MNNG-INDUCED GASTRIC-CARCINOMA IN FERRETS INFECTED WITH HELICOBACTER-MUSTELAE

N-Methyl-N-nitro-N'-nitrosoguanidine (MNNG) is a gastric carcinogen in several animal species and has been used in a number of systems to di ssect the co-carcinogenic potential of various compounds in the induct ion of gastric adenocarcinoma. Recent epidemiological evidence suggest s that Helicobacter pylori may play a role as a co-carcinogen in the e tiology of this tumor in humans and we have been interested in develop ing an animal model to study this possibility. A related organism, H.m ustelae, naturally colonizes the ferret stomach and causes persistent chronic gastritis. The pathology elicited by H.mustelae in ferrets has many similarities with the human disease including different stages o f multifocal atrophic gastritis which underlie the gastric ulcer and g astric carcinoma syndrome. There is little evidence, however, demonstr ating the susceptibility of ferrets toward chemical carcinogenesis. We have consequently undertaken a study to ascertain whether 10 6-month- old female ferrets given a single oral dose of MNNG (50 - 100 mg/kg) w ould develop adenocarcinoma of the stomach. Five age-matched unmanipul ated control animals were included for comparative purposes. All 15 fe rrets were infected with H.mustelae. Nine of 10 ferrets dosed with MNN G developed gastric adenocarcinoma (29 - 55 months after dosing), whil e none of the five historical control ferrets examined an average of 6 3 months after the initiation of the study developed gastric tumors. B y comparison, we have not observed gastric adenocarcinoma, nor has it been reported, in > 10 years of observation of untreated ferrets natur ally infected with H.mustelae. The H.mustelae-infected ferret, with de monstrated susceptibility to a gastric carcinogen, plus the recent ava ilability of specific pathogen-free ferrets, should now allow longitud inal studies in vivo to probe the role of Helicobacter in the developm ent of gastric cancer.