Effect of intracellular pH and two growth factors, epidermal growth factor and human hepatocyte growth factor, on DNA synthesis in non-regenerating and regenerating hepatocytes and hepatoma cells.

I examined the effects of intracellular pH (pHi) and the growth factors, epidermal growth factor (EGF) and human hepatocyte growth factor (HGF), on DNA synthesis in non-regenerating hepatocytes, regenerating hepatocytes and hepatoma cells. Non-regenerating and regenerating hepatocytes were isolated from the livers of intact adult rat and of the adult rat 24 hours after 70% hepatectomy, respectively. Hep G2 cells, a human hepatoma cell line, was employed as hepatoma cells. Regenerating hepatocytes and Hep G2 cells, but not non-regenerating hepatocytes displayed increased DNA synthesis with increasing pHi in the absence of EGF and HGF. However, non-regenerating hepatocytes displayed little increase, regenerating hepatocytes displayed substantial increase in DNA synthesis with increasing pHi in the presence of EGF or HGF. In contrast, Hep G2 cells displayed decreased DNA synthesis in the presence of HGF but not EGF. These findings indicate that pHi influences the fashion of proliferation in hepatocytes and cancer cells. EGF and HGF stimulate DNA synthesis in hepatocyte and inhibit that in cancer cell, suggesting that increasing pHi and administration of these growth factors may be one of the effective treatment for hepatoma.