title: Helicobacter pylori infection introduces DNA double-strand breaks in host cells.
abstract: Gastric cancer is an inflammation-related malignancy related to long-standing acute and chronic inflammation caused by infection with the human bacterial pathogen Helicobacter pylori. Inflammation can result in genomic instability. However, there are considerable data that H. pylori itself can also produce genomic instability both directly and through epigenetic pathways. Overall, the mechanisms of H. pylori-induced host genomic instabilities remain poorly understood. We used microarray screening of H. pylori-infected human gastric biopsy specimens to identify candidate genes involved in H. pylori-induced host genomic instabilities. We found upregulation of ATM expression in vivo in gastric mucosal cells infected with H. pylori. Using gastric cancer cell lines, we confirmed that the H. pylori-related activation of ATM was due to the accumulation of DNA double-strand breaks (DSBs). DSBs were observed following infection with both cag pathogenicity island (PAI)-positive and -negative strains, but the effect was more robust with cag PAI-positive strains. These results are consistent with the fact that infections with both cag PAI-positive and -negative strains are associated with gastric carcinogenesis, but the risk is higher in individuals infected with cag PAI-positive strains.
authors: Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Yufu City, Oita, Japan Department of Medicine-Gastroenterology, Baylor College of Medicine, and Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA.
authors: Katsuhiro
authors: K
authors: Hanada
authors: Department of Molecular Pathology, Faculty of Medicine, Oita University, Yufu City, Oita, Japan.
authors: Tomohisa
authors: T
authors: Uchida
authors: Department of Molecular Pathology, Faculty of Medicine, Oita University, Yufu City, Oita, Japan.
authors: Yoshiyuki
authors: Y
authors: Tsukamoto
authors: Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Yufu City, Oita, Japan Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu City, Oita, Japan.
authors: Masahide
authors: M
authors: Watada
authors: Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Yufu City, Oita, Japan.
authors: Nahomi
authors: N
authors: Yamaguchi
authors: Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Yufu City, Oita, Japan.
authors: Kaoru
authors: K
authors: Yamamoto
authors: Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Yufu City, Oita, Japan.
authors: Seiji
authors: S
authors: Shiota
authors: Department of Molecular Pathology, Faculty of Medicine, Oita University, Yufu City, Oita, Japan.
authors: Masatsugu
authors: M
authors: Moriyama
authors: Department of Medicine-Gastroenterology, Baylor College of Medicine, and Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA.
authors: David Y
authors: DY
authors: Graham
authors: Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Yufu City, Oita, Japan Department of Medicine-Gastroenterology, Baylor College of Medicine, and Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA yyamaoka@oita-u.ac.jp.
authors: Yoshio
authors: Y
authors: Yamaoka
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics; D053903:DNA Breaks, Double-Stranded; D004847:Epithelial Cells / Q000382:microbiology / Q000473:pathology; D005753:Gastric Mucosa / Q000382:microbiology / Q000473:pathology; D020869:Gene Expression Profiling; D042822:Genomic Instability; D016481:Helicobacter Infections / Q000473:pathology*; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D046228:Microarray Analysis; D015533:Transcriptional Activation
chemical_list: C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins