Expression of Drug-Metabolizing Enzymes in the Pancreas of Hamster, Mouse, and Rat, Responding Differently to the Pancreatic Carcinogenicity of BOPUlrich A.B. · Standop J. · Schmied B.M. · Schneider M.B. · Lawson T.A. · Pour P.M.
aUNMC Eppley Cancer Center, University of Nebraska Medical Center, Omaha, Nebr., USA; bDepartment of Visceral and Transplantation Surgery, University of Heidelberg, and cDepartment of Surgery, Rheinische Friedrich-Wilhelms-University, Bonn, Germany; dDepartment of Visceral and Transplantation Surgery, Inselspital, Bern, Switzerland; Departments of ePharmaceutical Sciences and fPathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebr., USA
Background/Methods: N-nitroso-bis(2-oxopropyl)amine (BOP) induces pancreatic ductal adenocarcinoma in Syrian golden hamsters, but not in rats or mice. To examine whether this difference is due to the diversity in the presence and distribution of enzymes involved in the metabolism of BOP, the cellular expression of nine cytochrome P-450 isozymes (CYP1A1, CYP1A2, CYP2B6, CYP2C8,9,19, CYP2D1, CYP2E1, CYP3A1, CYP3A2, and CYP3A4) and of three glutathione S-transferase isozymes (GST-π, GST-α, and GST-µ) was investigated in the pancreas of hamsters, rats, and mice by immunohistochemistry. Results: We found a wide species variation in the presence and cellular localization of the enzymes and a lack of several enzymes, including GST-α in islets, CYP2B6, CYP2C8,9,19, CYP3A1 in acinar cells, and CYP3A4 in ductal cells, in the rat as compared with hamster and mouse. Conclusion: Although the results could not clarify the reasons for the species differences in the pancreatic carcinogenicity of BOP, the presence of most of the cytochrome P-450 isozymes in pancreatic islets of all three species highlights the important role of the islets in drug metabolism.