Deficiency in OGG1 protects against inflammation and mutagenic effects associated with H. pylori infection in mouse.
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.
Touati
Eliette
E
Unité de Pathogénie Bactérienne des Muqueuses, Institut Pasteur, Paris, France. etouati@pasteur.fr
Michel
Valérie
V
Thiberge
Jean-Michel
JM
Avé
Patrick
P
Huerre
Michel
M
Bourgade
Franck
F
Klungland
Arne
A
Labigne
Agnès
A
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
D012333:RNA, Messenger; D045647:DNA Glycosylases; C485990:Ogg1 protein, mouse; C486216:Apex1 protein, mouse; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase