Selenium inhibition of DNA synthesis in mouse mammary epithelial cell line YN-4.

Previous results have documented that Na2SeO3 has a biphasic effect on the growth of mammary cells in vitro. In the experiments reported herein, the effects of selenium on several parameters of cell proliferation in the YN-4 mouse mammary cell line were investigated. The biphasic effect of selenium on cell growth was confirmed; i.e., 5 X 10(-8) M selenium stimulated cell growth, whereas 5 X 10(-6) M delayed cell growth and 5 X 10(-5) M was cytotoxic. The inhibition of cell growth by 5 X 10(-6) M selenium was reversible when this dose was removed from the growth medium. The increased cell growth at 5 X 10(-8) M selenium was reflected by an increased cell number, increased uptake of [3H]thymidine into DNA, increased DNA labeling index, and an increased rate of DNA synthesis. The decreased cell growth at 5 X 10(-6) M selenium was reflected by a decrease in all of these parameters of cell growth kinetics. The differential effects of selenium were manifested by 48 hr after addition of selenium to the cell culture medium. The results indicate that one of the mechanisms of selenium-mediated inhibition of carcinogenesis may be due to an inhibition of cell proliferation of responsive cells.