The calcium-dependent stimulation of the proliferation of neonatal rat hepatocytes by imidazole and indomethacin.

Low concentrations (e.g. 10(-12) and 10(-11) mol/l) of imidazole and indomethacin strongly stimulated DNA synthesis and mitosis of hepatocytes in 4-day-old primary cultures of neonatal rat liver. These agents seem to have acted by inducing quiescent hepatocytes to begin cycling rather than by affecting already cycling cells, because they did not shorten the total cell cycle time. Neither compound stimulated DNA synthesis by hepatocytes cultured in low (0.010 mol/l) calcium medium. Nevertheless, hepatocytes in calcium-deficient medium must have been mitogenically activated by these compounds and, hence, been able to reach a late stage of prereplicative development because they did initiate DNA synthesis very soon after the addition of calcium.