Transgenic mice expressing hepatitis B virus X protein are more susceptible to carcinogen induced hepatocarcinogenesis

被引:39
作者
Zhu, HZ [1 ]
Wang, Y
Chen, JQ
Cheng, GX
Xue, JL
机构
[1] Fudan Univ, Sch Life Sci, Inst Genet, State Key Lab Genet Engn, Shanghai 200433, Peoples R China
[2] Shanghai Transgen Res Ctr, Shanghai 201203, Peoples R China
关键词
hepatitis B virus; HBV X protein; transgenic; C57BL/6; mice; hepatic tumors; immunohistochemical staining; diethylnitrosamine;
D O I
10.1016/j.yexmp.2003.09.001
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
The hepatitis B virus X (HBx) protein is thought to be implicated in the development of human hepatocellular carcinoma (HCC), but its exact function remains controversial. To investigate whether the expression of the HBx gene alone can induce HCC on an inbred C5713L/6 strain that displays a lower spontaneous rate of liver cancer, and to determine if HBx transgenic mice are more susceptible to the effects of hepatocarcinogens, C57-TgN (HBx) X transgenic mice were bred with normal C5713L/6 mice strain. The F1 mice (about 50% HBx positive and 50% HBx negative) were treated with a single dose of diethylnitrosamme (DEN) at 7 days of age, or were untreated. Mice were killed at appropriate time points and were analyzed for histological change in the liver. The expression of HBx protein were examined by using immunohistochemical staining. Glycogen storage foci were examined by using periodic acid-Schiff (PAS) staining. In HBx transgenic mice untreated with DEN, HBx expression and glycogen storage foci were always observed in the liver after 8 weeks, but not obvious histological pathologic changes. Histological examination of liver tissue confirmed that DEN-treated HBx mice developed approximately twice as many focal lesions of basophilic hepatocytes as treated wild-type littermates. Hepatocellular adenomas and carcinomas were also more frequent in DEN-treated HBx-positive than HBx-negative mice. Taken together, our results suggest that HBx gene expression alone is not sufficient for carcinogenesis, but may act as a promoter for malignant transformation. (C) 2003 Elsevier Inc. All rights reserved.
引用
收藏
页码:44 / 50
页数:7
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