P21(WAF-1 CIP-1/SDI-1) IS EXPRESSED AT G1 PHASE IN PRIMARY CULTURE OFHEPATOCYTES FROM OLD RATS, PRESUMABLY PREVENTING THE CELLS FROM ENTERING THE S-PHASE OF THE CELL-CYCLE/

To elucidate whether p21(waf-1/cip-1/sdi-1) expression is associated w ith loss of growth potential of hepatocytes of old rats, we determined p21(waf-1/cip-1/sdi-1) expression of hepatocytes from old (30 months) rats during the cell cycle in primary culture. A high level of expres sion oi p21(waf-1/cip-1/sdi-1) was detected at the G1 phase in old-rat hepatocytes, but after the S phase in young-rat hepatocytes. Consiste ntly, the incidence of the cells positive for p21(waf-1/cip-1/sdi-1) i n nuclei before entering the S phase was significantly higher in old-r at hepatocytes than in young-rat hepatocytes. These results account fo r the loss of growth potential of old-rat hepatocytes in vitro and the marked retardation of regeneration of liver in old rats in vivo. (C) 1996 Academic Press, Inc.