mammary glands from adult mice of various strains can be maintained in a chemically defined medium for at least 23 days. The mammary epithelium in this in vitro system responds to selected steroid and polypeptide hormones in a manner similar to that observed in the explant cultures of immature mice. The incidence of spontaneous or carcinogen-induced lactogenic hormone-independent, putative preneoplastic MAL has a strong correlation with the age of mouse and the risk of developing mammary cancer. Selected fatty acids that are known to modulate mammary tumor incidence are also able to alter MAL incidence in mammary gland organ cultures from a high cancer incidence strain of mouse. Nontransformed mammary epithelial cells in culture respond to the potent mammary carcinogen DMBA by exhibiting increased proliferation and specific mutation that renders the cells resistant to cytotoxic TG. Selected fatty acids modulate DMBA-induced changes, at least in part, by modulating the process of metabolic cooperation between normal and mutant phenotypes. The present in vitro assays could be valuable to evaluate the direct effects of agents that initiate, promote and/or inhibit neoplastic transformation in mammary epithelium.