Studies of pancreatic carcinogenesis in different animal models.

Pancreatic carcinomas can be induced in rat, guinea pig and hamster by a variety of carcinogens. The types of neoplasms which arise vary with the species of rodent. In the rat, they consist exclusively of acinar cells, in the other species the lesions are adenocarcinomas resembling those derived from pancreatic ductules and ducts, those in hamster more so than in guinea pigs. Careful sequential studies in the guinea pig and hamster suggest that acinar cells together with ductular and duct cells are involved in the genesis of duct adenocarcinomas. In each rodent model, the acinar cell appears to be quite sensitive to continued exposure to carcinogen. In each instance, acini undergo modulation, and in the guinea pig and hamster, permanent metaplastic transformation to ductlike structures. Such cells assume an enhanced capacity for cell proliferation which persists following cessation of carcinogen treatment. Other studies suggest that adult pancreatic acinar cells possess a surprising degree of plasticity. Their involvement in the pathogenesis of neoplasms resembling pancreatic ducts is not unlike other carcinogenic sequences where extensive cell modulation and metaplasia precede and are an integral part of the neoplastic transformation.