Tumor necrosis factor-alpha is a potent endogenous mutagen that promotes cellular transformation.

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Yan, B; Wang, H; Rabbani, ZN; Zhao, Y; Li, W; Yuan, Y; Li, F; Dewhirst, MW; Li, C-Y

Published Date

  • December 15, 2006

Published In

Volume / Issue

  • 66 / 24

Start / End Page

  • 11565 - 11570

PubMed ID

  • 17178846

International Standard Serial Number (ISSN)

  • 0008-5472

Digital Object Identifier (DOI)

  • 10.1158/0008-5472.CAN-06-2540

Language

  • eng

Conference Location

  • United States