Reversible regulation by magnesium of chick embryo fibroblast proliferation

Abstract

The rates of ³H-thymidine incorporation and of cell proliferation in chick embryo fibroblast cultures are reduced coordinately when the [Mg²⁺] of the external medium is reduced below the physiological concentration of about 0.8 mM. These effects of moderately reduced [Mg²⁺] and the accompanying change in appearance of the cells, resemble the effects produced by lowering the [serum] of the medium. Cells subjected to severe Mg²⁺ deprivation, especially at low [Ca²⁺], die and detach from the culture dish. Cells kept at a reduced rate of proliferation for three days by moderate Mg²⁺ deprivation are quickly restored to rapid proliferation upon restoration of the normal [Mg²⁺] of the medium. The rate of proliferation of the chick embryo cells is reduced markedly by lowering [Ca²⁺] about 100-fold, but unlike the case of Mg²⁺-deprivation this can occur without significant effect on the rate of ³H-thymidine incorporation. More severe Ca²⁺ deprivation, which does lower the rate of ³H-thymidine incorporation, produces retraction of cells from one another and from the dish, and results in a distinctly abnormal, rounded appearance. The results lend weight to the thesis that free [Mg²⁺] plays a central role within the cell in the coordinate control of metabolism and growth. They also suggest that the effects produced by varying [Ca²⁺] in the medium are caused by changes at the external surface of the cell.