Gastric disease in ferrets: effects of Helicobacter mustelae, nitrosamines and reconstructive gastric surgery

Animal models are being used to study the mechanisms by which Helicobacter spp. induce gastric disease. To assess the effects of a natural gastric pathogen, Helicobacter mustelae, in the development of chronic gastritis, premalignancy and cancer, the ferret model was studied under natural and experimental conditions.

H. mustelae-infected ferrets were used to study the metabolism of nitrates/nitrites, which are dietary and endogenously formed substances that have been linked to gastric cancer. The ferret was also manipulated by performing gastric reconstructive surgery to study the processing of nitrite and nitrate and to assess the effect of surgery on gastric pathology. In addition, the ferret was tested for its suitability as an animal model for the induction of gastric cancer by oral dosing with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). The influence of these variables on gastric pathology and/or metabolic outcomes was examined, and the results in ferrets were compared to findings in humans.

The ferret appears to be an ideal model for studying various gastric parameters and how these factors influence the development of H. mustelae-associated gastric disease. Gastric reconstructive surgery did not effect nitrite processing or overall severity of gastritis in ferrets. However, a single dose of MNNG (50 mg/kg) produced an unprecedented 90% gastric carcinoma in H. mustelae-infected ferrets. This implies that chronic inflammation induced by the bacterium is a cofactor in gastric carcinogenesis.