목적 : H. pylori (HP) 감염성 위염에서 HP는 DNA 손상복구기능에 장애를 유발하여 위 상피세포의 유전자에 발생하는 돌연변이를 축적시켜 위암의 발생 위험을 증가시킬 수 있다. 본 연구는 Mongolian gerbil (MG) animal model을 이용한 in vivo 실험에서 만성적인 HP감염이 위 점막의 MSI를 발생시키는 지 알아보고자 하였다.방법 : 7주된 수컷 MG에 HP CA20 균주를 감염시킨 후 일정한 시점마다 동물을 희생시켜 위를 절제하였다. 위염부위의 위 상피를 미세박리하여 DNA를 추출한 후 Fam이나 Hex로 표지시킨 다섯 가지 gerbil MSI marker를 이용하여 중합효소연쇄반응을 실시한 후 310 genetic analyzer를 이용하여 MSI 분석을 시행하였다. 결과 : MSI는 정상부위(식도)에서는 관찰되지 않았고, 위염이 없는 부위에 비해 위염부위에서 빈번히 관찰되었다(p<0.05). 위염부위 중 6예에서는 low level MSI를 1예에서는 high level MSI를 관찰하였다(p<0.05).

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.(Korean J Med 71:17-23, 2006)

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.(Korean J Med 71:17-23, 2006)

Microsatellite instability, Helicobacter pylori, Animal model