Pancreatic necrosis and regeneration induced by 4-hydroxyaminoquinoline-1-oxide in the guinea pig.

A single intravenous injection of 4-hydroxyaminoquinoline-1-oxide, in a dose of 22.5 mg. per kg., induced marked necrosis of exocrine pancreas in inbred strain 13 guinea pigs within 48 hours. The pancreatic acinar cell necrosis was dose-dependent and was associated with a significantly elevated serum amylase level and reduction in amylase activity in the pancreatic tissue. The maximal necrotic changes in the exocrine pancreas were observed at 48 hours. After the necrotic phase, a striking regenerative response of pancreatic acinar tissue ensued. 3-H-thymidine autoradiographic studies revealed a labeling index of 28 per cent cells in several pancreatic lobules 66 hours after 4-hydroxyaminoquinoline-1-oxide injection. The acinar cell repair, as well as formation of the new acini in many pancreatic lobules, was complete by 84 hours. In some pancreatic lobules, pseudoacinar or ductular transformation was noted. The regenerative response in pancreatic acinar tissue and ductal epithelium induced by 4-hydroxyaminoquinolone-1-oxide in the guinea pig appeared to be severalfold higher than that noted during ethionine regeneration.