Sub cellular changes in exocrine pancreas of the guinea pig induced by azaserine

The effect of long term administration of azaserine (o diazoacetyl 1 serine) on the morphology of pancreas acinar cells in inbred strain II guinea pigs was investigated. This compound was administered twice weekly at a dose of 5 mg/kg b. wt. by i.p. injection and animals killed at selected intervals up to 24 wk. By light microscopy, mild to moderate atrophy of acinar cells of the exocrine pancreas was evident after 14 wk. The ultrastructural changes, first evident at 4 wk and increasing progressively with time, consisted of marked dilatation of endoplasmic reticulum channels and accumulation of intracisternal granules of varying size and density. The number of zymogen granules in the affected cells were considerably reduced or completely absent. These RER changes were persistent 9 wk after the withdrawal of treatment. These results indicate alteration of membrane synthesis and/or a block in the transport of synthesized proteins, leading to altered morphology of acinar cells. Hyperplastic nodules or carcinomas of the exocrine pancreas were not seen in animals killed at 24 wk.