Ultrastructural analysis of pancreatic carcinogenesis. V. Changes in differentiation of acinar cells during chronic treatment with N-nitrosobis(2-hydroxypropyl)amine.

An electron microscope study was carried out on changes in the pancreatic acinar tissues of male Syrian hamsters during the course of induction of pancreatic neoplasia by lifetime weekly injections of N-nitroso-bis(2-hydroxypropyl)amine (BHP). The dominant process observed was a loss of differentiation of the acinar cells, leading to the development of a new population of cells that closely resemble centro-acinar or ductular cells. During this process, the original centro-acinar and ductular cells appear to be relatively unaffected by exposure to BHP. Thus, acinar cell de-differentiation appears, in this experimental model, to be an important preliminary stage in neoplastic development. It is argued that these findings may have implications for the histogenesis of human pancreatic adenocarcinoma, considered hitherto to be ductal in origin.