TY - JOUR
T1 - Expression of drug-metabolizing enzymes in the pancreas of hamster, mouse, and rat, responding differently to the pancreatic carcinogenicity of BOP
AU - Ulrich, Alexis B.
AU - Standop, Jens
AU - Schmied, Bruno M.
AU - Schneider, Matthias B.
AU - Lawson, Terence A.
AU - Pour, Parviz M.
N1 - Funding Information:
This work was supported by the National Cancer Institutes’ SPORE Grant P50CA72712 and the American Cancer Society Special Institutional Grant. Alexis B. Ulrich is a recipient of a scholarship of the Deutsche Forschungsgemeinschaft, Germany.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
KW - BOP
KW - Cytochrome P-450
KW - Drug-metabolizing enzymes
KW - Glutathione S-transferase
KW - Hamster
KW - Islets
KW - Mouse
KW - Pancreas
KW - Rat
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U2 - 10.1159/000066094
DO - 10.1159/000066094
M3 - Article
C2 - 12435864
AN - SCOPUS:0036436768
SN - 1424-3903
VL - 2
SP - 519
EP - 527
JO - Pancreatology
JF - Pancreatology
IS - 6
ER -