Ultrastructures of atypical acinar cell nodules in rat pancreas induced by 4-hydroxyaminoquinoline-1-oxide.

A single intravenous injection of 4-hydroxyaminoquinoline-1-oxide (4HAQO) to rats induces multiple atypical acinar cell nodules in the pancreas. In this study, the ultrastructure of cells in these nodules was examined at 6, 9, and 12 months, and the features were compared to those of developing embryonal pancreas. The cells in the nodules are exocrine acinar cells in type and exhibited several features which distinguish them from the nonnodular acinar cells. Irregular nuclear shape with enlarged nucleoli was frequently observed. Zymogen granules in the nodular cells appeared as vesicles with contents of extreme electrom lucency and their ultrastructural appearance was similar to those of developing embryonic pancreatic acinar cells at 16 and 18 days of gestation. At the cell periphery, the lateral cell membrane showed bizarre interdigitation and the ectoplasm showed hyaloplasmic rarefaction. These findings indicate that the acinar cell nodules induced by 4-hydroxyaminoquinoline-1-oxide are composed of a new population of phenotypically altered acinar cells showing nuclear abnormalities, modified cell to cell interaction, and a possible defect in synthesis and/or maturation of secretory enzymes. The latter may indicate an arrest in the differentiation of acinar cells. The significance of these findings is discusses, and it is suggested that the atypical nodules in the pancreas induced by 4-hydroxyaminoquinoline-1-oxide may represent early neoplastic foci.