INVOLVEMENT OF DNA POLYMERASE-BETA IN PROLIFERATION OF RAT-LIVER INDUCED BY LEAD NITRATE OR PARTIAL-HEPATECTOMY

We have studied the expression pattern of DNA polymerase-beta in two different models of in vivo cell proliferation. Both mRNA levels and enzyme activity of DNA polymerase-beta markedly increased before and/or during DNA synthesis in proliferating hepatocytes in mitogen-treated and partially hepatectomized rats. The time-courses of the expression of the gene coding for DNA polymerase-beta were significantly different in the two cell systems. A 5-fold increase in DNA polymerase-beta mRNA was observed 8 h after lead nitrate administration, i.e. well before the onset of DNA synthesis. In the regenerative liver cells a 3-fold increase in the amount of mRNA was observed 24-48 h after partial hepatectomy, the event being coincident with extensive DNA synthesis. In both systems, the increase of mRNA levels was always paralleled by an increase in enzyme activity, suggesting that DNA polymerase-beta activity may be regulated at a pre-translational level.