Helicobacter pylori Infection Introduces DNA Double-Strand Breaks in Host Cells

Abstract

ABSTRACTGastric cancer is an inflammation-related malignancy related to long-standing acute and chronic inflammation caused by infection with the human bacterial pathogenHelicobacter pylori. Inflammation can result in genomic instability. However, there are considerable data thatH. pyloriitself can also produce genomic instability both directly and through epigenetic pathways. Overall, the mechanisms ofH. pylori-induced host genomic instabilities remain poorly understood. We used microarray screening ofH. pylori-infected human gastric biopsy specimens to identify candidate genes involved inH. pylori-induced host genomic instabilities. We found upregulation ofATMexpressionin vivoin gastric mucosal cells infected withH. pylori. Using gastric cancer cell lines, we confirmed that theH. pylori-related activation of ATM was due to the accumulation of DNA double-strand breaks (DSBs). DSBs were observed following infection with bothcagpathogenicity island (PAI)-positive and -negative strains, but the effect was more robust withcagPAI-positive strains. These results are consistent with the fact that infections with bothcagPAI-positive and -negative strains are associated with gastric carcinogenesis, but the risk is higher in individuals infected withcagPAI-positive strains.