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| Publications [#168941] of Mark W. Dewhirst
Papers Published
- B Yan, H Wang, ZN Rabbani, Y Zhao, W Li, Y Yuan, F Li, MW Dewhirst, CY Li, Tumor necrosis factor-alpha is a potent endogenous mutagen that promotes cellular transformation.,
Cancer research, United States, vol. 66 no. 24
(December, 2006),
pp. 11565-70, ISSN 0008-5472
(last updated on 2009/12/31)
Abstract:
Tumor necrosis factor-alpha (TNF-alpha) is an important inflammation cytokine without known direct effect on DNA. In this study, we found that TNF-alpha can cause DNA damages through reactive oxygen species. The mutagenic effect of TNF-alpha is comparable with that of ionizing radiation. TNF-alpha treatment in cultured cells resulted in increased gene mutations, gene amplification, micronuclei formation, and chromosomal instability. Antioxidants significantly reduced TNF-alpha-induced genetic damage. TNF-alpha also induced oxidative stress and nucleotide damages in mouse tissues in vivo. Moreover, TNF-alpha treatment alone led to increased malignant transformation of mouse embryo fibroblasts, which could be partially suppressed by antioxidants. As TNF-alpha is involved in chronic inflammatory diseases, such as chronic hepatitis, ulcerative colitis, and chronic skin ulcers, and these diseases predispose the patients to cancer development, our results suggest a novel pathway through which TNF-alpha promotes cancer development through induction of gene mutations, in addition to the previously reported mechanisms, in which nuclear factor-kappaB activation was implicated.
Keywords:
Animals • Cell Line, Tumor • Cell Transformation, Neoplastic* • Colonic Neoplasms • Cytochalasin B • DNA Damage* • Fluoresceins • Gene Amplification • Humans • Mice • Mutagens* • Mutation • Oxidative Stress • Plasmids • Reactive Oxygen Species • Tumor Necrosis Factor-alpha • drug effects • genetics • metabolism • pharmacology • pharmacology*
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