[Observation on experimental liver fibrosis and hepatic carcinogenesis of HBV gene knock-in transgenic mice induced by CCl4/ethanol].
OBJECTIVE
To study the effects of carbon tetrachloride (CCl4)/ethanol induction upon experimental liver fibrosis and hepatic carcinogenesis of HBV transgenic mice.


METHODS
The wild-type mice, p21-HBx transgenic mice with integration of p21 locus by HBx gene and p21-HBsAg transgenic mice with integration of p21 locus by HBsAg gene were induced separately by CCl4/ethanol twice weekly for 20 weeks. The investigators observed the development of liver fibrosis and hepatic carcinogenesis in three groups and detected the gene expressions of HBx and HBsAg by RT-PCR.


RESULTS
The expression of HBx or HBsAg mRNA existed in both control and induced transgenic mice, but in none of wild-type mice. Comparing with wild-type mice, p21 genes was not expressed in livers of transgenic mice. After induction by CCl4/ethanol, the fibrotic degrees of liver were not significantly different among wild-type mice, p21-HBx transgenic mice and p21-HBsAg transgenic mice, as well as between male and female mice. Reversely, the incidence rates of hepatic carcinogenesis of two HBV gene knock-in transgenic mouse lines (p21-HBx & p21-HBsAg) were higher than that of wild-type mice. And the incidence rate of hepatic carcinogenesis in males was also markedly higher than that in females. Induction by CCl4/ethanol markedly promoted and accelerated hepatic carcinogenesis in transgenic mice.


CONCLUSIONS
Integration of HBsAg and HBx genes into the murine p21 locus can significantly promote the progression of hepatic carcinogenesis, but failed to promote the progression of liver fibrosis. The male mouse is more likely to develop experimental hepatocellular carcinoma than the female mouse. Experimental hepatocellular carcinoma induced by CCl4/ethanol in p21-HBx and p21-HBsAg transgenic mice is a feasible animal model.
Xu
Xin-bao
XB
Department of Hepatobiliary Surgery, Air Force General Hospital of Chinese PLA, Beijing 100142, China. xu_xinbao@sohu.com
Leng
Xi-sheng
XS
He
Zhen-ping
ZP
Chen
Lei
L
Zhang
Hong-yi
HY
Zhang
Hong-yi
HY
Zhang
Hui
H
Xiao
Mei
M
Liu
Cheng-li
CL
Feng
Zhi-Qiang
ZQ
D000818:Animals; D002251:Carbon Tetrachloride / Q000009:adverse effects; D004195:Disease Models, Animal; D000431:Ethanol / Q000009:adverse effects; D005260:Female; D055879:Gene Knock-In Techniques; D006514:Hepatitis B Surface Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000821:virology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000821:virology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D015534:Trans-Activators / Q000235:genetics*; D054334:Viral Regulatory and Accessory Proteins
D006514:Hepatitis B Surface Antigens; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D000431:Ethanol; D002251:Carbon Tetrachloride