title: Helicobacter pylori infection generates genetic instability in gastric cells.
abstract: The discovery that Helicobacter pylori is associated with gastric cancer has led to numerous studies that investigate the mechanisms by which H. pylori induces carcinogenesis. Gastric cancer shows genetic instability both in nuclear and mitochondrial DNA, besides impairment of important DNA repair pathways. As such, this review highlights the consequences of H. pylori infection on the integrity of DNA in the host cells. By down-regulating major DNA repair pathways, H. pylori infection has the potential to generate mutations. In addition, H. pylori infection can induce direct changes on the DNA of the host, such as oxidative damage, methylation, chromosomal instability, microsatellite instability, and mutations. Interestingly, H. pylori infection generates genetic instability in nuclear and mitochondrial DNA. Based on the reviewed literature we conclude that H. pylori infection promotes gastric carcinogenesis by at least three different mechanisms: (1) a combination of increased endogenous DNA damage and decreased repair activities, (2) induction of mutations in the mitochondrial DNA, and (3) generation of a transient mutator phenotype that induces mutations in the nuclear genome.
authors.affiliation: Department of Science, Systems and Models, University of Roskilde, Denmark.
authors.forename: Ana Manuel Dantas
authors.initials: AM
authors.lastname: Machado
authors.forename: Céu
authors.initials: C
authors.lastname: Figueiredo
authors.forename: Raquel
authors.initials: R
authors.lastname: Seruca
authors.forename: Lene Juel
authors.initials: LJ
authors.lastname: Rasmussen
mesh_terms: D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D004249:DNA Damage; D004260:DNA Repair; D004272:DNA, Mitochondrial / Q000235:genetics; D042822:Genomic Instability; D016481:Helicobacter Infections / Q000150:complications* / Q000235:genetics; D016480:Helicobacter pylori; D006801:Humans; D013274:Stomach Neoplasms / Q000209:etiology*
chemical_list: D004272:DNA, Mitochondrial