We have been systematically testing the idea that the intracellular concentration of sodium is higher in transformed cells than in their normal counterparts and the idea that the sodium concentration is also higher in rapidly dividing cell populations than in slowly dividing cell populations. Unfixed freeze-dried and uncoated tissue sections of 18 normal and 4 tumor cell populations were subjected to electron microprobing of the nucleus and the cytoplasm. Energy-dispersive X-ray microanalysis was done to determine concentration (mmol/kg dry weight) for sodium, magnesium, phosphorus, sulfur, chlorine, and potassium. The following list is a classification of the cell populations and their mean sodium concentration: tumorous cells (two hepatomas and two mammary adenocarcinomas), 451 ± 6 (S.E.); nontumorous counterpart cells (hepatocytes from two species and lactating mammary cells from two species), 138 ± 11; rapidly dividing cells (enterocytes from the crypts of the small and large intestines, neonatal cells, thymocytes), 196 ± 12; and slowly dividing cells (pancreatic acinar cells, smooth muscle, liver hepatocytes, etc.), 140 ± 8. Statistical analysis shows sodium concentration to be significantly higher in the tumorous cells than in any of the other cell populations. The rapidly dividing cells had significantly higher sodium concentration than did the slowly dividing cells but significantly less sodium than did the tumor cells. Chlorine showed the same significant concentration pattern as sodium. For both sodium and chlorine, the concentration was about the same in the nucleus and cytoplasm of each cell type studied. A number of significant and previously unreported correlations between the concentrations of various elements in the cytoplasm and the nucleus of the cells are revealed. Briefly, our data support the contentions that high intracellular sodium and chlorine concentrations are associated with mitogenesis and that even higher sodium and chlorine concentrations are associated with oncogenesis. Also, an elevated intracellular concentration of potassium and of magnesium is associated with the maintenance of a high rate of mitotic activity in the nontumorous cells but is not necessary for the maintenance of a high rate of mitotic activity in the tumor cells.

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