title: Deficiency in OGG1 protects against inflammation and mutagenic effects associated with H. pylori infection in mouse.
abstract: BACKGROUND
  Helicobacter pylori infection is associated with gastric cancer. Study with the Big Blue mouse model has reported a mutagenic effect associated with the H. pylori infection, as a result in part of oxidative DNA damage. The present work investigates the consequences of a deficiency in the OGG1 DNA glycosylase, responsible for the excision of 8-oxo guanine, on the inflammatory and genotoxic host response to the infection.
  
  
  METHODS
  Big Blue Ogg1-/- C57BL/6 mice were orally inoculated with H. pylori strain SS1 or vehicle only, and sacrificed after 1, 3, or 6 months. The serologic response, histologic lesions, mutant frequency, and spectra of mutations were assessed in the stomach and compared to what observed in the wild-type (Wt) context.
  
  
  RESULTS
  Inflammatory lesions induced in the gastric mucosa of H. pylori-infected mice, corresponding to a moderate gastritis, were less severe in Ogg1-/- than in Wt Big Blue mice. Analysis of antimicrobial humoral immunity exhibited a lower IgG2a serum level (Th1 response) after 6 months of infection in Ogg1-/- than in the Wt mice. In these conditions, the H. pylori-SS1 infection in the Ogg1-/- mice did not induce a mutagenic effect at the gastric epithelial cells level, either after 3 or 6 months.
  
  
  CONCLUSIONS
  The inactivation of the OGG1 DNA glycosylase in mouse leads to less severe inflammatory lesions and abolished the mutagenic effect at the gastric epithelial cells level, induced by the H. pylori infection. These data suggest for the OGG1deficiency a protective role against inflammation and genotoxicity associated to the H. pylori infection.
authors.affiliation: Unité de Pathogénie Bactérienne des Muqueuses, Institut Pasteur, Paris, France. etouati@pasteur.fr
authors.forename: Eliette
authors.initials: E
authors.lastname: Touati
authors.forename: Valérie
authors.initials: V
authors.lastname: Michel
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Thiberge
authors.forename: Patrick
authors.initials: P
authors.lastname: Avé
authors.forename: Michel
authors.initials: M
authors.lastname: Huerre
authors.forename: Franck
authors.initials: F
authors.lastname: Bourgade
authors.forename: Arne
authors.initials: A
authors.lastname: Klungland
authors.forename: Agnès
authors.initials: A
authors.lastname: Labigne
mesh_terms: D000818:Animals; D002869:Chromosome Aberrations; D004249:DNA Damage; D045647:DNA Glycosylases / Q000172:deficiency* / Q000235:genetics; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000378:metabolism; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D005756:Gastritis / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D016481:Helicobacter Infections / Q000235:genetics* / Q000473:pathology; D016480:Helicobacter pylori; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D045647:DNA Glycosylases; C485990:Ogg1 protein, mouse; C486216:Apex1 protein, mouse; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase