Stimulation of the growth of azaserine-induced nodules in the rat pancreas by dietary camostate (FOY-305)

Abstract

The effects of dietary camostate (FOY-305), a synthetic trypsin inhibitor, on the early stages of pancreatic carcinogenesis in the rat were studied because of earlier reports that feeding soy bean trypsin inhibitor stimulated growth and promoted carcinogenesis in the pancreas of rats. These effects are attributed to excess secretion of cholecystokinin, a trophic hormone for pancreatic acinar cells. Camostate has been shown to induce pancreatic enlargement in rats by the same mechanism. In preliminary experiments, pancreatic growth was studied in adult Fischer 344 (F344) and Lewis rats fed camostate mixed in the diet to define a level that induced pancreatic hypertrophy and hyperplasia. As little as 0.02% fed 3 days per week was effective. In a second experiment, F344 rats were injected with azaserine and thereafter were given camostate by gavage 5 days a week until autopsy 18 weeks later. In a third experiment, azaserine-treated Lewis rats were fed camostate in the diet 3 days a week for 8 or 16 weeks until autopsy. In the latter two experiments the number and size of atypical acinar cell foci and nodules (AACN) were measured in pancreas sections. Growth of acidophilic AACN was stimulated in camostate-fed groups; both the number and the size were increased in comparison with the control groups. The data suggest a promoting effect of dietary camostate on the growth of azaserine-induced preneoplastic lesions in the pancreas of both rat strains. The number of basophilic AACN was decreased in camostate-fed Lewis rats suggesting that the camostate diet also affected the phenotype of the carcinogen-induced AACN.