Pancreas acinar cell regeneration. IX. Effect of actinomycin D on microstructure

The morphologic effects of actinomycin D (ACTD) on normal and regenerating rat pancreas at three dosage levels were studied. ACTD at 1.0 and 0.5 mug/g total body weight produced reversible nucleolar and cytoplasmic changes in the acinar cells of the normal rat pancreas. The nucleolar alteration, zonal segregation, preceded the appearance of cytoplasmic lesions, implying a precursor relationship of the former to the latter. ACTD-induced cytoplasmic lesions were similar to those produced by ethionine. Since ethionine failed to produce nucleolar changes, it is suggested that the primary mechanisms of action of these two compounds are different, although the cytoplasmic lesions may occur by a common metabolic route. Regeneration of exocrine pancreas after injection of ethionine was affected by ACTD to different degrees depending upon the time of ACTD administration. Regeneration was prevented when ACTD, 0.5 mug/g, was given at day 11, the first day after the ethionine regimen; it was markedly decreased when ACTD was given at day 12, but much less affected when ACTD was given at later days. The effects at days 11 and 12 may have been related to prevention of DNA transcription and the formation of mRNAs at these days. The 0.05 mug/g dosage of ACTD had much less effect on normal and regenerating acinar cells, causing reduced cytoplasmic basophilia, decreased ergastoplasm and fewer free ribosomes, which suggests impairment of rRNA synthesis.