PMID- 31479813
OWN - NLM
STAT- MEDLINE
DCOM- 20191223
LR  - 20191223
IS  - 1873-6424 (Electronic)
IS  - 0269-7491 (Linking)
VI  - 254
IP  - Pt B
DP  - 2019 Nov
TI  - A mixture of persistent organic pollutants relevant for human exposure inhibits 
      the transactivation activity of the aryl hydrocarbon receptor in vitro.
PG  - 113098
LID - S0269-7491(19)33697-8 [pii]
LID - 10.1016/j.envpol.2019.113098 [doi]
AB  - While humans are exposed to mixtures of persistent organic pollutants (POPs), 
      their risk assessment is usually based on a chemical-by-chemical approach. To 
      assess the health effects associated with mixed exposures, knowledge on mixture 
      toxicity is required. Several POPs are potential ligands of the Aryl hydrocarbon 
      receptor (AhR), which involves in xenobiotic metabolism and controls many 
      biological pathways. This study assesses AhR agonistic and antagonistic 
      activities of 29 POPs individually and in mixtures by using Chemical-Activated 
      LUciferase gene eXpression bioassays with 3 transgenic cell lines (rat hepatoma 
      DR-H4IIE, human hepatoma DR-Hep G2 and human mammary gland carcinoma DR-T47-D). 
      Among the 29 POPs, which were selected based on their abundance in Scandinavian 
      human blood, only 4 exerted AhR agonistic activities, while 16 were AhR 
      antagonists in DR-H4IIE, 5 in DR-Hep G2 and 7 in DR-T47-D when tested 
      individually. The total POP mixture revealed to be AhR antagonistic. It 
      antagonized EC(50) TCDD inducing AhR transactivation at a concentration of 125 
      and 250 and 500 fold blood levels in DR-H4IIE, DR-T47-D and DR-Hep G2, 
      respectively, although each compound was present at these concentrations lower 
      than their LOEC values. Such values could occur in real-life in food 
      contamination incidents or in exposed populations. In DR-H4IIE, the antagonism of 
      the total POP mixture was due to chlorinated compounds and, in particular, to 
      PCB-118 and PCB-138 which caused 90% of the antagonistic activity in the POP 
      mixture. The 16 active AhR antagonists acted additively. Their mixed effect was 
      predicted successfully by concentration addition or generalized concentration 
      addition models, rather than independent action, with only two-fold IC(50) 
      underestimation. We also attained good predictions for the full dose-response 
      curve of the antagonistic activity of the total POP mixture.
CI  - Copyright (c) 2019 Elsevier Ltd. All rights reserved.
FAU - Doan, T Q
AU  - Doan TQ
AD  - Laboratory of Food Analysis, FARAH-Veterinary Public Health, University of Liege, 
      Liege, 4000, Belgium.
FAU - Berntsen, H F
AU  - Berntsen HF
AD  - Department of Production Animal Clinical Sciences, Section of Experimental 
      Biomedicine, NMBU - Faculty of Veterinary Medicine, Oslo, N-0033, Norway; 
      Department of Administration, Lab Animal Unit, National Institute of Occupational 
      Health, P.O. Box 8149 Dep, Oslo, N-0033, Norway.
FAU - Verhaegen, S
AU  - Verhaegen S
AD  - Department of Production Animal Clinical Sciences, Section of Experimental 
      Biomedicine, NMBU - Faculty of Veterinary Medicine, Oslo, N-0033, Norway.
FAU - Ropstad, E
AU  - Ropstad E
AD  - Department of Production Animal Clinical Sciences, Section of Experimental 
      Biomedicine, NMBU - Faculty of Veterinary Medicine, Oslo, N-0033, Norway.
FAU - Connolly, L
AU  - Connolly L
AD  - Institute for Global Food Security, School of Biological Sciences, Queen's 
      University Belfast, Northern Ireland, BT7 1NN, UK.
FAU - Igout, A
AU  - Igout A
AD  - Department of Biomedical and Preclinical Sciences, Faculty of Medicine, 
      University of Liege, Liege, 4000, Belgium.
FAU - Muller, M
AU  - Muller M
AD  - GIGA-R, Laboratory for Organogenesis and Regeneration, University of Liege, 
      Liege, 4000, Belgium.
FAU - Scippo, M L
AU  - Scippo ML
AD  - Laboratory of Food Analysis, FARAH-Veterinary Public Health, University of Liege, 
      Liege, 4000, Belgium. Electronic address: mlscippo@uliege.be.
LA  - eng
PT  - Journal Article
DEP - 20190828
PL  - England
TA  - Environ Pollut
JT  - Environmental pollution (Barking, Essex : 1987)
JID - 8804476
RN  - 0 (Environmental Pollutants)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 2B2AQE8U50 (2,3',4,4',5-pentachlorobiphenyl)
RN  - 7Y6JIG1867 (2,2',3',4,4',5-hexachlorobiphenyl)
RN  - DFC2HB4I0K (Polychlorinated Biphenyls)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Environmental Pollutants/*pharmacology
MH  - Humans
MH  - Polychlorinated Biphenyls/chemistry/*pharmacology
MH  - Rats
MH  - Receptors, Aryl Hydrocarbon/agonists/antagonists & inhibitors/*chemistry
MH  - Transcriptional Activation/*drug effects
OTO - NOTNLM
OT  - Antagonistic activity
OT  - Aryl hydrocarbon receptor
OT  - Generalized concentration addition model
OT  - Human relevant mixture
OT  - Persistent organic pollutants
EDAT- 2019/09/04 06:00
MHDA- 2019/12/24 06:00
CRDT- 2019/09/04 06:00
PHST- 2019/07/10 00:00 [received]
PHST- 2019/08/16 00:00 [revised]
PHST- 2019/08/21 00:00 [accepted]
PHST- 2019/09/04 06:00 [pubmed]
PHST- 2019/12/24 06:00 [medline]
PHST- 2019/09/04 06:00 [entrez]
AID - S0269-7491(19)33697-8 [pii]
AID - 10.1016/j.envpol.2019.113098 [doi]
PST - ppublish
SO  - Environ Pollut. 2019 Nov;254(Pt B):113098. doi: 10.1016/j.envpol.2019.113098. 
      Epub 2019 Aug 28.