Helicobacter pylori infection, oxidative DNA damage, gastric carcinogenesis, and reversibility by rebamipide.

Abstract

Several epidemiological studies have demonstrated a close association between Helicobacter pylori infection and carcinoma of the mid- or distal stomach. If this can be shown to be a causal association, eradication of the organism may prevent later development of cancer. Several mechanisms have been proposed by which H. pylori infection might lead to predisposition for gastric cancer. Although many potential pathogenic mechanisms, such as increased proliferative gastric epithelial response to H. pylori, lowered gastric ascorbic acid levels, and high occurrences of atrophic gastritis, have been proposed, there is little evidence as to which might be of direct importance to such H. pylori-related disease in vivo. H. pylori-associated inflammation may interact with other causal factors related to gastric carcinogenesis and can result in the intestinal type of gastric cancer and then DNA damage due to oxygen radicals induced by persistent inflammatory cell infiltrations in the gastric mucosa may lead to alterations of the gene and result in the development of diffuse-type carcinoma. In order to know the influence of H. pylori on changes of inflammation-related DNA damage, we measured the sequential changes of 8-hydroxydeoxyguanosine (8-OHdG) contents of DNA and the changes of two biomarkers inducible nitric oxide synthase (iNOS) and apoptosis from human gastric mucosa according to the status of H. pylori. The increased levels of oxidative DNA damage, increased occurrences of apoptosis, and increased expressions of iNOS seem to provide the mechanistic links between H. pylori infection and gastric carcinogenesis and rebamipide can abrogate the levels of these hazard factors.