Expression of hepatitis C virus core protein impairs DNA repair in human hepatoma cells

Several studies have documented the important association between hepatitis C virus (HCV) infection and hepatocellular carcinoma. The mechanisms involved are still unknown and could involve viral proteins. We investigated the effect of HCV-core protein on DNA repair after UV-induced DNA damage. Ther...

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Bibliographic Details
Published in:Cancer letters 2004-06, Vol.209 (2), p.197-205
Main Authors: van Pelt, Jos F, Severi, Tamara, Crabbé, Tina, Eetveldt, Annemie Van, Verslype, Chris, Roskams, Tania, Fevery, Johan
Format: Article
Language:English
Subjects:
Apoptosis
Cancer
Carcinoma, Hepatocellular - genetics
Carcinoma, Hepatocellular - metabolism
Carcinoma, Hepatocellular - pathology
Cell cycle
Cell Division - drug effects
Cell growth
Cloning
Deoxyribonucleic acid
DNA
DNA Damage - radiation effects
DNA Repair
DNA, Neoplasm - genetics
Gene Expression
Gene Expression Regulation, Neoplastic - physiology
Hepatitis
Hepatitis C Antigens - genetics
Hepatitis C Antigens - metabolism
Hepatitis C virus
Hepatocellular carcinoma
Humans
Liver
Liver Neoplasms - genetics
Liver Neoplasms - metabolism
Liver Neoplasms - pathology
Protein expression
Proteins
Studies
Telomerase
Telomerase - metabolism
Transfection
Tumor Cells, Cultured
Tumour
Viral Core Proteins - genetics
Viral Core Proteins - metabolism
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Summary:Several studies have documented the important association between hepatitis C virus (HCV) infection and hepatocellular carcinoma. The mechanisms involved are still unknown and could involve viral proteins. We investigated the effect of HCV-core protein on DNA repair after UV-induced DNA damage. Therefore, we developed and characterized stably transfected HepG2 cell lines that express HCV-core protein as demonstrated by immunohistochemistry. These cells were significantly less capable to repair the DNA damage than control cells. This suppression of DNA repair by HCV-core protein renders the cells more sensitive to acquire mutations that in combination with enhanced in vivo cell turnover in the infected liver might increase the likelihood of malignant transformation of HCV-infected cells by other viral factors or upon exposure to environmental factors (food, drugs, smoking, alcohol, etc.). Interestingly, expression of the full-length HCV core did increase the cell doubling time in one of the cell lines we had developed that could not be attributed to an increase in apoptosis or change in telomerase activity in these cells.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2003.11.035