Helicobacter pylori, N-methyl-N '-nitro-N '-nitrosoguanidine, and bile modulate gastric cell kinetics in experimental cancer

Helicobacter pylori infection is a risk factor for gastric cancer. How the bacterium contributes to this process is still unclear. We present a new Wi star rat model that was used to evaluate the effect of H. pylori on early p reneoplastic events as judged from epithelial cell turnover and histopathol ogical changes. One hundred and four rats were colonized with H. pylori and exposed to MNNG (N-methyl-N ' -nitro-N ' -nitrosoguanidine) and/or tauroch olic acid. Inflammation, goblet cell-like metaplasia, atrophy, dysplasia, a nd adenocarcinoma were scored in a blinded manner. Apoptotic cells were cou nted after staining with terminal uridine deoxynucleotidyl nick end labelin g. and epithelial cell proliferation was determined by means of the Ki-67 l abeling index. No early tumor enhancement with H. pylori could be found in ordinary histology. However, H. pylori significantly enhanced the epithelia l cell proliferation compared with the control group, and the combination w ith taurocholic acid appeared to have a synergistic effect. MNNG significan tly increased the normal gastric epithelial apoptosis. This increase was re duced in antral mucosa with H. pylori infection. The findings suggest that H. pylori, especially when combined with bile, has an influence on cell kin etics, contributing to the development of gastric cancer. The reduced apopt osis of MNNG also observed in infected animals indicates a dual function of H. pylori.