The role of gastric Helicobacter and N-methyl-N′-nitro-N-nitrosoguanidine in carcinogenesis of mice

Background. The aim of this study was to determine whether gastric epithelial proliferation due to gastric Helicobacter infection in mice represents a preneoplastic lesion. Materials and Methods. Helicobacter heilmannii infected and uninfected mice were treated with 150 mu g/ml N-methyl-N'-nitro-N-nitrosoguanidine in drinking water for either 20 or 38 weeks. Mice were killed 12 or 18 months after bacterial inoculation. Results. All infected mice developed lymphoplasmocytic gastritis and epithelial hyperplasia. Proliferative gastric lesions were characterised by nodular hypertrophy of the glandular mucosa, multifocal epithelial hyperplasia, and elevated BrdU labeling index. Intestinal metaplasia and true atrophy were not present but proliferative glands were poorly differentiated, lined by mucus-type epithelial cells with no parietal, chief or other specialized cell types. Neoplasms developed only in MNNG-treated mice. of the 180 treated mice the following neoplasms developed: 14 squamous cell carcinomas of mouth and forestomach; 37 hemangiosarcomas of the intestinal serosa; and 15 splenic lymphomas. No tumors were present in the glandular gastric mucosa, and infection did not affect tumor incidence. p53 overexpression occurred in 79% of hemangiosarcomas and 71% of squamous cell carcinomas but not in normal or proliferative gastric glandular mucosa. Conclusions. Gastric proliferative lesions in Helicobacter infected mice are not preneoplastic, and the combination of an alkylating agent and non-neoplastic proliferation does not result in gastric carcinogenesis in mice.