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Increased sensitivity to the hepatocarcinogen diethylnitrosamine in transgenic mice carrying the hepatitis B virus X gene

✍ Scribed by Betty L. Slagle; Teh-Hsiu Lee; Daniel Medina; Milton J. Finegold; Janet S. Butel

Book ID: 102656963
Publisher: John Wiley and Sons
Year: 1996
Tongue: English
Weight: 927 KB
Volume: 15
Category: Article
ISSN: 0899-1987
DOI: 10.1002/(sici)1098-2744(199604)15:4<261::aid-mc3>3.0.co;2-j

No coin nor oath required. For personal study only.

✦ Synopsis

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 t h e human a-I-antitrypsin regulatory elements) (ATX mice) display only minor histopathologic alterations of the liver. To determine if ATX mice are more susceptible to the effect!; of hepatocarcinogens, 12-to 15-d-old male ATX and control littermate mice were injected with a single dose (2 pg/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 ATX mice developed abnormal liver lesions. When 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 lesions 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. o 1996 Wiley-Liss, Inc.

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