Studies on hepatocyte apoptosis, proliferation and oncogene c-fos expression in carbon tetrachloride-induced cirrhotic rat liver.

To investigate the significance of hepatocyte apoptosis, proliferation and oncogene c-fos expression in carbon tetrachloride (CCl4)-induced cirrhotic rat liver. Rat cirrhosis was induced by subcutaneous injection of 50% (v:v 1:1) CCl4. Hepatocyte apoptosis, proliferation and oncogene c-fos expression were examined with TUNEL, PCNA and c-fos immunohistochemical methods in control group and treatment group 72 h, 5, 7, 11 and 15 weeks after CCl4 induction. Hepatocyte apoptosis was rarely seen in control rat liver. The hepatocyte apoptosis was obviously increased 72 h after treatment. Fifteen weeks after treatment, the apoptosis was still more obvious in treatment group than that in controls. PCNA was constantly expressed in CCl4 group, with highest level at middle phase. C-fos was positive 7 and 11 weeks after CCl4 treatment. The results suggest that: 1) apoptosis is involved in rat liver damage at the early phase in CCl4-induced injury, and the process can alleviate nodule reconstruction or eradicate potentially mutational hepatocytes at the later phase; 2) hepatocytes constantly proliferate in CCl4-induced rat liver cirrhosis, especially at the middle phase; 3) c-fos might modulate hepatocyte proliferation in CCl4-induced rat liver cirrhosis.