Paper published in a journal (Scientific congresses and symposiums)
A realistic mixture of Persistent Organic Pollutants (POPs) reveals possible synergism to inhibit the transactivation activities of the rat Aryl hydrocarbon Receptor (rAhR) in vitro
Doan Thi Que; Muller, Marc; Berntsen, HF et al.
2018In Toxicology Letters, p. 131-132
Peer Reviewed verified by ORBi
 

Files


Full Text
EUROTOX&BDS_2018_QD.pdf
Publisher postprint (9.42 MB)
Download

All documents in ORBi are protected by a user license.

Send to



Details



Keywords :
Persistent Organic Pollutants; DR-CALUX; Aryl hydrocarbon Receptor; Antagonistic; Synergistic mixture effect
Abstract :
[en] While organisms are exposed to mixtures of persistent organic pollutants (POPs), scientific studies usually focus on the toxicity of a single compound at a time and few have addressed the mixture effect. This study aims to determine how a realistic mixture of POPs can affect transactivation of the rat Aryl hydrocarbon Receptor (rAhR) in vitro. Luciferase reporter Dioxin responsive rat hepatoma cell lines (DR-H4IIE) were used to screen both rAhR agonistic and antagonistic activities of 29 compounds: six perfluorinated (PFAA), seven brominated (Br), and 16 chlorinated (Cl) compounds (seven polychlorinated biphenyls (PCBs) and nine organochlorine pesticides) listed as POPs under the 2001 Stockholm Convention. Only 5 (2 Cl and 3 Br) out of the 29 compounds presented rAhR agonistic activities while 16 (13 Cl and 3 Br) were rAhR antagonists. No effect was observed for PFAAs. To test possible interactions between these compounds, a mixture of these 29 POPs and six sub-mixtures (PFAA, Br, Cl, Cl + Br, Cl + PFAA and Br + PFAA), prepared based on the respective concentrations found in Scandinavian human blood with a normal daily intake, were tested for the same activities. Not surprisingly, POP mixture also displayed a rAhR antagonistic activity (IC50 = 371 ± 52 times the blood level) with the lowest effective concentration found at 75-time blood level. This level could be plausibly reached in humans after a food contamination incident or in highly exposed sub-populations. Testing the sub-mixtures showed that the Cl mixture is responsible for the antagonism of the POP mixture, contributing to 80% of the POP response. When DR-H4IIE cells were exposed to the Cl + PFAA mixture, the antagonist level was the same as the response of the POP mixture. This indicates that PFAAs are probably non-specific rAhR antagonists as they did not induce any antagonist response when tested alone. The IC50 of the Cl mixture calculated from the measured IC50 of all 13 active chlorinated compounds, using an additive model, was about the same as the measured IC50, 1.9 M and 2.3 M, respectively. This suggests that these compounds act additively in the Cl mixture. In contrast, the calculated and measured IC50 for the total POP mixture were 22 M and 43.2 M, respectively, along with non-specific rAhR antagonism of PFAA mixture, indicating a possible synergistic effect.
Research center :
FARAH - Fundamental and Applied Research for Animals and Health - ULiège
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Doan Thi Que ;  Université de Liège - ULiège > Form. doct. sc. (bioch., biol. mol. cel., bioinf. - paysage)
Muller, Marc  ;  Université de Liège - ULiège > Département des sciences de la vie > I3-Laboratory for Organogenesis and Regeneration
Berntsen, HF;  NMBU-Faculty of Veterinary Science, Oslo ,Norway > Department of Production Animal Clinical Sciences, Section of Experimental Biomedicine
Zimmer, KE;  NMBU-Faculty of Veterinary Science, Oslo , Norwa > Department of Basic Sciences and Aquatic Medicine, Section of Biochemistry and Physiology
Verhaegen, S;  NMBU-Faculty of Veterinary Science, Oslo ,Norway > Department of Production Animal Clinical Sciences, Section of Experimental Biomedicine
Ropstad, E;  NMBU-Faculty of Veterinary Science, Oslo ,Norway > Department of Production Animal Clinical Sciences, Section of Experimental Biomedicine
Connolly, L;  Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast. Northern Ireland, UK
Scippo, Marie-Louise  ;  Université de Liège - ULiège > Département de sciences des denrées alimentaires (DDA) > Analyse des denrées alimentaires
Language :
English
Title :
A realistic mixture of Persistent Organic Pollutants (POPs) reveals possible synergism to inhibit the transactivation activities of the rat Aryl hydrocarbon Receptor (rAhR) in vitro
Publication date :
01 October 2018
Event name :
EUROTOX, European Societies of Toxicology
Event date :
02-09-2018 to 05/09/2018
Audience :
International
Journal title :
Toxicology Letters
ISSN :
0378-4274
eISSN :
1879-3169
Publisher :
Elsevier, Netherlands
Pages :
131-132
Peer reviewed :
Peer Reviewed verified by ORBi
European Projects :
H2020 - 722634 - PROTECTED - PROTECTion against Endocrine Disruptors; Detection, mixtures, health effects, risk assessment and communication.
Funders :
UE - Union Européenne [BE]
Available on ORBi :
since 13 February 2019

Statistics


Number of views
126 (8 by ULiège)
Number of downloads
128 (6 by ULiège)

OpenCitations
 
0

Bibliography


Similar publications



Contact ORBi