Microsatellite instability in mongolian gerbils induced by Helicobacter pylori / 대한내과학회지

ABSTRACT

BACKGROUND: During Helicobacter pylori (HP) gastritis, the organisms cause an impairment of DNA repair that results in accumulation of mutations in the genome of epithelial cells and an increased risk of gastric carcinoma. The aim of this study was to determine whether microsatellite instability (MSI) could be induced by chronic HP infection in the Mongolian gerbil model. METHODS: Seven-weeks old, specific pathogen-free male Mongolian gerbils were infected with the HP strain CA20. They were sacrificed at the each time points (1, 2, 3, 6, 9, 12 months). Areas of gastritis were carefully microdissected. DNA from tissues was analyzed for the presence of MSI by genomic DNA amplification with five gerbil microsatellite markers per sample. Gerbil markers labelled with Fam or Hex were obtained to perform MSI analysis using the 310 Genetic Analyzer. RESULTS: MSI was more frequent in the area of gastritis than in that of normal (p<0.05). Six showed MSI-low and one showed MSI-high within the area of gastritis (p<0.05). CONCLUSIONS: This study shows that chronic HP infection in the Mongolian gerbil induces MSI. This finding indicates that HP infection causes a decrease in DNA MMR proteins in epithelial cells of the stomach that may reach critically low levels, allowing for the accumulation of mutations such as those seen in microsatellite regions.