SELECTIVE EFFECTS BY VALINOMYCIN ON CYTO-TOXICITY AND CELL-CYCLE ARREST OF TRANSFORMED VERSUS NONTRANSFORMED RODENT FIBROBLASTS INVITRO

  • 1 January 1985
    • journal article
    • research article
    • Vol. 45  (7) , 3022-3028
Abstract
The effect of submicromolar concentrations of the K+ ionophore valinomycin on proliferation, viability, distribution of cell population over phases of the cell cycle and cellular ATP content of different permanent rodent cell lines in vitro was investigated. Valinomycin inhibits proliferation of all cell lines tested with a saturating effect at about 20-100 nM. The effect of valinomycin on nontransformed 3T3 mouse and Rat-1 cells is nontoxic; it acts with increasing toxicity on the transformed cells in the order 3T6 mouse, polyoma-3T3 mouse, temperature-sensitively Rous sarcoma virus-transformed Rat-1 at permissive temperature and SV40-3T3 cells. According to these and some other criteria, the essential action of valinomycin appears to be to impose on the cells at low growth densities a state of limiting growth condition which normally is encountered only at high densities and/or low serum concentration. Nontransformed cells are proliferation arrested by valinomycin essentially in the G1 phase of the cell cycle; all transformed cells under this condition are not arrested selectively in G1. In all cell lines tested (3T3, 3T6 and SV40-3T3), cellular ATP content is decreased by about 33% upon treatment with 20 nM valinomycin. Evidence is presented for a mitochondrial site of action of valinomycin.