Histogenesis of early preneoplastic lesions induced by N-nitrosobis(2-oxopropyl)amine in exocrine pancreas of hamsters.

The histogenesis of early putative preneoplastic lesions, arising in exocrine pancreas of Syrian hamsters after treatment with N-nitrosobis(2-oxopropyl) amine (BOP), was evaluated using electron microscopy and immunohistochemistry. Electron microscopical examination of pseudoductular lesions, present in hamster pancreas 2-4 mo after treatment with BOP, demonstrated that acinar cells forming part of these lesions frequently lose their zymogen granules. However, convincing evidence of dedifferentiation of acinar cells to proliferating ductal/ductular cells was not found. Most ductal/ductular cells of the BOP-induced pseudoductular lesions stained positively with cytokeratins specific to ductal/ductular cells. Acinar cells were all negative and, moreover, those lining the pseudoductular lesions were frequently surrounded by cytoplasmic processes of adjacent cells that stained strongly positive with the cytokeratin antibody. The present findings indicate that the early pseudoductular lesions, induced in exocrine pancreas of hamsters by BOP, originate from proliferating ductal/ductular rather than proliferating dedifferentiated acinar cells.