Differential Effects of Selenium on Normal and Neoplastic Canine Mammary Cells1'2

Four different canine mammary tumor (CMT) cell lines and a nonneo plastic primary culture of mammary cells were examined for their in vitro responsiveness to selenium supplementation. These cell lines were found to vary in their metabolic response to increasing concentrations of selenium. Sensitivity to selenium, as sodium selenite, increased with increasing concentrations of this trace element in all of the neoplastic lines. These data also suggest that increasing the plating density of tumor cells further increases the sensitivity to selenium. A relatively seleniumsensitive cell line (CMT-13) and relatively insensitive cell line ((Mi ll) were characterized on the basis of reduced growth resulting from selenium supplementation. Increasing the concentration of selenium to 0.75 »ig/ml depressed the growth of CMT-13 and CMT-11 cells by 75% and 11%, respectively, while no inhibition was observed in nonneoplastic cells. These cell lines also varied in their sensitivity to different forms of selenium. Selenodiglutathione was the most effective form of selenium examined that inhibited tumor cell growth. The sensitivity of the neo plastic lines was selenodiglutathione »sodium selenite »selenocystine > selenomethionine. None of the forms of selenium examined inhibited the growth of the nonneoplastic mammary cells in culture. Supplemen tation with sodium selenite (l »ig Se per ml) for 60 min resulted in a dramatic depression in RNA biosynthesis in CMT-13, but not CMT-11 or nonneoplastic cells.