Decreased Helicobacter pylori associated gastric carcinogenesis in mice lacking inducible nitric oxide synthase. Issue 9 (11th August 2004)

• Record Type: Journal Article
• Authors: Nam, K T; Oh, S-Y; Ahn, B; Kim, Y B; Jang, D D; Yang, K-H; Hahm, K-B; Kim, D-Y
• Is Part Of: Gut. Volume 53:Issue 9(2004)
• Page Start: 1250
• Page End: 1255
• Publication Date: 2004-08-11
• Subjects: NO, nitric oxide -- NOS, NO synthase -- iNOS, inducible NOS -- eNOS, endothelial NOS -- nNOS, neuronal NOS -- MNU, N-methyl-N-nitrosourea -- ROS, reactive oxygen species -- CFU, colony forming unit -- AG, aminoguanidine; Helicobacter pylori -- inducible nitric oxide synthase -- gastric cancer -- knockout mouse -- carcinogenesis; Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gut.2003.030684
• Languages: English
• ISSNs: 0017-5749

Abstract

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.