Effect of proapoptosis protein on hepatocarcinogenesis

The goal of the present study was to determine how proapoptosis proteins regulate the progression of liver proliferative foci and tumorigenesis initiated by a chemical carcinogen, diethylnitrosamine (DEN).

Bid-deficient mice (15-day-old) were injected with 15 microg/g of DEN, then killed at 3 and 10 days, and 4 and 8 months after injection for analysis of hepatocellular proliferation, apoptosis and tumorigenesis.

The rate of apoptosis in the hepatocytes of the wild-type mice was significantly higher than in the Bid-deficient mice at 10 days after DEN exposure (P < 0.0001); the results of BrdU labeling agreed with the measurement of apoptosis in these animals, showing an obvious increase in the wild-type mice compared with the Bid-deficient mice (P < 0.0001). Four months after DEN exposure, the number and size of lesion foci or nodules in the wild-type mice were both greater than in the Bid-deficient mice (P < 0.05 and P < 0.001, respectively), but there was no significant difference between the two groups of mice at 8 months.

These results suggest that a lack of apoptosis in liver tissue in the early stage after DEN exposure decreased some of the tumorigenesis potential of DEN.