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㎎, 10㎎, 20㎎ and 30㎎ per 1㎏ 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 r in diameter. Each hyperplastic
nodule was uniformly composed of larger cells in two folds of normal cells with
hyperchromatic nuclei 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.
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