Carcinogenesis, Vol. 20, No. 3, 479-483,
March 1999
© 1999 Oxford University Press
Downregulation of DNA excision repair by the hepatitis B virus-x protein occurs in p53-proficient and p53-deficient cells
Lady Davis Institute of the Sir Mortimer B.Davis Jewish General Hospital, Departments of Medicine and Oncology and the McGill Centre for Translational Research in Cancer, McGill University, 3755 Chemin de la Cote-Ste-Catherine, Montreal H3T 1E2, Canada,
1 Department of Virology, Royal Postgraduate Medical School, London W12 0NN, UK and
2 School of Hygiene and Public Health, Johns Hopkins Universiy, Baltimore, MD 21205, USA
Synergism between exposure to chemical carcinogens and infection with the hepatitis B virus (HBV) has been implicated in the high incidence of hepatocellular carcinoma. In this study we report that the HBV protein HBx, inhibits cellular DNA repair capacity in a p53-independent manner. Two alternative assays were used: the host cell reactivation assay, which measures the cell's capacity to repair DNA damage in a reporter plasmid, and unscheduled DNA synthesis, which measures the overall DNA repair capacity in damaged cells. Two p53-proficient cell lines, the hepatocellular carcinoma cell line HepG2 and liver epithelial cell line CCL13, were co-transfected with the pCMV–HBx reporter plasmid and the pCMV–CAT plasmid damaged with UVC radiation. Compared with cells transfected with control plasmid, the presence of HBx resulted in ~50% inhibition of the cell's capacity to reactivate CAT activity of UVC-damaged plasmid, and ~25% inhibition of unscheduled DNA synthesis in cells treated with either aflatoxin B1 epoxide or UVC radiation. Using the p53-deficient cell line Saos-2, we demonstrated that expression of HBx also resulted in diminished overall cellular DNA repair of damage induced by both aflatoxin B1 epoxide and UVC radiation, using both the host cell reactivation and unscheduled DNA synthesis assays. In summary, this study provides evidence for p53-independent regulation of DNA repair by HBx.
Abbreviations: CAT, chloramphenicol acetyl transferase; CMV, cytomegalovirus; HBV, hepatitis B virus; HBx, hepatitis B virus-x protein; HCC, hepatocellular carcinoma; HCR, host cell reactivation; NER, nucleotide excision repair; UDS, unscheduled DNA synthesis.
3 To whom correspondence should be addressed Email: mdaj{at}musica.mcgill.ca
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