Helicobacter pylori alters gastric epithelial cell cycle events and gastrin secretion in mongolian gerbils

Background & Aims: Human colonization with Helicobacter pylori increases th e risk for distal gastric adenocarcinoma, possibly by altering gastric epit helial cell cycle events and/or gastrin secretion. This study aimed to dete rmine whether H, pylori virulence-related characteristics affect apoptosis, proliferation, and gastrin levels in a rodent model of gastric adenocarcin oma. Methods: Mongolian gerbils were challenged with H, pylori wild-type or isogenic cagA(-) and vacA(-) mutants, and apoptotic and proliferating cell s were identified by terminal deoxynucleotidyl transferase-mediated deoxyur idine triphosphate nick-end labeling and proliferating cell nuclear antigen immunohistochemistry, respectively. Serum gastrin levels were determined b y radioimmunoassay, Results: Gastric epithelial cell turnover was no differ ent after infection with the wild-type, cagA(-), or vacA(-) strains. H, pyl ori infection significantly increased antral apoptosis 2-4 weeks after chal lenge, before apoptotic indices decreased to baseline. In contrast, antral proliferation rates were significantly higher 16-20 weeks after inoculation , but then decreased by 40 weeks, Antral proliferation was significantly re lated to serum gastrin levels, whereas antral apoptosis was inversely relat ed to acute inflammation and lymphoid follicles, Conclusions: In H. pylori- infected gerbils, enhanced antral apoptosis is an early and transient cell cycle event. Epithelial cell proliferation peaks later and is significantly related to increased gastrin levels, suggesting that epithelial cell growt h in H. pylori-colonized mucosa may be mediated by gastrin-dependent mechan isms.