hepatocyte proliferation in vitro Summary

Recently reports have indicated that both cimetidine and ranitidine delay cell proliferation in rats following 7W/c partial hepatectomy and result in an increased mortality following this procedure. The present study was de-signed to determine whether three Hz blocking agents (cimetidine, ranitidine, famotidine) and a new, powerful antisecretory drug (omeprazole) specifically influence hepatocyte proliferation in primary culture. Hepatocytes were isolated from livers of normal male rats by the standard collagenase perfusion technique. Hepatic DNA synthesis and percent of labelled nuclei were determined after 48 h incubation. Hepatocytes in culture were incu-bated with the Hz blocking agents and omeprazole or with different concentrations of serum obtained from sham-operated or 70 % hepatectomized rats treated or not with the same agents. Rats were injected intraperitoneally at 8:00 a.m. on two consecutive days. In hepatectomized rats, the first dose was injected at 1'\:00 a.m. immediately after surgery, the second, 24 h later. The serum of sham-operated or 70O/C hepatectomized rats that did not re-ceive drugs served as control. No changes in DNA synthesis, percentage of labelled nuclei and transaminase were detected when the agents were added to the hepatocytes in culture at concentrations within the effective pharmacological dosage and 30 times higher. Similarly, no changes in these parameters were obtained when dif-ferent concentrations of serum obtained from sham-operated rats treated with Hz blocking agents or omeprazole were added to the basal culture medium. However, a significant inhibition of DN A synthesis and of percentage o