• Na+:H+ antiport;
  • pH regulation;
  • cell proliferation;
  • neoplastic transformation


Mutants unable to regulate intracellular pH through the Na+:H+ antiport system were found to evolve tumors less frequently than wild-type CCL39 hamster lung fibroblasts, after transplantation in athymic nude mice. When rare tumors arose, they comprised cells which were transformed in vitro, but which upon retransplantation grew at a lower rate than tumor cells originating from CCL39 cells. Both parental and mutant cells became transformed after transfection of the activated Harvey ras oncogene, but transfectants derived from the mutants had a weaker tumorigenic potential. These results suggest that transformed characteristics can be acquired independently from the Na+:H+ antiporter. However, the presence of this system provides a selective growth advantage when cells are confronted with natural environments, as it occurs during the expansion of tumors in a host.