Abstract

Pancreatic hyperplastic nodules were experimentally produced in male Sprague-Dawley rats by single doses of intravenous injection of 4-hydroxyaminoquinoline-1-oxide(4-HAQO), 5 mg, 10 mg, 20 mg and 30 mg per 1kg of body weight. Every ten rats were sacrificed after 1 day, 1 week and monthly until 6 months. Within the first week, pancreatic acini and islets were severely affected with necrosis and the adjacent acinar cells underwent vacuolization. But, pancreatic ductules remained relatively unaffected. The degrees of acinar cell degeneration were proportionally increased as with the increased doses of 4-HAQO administration. The levels of blood glucose and serum amylase were closely corresponding to the light microscopic features of the pancreas. Two months after administration of 4-HAQO, the nongranular acinar cells started to proliferate and their proportion of total acinar cells was 35%, whereas that of control group was 15%, after 3 months the proportion of nongranular cells was decreased. After 6 months, multiple hyperplastic nodules were discovered within the pancreatic acini of all 12 rats, and the largest one measured 500 micro in diameter. Each hyperplastic nodule was uniformly composed of larger cells in two folds of normal cells with hyperchromatic muclei and prominent nucleoli together with a few zymogen granules in their cytoplasms. Ultrastructurally, the cells contained abundant dilated endoplasmic reticulum and markedly decreased zymogen granules. Nuclear heterochromatin became finely dispersed with loss of marginal clumping. During the regeneration process, admixture of islet cells with membrance-bounded granules was identified among the clusters of regenerating acinar cells. On the basis of above findings, the induction of hyperplastic nodules in rat pancreas by 4-HAQO was confirmed, and its histogenesis may reflect a nodular hyperplasia of non-granular acinar cells with potential progress as a neoplastic lesion. And the evidence of the hypothesis that the pancreatic exocrine cells and endocrine cells are in same origin, was presented.