King Saud University Repository >
King Saud University >
Health Colleges >
College of Pharmacy >
College of Pharmacy >

Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/17120

Authors: Wael M. El-Sayed
Tarek Aboul-Fadl
Jeanette C. Roberts
John G. Lamb
Issue Date: 2007
Publisher: Toxicol In Vitro
Abstract: Murine (Hepa1c1c7) hepatoma cells are a suitable in vitro system for investigating the regulation of chemoprotective enzymes by selenazolidines, novel L-selenocysteine prodrugs developed as potential chemopreventive agents. They are less sensitive to the cytotoxic effects of both selenite and the less toxic selenazolidines than rat hepatoma (H4IIE) cells. All four selenazolidine 4-carboxylic acid (SCA) derivatives examined elevated thioredoxin reductase (Txnrd1), alpha-class glutathione transferases (Gsta), and UDP-glucuronosyltransferase (Ugt)1a6 mRNAs. NAD(P)Hquinone oxidoreductase (Nqo1) was induced by the three 2-alkyl derivatives (2-cyclohexylSCA, 2-butylSCA, and 2-methylSCA) but not SCA itself. Transcripts of mu- and pi-class glutathione transferases were induced only by 2-cyclohexylSCA and 2-butylSCA. Only Gsta and Txnrd1transcripts were elevated by L-selenomethionine, L-selenocystine, or Se-methyl-L-selenocysteine. Txnrd1, Gsta, Nqo1, and Gstp responses to selenazolidines were all abolished by actinomycin D while Ugt1a6 responses were not. Induction responses to the selenazolidines were also eliminated (most) or reduced (Txnrd1 by 2-methylSCA) by cycloheximide, with the exception of Ugt1a6. The Ugt1a6 mRNA levels in the presence of SCAs and cycloheximide were similar to those with cycloheximide alone, and were almost double those of vehicle-treated cells. Thus, Hepa1c1c7 cells appear to provide a viable platform for the study of protective enzyme regulation by selenocompounds, and with the exception of Ugt1a6, the mRNA elevations from selenazolidines are transcriptionally dependent .
URI: http://hdl.handle.net/123456789/17120
Appears in Collections:College of Pharmacy

Files in This Item:

File Description SizeFormat
8.doc53 kBMicrosoft WordView/Open

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.


DSpace Software Copyright © 2002-2009 MIT and Hewlett-Packard - Feedback