Reference : A realistic mixture of Persistent Organic Pollutants (POPs) reveals possible synergis...
Scientific congresses and symposiums : Paper published in a journal
Life sciences : Biochemistry, biophysics & molecular biology
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, mailto [Université de Liège - ULiège > > > Form. doct. sc. (bioch., biol. mol. cel., bioinf. - paysage)]
Muller, Marc mailto [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 mailto [Université de Liège - ULiège > Département de sciences des denrées alimentaires (DDA) > Analyse des denrées alimentaires >]
Toxicology Letters
Yes (verified by ORBi)
EUROTOX, European Societies of Toxicology
02-09-2018 to 05/09/2018
[en] Persistent Organic Pollutants ; DR-CALUX ; Aryl hydrocarbon Receptor ; Antagonistic ; Synergistic mixture effect
[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.
Fundamental and Applied Research for Animals and Health - FARAH
EU Horizon 2020 Marie Skłodowska-Curie Actions Innovative Training Networks (ITN) – European Training Network (ETN) Grant No 722634.
H2020 ; 722634 - PROTECTED - PROTECTion against Endocrine Disruptors; Detection, mixtures, health effects, risk assessment and communication.

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