In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 66, No. 24 ( 2006-12-15), p. 11565-11570
Abstract:
Tumor necrosis factor-α (TNF-α) is an important inflammation cytokine without known direct effect on DNA. In this study, we found that TNF-α can cause DNA damages through reactive oxygen species. The mutagenic effect of TNF-α is comparable with that of ionizing radiation. TNF-α treatment in cultured cells resulted in increased gene mutations, gene amplification, micronuclei formation, and chromosomal instability. Antioxidants significantly reduced TNF-α–induced genetic damage. TNF-α also induced oxidative stress and nucleotide damages in mouse tissues in vivo. Moreover, TNF-α treatment alone led to increased malignant transformation of mouse embryo fibroblasts, which could be partially suppressed by antioxidants. As TNF-α 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-α promotes cancer development through induction of gene mutations, in addition to the previously reported mechanisms, in which nuclear factor-κB activation was implicated. (Cancer Res 2006; 66(24): 11565-70)
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/0008-5472.CAN-06-2540
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2006
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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