Animal models of exocrine pancreatic carcinogenesis

Abstract

In order to understand the evolution, histogenesis, and biological behaviour of exocrine pancreatic carcinoma, some reproducible experimental models have been developed in certain rodent species. To date, more than 16 chemicals, many of them structurally unrelated, have been shown to induce pancreatic tumors. Although some of these chemicals appear species specific in their effect on the pancreas, others have been shown to be capable of inducing pancreatic tumors in more than one species. In hamsters, the administration of diisopropylnitrosamine or its oxidized metabolites leads to the development of ductal adenocarcinomas that histologically resemble human pancreatic carcinomas. The histogenesis of the ductal type of adenocarcinoma in hamsters is complex, and appears to involve both the duct cells and dedifferentiated acinar cells. All pancreatic tumors in rats develop from acinar cells showing variable degrees of differentiation, regardless of the type of carcinogen used. The type of pancreatic lesions that develop in mice are also of acinar cell origin. In guinea pigs the tumors are adenocarcinomas of the ductal type and are shown to be derived from dedifferentiated acinar cells that have undergone duct-like transformation. Irrespective of the type of tumor that develops in these experimental animals, all of these models can be successfully used to evaluate the various modifying (risk) factors and biological behaviour of these neoplasms.