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Decreased Helicobacter pylori associated gastric carcinogenesis in mice lacking inducible nitric oxide synthase
1Department of Veterinary Pathology, College of Veterinary Medicine, Seoul National University, San 56-1, Shillim-dong, Kwanak-gu, Seoul 151-742, Korea.
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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