Enhanced glutathione S-transferase expression in 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine-resistant IEC-18 cells.
In the present study we show that repeated exposure of the rat intestinal epithelial cell line IEC-18 to 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N-OH-PhIP), from a toxicological point of view the most relevant phase-1 metabolite of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP, the main heterocyclic aromatic amine present in processed meat), led to the selection of N-OH-PhIP-resistant IEC-18 cells. This phenomenon was accompanied by a fivefold increase in total glutathione S-transferase (GST) activity, measured with the broad-spectrum substrate 1-chloro-2,4-dinitrobenzene, in the N-OH-PhIP-resistant IEC-18 cells. Furthermore, a Western blotting analysis revealed that the expression of GST subunits A1, A3, A4, M1 and P1 was enhanced in the N-OH-PhIP-resistant IEC-18 cells.
Teubner
W
W
Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.
Fuchs
J I
JI
Steinberg
P
P
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004351:Drug Resistance; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression; D005982:Glutathione Transferase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D007093:Imidazoles / Q000378:metabolism / Q000633:toxicity*; D008460:Meat / Q000032:analysis / Q000633:toxicity; D009153:Mutagens / Q000378:metabolism / Q000633:toxicity*; D011725:Pyridines / Q000378:metabolism / Q000633:toxicity*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats
D007093:Imidazoles; D009153:Mutagens; D011725:Pyridines; D012333:RNA, Messenger; C060533:2-hydroxyamino-1-methyl-6-phenylimidazo(4,5-b)pyridine; C491107:GSTT2 protein, human; D005982:Glutathione Transferase