Reversible regulation by magnesium of chick embryo fibroblast proliferation

The rates of 3 H‐thymidine incorporation and of cell proliferation in chick embryo fibroblast cultures are reduced coordinately when the [Mg 2+ ] of the external medium is reduced below the physiological concentration of about 0.8 mM. These effects of moderately reduced [Mg 2+ ] and the accompanying change in appearance of the cells, resemble the effects produced by lowering the [serum] of the medium. Cells subjected to severe Mg 2+ deprivation, especially at low [Ca 2+ ], die and detach from the culture dish. Cells kept at a reduced rate of proliferation for three days by moderate Mg 2+ deprivation are quickly restored to rapid proliferation upon restoration of the normal [Mg 2+ ] of the medium. The rate of proliferation of the chick embryo cells is reduced markedly by lowering [Ca 2+ ] about 100‐fold, but unlike the case of Mg 2+ ‐deprivation this can occur without significant effect on the rate of 3 H‐thymidine incorporation. More severe Ca 2+ deprivation, which does lower the rate of 3 H‐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 [Mg 2+ ] plays a central role within the cell in the coordinate control of metabolism and growth. They also suggest that the effects produced by varying [Ca 2+ ] in the medium are caused by changes at the external surface of the cell.