Document Detail

Food flavonoid aryl hydrocarbon receptor-mediated agonistic/antagonistic/synergic activities in human and rat reporter gene assays.
MedLine Citation:
PMID:  19286049     Owner:  NLM     Status:  MEDLINE    
Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor mediating the adverse effects of dioxins and polycyclic aromatic hydrocarbons (PAHs). In this study, we investigated the genetic-, time-, dose-, species- and tissue-dependent AhR-mediated agonistic/antagonistic activities of three food flavonoids: quercetin, chrysin and genistein. To that end, four stably transfected cell lines were used in cell-based luciferase reporter gene assays: three lines were transformed with the ptKLuc vector harbouring four dioxin-responsive elements (DREs) upstream of the thymidine kinase promoter and the luciferase gene (HepG2-Luc, T-47D-Luc and H4IIE-ULg). The fourth is a patented cell line transformed with a different construct: H4IIE DR-CALUX((R)). Both H4IIE cells were compared for their genetic construction. Human hepatoma (HepG2-Luc) and human breast tumour (T-47D-Luc) cells were compared for tissue-dependent effects. Rat hepatoma (H4IIE-ULg) and human hepatoma (HepG2-Luc) cells were compared for species-dependent activities. We concluded that quercetin, chrysin and genistein act in a time-, dose-, species- and tissue-specific way. For example, genistein displayed agonistic activities when exposed to rat hepatoma cells during 6h but not after 24h. Flavonoids displayed agonistic/antagonistic activities in human breast tumour cells, depending on the exposure time, while in human hepatoma cells, only antagonistic activities of flavonoids were measured. In addition, we report, in all the cells, a synergy between an isoflavone and two food contaminants; the 2,3,7,8-tetrachlorodibenzo-p-dioxin and 3-methylcholanthrene, a PAH. In rat cells, this synergy occurred when cells were exposed to flavonoids and contaminant for 6h, while it was observed in human cells only after 24h.
Edwige Van der Heiden; Nathalie Bechoux; Marc Muller; Thérèse Sergent; Yves-Jacques Schneider; Yvan Larondelle; Guy Maghuin-Rogister; Marie-Louise Scippo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-10-07
Journal Detail:
Title:  Analytica chimica acta     Volume:  637     ISSN:  1873-4324     ISO Abbreviation:  Anal. Chim. Acta     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-03-16     Completed Date:  2009-06-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370534     Medline TA:  Anal Chim Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  337-45     Citation Subset:  IM    
Department of Food Sciences, Laboratory of Food Analysis, Faculty of Veterinary Medicine, CART (Centre of Analysis of Residue in Traces), University of Liège, B43b, bld de Colonster 20, Sart-Tilman, B-4000 Liège, Belgium.
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MeSH Terms
Biological Assay / methods*
Cell Line, Tumor
Dose-Response Relationship, Drug
Flavonoids / analysis*,  pharmacology
Food Contamination / analysis*
Genes, Reporter*
Genistein / analysis,  pharmacology
Luciferases / metabolism
Luminescent Agents / metabolism
Quercetin / analysis,  pharmacology
Receptors, Aryl Hydrocarbon / agonists*,  antagonists & inhibitors*,  genetics
Time Factors
Reg. No./Substance:
0/Flavonoids; 0/Luminescent Agents; 0/Receptors, Aryl Hydrocarbon; 117-39-5/Quercetin; 446-72-0/Genistein; 480-40-0/chrysin; EC 1.13.12.-/Luciferases

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