Method of provoke abnormal proliferation of hepatic cells by carbone tetrachloride and diethylnitrosamine

ABSTRACT

Two-stage carcinogenesis has been widely used as a method for evaluating precancerous lesion on animal experiments. Here we used diethylnitrosamine (DEN), a tumor trigger, and carbon tetrachloride (CCl4), a tumor promoter, to mimic the first two stages of hepatic carcinogenesis. Single intra-peritoneal injection of DEN 1% in combination with repeated intra-peritoneal injection of CCl4 4% for 16 weeks led to the formation of hyperplasia nodules on mouse livers. Microscopic examination also revealed dramatic changes in hepatocellular morphology and architecture increased cell density and proliferation, abnormalities in cell division and nucleus structure. These changes were not observed in animal treated with NaCI or DEN alone. Repeated injection of CCl4 alone led to alterations on microscopic pictures but did not cause hyperplasia nodules. Our results indicate that DEN in combination of CCl4 causes abnormal proliferation of hepatic cells and evokes hepatic hyperplasia