Mg2+-sensitive alterations in Ca2+ regulation associated with cell transformation.

The intracellular Ca2+ content of nontransformed Balb/c3T3 cells is two to three times higher than that of a spontaneously transformed derivative. Depriving either cell type of extracellular Mg2+ causes a 2- to 3-fold increase in their Ca2+ content over a 24-hr period. Restoring Mg2+ to the medium decreases the Ca2+ content of the cells to their original values in about the same time. The increase in Ca2+ content is not blocked by cycloheximide suggesting that normal rates of protein synthesis are not required to produce this effect. Mg2+ deprivation also decreases the initial rate of Ca2+ efflux from the transformed cells and increases the size of the slowly exchanging fraction of Ca2+ to the levels found in the nontransformed cells. Since Mg2+ deprivation normalizes the appearance and growth behavior of the transformed cells, the possible intermediary role of Ca2+ in this normalization was studied. Large changes in extracellular Ca2+ produced large changes in the Ca2+ content of the transformed cells with little change in appearance or thymidine incorporation rate. Ca2+ deprivation did inhibit thymidine incorporation in early passage nontransformed cells; however with repeated passage, this effect decreased, as did the Ca2+ content of these cells. The possible role of Mg2+ in regulating cellular Ca2+ content and distribution is discussed, as is the relation of Ca2+ content and distribution to the development of the transformed state.