ORGANIC AND INORGANIC SELENIUM-COMPOUNDS INHIBIT MOUSE MAMMARY CELL-GROWTH IN-VITRO BY DIFFERENT CELLULAR PATHWAYS

Selenium, both organic and inorganic forms, inhibit mammary tumorigene sis in vivo and mammary cell growth in vitro. In the present study, so dium selenite was compared to methylselenocysteine (MSC) for their ind ividual effects on cell growth, cdc2/cdk2 kinase activities and the le vels of cyclins D1, E and A bound to cdk2 in a mouse mammary epithelia l cell culture model. Selenite arrested the growth of cells in S-G2-M phase in contrast to MSC which arrested or delayed the cells in G1. In MSC-treated cells there was a 57% drop in the cdk2 kinase activity ac companied by a 73.5% decrease in cyclin E-cdk2 content as compared to the control cells, Selenite treatment increased the cdk2 kinase activi ty by 30% without any appreciable change in either of the cyclins D1, E or A bound to cdk2 when compared to the control cells. These data su pport the hypothesis that selenite and MSC have distinct modes of acti on in the inhibition of cell growth in vitro. Selenite has a strong ge notoxic effect on the tumor cells; in contrast, MSC appears to inhibit cell growth via specific inhibition of cell cycle regulatory proteins .