Tumor necrosis factor-alpha is a potent endogenous mutagen that promotes cellular transformation.
Cancer Res
; 66(24): 11565-70, 2006 Dec 15.
Article
em En
| MEDLINE
| ID: mdl-17178846
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.
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Bases de dados:
MEDLINE
Assunto principal:
Dano ao DNA
/
Transformação Celular Neoplásica
/
Fator de Necrose Tumoral alfa
/
Mutagênicos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Estados Unidos