Publications [#168941] of Mark W. Dewhirst

Papers Published

  1. 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)

    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.

    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*