Cellular concentration of magnesium and other ions in relation to protein synthesis, cell proliferation and cancer.

This report concerns the possible regulatory roles of intracellular Mg, Na, K, Cl, H and Ca ions in protein synthesis, mitogenesis and oncogenesis. Our main approach was to measure the intracellular concentration of various ions in different mammalian tissue cell populations for correlation with the rate of protein synthesis, the rate of cell proliferation and the tumorigenic cell state. Mg concentration alone showed a significant positive correlation to protein synthetic rate, suggesting a key role for Mg in regulation of protein synthesis. All ions measured (Mg, Na, K, Cl) showed a significant positive correlation to the rate of cell proliferation in normal populations of tissue cells. Likewise rapidly dividing tumor cells showed markedly elevated concentrations of Na and Cl but not Mg and K. The tumor cells are therefore unique in terms of their ionic composition. The injection of tumorous mice with amiloride (a drug which blocks the passive influx of Na into cells and blocks the Na-H antiport process) lowered intracellular Na concentration without significantly changing the concentration of Mg or K in the rapidly dividing tumor cells. The cell proliferation rates of both normal and of tumor cell populations were decreased by this amiloride treatment. These data strongly suggest a regulatory role for Na and H concentration on the rate of cell proliferation in both normal and tumor cells. Recent reports have shown that a brief surge in free Ca occurs after mitogenic stimulation and at several other key points in the cell cycle. These findings suggest a signaling role for free Ca in cells. A model of the temporal sequence of ionic events in the cell cycle is presented. The report ends with a brief discussion of the role of ions in tumorigenic cell transformation.