Effect of aging on proliferative activity of normal and carcinogen-altered hepatocytes in rat liver after a two-thirds partial hepatectomy.

Proliferative activity of normal and carcinogen-altered hepatocytic populations was investigated in Wistar rats of various ages ranging from 5 to 109 weeks old before and after a two-thirds hepatectomy. gamma-Glutamyltranspeptidase (GGT)-positive hepatocytic foci were induced by administration of a single dose of diethylnitrosamine. The incidence of nuclear labeling with [3H]thymidine was examined using simultaneous GGT histochemistry and radioautography. The [3H]thymidine index of hepatocytes in the GGT-positive foci was not greater than that of normal hepatocytes in both young and old non-hepatectomized rats. GGT-positive hepatocytes responded by proliferating after a two-thirds hepatectomy in all age groups. Although the response of normal hepatocytes to the growth stimulus markedly decreased in old rats, GGT-positive hepatocytic populations retained relatively high responses to the growth stimulus. These observations indicate that in old rats carcinogen-altered hepatocytes have a greater growth advantage than normal hepatocytes to exogenous and endogenous proliferative stimuli.