| Summary: | <i>H. pylori</i> is a significant risk factor of gastric cancer that induces chronic inflammation and oxidative DNA damage to promote gastric carcinoma. Base excision repair (BER) is required to maintain the genome integrity and prevent oxidative DNA damage. Mutation in DNA polymerase beta (Pol β) impacts BER efficiency and has been reported in approximately 30−40% of gastric carcinoma tumors. In this study, we examined whether reduced BER capacity associated with mutation in the <i>POLB</i> gene, along with increased DNA damage generated by <i>H. pylori</i> infection, accelerates gastric cancer development. By infecting a Pol β mutant mouse model that lacks dRP lyase with <i>H. pylori</i>, we show that reactive oxygen and nitrogen species (RONS) mediated DNA damage is accumulated in Pol β mutant mice (L22P). In addition, <i>H. pylori</i> infection in Leu22Pro (L22P) mice significantly increases inducible nitric oxide synthesis (iNOS) mediated chronic inflammation. Our data show that L22P mice exhibited accelerated <i>H. pylori</i> induced carcinogenesis and increased tumor incidence. This work shows that Pol β mediated DNA repair under chronic inflammation conditions is an important suppressor of <i>H. pylori</i> induced stomach carcinogenesis.
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