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. MATERIALS AND 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.
