TNF-α induced DNA damage in primary murine hepatocytes

  • Authors:
    • Nicholas M. Wheelhouse
    • Yuen-Sum Chan
    • Sheona E. Gillies
    • Helen Caldwell
    • James A. Ross
    • David J. Harrison
    • Sandrine Prost
  • View Affiliations

  • Published online on: December 1, 2003     https://doi.org/10.3892/ijmm.12.6.889
  • Pages: 889-894
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Abstract

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, usually arising from a background of chronic inflammatory disease. Tumor necrosis factor α (TNF-α) is a pro-inflammatory cytokine produced in response to tissue injury, endotoxin exposure or infection and TNF-α signalling in hepatocytes is associated with an increase in oxidative stress. DNA is vulnerable to reactive oxygen species (ROS)-induced damage, which is highly mutagenic. Cells respond to DNA damage through the stabilisation of the tumor suppressor p53, which maintains genomic fidelity through induction of a cell cycle arrest in order to allow repair or elimination of the damaged cell through apoptosis. This study was carried out to determine if TNF-α caused oxidative DNA damage in primary cultures of murine hepatocytes and whether any damage would result in the induction of the tumor suppressor p53 and cell-cycle arrest. Using a modified Comet assay, to measure DNA damage we have demonstrated that TNF-α causes the formation of 8-oxo-deoxyguanosine (8-oxodG), an established marker of oxidative DNA damage, and a lesion associated with chronic hepatitis in human livers. In addition, the increase in DNA damage did not result in p53 stabilisation and TNF-α caused an increase in cell-cycle progression. We believe that this study indicates a possible putative role for TNF-α in the early stages of malignant transformation of hepatocytes.

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December 2003
Volume 12 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Wheelhouse NM, Chan Y, Gillies SE, Caldwell H, Ross JA, Harrison DJ and Prost S: TNF-α induced DNA damage in primary murine hepatocytes. Int J Mol Med 12: 889-894, 2003
APA
Wheelhouse, N.M., Chan, Y., Gillies, S.E., Caldwell, H., Ross, J.A., Harrison, D.J., & Prost, S. (2003). TNF-α induced DNA damage in primary murine hepatocytes. International Journal of Molecular Medicine, 12, 889-894. https://doi.org/10.3892/ijmm.12.6.889
MLA
Wheelhouse, N. M., Chan, Y., Gillies, S. E., Caldwell, H., Ross, J. A., Harrison, D. J., Prost, S."TNF-α induced DNA damage in primary murine hepatocytes". International Journal of Molecular Medicine 12.6 (2003): 889-894.
Chicago
Wheelhouse, N. M., Chan, Y., Gillies, S. E., Caldwell, H., Ross, J. A., Harrison, D. J., Prost, S."TNF-α induced DNA damage in primary murine hepatocytes". International Journal of Molecular Medicine 12, no. 6 (2003): 889-894. https://doi.org/10.3892/ijmm.12.6.889