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 Wistar rat model that was used to evaluate the effect of H. pylori on early preneoplastic events as judged from epithelial cell turnover and histopathological changes. One hundred and four rats were colonized with H. pylori and exposed MNNG (N-methyl-N'-nitro-N'-nitrosoguanidine) and/or taurocholic acid. Inflammation, goblet cell-like metaplasia, atrophy, dysplasia, and adenocarcinoma were scored in a blinded manner. Apoptotic cells were counted after staining with terminal uridine deoxynucleotidyl nick end labeling, and epithelial cell proliferation was determined by means of the Ki-67 labeling index. No early tumor enhancement with H. pylori could be found in ordinary histology. However, H. pylori significantly enhanced the epithelial cell proliferation compared with the control group, and the combination with taurocholic acid appeared to have a synergistic effect. MNNG significantly increased the normal gastric epithelial apoptosis. This increase was reduced in antral mucosa with H. pylori infection. The findings suggest that H. pylori, especially when combined with bile. has an influence on cell kinetics, contributing to the development of gastric cancer. The reduced apoptosis of MNNG also observed in infected animals indicates a dual function of H. pylori.

Effects of Helicobacter pylori and bile on N-methyl-N'-nitro-N'-nitrosoguanidine exposed antral mucosa of C57BU6 mice.

The aim of this study was to evaluate the early influence of Helicobacter pylori infection on cell kinetics in the antral mucosa of mice exposed to N-methyl-N'-nitro-N'-nitrosoguanidine (MNNG) and bile alone or in combinations. Four hundred and one C57BL/6 male and female mice were assigned into seven treatment groups and one non-treated control group. The gastric antrums were assessed by histology and immunohistochemistry for studies of cell proliferation and apoptosis at 32 and 44 weeks. One female and one male mouse had developed dysplastic adenomas in the pylorus mucosa and one male animal had dysplastic proliferation in the antrum. Only one of these lesions occurred in a H. pylori colonized animal. H. pylori infection significantly increased the cell proliferation at 32 weeks and promoted the cell proliferation in the MNNG and bile group at 44 weeks. Female mice showed less increase in cell proliferation than did the males. No change in apoptosis was seen in any of the groups. Bile had no promotional effect on cell proliferation. These results indicate that H. pylori infection has the potential to alter epithelial cell kinetics as well as antrum mucosa of an animal species that is regarded as resistant to MNNG. However, this change is not sufficient to promote the early development of neoplastic lesions.

Mutagenicity from neutrophils after challenge with Helicobacter pylori and bile.

OBJECTIVE: To study some mechanisms involved in Helicobacter pylori (H. pylori)-induced gastric carcinogenesis. DESIGN: In vitro study. SETTING: Medical centre hospital, Sweden. INTERVENTIONS: Mutagenicity in Ames' test of neutrophils challenged for 2 hours or more by two different strains of H. pylori. One strain designated NCTC 11637 by the National College of Type Cultures activated neutrophils to an oxidative burst and producing vacuolating cytotoxin, the other strain C-7050 lacked these abilities. Mutagenicity was also studied with sterile human gall bladder bile alone added to neutrophils or in combination with both neutrophils and H. pylori. RESULTS: There was no increase in the number of revertants with the crude suspension or the supernatant of neutrophils challenged for 1 hour or less with H. pylori, bile, or the combination of both. However, in 5 out of 19 experiments there was significant mutagenicity after challenge of neutrophils for 2 hours or more with either strain of H. pylori, bile, or the combination of the two. The strongest mutagenicity was obtained after challenge over night (18 hours) with the combination of H. pylori and bile. CONCLUSION: Mutagenicity occurs when neutrophils are challenged with H. pylori and bile. Factors other than reactive oxygen metabolites seem to be responsible.