MODULATION OF CELL-PROLIFERATION AND CELL-CYCLE, AND INHIBITION OF CYTOKINESIS BY 1,25-DIHYDROXYVITAMIN-D3 IN C3H 10T1/2 FIBROBLASTS/

The growth-modulating effects of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D 3] were studied on three mouse embryo fibroblast cell lines. Concentra tions ranging from 0.1 to 100 nM inhibited dose-dependently proliferat ion in the non-tumorigenic C3H/10T1/2 Cl 8 (10T1/2) and the chemically transformed C3H/10T1/2 Cl 16 (Cl 16) cells. The hormone had a biphasi c effect on the transformed cell line C3H/10T1/2 TPA 482 (TPA 482) in which growth was stimulated by low concentrations. Exposure to 10 nM 1 ,25-(OH)2D3 for 5 days resulted in a 90% growth inhibition of 10T1/2 c ells, and the hormone was 10 and 100 times less potent in Cl 16 and TP A 482 cells, respectively. The inhibition of cell replication was full y reversible on removal of the hormone. Treatment of 10T1/2 and Cl 16 cells with 10 nM 1,25-(OH)2D3 reduced the saturation density to 30 and 37% that of controls, respectively, suggesting an enhancement of cell -cell contact mediated growth inhibition. 1,25-(OH)2D3 inhibited cytok inesis in 10T1/2 cells, inducing the formation of binucleated cells. F low cytometric studies showed that 1,25-(OH)2D3-treated cells accumula ted in the G0/G1 phase while the number of cells in S phase decreased. This in vitro model system seems to be useful for studies of the mole cular mechanisms of the growth modulating effect of 1,25-(OH)2D3.