4.5 Article

Potency of isothiocyanates to induce luciferase reporter gene expression via the electrophile-responsive element from murine glutathione S-transferase Ya

期刊

TOXICOLOGY IN VITRO
卷 23, 期 4, 页码 617-621

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PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tiv.2009.02.005

关键词

Isothiocyanate; Electrophile-responsive element; Antioxidant

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Isothiocyanates are electrophiles that are able to induce phase 11 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 mu M) 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 mu M 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. (C) 2009 Elsevier Ltd. All rights reserved.

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