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 pancrea tic injury when given to animals in large amounts. To determine the course of CHB-induced pancreatopathy, rats were given a single subcutaneous dose o f CHB and the pancreas weighed and examined by light and electron microscop y and immunohistochemistry at intervals from 2 h to 28 days. The pancreatic lesion was unusual in that there was marked early oedema with limited infl ammatory cell infiltration, rapid synchronous onset of acinar cell apoptosi s and early advanced atrophy engendering only a limited regenerative respon se. Acinar cell apoptosis was atypical in that cell fragmentation was limit ed and phagocytosis delayed, resulting in extensive secondary necrosis. As ducts were unaffected by CHB, the crowded ducts making up the epithelial co mponent of atrophic lobules could be clearly shown to derive from their con densation and proliferation, not the redifferentiation of pre-existing acin ar cells, widely held to produce this lesion. Although the basis of CHB sel ectivity and toxicity for pancreatic acinar cells remains unknown, the pote ntial therapeutic benefit of such an agent in patients with pancreatitis or pancreatic tumours warrants further investigation.