First Author | Nam KT | Year | 2004 |
Journal | Gut | Volume | 53 |
Issue | 9 | Pages | 1250-5 |
PubMed ID | 15306579 | Mgi Jnum | J:92904 |
Mgi Id | MGI:3054712 | Doi | 10.1136/gut.2003.030684 |
Citation | Nam KT, et al. (2004) Decreased Helicobacter pylori associated gastric carcinogenesis in mice lacking inducible nitric oxide synthase. Gut 53(9):1250-5 |
abstractText | 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. |