Skip Navigation


Carcinogenesis Advance Access originally published online on June 3, 2004
Carcinogenesis 2004 25(10):2023-2032; doi:10.1093/carcin/bgh207
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
25/10/2023    most recent
bgh207v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (34)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Hsieh, Y.-H.
Right arrow Articles by Huang, W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hsieh, Y.-H.
Right arrow Articles by Huang, W.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Carcinogenesis vol.25 no.10 © Oxford University Press 2004; all rights reserved.

ARTICLE

Pre-S mutant surface antigens in chronic hepatitis B virus infection induce oxidative stress and DNA damage

Yi-Hsuan Hsieh1,4, Ih-Jen Su5, Hui-Ching Wang1, Wen-Wei Chang1,2, Huan-Yao Lei1,2, Ming-Derg Lai1,3, Wen-Tsan Chang1,3 and Wenya Huang1,4,6

1 Institute of Basic Medical Sciences, 2 Department of Microbiology and Immunology, 3 Department of Biochemistry, 4 Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng-Kung University, Tainan 70101, Taiwan and 5 Division of Clinical Research, National Health Research Institute, Taipei, Taiwan

6 To whom correspondence should be addressed Email: whuang{at}mail.ncku.edu.tw

Ground glass hepatocytes (GGHs) are the historic hallmarks for the hepatocytes in the late and non-replicative stages of hepatitis B virus (HBV) infection. We have identified type I and type II GGHs that contain two mutant types of large HBV surface antigens (HBsAg) with deletions over the pre-S1 and pre-S2 regions, respectively. These pre-S mutant HBVsAg accumulate in endoplasmic reticulum (ER), resulting in strong ER stress. Type II GGHs often appear in hepatic nodules in the late phases of HBV infection and proliferate in clusters, suggesting that these mutant pre-S1/S2 HBsAg may be involved in HBV-related hepatocarcinogenesis, associated with ER stress. In this study, we investigated the potential genomic instability imposed by pre-S mutant HBsAg. Based on the analysis of comet assays, we found that the pre-S1 and pre-S2 mutant HBsAg caused oxidative stress and DNA damage. The DNA repair gene ogg1 was greatly induced by over-expression of pre-S mutant HBsAg. Induction of the DNA repair gene ogg1 was also detected in the pre-S2 HBsAg transgenic mice, as well as the type II GGHs from patients with hepatocellular carcinoma, strongly suggesting that the pre-S mutant HBsAg contributes to the oxidative DNA damage to hepatocytes. In addition, the mutation rates in the X-linked hprt gene were enhanced in mouse hepatoma ML1-4a cells, which constitutively expressed the pre-S1/S2 HBsAg. These results indicate that pre-S1/S2 mutant HBsAg, which make up GGHs, induce oxidative DNA damage and mutations in hepatocytes in the late stages of HBV infection.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Virol.Home page
J. J. Y. Sung, S. K. W. Tsui, C.-H. Tse, E. Y. T. Ng, K.-S. Leung, K.-H. Lee, T. S. K. Mok, A. Bartholomeusz, T. C. C. Au, K. K. F. Tsoi, et al.
Genotype-Specific Genomic Markers Associated with Primary Hepatomas, Based on Complete Genomic Sequencing of Hepatitis B Virus
J. Virol., April 1, 2008; 82(7): 3604 - 3611.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
Y.-F. Wu, S.-L. Fu, C.-H. Kao, C.-W. Yang, C.-H. Lin, M.-T. Hsu, and T.-F. Tsai
Chemopreventive Effect of Silymarin on Liver Pathology in HBV X Protein Transgenic Mice
Cancer Res., March 15, 2008; 68(6): 2033 - 2042.
[Abstract] [Full Text] [PDF]

Home page
 Mol Cancer ResHome page
Y.-H. Hsieh, I.-J. Su, H.-C. Wang, J.-H. Tsai, Y.-J. Huang, W.-W. Chang, M.-D. Lai, H.-Y. Lei, and W. Huang
Hepatitis B Virus Pre-S2 Mutant Surface Antigen Induces Degradation of Cyclin-Dependent Kinase Inhibitor p27Kip1 through c-Jun Activation Domain-Binding Protein 1
Mol. Cancer Res., October 1, 2007; 5(10): 1063 - 1072.
[Abstract] [Full Text] [PDF]

Home page
 J. Gen. Virol.Home page
I-C. Huang, C.-Y. Chien, C.-R. Huang, and S. J. Lo
Induction of hepatitis D virus large antigen translocation to the cytoplasm by hepatitis B virus surface antigens correlates with endoplasmic reticulum stress and NF-{kappa}B activation
J. Gen. Virol., June 1, 2006; 87(6): 1715 - 1723.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
P. Meuleman, L. Libbrecht, S. Wieland, R. De Vos, N. Habib, A. Kramvis, T. Roskams, and G. Leroux-Roels
Immune Suppression Uncovers Endogenous Cytopathic Effects of the Hepatitis B Virus
J. Virol., March 15, 2006; 80(6): 2797 - 2807.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J.-H. Hung, I.-J. Su, H.-Y. Lei, H.-C. Wang, W.-C. Lin, W.-T. Chang, W. Huang, W.-C. Chang, Y.-S. Chang, C.-C. Chen, et al.
Endoplasmic Reticulum Stress Stimulates the Expression of Cyclooxygenase-2 through Activation of NF-{kappa}B and pp38 Mitogen-activated Protein Kinase
J. Biol. Chem., November 5, 2004; 279(45): 46384 - 46392.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.