An ultrastructural study of precancerous and cancerous lesions of the pancreas in Syrian golden hamsters induced by N-nitrosobis(2-oxopropyl)amine.

Abstract

Transmission electron microscopic studies of precancerous and cancerous lesions in the pancreas of hamsters induced by N-nitrosobis(2-oxopropyl)amine (BOP) are presented. BOP was injected subcutaneously once weekly for 10 weeks and hamsters were sacrificed every 5 weeks after initiation of the experiment. The ultrastructural findings indicated that serial changes occurred in the epithelium of the pancreatic duct. The epithelial cells became cuboidal and showed increased secretions at 5 weeks. Probably precancerous cells with prominent nucleoli and irregular rough endoplasmic reticulum were found in the main duct at 10 weeks. At 15 weeks, pancreatic tumors forming a duct arrangement were seen, in good accord with the histological appearance. Well differentiated adenocarcinoma cells showing a tubular pattern had oval nuclei with granular chromatin. Poorly developed rough endoplasmic reticulum was irregularly distributed throughout the cytoplasm and the cell surface was covered with microvilli. Poorly differentiated adenocarcinoma showed poor gland formation and had distorted nuclei with prominent nucleoli. These cells were loosely joined. Mitochondria and rough endoplasmic reticulum were poorly developed, and the tumor cells were devoid of secretory granules. The most characteristic and common change of the precancerous and cancerous lesions in this experiment was the appearance of numerous microvilli on the luminal surface and loss of cytodifferentiation. These findings were obviously different from those of normal epithelial cells or those seen in inflammation. The findings in this study confirm that the pancreatic carcinoma induced by N-nitrosobis(2-oxopropyl)amine in Syrian hamsters is of duct cell origin. No evidence of acinar cells was obtained.