ETHIONINE-INDUCED ATROPHY OF RAT PANCREAS INVOLVES APOPTOSIS OF ACINAR-CELLS

The mechanism of acinar cell loss occurring during ethionine-induced a trophy of the pancreas was investigated. Rats were given a standard di et, a protein-depletion diet (PDD), or a PDD with low- (0.04 g/kg body wt; LDE) or high- (0.4 g/kg; HDE) dose ethionine administered intrape ritoneally daily for 10 days. Changes were most extensive in the anima ls given a PDD and HDE: After 10 days, pancreatic weight was reduced b y 72%, and most of the acinar cells had disappeared. Prior to their de letion, these cells showed cytoplasmic vacuolation and enhanced autoph agy. The main mechanism involved in their deletion was apoptosis, the apoptotic bodies being phagocytosed and degraded by adjacent acinar ce lls and intraepithelial macrophages. In contrast, necrosis of acinar c ells was rare. Interstitial inflammation and apoptosis of capillary en dothelial cells were also observed. In animals given a PDD and LDE, en hanced apoptosis occurred later and was more limited in extent, and ad ditional manifestations of cell injury were not evident. As in other c ircumstances where glandular atrophy is effected by apoptosis, the bas ic tissue architecture was preserved, thus explaining the known capaci ty for the pancreas to regenerate after ethionine is discontinued.