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Decreased Helicobacter pylori associated gastric carcinogenesis in mice lacking inducible nitric oxide synthase

 K T Nam  ;  S-Y Oh  ;  D-Y Kim  ;  K-B Hahm  ;  K-H Yang  ;  D D Jang  ;  Y B Kim  ;  B Ahn 
 GUT, Vol.53(9) : 1250-1255, 2004 
Journal Title
Issue Date
Adenocarcinoma/enzymology ; Adenocarcinoma/microbiology ; Adenocarcinoma/pathology ; Adenoma/enzymology ; Adenoma/microbiology ; Adenoma/pathology ; Animals ; Cell Transformation, Neoplastic/metabolism ; Cell Transformation, Neoplastic/pathology ; Gastric Mucosa/metabolism ; Gastritis/enzymology ; Gastritis/microbiology ; Gastritis/pathology ; Helicobacter Infections/complications* ; Helicobacter pylori*/growth & development ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Nitric Oxide Synthase/genetics ; Nitric Oxide Synthase/metabolism ; Nitric Oxide Synthase/physiology* ; Nitric Oxide Synthase Type II ; Stomach/microbiology ; Stomach Neoplasms/enzymology ; Stomach Neoplasms/microbiology* ; Stomach Neoplasms/pathology ; Tyrosine/analogs & derivatives* ; Tyrosine/metabolism
BACKGROUND AND AIMS: Overproduction of nitric oxide via inducible nitric oxide synthase (iNOS) is suggested to be a significant pathogenic factor in Helicobacter pylori induced gastritis. The purpose of this study was to examine the role of iNOS in H pylori associated gastric carcinogenesis. METHODS: Two types of mice were used in this study: iNOS deficient mice (iNOS-/-) and wild-type littermates. Gastric cancer was generated in mice using a combination treatment comprising N-methyl-N-nitrosourea administration and H pylori infection. Fifty weeks after treatment, tumours in gastric tissues from both types of mice were examined using histopathology, immunohistochemistry, and immunoblotting for iNOS and 3-nitrotyrosine. RESULTS: The overall incidence of gastric cancer at week 50 was significantly lower in iNOS-/- compared with iNOS wild-type mice (p<0.05). When analysed according to tumour pathology, the incidence of gastric adenocarcinoma was significantly lower in iNOS-/- compared with iNOS wild-type mice (p<0.05). Immunostaining for iNOS was clearly observed in adenocarcinoma cells of iNOS wild-type mice, and was characterised by a strong cytoplasmic expression pattern. 3-Nitrotyrosine was expressed mostly in the area of the lamina propria of gastritis and adenoma lesions in iNOS wild-type mice. Immunoblotting analyses showed that iNOS and 3-nitrotyrosine were also expressed in both adenoma and adenocarcinoma tissues from iNOS wild-type mice. iNOS and 3-nitrotyrosine expression was greater in tumour tissues than in non-tumour tissues. CONCLUSIONS: These findings suggest that iNOS contributes to H pylori associated gastric carcinogenesis in mice.
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Yonsei Authors
Nam, Ki Taek(남기택)
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