AbstractAdult rat hepatocytes were grown in serum‐free medium containing 0.05‐4 mM Ca+ +and 40 ng/ml EGF. After 48 hours of cultivation the mitotic index and the percentage of second division metaphases were determined. The results demonstrated a maximum proliferation response to EGF at a Ca+ +concentration of 0.4 mM. With lower and higher external Ca+ +concentrations the fraction of cells undergoing more than one cell division decreased. At lower Ca+ +concentrations this decrease appears to result from a reduced viability. In contrast, the low response to EGF at higher Ca+ +concentrations—especially in the physiological range—may reflect the influence of Ca+ +on the state of hepatocyte differen
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