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Differences in Immunohistochemical Expression of Xenobiotic-Metabolizing Enzymes Between Normal Pancreas, Chronic Pancreatitis and Pancreatic Cancer

UNMC Eppley Cancer Center, Department Surgery, Rheinische Friedrich-Wilhelms-University, Bonn, Germany

Matthias Schneider

UNMC Eppley Cancer Center

Alexis Ulrich

UNMC Eppley Cancer Center, Department of Surgery, University of Heidelberg, Germany

Markus W. Büchler

Department of Surgery, University of Heidelberg, Germany

Parviz M. Pour

UNMC Eppley Cancer Center, ppour{at}unmc.edu, Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, USA

Metabolic activation of many toxins, carcinogens, drugs, and anti-cancer agents is governed by the cytochrome P450 (CYP) drug-metabolizing enzyme system. To help elucidate the role of this enzyme system in the pathogenesis of chronic inflammatory and malignant pancreatic diseases, we compared the immunohistochemical expression pattern of 8 CYP-enzymes in 24 normal, 20 chronic pancreatitis, and 21 pancreatic cancer specimens using antibodies to CYP 1A1, 1A2, 2B6, 2C8/9/19, 2D6, 2E1, and 3A4, and the NADPH cytochrome P450 oxido-reductase (NA-OR). Compared to the normal pancreas, a higher frequency of immunopositivity for CYP 1A2, 2B6, 2C8/9/19, 2D6, and NA-OR was found in chronic pancreatitis, and of all CYPs but 1A2 in pancreatic cancer. On the other hand, CYP 1A1 and 2E1 antibody staining was less frequently observed in chronic pancreatitis. In all specimens with pancreatic polypeptide (PP)-rich regions (pancreas head), more islet cells than ductal and acinar cells were immunopositive. Moreover, the immunoreactivity of islet cells from PP-rich specimens with anti-CYP antibodies was consistently more frequent and intense than in islet cells from PP-poor areas (body and tail). Immunoreactivity for xenobiotic-metabolizing enzymes was frequently observed in the normal pancreas, chronic pancreatitis, and pancreatic cancer, and displayed differences of its frequency and intensity between the 3 groups. Considering immunohistochemical evidence of enzyme expression and pancreatic blood supply together, islet cells appear to be an important and possible early site of CYP-enzyme induction in pancreatic diseases.

Key Words: Cytochrome P450 • drug metabolism • islets of Langerhans • pancreatic polypeptide.

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Toxicologic Pathology, Vol. 31, No. 5, 506-513 (2003)
DOI: 10.1080/01926230390226041


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This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Standop, J. Articles by Pour, P. M. Search for Related Content PubMed PubMed Citation Articles by Standop, J. Articles by Pour, P. M. Social Bookmarking                         What's this?