Malignant transformation and differentiation of adult rat pancreatic duct cells in vitro

The development of animal models for pancreatic cancer has magnified the controversy regarding the cell of origin of the tumor in animals and man. In rats, most pancreatic tumors have an acinar histology. By contrast, tumors in hamsters have a ductular morphology, resembling the predominant type of human exocrine pancreatic cancer. While some workers advocate a ductular origin for hamster tumors, others insist that the progenitor is an acinar cell.With the use of normal adult rat pancreatic ductular cell lines, this work shows that four representative pancreatic carcinogens all display dose-related genotoxicity to rat pancreatic ductular cells in vitro. Further, repeated exposure to sublethal doses induced anchorage-independent growth. Transformed cells, injected subcutaneously into isogeneic newborn rats, produced malignant tumors with ductular morphology. A novel achievement of this work was the production of ductular adenocarcinomas using streptozotocin, previously reported as only inducing islet cell tumors