title: Effect of d,l-ethionine administration on the histomorphology of canine pancreatic acinar and beta-cells.
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 pathological alterations after intravenous administration of d,l-ethionine in normal dogs. Histomorphological changes in pancreatic acinar cells and beta-cells were assessed 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. Severe acinar destruction occurred resulting in significant (p < 0.001) shrinkage of the pancreas in all groups. Although there was variability in histomorphology within groups, pancreases of group I generally exhibited widespread loss of pancreatic acinar structure. Remaining acinar cells were difficult to discern from other cell types within lobules and were surrounded by infiltrates, predominantly of lymphocytes. Partial acinar cellular regeneration had occurred by day 29, but was still incomplete at day 43. Immunohistochemistry suggested that the effect of d,l-ethionine administration on the histomorphology of beta-cells in the left lobe was minimal; however, morphometry demonstrated a significant (p < 0.05) increase in the number of individual beta-cells in groups II and III, and clusters of 2-10, 10-20 and 20+ cells in Group II. It is probable that the apparent increase in the number of individual and other beta-cell arrangements observed in some groups resulted primarily from alterations in the exocrine tissue, although some beta-cell hyperplasia cannot be excluded completely.
authors.affiliation: Faculty of Veterinary Science, The University of Sydney, Australia. M.Govendir@vetc.usyd.edu.au
authors.forename: Merran
authors.initials: M
authors.lastname: Govendir
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Canfield
authors.forename: David B
authors.initials: DB
authors.lastname: Church
mesh_terms: D000818:Animals; D000963:Antimetabolites / Q000009:adverse effects / Q000494:pharmacology*; D004285:Dogs; D005001:Ethionine / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D006965:Hyperplasia; D007150:Immunohistochemistry; D007262:Infusions, Intravenous; D007515:Islets of Langerhans / Q000187:drug effects* / Q000473:pathology*; D008297:Male; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000473:pathology
chemical_list: D000963:Antimetabolites; D005001:Ethionine