Massive acinar cell apoptosis with secondary necrosis, origin of ducts in atrophic lobules and failure to regenerate in cyanohydroxybutene pancreatopathy in rats.
Cyanohydroxybutene (CHB), a glycosinolate breakdown product, causes pancreatic injury when given to animals in large amounts. To determine the course of CHB-induced pancreatopathy, rats were given a single subcutaneous dose of CHB and the pancreas weighed and examined by light and electron microscopy and immunohistochemistry at intervals from 2 h to 28 days. The pancreatic lesion was unusual in that there was marked early oedema with limited inflammatory cell infiltration, rapid synchronous onset of acinar cell apoptosis and early advanced atrophy engendering only a limited regenerative response. Acinar cell apoptosis was atypical in that cell fragmentation was limited and phagocytosis delayed, resulting in extensive secondary necrosis. As ducts were unaffected by CHB, the crowded ducts making up the epithelial component of atrophic lobules could be clearly shown to derive from their condensation and proliferation, not the redifferentiation of pre-existing acinar cells, widely held to produce this lesion. Although the basis of CHB selectivity and toxicity for pancreatic acinar cells remains unknown, the potential therapeutic benefit of such an agent in patients with pancreatitis or pancreatic tumours warrants further investigation.
Kelly
L
L
Department of Pathology, University of Queensland, Herston, Australia.
Reid
L
L
Walker
N I
NI
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D000440:Butanols / Q000633:toxicity*; D018450:Disease Progression; D008297:Male; D008854:Microscopy, Electron; D009336:Necrosis; D010179:Pancreas / Q000473:pathology* / Q000502:physiology / Q000648:ultrastructure; D010182:Pancreatic Diseases / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration
D000440:Butanols; C077218:1-chloro-2-hydroxy-3-butene