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

K. T. Nam, S. Y. Oh, B. Ahn, Y. B. Kim, D. D. Jang, K. H. Yang, K. B. Hahm, D. Y. Kim

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Abstract

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.

Original languageEnglish
Pages (from-to)1250-1255
Number of pages6
JournalGut
Volume53
Issue number9
DOIs
Publication statusPublished - 2004 Sep

All Science Journal Classification (ASJC) codes

  • Gastroenterology

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    Nam, K. T., Oh, S. Y., Ahn, B., Kim, Y. B., Jang, D. D., Yang, K. H., Hahm, K. B., & Kim, D. Y. (2004). Decreased Helicobacter pylori associated gastric carcinogenesis in mice lacking inducible nitric oxide synthase. Gut, 53(9), 1250-1255. https://doi.org/10.1136/gut.2003.030684