Cellular proliferation in the canine pancreas after d,l-ethionine dosage as detected by double immunohistochemical labelling

Abstract

d,l-Ethionine produces pancreatic exocrine necrosis and islet proliferation in hamsters and dogs. As a first step in examining whether induction of islet proliferation has therapeutic applications in animals with exhausted or destroyed insulin-producing beta-cells, we studied pancreatic cellular proliferation after intravenous administration of d,l-ethionine in normal dogs. Double immunohistochemical labelling of pancreatic tissue was used to identify proliferating cells in three groups of six clinically normal crossbred dogs administered d,l-ethionine (100 mg/kg) intravenously three times a week for two weeks. Six additional dogs served as untreated controls. Group I was euthanased and necropsied on day 15 (72 hours after the final dose of ethionine). Groups II and III were euthanased on days 29 and 43 respectively. Utilising markers for proliferating nuclei, insulin and cytokeratin, proliferating cells were classified as acinar, endocrine (both intra or extra-islet), duct or 'other' (i.e. infiltrative or interstitial) and counted under the light microscope (40x magnification). Compared to controls, an increase in the number of proliferating cells was found in all categories except ducts. Acinar cells demonstrated statistically significant (p < 0.05) proliferation, greatest two weeks after ethionine cessation continuing over four weeks. The interstitial, infiltrative or 'other' group also showed proliferation, however this was a more immediate response, which substantially decreased two weeks after ethionine administration. Endocrine cells showed only minor and non-significant proliferative activity and were probably not responsible for a significant increase in apparent beta-cell mass. The number of proliferating duct cells was inconsequential and there appeared to be no specific relationship between any cell populations and duct cells.