Hepatitis B virus promotes hepatocarcinogenesis in transgenic mice.
HBV is a major risk factor for hepatocellular carcinoma (HCC). However, whether HBV can directly cause HCC or only indirectly via the induction of chronic liver inflammation has been controversial. By using transgenic mice carrying the entire HBV genome as a model, we now demonstrate that HBV by itself is an inefficient carcinogen. However, it can efficiently promote hepatocarcinogenesis initiated by the carcinogen diethylnitrosamine (DEN). This effect of HBV does not involve chronic liver inflammation, is apparently due to enhanced hepatocellular apoptosis and compensatory regeneration following DEN treatment, and does not require the HBV X protein.


CONCLUSIONS
Our results demonstrate a direct role of HBV in a hepatocarcinogenesis pathway that involves the interaction between this virus and a dietary carcinogen.
Zheng
Yanyan
Y
Department of Molecular Microbiology and Immunology, University of Southern California, Los Angeles, CA 90033, USA.
Chen
Wen-ling
WL
Louie
Stan G
SG
Yen
T S Benedict
TS
Ou
Jing-hsiung James
JH
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002273:Carcinogens; D002471:Cell Transformation, Neoplastic; D004279:DNA, Viral / Q000235:genetics; D004052:Diethylnitrosamine; D005260:Female; D015967:Gene Expression Regulation, Viral; D006515:Hepatitis B virus / Q000235:genetics / Q000472:pathogenicity*; D008099:Liver / Q000473:pathology / Q000821:virology*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology / Q000821:virology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D012307:Risk Factors; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000378:metabolism
D002273:Carcinogens; D004279:DNA, Viral; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D004052:Diethylnitrosamine