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Vol. 2, No. 6, 2002
Issue release date: 2002
Section title: Original Paper
Pancreatology 2002;2:519–527
(DOI:10.1159/000066094)

Expression of Drug-Metabolizing Enzymes in the Pancreas of Hamster, Mouse, and Rat, Responding Differently to the Pancreatic Carcinogenicity of BOP

Ulrich 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

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 12/3/2001
Accepted: 6/11/2002
Published online: 11/28/2002

Number of Print Pages: 9
Number of Figures: 6
Number of Tables: 1

ISSN: 1424-3903 (Print)
eISSN: 1424-3911 (Online)

For additional information: http://www.karger.com/PAN

Abstract

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.


  

Author Contacts

Parviz M. Pour, MD
Eppley Institute for Research in Cancer
University of Nebraska Medical Center 986805 Nebraska Medical Center
Omaha, NE 68198-6805 (USA)
Tel. +1 402 559 4495, Fax +1 402 559 4651, E-Mail ppour@unmc.edu

  

Article Information

Received: December 3, 2001
Accepted: June 11, 2002
Number of Print Pages : 9
Number of Figures : 6, Number of Tables : 1, Number of References : 53

  

Publication Details

Pancreatology
Official Publication of the International Association of Pancreatology (IAP); Official Publication of the European Pancreatic Club (EPC); Official Publication of the Spanish Pancreatic Club; Official Publication of the Club Português do Pancreas; Official Publication of the Pancreatic Society of Great Britain and Ireland; Official Publication of the Associazione Italiana per lo Studio del Pancreas

Vol. 2, No. 6, Year 2002 (Cover Date: 2002)

Formerly International Journal of Pancreatology

Journal Editor: Manfred V. Singer, Mannheim; Clem W. Imrie, Glasgow
ISSN: 1424–3903 (print), 1424–3911 (Online)

For additional information: http://www.karger.com/journals/pan


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 12/3/2001
Accepted: 6/11/2002
Published online: 11/28/2002

Number of Print Pages: 9
Number of Figures: 6
Number of Tables: 1

ISSN: 1424-3903 (Print)
eISSN: 1424-3911 (Online)

For additional information: http://www.karger.com/PAN


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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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