Increased sensitivity to the hepatocarcinogen diethylnitrosamine in transgenic mice carrying the hepatitis B virus X gene.
The role of the hepatitis B virus (HBV) X protein in liver tumorigenesis is unresolved. Transgenic mice harboring the X gene (nt 1376-1840 under the control of the human alpha-1-antitrypsin regulatory elements) (ATX mice) display only minor histopathologic alterations of the liver. To determine if ATX mice are more susceptible to the effects of hepatocarcinogens, 12- to 15-d-old male ATX and control littermate mice were injected with a single dose (2 microgram/g body weight) of diethylnitrosamine (DEN). The animals were killed 6-10 mo after exposure and were analyzed for histological changes in the liver. One hundred percent of the DEN-treated AXT mice developed abnormal liver lesions. Then their liver tissues were compared by stereological analysis with those of non-transgenic animals, the ATX mice had a relative twofold increase in the total number of focal lesion and a twofold increase in the incidence of hepatocellular carcinoma. Elevated levels of X protein and p53 protein were not detected in carcinogen-induced nodules or tumors. These results are consistent with a model in which the expression of the HBV X protein potentiates the induction of DEN-mediated liver disease.
Slagle
B L
BL
Division of Molecular Virology, Baylor College of Medicine, Houston, Texas 77030, USA.
Lee
T H
TH
Medina
D
D
Finegold
M J
MJ
Butel
J S
JS
D000367:Age Factors; D000477:Alkylating Agents / Q000008:administration & dosage*; D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage*; D004279:DNA, Viral; D004052:Diethylnitrosamine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral; D006515:Hepatitis B virus / Q000235:genetics; D008113:Liver Neoplasms / Q000139:chemically induced / Q000235:genetics*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D015534:Trans-Activators / Q000235:genetics*; D054334:Viral Regulatory and Accessory Proteins; D015678:Viral Structural Proteins / Q000235:genetics
D000477:Alkylating Agents; D002273:Carcinogens; D004279:DNA, Viral; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; D015678:Viral Structural Proteins; C057628:hepatitis B virus X protein; D004052:Diethylnitrosamine