Expression of drug-metabolizing enzymes in the pancreas of hamster, mouse, and rat, responding differently to the pancreatic carcinogenicity of BOP.
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-pi, GST-alpha, and GST-mu) 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-alpha in islets, CYP2B6, CYP2C8,9,19, CYP3A1 in acinar cells, and CYP3A4 in ductal cells, in the rat as compared with hamster and mouse.


CONCLUSIONS
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.
Ulrich
Alexis B
AB
UNMC Eppley Cancer Center, University of Nebraska Medical Center, Omaha 68198, USA.
Standop
Jens
J
Schmied
Bruno M
BM
Schneider
Matthias B
MB
Lawson
Terence A
TA
Pour
Parviz M
PM
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D002273:Carcinogens / Q000378:metabolism* / Q000494:pharmacology; D006224:Cricetinae / Q000378:metabolism*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism*; D007515:Islets of Langerhans / Q000201:enzymology; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D051379:Mice / Q000378:metabolism*; D008819:Mice, Nude; D009602:Nitrosamines / Q000378:metabolism* / Q000494:pharmacology; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology*; D051381:Rats / Q000378:metabolism*; D017208:Rats, Wistar; D013045:Species Specificity; D014018:Tissue Distribution
D002273:Carcinogens; D007527:Isoenzymes; D009602:Nitrosamines; C013622:nitrosobis(2-oxopropyl)amine; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C465138:Cyp3a23-3a1 protein, rat; D051544:Cytochrome P-450 CYP3A; D005982:Glutathione Transferase