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Journal of Virology, June 2000, p. 5266-5272, Vol. 74, No. 11
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Expression of Hepatitis B Virus X Protein Does Not Alter the Accumulation of Spontaneous Mutations in Transgenic Mice

Charles R. Madden,1 Milton J. Finegold,2 and Betty L. Slagle1,*

Department of Molecular Virology and Microbiology,1 and Department of Pathology,2 Baylor College of Medicine, Houston, Texas 77030

Received 14 December 1999/Accepted 10 March 2000

Chronic infection with hepatitis B virus (HBV) is one of the major etiological factors in the development of human hepatocellular carcinoma. Transgenic mice that express the HBV X protein (HBx) have previously been shown to be more sensitive to the effects of hepatocarcinogens, although the mechanism for this cofactor role remains unknown. The ability of HBx to inhibit DNA repair in transiently transfected cell lines suggests one possible pathway. In the present study, primary hepatocytes isolated from transgenic mice that possess the HBV X gene under the control of the human alpha -1-antitrypsin regulatory region (ATX mice) were found to be deficient in their ability to conduct unscheduled DNA synthesis in response to UV-induced DNA damage. In order to measure the impact of HBx expression on DNA repair in vivo, double-transgenic mice that express HBx and possess a bacteriophage lambda transgene were sacrificed at 30, 90, and 240 days of age. Mutation frequency was determined for high-molecular-weight liver DNA of ATX and control mice by functional analysis of the lambda transgene. Expression of HBx did not significantly increase the accumulation of spontaneous mutations. These results are consistent with previous studies of HBx transgenic mice in which no effect of HBx on liver histology was apparent. This new animal model provides a powerful system in which to investigate the in vivo cooperation between HBx expression and environmental carcinogens.

* Corresponding author. Mailing address: Department of Molecular Virology and Microbiology, Mailstop BCM-385, One Baylor Plaza, Baylor College of Medicine, Houston, TX 77030-3411. Phone: (713) 798-3006. Fax: (713) 798-5075. E-mail: bslagle{at}bcm.tmc.edu.

Journal of Virology, June 2000, p. 5266-5272, Vol. 74, No. 11
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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