PMID- 17178846
OWN - NLM
STAT- MEDLINE
DCOM- 20070125
LR  - 20220225
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 66
IP  - 24
DP  - 2006 Dec 15
TI  - Tumor necrosis factor-alpha is a potent endogenous mutagen that promotes cellular 
      transformation.
PG  - 11565-70
AB  - 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.
FAU - Yan, Bin
AU  - Yan B
AD  - Department of Radiation Oncology, Duke University Medical Center, Durham, North 
      Carolina, USA.
FAU - Wang, Huili
AU  - Wang H
FAU - Rabbani, Zahid N
AU  - Rabbani ZN
FAU - Zhao, Yulin
AU  - Zhao Y
FAU - Li, Wenrong
AU  - Li W
FAU - Yuan, Yuqing
AU  - Yuan Y
FAU - Li, Fang
AU  - Li F
FAU - Dewhirst, Mark W
AU  - Dewhirst MW
FAU - Li, Chuan-Yuan
AU  - Li CY
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Fluoresceins)
RN  - 0 (Mutagens)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 2044-85-1 (diacetyldichlorofluorescein)
RN  - 3CHI920QS7 (Cytochalasin B)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - *Cell Transformation, Neoplastic
MH  - Colonic Neoplasms
MH  - Cytochalasin B/pharmacology
MH  - *DNA Damage
MH  - Fluoresceins
MH  - Gene Amplification
MH  - Humans
MH  - Mice
MH  - *Mutagens
MH  - Mutation
MH  - Oxidative Stress/drug effects
MH  - Plasmids
MH  - Reactive Oxygen Species/metabolism
MH  - Tumor Necrosis Factor-alpha/genetics/*pharmacology
EDAT- 2006/12/21 09:00
MHDA- 2007/01/26 09:00
CRDT- 2006/12/21 09:00
PHST- 2006/12/21 09:00 [pubmed]
PHST- 2007/01/26 09:00 [medline]
PHST- 2006/12/21 09:00 [entrez]
AID - 66/24/11565 [pii]
AID - 10.1158/0008-5472.CAN-06-2540 [doi]
PST - ppublish
SO  - Cancer Res. 2006 Dec 15;66(24):11565-70. doi: 10.1158/0008-5472.CAN-06-2540.