Expression of drug-metabolizing enzymes in the pancreas of hamster, mouse, and rat, responding differently to the pancreatic carcinogenicity of BOP

Alexis B. Ulrich, Jens Standop, Bruno M. Schmied, Matthias B. Schneider, Terence A. Lawson, Parviz M. Pour

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)519-527
Number of pages9
JournalPancreatology
Volume2
Issue number6
DOIs
StatePublished - Jan 1 2002

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Cricetinae
Isoenzymes
Cytochrome P-450 CYP3A
Pancreas
Enzymes
Pharmaceutical Preparations
Cytochrome P-450 CYP2E1
Cytochrome P-450 CYP1A2
Cytochrome P-450 CYP1A1
Acinar Cells
Mesocricetus
Glutathione Transferase
Islets of Langerhans
Cytochrome P-450 Enzyme System
Amines
Adenocarcinoma
Immunohistochemistry
Cytochrome P-450 CYP2C8
Cytochrome P-450 CYP2B6

Keywords

  • BOP
  • Cytochrome P-450
  • Drug-metabolizing enzymes
  • Glutathione S-transferase
  • Hamster
  • Islets
  • Mouse
  • Pancreas
  • Rat

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Gastroenterology

Cite this

Expression of drug-metabolizing enzymes in the pancreas of hamster, mouse, and rat, responding differently to the pancreatic carcinogenicity of BOP. / Ulrich, Alexis B.; Standop, Jens; Schmied, Bruno M.; Schneider, Matthias B.; Lawson, Terence A.; Pour, Parviz M.

In: Pancreatology, Vol. 2, No. 6, 01.01.2002, p. 519-527.

Research output: Contribution to journalArticle

Ulrich, Alexis B. ; Standop, Jens ; Schmied, Bruno M. ; Schneider, Matthias B. ; Lawson, Terence A. ; Pour, Parviz M. / Expression of drug-metabolizing enzymes in the pancreas of hamster, mouse, and rat, responding differently to the pancreatic carcinogenicity of BOP. In: Pancreatology. 2002 ; Vol. 2, No. 6. pp. 519-527.
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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.

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