Concentrations were higher in chronic atrophic gastritis, but not signicantly so, and the only parameter that was signicantly correlated with a clear cut increase in TBARS was the presence of H pyloriinfection.These results provide only par tial confirmation of previously published ndings.Fur thermore, damage to DNA, lipids, proteins, or carbohydrates depends on the type of cell under oxidative stress and on the mechanisms involved.The authors also found no correlation between baseline vitamin C in the gastric juice and DNA adduct concentrations, and this conrms our own data.These observations imply that gastric juice vitamin C concentrations may vary in relation to different factors and that a specic correlation with the extent of mucosal DNA oxidative damage cannot be conrmed.This indicates that H pyloriinfection is the most impor tant factor in causing accumulation of oxidative DNA mutations.As H pyloriinfection is also correlated with an increase in the proliferative activity of the gastric epithelia, it can be concluded that the bacterium may act as both a potential initiator and as a promoter of gastric carcinogenesis.This damage correlates with the development of precancerous mucosal changes and specically with the onset of atrophy and extensive intestinal metaplasia.Formation of hydroxydeoxyguanosine in DNA by oxygen radicals and its biological signicance.Cancer. Helicobacter pylori and increased epithelial cell proliferation: a risk factor for cancer.Gut: firstpublished as. Protectedbycopyright. In cancer treatment, the DDR occurs in response to various genotoxic insults by diverse cytotoxic agents and radiation, representing an important mechanism limiting chemotherapeutic and radiotherapeutic efficacy.V ariousendog enousmet abolicin sults or reasch Famciclovir environmental insults cause DNA damage. If repair fails, checkpoints trigger pdependent or independent apoptosis.Thus, checkpoints represent central orchestrators of the DDR network ranging from damage sensing to repair or apoptosis.Significantly, checkpoints are characteristically de fective intrans fo rmed cells. ATM and ATR transduce signals to distal transducer checkpoint kinases. MAPKAP kinase, a downstream target of the stressresponse p MAPK pa thway, may representth irddis taltransducer. Cdc inactivation and p accumulation halt cell cycle progression at specific phases.In S phase, endogenousexogenous insults hinder replication fork progress ion, re sult ing installed fo rks thata re unstab le and breakageprone. Notably, whereas S is essential for kinase activation and function, S plays only a contributory role. Moreover, different phosphorylation sites also play disparate ro les in essentialcell su rv ival functions.Mo reover, the se transducers also phosphorylate multiple other effectors involved in checkpoints, as well as other DDR mechanisms. In this context, the ATRATPIP complex is recruited to ssDNA lesions via binding of ATRIP with RPA that recognizes and coats ssDNA.Chk has recently been implicated in translesion DNA synthesis mediated by ubiquitinated proliferating cell nuclear antigen. Both are important for continuous replication of damaged DNA and avoidance of fork collapse.Proximal transducers comprise the core of DDR signaling networks.Theoretically, inhibition of each could improve chemotherapeutic or radiotherapeutic efficacy.ATM is a rationalcand ida te, but ATM inhibitors are at early preclinical stages of development.Therefore, whether the targeting of ATM, ATR, or both will be effective strategies remains to be determined.Chk is involved in checkpoints induced bydiversest imuli, as well as DNA replication stresses.