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Aryl hydrocarbon receptor transactivation assays to study health impacts of exposure to mixtures of endocrine disrupting chemicals
Doan Thi Que


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Abstract :
[en] While most of the experimental studies investigated endocrine disruptors (EDs) as single compounds, there is a need for studying their mixture effect, which is more relevant to human exposure routes and impacts. This study aims to reveal the health impacts of exposure to mixture EDs at the level of the aryl hydrocarbon receptor (AhR) function, a key receptor to cope with xenobiotic compounds including EDs. In this study, DR-CALUX cell-based assays, wich are quick, relevant and effective tools using luciferase as a reporter gene, have been used to screen AhR transactivation activities i.e. agonistic and antagonistic of 29 different chlorinated, brominated and perfluorinated compounds listed as persistent organic pollutants (POPs) under the Stockholm Convention on Persistent Organic Pollutants (SCPOP). Three different reporter gene transformed cell lines (rat hepatoma H4IIE, human mammary gland carcinoma T47-D and human hepatoma Hep G2 cells) have been selected for this study. To evaluate the mixture effect, transactivation activities of individual EDs will, first, be identified. Then, each compound will be assigned for a response index. A mixture of the compounds with high indexes (>5% of the maximum response of the reference compounds is considered as positive) will be constructed for identifying their activity contribution for the total effects. Initially, there are variations among compounds and cell lines. Hep G2 cell lines gave no responses with all 29 compounds, while H4IIE and T47-D cell lines shown some significant AhR agonistic activities with PBDE 99 (EC50 of PBDE 99 = 148.5 ±70.3 nM and 1866 ±1756 nM, respectively), while PCB 138 activated H4IIE only; gamma HCH did the same with T47-D only. Interestingly, trans-nonachlor and alpha-chlordane inhibited the activities of endogenous AhR ligands with negative responses in H4IIE, but they are positive T47-D AhR ligands, activating AhR transactivation in T47-D.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Doan Thi Que ;  Université de Liège - ULiège > Form. doct. sc. (bioch., biol. mol. cel., bioinf. - paysage)
Language :
Title :
Aryl hydrocarbon receptor transactivation assays to study health impacts of exposure to mixtures of endocrine disrupting chemicals
Publication date :
October 2017
Event name :
4th FARAH DAY 2017
Event date :
European Projects :
H2020 - 722634 - PROTECTED - PROTECTion against Endocrine Disruptors; Detection, mixtures, health effects, risk assessment and communication.
Name of the research project :
Funders :
H2020-MSCA-ITN-2016 (Marie Skłodowska-Curie Innovative Training Networks)
CE - Commission Européenne [BE]
Available on ORBi :
since 12 February 2019


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