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These studies reveal that a series of tumorigenic Chinese hamster embryo fibroblast (CHEF) cell lines maintain an internal pH (pHi) that is 0.12 +/- 0.04 pH unit above that of the nontumorigenic CHEF/18 parental line. This increase of pHi in the tumorigenic CHEF cells is not due to autocrine growth factor production or to the persistent activation of pathways previously shown to modulate Na+/H+-antiporter activity present in the CHEF/18 line. These findings suggest that the defect in pHi regulation in the tumorigenic CHEF/18 derivatives lies in the Na+/H+ antiporter itself. Further studies to determine the biological significance of an increased pHi show that the external pH (pHo)-dependence curve for initiation of DNA synthesis in the tumorigenic CHEF lines is shifted by approximately 0.2 pH unit toward acidic values relative to that of the nontumorigenic CHEF/18 parent. These data show a critical role for pHi in the regulation of DNA synthesis in Chinese hamster embryo fibroblasts and demonstrate that aberrations in pHi can contribute to the acquisition of altered growth properties.

Intracellular pH is increased after transformation of Chinese hamster embryo fibroblasts.