Article Text
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.
- 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