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