A scavenger of electrophiles suppresses inflammation-mediated carcinogenesis in the gastrointestinal tract
The bacterial pathogen, Helicobacter pylori, which ubfects half of the world's population, is the primary causal factor for stomach cancer, with an attributable risk of approximately 90%. This infection universally causes chronic gastric inflammation in all those infected, and this chronic active gastritis can progress to gastric cancer.Herein, we show that electrophiles may represent a molecular bridge between inflammation and formation of somatic genomic abnormalities in the gastrointestinal epithelium and thus favor carcinogenesis. We found that 5-ethyl-2-hydroxybenzylamine (EtHOBA), a potent scavenger of all dicarbonyl electrophiles, which reacts at a rate 3 orders of magnitude faster than lysine and protects histones from covalent adduction by dicarbonyl electrophiles, prevents adduct formation with cellular macromolecules in the inflamed mucosa, epithelial genomic instability, and cancer development in two models of H. pylori-induced gastric cancer and in a model of colitis-associated cancer (CAC).