H Pylori
Copyright ©The Author(s) 2004. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 1, 2004; 10(15): 2232-2240
Published online Aug 1, 2004. doi: 10.3748/wjg.v10.i15.2232
Increased oxidative DNA damage, inducible nitric oxide synthase, nuclear factor κB expression and enhanced antiapoptosis-related proteins in Helicobacter pylori-infected non-cardiac gastric adenocarcinoma
Chi-Sen Chang, Wei-Na Chen, Hui-Hsuan Lin, Cheng-Chung Wu, Chau-Jong Wang
Chi-Sen Chang, Wei-Na Chen, Division of Gastroenterology, Chung Shan Medical University, Taichung, Taiwan, china
Chi-Sen Chang, Wei-Na Chen, Division of Gastroenterology, Taichung Veterans General Hospital, Taichung, Taiwan, china
Cheng-Chung Wu, Division of General Surgery, Taichung Veterans General Hospital, Taichung, Taiwan, china
Chi-Sen Chang, Wei-Na Chen, Hui-Hsuan Lin, Chau-Jong Wang, Institute of Biochemistry, Chung Shan Medical University, Taichung, Taiwan, china
Cheng-Chung Wu, National Young-Min Medical University, Taipei, Taiwan, china
Author contributions: All authors contributed equally to the work.
Correspondence to: Chau-Jong Wang, Institute of Biochemistry, College of Medicine, Chung Shan Medical University, No. 110, Sec. 1, Chien Kuo North Road, 402, Taichung, Taiwan, china. wcj@csmu.edu.tw
Telephone: +886-4-24730022 Fax: +886-4-23248167
Received: March 15, 2004
Revised: April 2, 2004
Accepted: April 9, 2004
Published online: August 1, 2004
Abstract

AIM: Several epidemiological studies have demonstrated a close association between Helicobacter pylori (H Pylori) infection and non-cardiac carcinoma of the stomach. H pylori infection induces active inflammation with neutrophilic infiltrations as well as production of oxygen free radicals that can cause DNA damage. The DNA damage induced by oxygen free radicals could have very harmful consequences, leading to gene modifications that are potentially mutagenic and/or carcinogenic. The aims of the present study were to assess the effect of H pylori infection on the expression of inducible nitric oxidative synthase (iNOS) and the production of 8 -hydroxy-deoxyguanosine (8-OHdG), a sensitive marker of oxidative DNA injury in human gastric mucosa with and without tumor lesions, and to assess the possible factors affecting cell death signaling due to oxidative DNA damage.

METHODS: In this study, 40 gastric carcinoma specimens and adjacent specimens were obtained from surgical resection. We determined the level of 8-OHdG formation by HPLC-ECD, and the expression of iNOS and mechanism of cell death signaling [including nuclear factor-κB(NFκB), MEKK-1, Caspase 3, B Cell lymphomal leukemia-2 (Bcl-2), inhibitor of apoptosis protein (IAP ) and myeloid cell leukemia-1 (Mcl-1)] by Western-blot assay.

RESULTS: The concentrations of 8-OHdG, iNOS, NFκB, Mcl-1 and IAP were significantly higher in cancer tissues than in adjacent non-cancer tissues. In addition, significantly higher concentrations of 8-OHdG, iNOS, NFκB, Mcl-1 and IAP were detected in patients infected with H pylori compared with patients who were not infected with H pylori. Furthermore, 8-OHdG, iNOS, NFκB, Mcl-1 and IAP concentrations were significantly higher in stage 3 and 4 patients than in stage 1 and 2 patients.

CONCLUSION: Chronic H pylori infection induces iNOS expression and subsequent DNA damage as well as enhances anti-apoptosis signal transduction. This sequence of events supports the hypothesis that oxygen-free radical-mediated damage due to H pylori plays a pivotal role in the development of gastric carcinoma in patients with chronic gastritis.

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