Title
Potency of isothiocyanates to induce luciferase reporter gene expression via the electrophile-responsive element from murine glutathione S-transferase Ya
Author
Vermeulen, M.
Boerboom, A.M.M.J.F.
Blankvoort, B.M.G.
Aarts, J.M.M.J.G.
Rietjens, I.M.C.M.
van Bladeren, P.J.
Vaes, W.H.J.
TNO Kwaliteit van Leven
Publication year
2009
Abstract
Isothiocyanates are electrophiles that are able to induce phase II biotransformation enzyme gene expression via an electrophile-responsive element (EpRE) in the gene regulatory region. To study the potency of different isothiocyanates to induce the expression of EpRE-regulated genes, a Hepa-1c1c7 luciferase reporter cell line was exposed to structurally different isothiocyanates. The reporter cell line, EpRE(mGST-Ya)-LUX, contains the EpRE from the regulatory region of the mouse glutathione S-transferase Ya gene. Isothiocyanates containing a methyl-sulfur side chain, e.g. sulforaphane, showed a lower EC50 (0.8-3.2 μM) and a comparable induction factor (17-22.4) compared to the structurally different isothiocyanates containing an alkyl or aromatic side chain, e.g. allyl and phenylethyl isothiocyanate (EC50 3.9-6.5 μM, induction factor 17.5-23). After 24 h of exposure, on average (±SD) 23 ± 5% of the isothiocyanate was found in the cells and 77% in the cell medium. Isothiocyanates prove to be strong inducers of electrophile-responsive element-mediated gene expression at physiological concentrations. The here described luciferase reporter cell line is a suitable assay to measure the potency of compounds to induce EpRE-regulated gene expression. © 2009 Elsevier Ltd. All rights reserved.
Subject
Biology
Analytical research
Antioxidant
Electrophile-responsive element
Isothiocyanate
electrophile
glutathione s transferase Ya
glutathione transferase
isothiocyanic acid derivative
luciferase
phenyl isothiocyanate
sulforaphane
unclassified drug
animal cell
article
cell assay
cell line
chemical structure
concentration response
controlled study
drug potency
enzyme induction
gene expression regulation
gene induction
gene location
mouse
nonhuman
reporter gene
Animals
Cell Line
Cell Survival
Gene Expression Regulation
Genes, Reporter
Glutathione Transferase
Isothiocyanates
Luciferases
Mice
Response Elements
Murinae
To reference this document use:
http://resolver.tudelft.nl/uuid:425a161e-cb33-486a-a38f-d453a57d532c
DOI
https://doi.org/10.1016/j.tiv.2009.02.005
TNO identifier
241580
ISSN
0887-2333
Source
Toxicology in Vitro, 23 (4), 617-621
Document type
article