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

Authors
Nam, KT; Oh, SY; Ahn, B; Kim, YB; Jang, DD; Yang, KH; Hahm, KB; Kim, DY
Citation
Gut, 53(9):1250-1255, 2004
Journal Title
Gut
ISSN
0017-57491468-3288
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.
MeSH terms
Adenocarcinoma/enzymology/microbiology/pathologyAdenoma/enzymology/microbiology/pathologyAnimalsCell Transformation, Neoplastic/metabolism/pathologyGastritis/enzymology/microbiology/pathologyHelicobacter Infections/*complications*Helicobacter pylori/growth & developmentMaleMiceMice, Inbred C57BLMice, KnockoutNitric Oxide Synthase/genetics/metabolism/*physiologyNitric Oxide Synthase Type IIStomach/metabolism/microbiologyStomach Neoplasms/enzymology/*microbiology/pathologyTyrosine/*analogs & derivatives/metabolism
DOI
10.1136/gut.2003.030684
PMID
15306579
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pathology
Journal Papers > School of Medicine / Graduate School of Medicine > Gastroenterology
AJOU Authors
김, 영배함, 기백
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