PMID- 17145855
OWN - NLM
STAT- MEDLINE
DCOM- 20070110
LR  - 20231213
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 66
IP  - 23
DP  - 2006 Dec 1
TI  - Tumor necrosis factor-alpha increases reactive oxygen species by inducing 
      spermine oxidase in human lung epithelial cells: a potential mechanism for 
      inflammation-induced carcinogenesis.
PG  - 11125-30
AB  - Inflammation has been implicated in the development of many human epithelial 
      cancers, including those of the stomach, lung, colon, and prostate. Tumor 
      necrosis factor-alpha (TNF-alpha) is a potent pleiotropic, proinflammatory 
      cytokine produced by many cells in response to injury and inflammation. Here, we 
      show that TNF-alpha exposure results in increased production of reactive oxygen 
      species (ROS), with a concomitant increase in the production of 
      8-oxo-deoxyguanosine, a marker for oxidative DNA damage, in human lung bronchial 
      epithelial cells. The source of the ROS in TNF-alpha-treated cells was determined 
      by both pharmacologic and small interfering RNA (siRNA) strategies to be spermine 
      oxidase (SMO/PAOh1). SMO/PAOh1 oxidizes spermine into spermidine, 
      3-aminopropanal, and H(2)O(2). Inhibition of TNF-alpha-induced SMO/PAOh1 activity 
      with MDL 72,527 or with a targeted siRNA prevented ROS production and oxidative 
      DNA damage. Further, similar induction in SMO/PAOh1 is observed with treatment of 
      another inflammatory cytokine, interleukin-6. The data are consistent with a 
      model that directly links inflammation and DNA damage through the production of 
      H(2)O(2) by SMO/PAOh1. Further, these results suggest a common mechanism by which 
      inflammation from multiple sources can lead to the mutagenic changes necessary 
      for the development and progression of epithelial cancers.
FAU - Babbar, Naveen
AU  - Babbar N
AD  - The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, 
      Maryland 21231, USA.
FAU - Casero, Robert A Jr
AU  - Casero RA Jr
LA  - eng
GR  - CA 51085/CA/NCI NIH HHS/United States
GR  - CA 98454/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 2FZ7Y3VOQX (Spermine)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 1.5.- (Oxidoreductases Acting on CH-NH Group Donors)
RN  - EC 2.3.1.- (Acetyltransferases)
RN  - EC 2.3.1.57 (diamine N-acetyltransferase)
SB  - IM
MH  - Acetyltransferases/genetics/metabolism
MH  - Aged
MH  - Amino Acid Sequence
MH  - Blotting, Western
MH  - Cell Line
MH  - Cell Line, Transformed
MH  - DNA Damage
MH  - Dose-Response Relationship, Drug
MH  - Epithelial Cells/cytology/*drug effects/metabolism
MH  - Female
MH  - Humans
MH  - Hydrogen Peroxide/metabolism
MH  - Inflammation/complications/genetics/metabolism
MH  - Lung/cytology
MH  - Molecular Sequence Data
MH  - Neoplasms/etiology/genetics/metabolism
MH  - Oxidation-Reduction/drug effects
MH  - Oxidoreductases Acting on CH-NH Group Donors/genetics/*metabolism
MH  - RNA, Small Interfering/genetics
MH  - Reactive Oxygen Species/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Spermine/metabolism
MH  - Transfection
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - Polyamine Oxidase
EDAT- 2006/12/06 09:00
MHDA- 2007/01/11 09:00
CRDT- 2006/12/06 09:00
PHST- 2006/12/06 09:00 [pubmed]
PHST- 2007/01/11 09:00 [medline]
PHST- 2006/12/06 09:00 [entrez]
AID - 66/23/11125 [pii]
AID - 10.1158/0008-5472.CAN-06-3174 [doi]
PST - ppublish
SO  - Cancer Res. 2006 Dec 1;66(23):11125-30. doi: 10.1158/0008-5472.CAN-06-3174.