H. pylori infection on base excision repair and mismatch repair (MMR) was analyzed by reverse transcription-PCR,Western blot, and activity assays. In mice, MMR expression was analyzed by reverse transcription-PCR and the CA repeat instabilities were examined by Mutation Detection Enhancement gel lectrophoresis.Mutation spectra in AGS cells and chronic gastritis tissuewere
determined by PCR, single-stranded conformation polymorphism, and sequencing. H. pylori vacA and cagA genotyping was determined by multiplex PCR and reverse hybridization.
Results: Following H. pylori infection, the activity and expression of base excision repair and MMR are down-regulated both in vitro and in vivo. Moreover, H. pylori induces genomic instability in nuclear CA repeats in mice and in mtDNA of AGS cells and chronic gastritis tissue, and this effect inmtDNAis associated with bacterial virulence.
Conclusions: Our results suggest that H. pylori impairs central DNA repair mechanisms, inducing a transientmutator phenotype, rendering gastric epithelial cells vulnerable to the accumulation of genetic instability and thus contributing to gastric carcinogenesis in infected individuals.