The regeneration of the pancreatic acinar cell was studied at four time periods after ethionine had destroyed most of the acinar cells. Within 2 days of the last ethionine injection, small basophilic cells (pre-acinar cells) with whorls of ergastoplasm or nebenkern were present. These cells also contained a decreased amount of Golgi substance, small zymogen granules, and a fine granularity of the nuclear matrix. They showed persistence of the characteristic ergastoplasm lesion produced by ethionine. Eight days after the last ethionine injection, the nebenkern was replaced by approximately normal appearing ergastoplasm and the nucleoli and Golgi bodies were enlarged. Zymogen granules were less dense but more abundant. Mitochondria were considerably enlarged. Most cells showed no ethionine lesions or only small foci of damage. Eighteen days after the cessation of ethionine, a good approximation of the normal acinar cell was present. The whorls of ergastoplasm appeared at a time (day 12) when basophilia was pronounced. Other studies showed that nucleic acid and protein precursors began to show an increased concentration in acinar cells at this time. The appearance of nebenkern during a phase of cellular recovery and its absence during a phase of replication when mitotic indices were high suggest that its presence is more indicative of ergastoplasmic synthesis than of cell multiplication as such. Possibly the increased density of zymogen granules was a reflection of this increased protein synthesis. The increase in size of Golgi apparatus occurred prior to the replenishment of zymogen granules and thus satisfied a precursor relationship for a possible role in the formation of these secretory structures. Evidence suggests that some injured acinar cells recover from the ethionine and protein-free regimen and give rise to most of the new acinar cells formed. It is possible that, under the severe conditions which prevailed, the centroacinar ductule cells may also have given rise to some acinar cells.

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