Pancreatic carcinoma in azaserine-treated rats: induction, classification and dietary modulation of incidence

Pancreatic carcinomas have been induced in Wistar and W/LEW rats by administration of total azaserine doses of 150-520 mg/kg by injection or oral routes over periods of 5-52 weeks. The latent period for development of invasive carcinomas was 1-2 years, but focal abnormalities in acinar cells appear earlier. The incidence of carcinomas varied with total dose, route, and schedule of azaserine administration. The spectrum of histologic patterns of the carcinomas included well and poorly differentiated acinar cell, ductlike, and undifferentiated carcinomas. Rats fed a purified diet developed more pancreatic neoplasms than rats fed a commercial laboratory chow. Selective feeding of these diets during the administration of carcinogen and following completion of carcinogen treatment indicated that the inhibitory effect of chow on pancreatic carcinogenesis was exerted during the postinitiation phas. Supplementation of diet with 0.025% retinyl acetate during the postinitiation phase also inhibited the progression of azaserine-induced lesions in the pancreas.