Immunohistochemical localization of carcinogen-metabolizing enzymes within the rat and hamster exocrine pancreas

The P-450 cytochromes, reduced nicotinamide adenine dinucleotide phosphate-cytochrome P-450 reductase, epoxide hydrolase, and glutathione S-transferases all play important roles in the bioactivation and detoxication of various classes of chemical mutagens and carcinogens. The present investigation was undertaken to determine if and where these enzymes are located within the exocrine pancreas, a tissue that is a target for chemically induced neoplasia. In this study, reduced nicotinamide adenine dinucleotide phosphate-cytochrome P-450 reductase, two isozymes of cytochrome P-450 (cytochromes P-450 PB-B and BNF-B), epoxide hydrolase, and glutathione S-transferases B, C/A, and E were each localized at the light microscopic level within exocrine pancreases of untreated rats and hamsters utilizing the unlabeled antibody peroxidase-antiperoxidase staining technique. Immunohistochemical staining for each of these enzymes was apparent within acinar cells in pancreases of Holtzman, Sprague-Dawley, Wistar, and Fischer 344 rats. Staining for the reductase, the epoxide hydrolase, and the glutathione S-transferases was also observed within the epithelia of both interlobular and intralobular ducts in the exocrine pancreases of these rat strains, whereas staining for cytochromes P-450 PB-B and BNF-B was not readily detectable within epithelial cells of the rat pancreatic duct system. In the exocrine pancreas of the Syrian golden hamster, immunohistochemical staining for reduced nicotinamide adenine dinucleotide phosphate-cytochrome P-450 reductase, epoxide hydrolase, and glutathione S-transferases B and C/A was similar to that observed within the rat exocrine pancreas. In contrast, acinar and duct cells in the hamster pancreas both appeared to be stained for cytochrome P-450 PB-B, whereas staining for cytochrome P-450 BNF-B could not be readily detected within either acinar or duct cells, and staining for glutathione S-transferases E did not appear to be present within duct cells in the hamster pancreas. The results of this investigation therefore suggest that highly reactive and toxic electrophilic metabolites of procarcinogens may be generated to the greatest extent within acinar cells in the rat pancreas, whereas these metabolites may be produced within both acinar and duct cells in the hamster pancreas. Regardless of where they are formed, reactive metabolites may be enzymatically detoxicated within both acinar and duct cells in the rat and hamster exocrine pancreas.