Response of chemically induced hepatocytelike cells in hamster pancreas to methyl clofenapate, a peroxisome proliferator.

Abstract

Administration of N-nitrosobis(2-oxopropyl)amine during peak DNA synthesis of regenerating pancreas in hamsters was shown to induce hepatocyte-like cells in pancreas. Such cells respond to methyl clofenapate, a peroxisome proliferator. The response includes a marked proliferation of peroxisomes and enhanced activity of peroxisomal enzymes enoyl-CoA hydratase (8.5 to 13-fold), [1-14C]-palmitoyl-CoA oxidation (2.8 to 3.9-fold), catalase (1.6 to 3.4-fold) and carnitine acetyltransferase (> 2000-fold). Cytochemical localization of catalase by the alkaline 3,3''-diaminobenzidine procedure and immunofluorescence localization of heat-labile enoyl-CoA hydratase showed that these peroxisome-associated enzymes are localized strictly in pancreatic heptocyte-like cells, while adjacent acinar, duct and islet cells appeared consistently negative. Morphometric analyses of hepatocyte-like cells showed a significant increase in the numerical density and an 8-fold increase in the volume density of peroxisomes in methyl clofenapate-treated animals. The hepatocyte-like cells are responsible for the observed peroxisomal enzyme activity in pancreas of hamsters and the derepressed peroxisome specific genes in these cells may respond to a peroxisome proliferator as do parenchymal cells in hamster liver.