Effect of proapoptosis protein on hepatocarcinogenesis.
OBJECTIVE
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).


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Li
Bai
B
Department of Digestive Diseases, General Air Force Hospital, Beijing, China. bai_li@hotmail.com
Cao
Chuan-Ping
CP
Mao
Gao-Ping
GP
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051023:BH3 Interacting Domain Death Agonist Protein; D002352:Carrier Proteins / Q000502:physiology*; D049109:Cell Proliferation; D004052:Diethylnitrosamine / Q000009:adverse effects; D018450:Disease Progression; D022781:Hepatocytes / Q000502:physiology; D020287:In Situ Nick-End Labeling; D008113:Liver Neoplasms / Q000139:chemically induced / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout
D051023:BH3 Interacting Domain Death Agonist Protein; C494815:Bid protein, mouse; D002352:Carrier Proteins; D004052:Diethylnitrosamine