Kinetics of DNA synthesis in feeding-dependent and independent hepatocyte populations of rats after partial hepatectomy.

Abstract

The effects of food consumption on the kinetics of hepatic DNA synthesis after partial hepatectomy (PH) have been studied in rats. Short-term (4-24 hr) fasting before or after PH resulted in depression and/or delay of DNA synthesis on days 1, 2 and 3 of regeneration. This depression was found in hepatocytes and, to a lesser extent, in littoral cells. Re-feeding resulted in an increase of DNA synthesis within 3-8 hr. The results suggest that two different hepatocyte subpopulations exist in regenerating rat liver: one which proceeds to DNA synthesis without apparent exogenous signals, and another one which needs, in addition to the specific mitogenic action of PH, food intake as a secondary permissive signal in order to initiate DNA synthesis. In the latter population food consumption appears to be required at two different stages: (1) in G0 or the early pre-replicative phase (PRP); (2) in the late PRP 3-8 hr before initiation of DNA synthesis. In the latter stage dietary protein is needed, but no so in the former. The dependence on feeding in the late PRP increases relatively with time after PH. No evidence was found to suggest a different distribution of the two cell populations throughout the liver acinus. The findings support the hypothesis that the known effects of the light-dark rhythm on the timing of DNA synthesis after PH are mediated by the natural feeding rhythm of rats fed ad libitum. In addition they offer a means for improving the synchrony of hepatocyte proliferation in regenerating rat liver.