MNNG-induced gastric carcinoma in ferrets infected with Helicobacter mustelae

N-Methyl-N-nitro-N'-nitrosoguanidine (MNNG) is a gastric carcinogenin several animal species and has been used in a number of systemsto dissect the co-carcinogenic potential of various compoundsin the induction of gastric adeno-carcinoma. Recent epidemiologicalevidence suggests that Helicobacter pylori may play a role asa co-carcinogen in the etiology of this tumor in humans andwe have been interested in developing an animal model to studythis possibility. A related organism, H.mustelae, naturallycolonizes the ferret stomach and causes persistent chronic gastritis.The pathology elicited by H.mustelae in ferrets has many similaritieswith the human disease including different stages of multifocalatrophic gastritis which underlie the gastric ulcer and gastriccarcinoma syndrome. There is little evidence, however, demonstratingthe susceptibility of ferrets toward chemical carcinogenesis.We have consequently undertaken a study to ascertain whether10 6-month-old female ferrets given a single oral dose of MNNG(50–100 mg/kg) would develop adeno-carcinoma of the stomach.Five age-matched unmanipulated control animals were includedfor comparative purposes. All 15 ferrets were infected withH.mustelae. Nine of 10 ferrets dosed with MNNG developed gastricadenocarcinoma (29–55 months after dosing), while noneof the five historical control ferrets examined an average of63 months after the initiation of the study developed gastrictumors. By comparison, we have not observed gastric adenocarcinoma,nor has it been reported, in >10 years of observation ofuntreated ferrets naturally infected with H.mustelae. The H.mustelae-infectedferret, with demonstrated susceptibility to a gastric carcinogen,plus the recent availability of specific pathogen-free ferrets,should now allow longitudinal studies in vivo to probe the roleof Helicobacter in the development of gastric cancer.