The modulation of growth of normal rat liver epithelial cells in calcium-poor medium by epidermal growth factor, phenobarbital, phorbol ester, and retinoic acid.

The ability of a normal rat liver epithelial cell line with phenotypic characteristics of "oval" cells to grow in calcium-poor medium has been investigated. The growth of these cells could be arrested in medium containing 0.03 mM Ca2+, a concentration below which cell necrosis began to occur 24 h postexposure. With increasing calcium concentration, progressive cell proliferation was observed. Epithelial growth factor (EGF) (10 ng/ml) increased the survival and proliferation of cells in calcium-poor medium and the response was inversely correlated with the extracellular calcium concentration. In contrast, phenobarbital (0.2 to 2 mM), 12-O-tetradecanoylphorbol-13-acetate (0.01 to 1 microgram/ml), or retinoic acid (0.001 to 0.1 microgram/ml) depressed growth of cells in calcium-poor medium. The results confirm the ability of EGF to lower the calcium requirement for proliferation of normal cells, but such an effect does not seem to be a universal property of tumor promoters.