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Environ Int. 2021 Oct 01;158:106900. doi: 10.1016/j.envint.2021.106900. Epub 2021 Oct 01.

A human relevant mixture of persistent organic pollutants induces reactive oxygen species formation in isolated human leucocytes: Involvement of the β2-adrenergic receptor.

Environment international

Hanne Friis Berntsen, Johanna Bodin, Johan Øvrevik, Christopher Friis Berntsen, Gunn C Østby, Bendik C Brinchmann, Erik Ropstad, Oddvar Myhre

Affiliations

  1. Department of Production Animal Clinical Sciences, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, P.O. Box 5003 NMBU, NO-1432 Ås, Norway; National Institute of Occupational Health, P.O. Box 5330, Majorstuen, 0304 Oslo, Norway. Electronic address: [email protected].
  2. Department of Methods Development and Analytics, Norwegian Institute of Public Health, N-0456 Oslo, Norway. Electronic address: [email protected].
  3. Department of Environmental Health, Norwegian Institute of Public Health, N-0456 Oslo, Norway; Department of Biosciences, University of Oslo, Norway. Electronic address: [email protected].
  4. Department of Internal Medicine, Sykehuset Innlandet Hospital Trust, Gjøvik, Norway; Department of Internal Medicine, Lovisenberg Diaconal Hospital, Oslo, Norway. Electronic address: [email protected].
  5. Department of Production Animal Clinical Sciences, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, P.O. Box 5003 NMBU, NO-1432 Ås, Norway. Electronic address: [email protected].
  6. National Institute of Occupational Health, P.O. Box 5330, Majorstuen, 0304 Oslo, Norway; Department of Environmental Health, Norwegian Institute of Public Health, N-0456 Oslo, Norway. Electronic address: [email protected].
  7. Department of Production Animal Clinical Sciences, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, P.O. Box 5003 NMBU, NO-1432 Ås, Norway. Electronic address: [email protected].
  8. Department of Environmental Health, Norwegian Institute of Public Health, N-0456 Oslo, Norway. Electronic address: [email protected].

PMID: 34607039 DOI: 10.1016/j.envint.2021.106900

Abstract

Exposure to chlorinated (Cl), brominated (Br) and perfluoroalkyl acid (PFAA) persistent organic pollutants (POPs) is associated with immunotoxicity and other adverse effects in humans and animals. Previous studies on POPs have mainly focused on single chemicals, while studies on complex mixtures are limited. Using DCF and luminol assays we examined effects on ROS generation in isolated human neutrophils, monocytes and lymphocytes, after in vitro exposure to a total mixture and sub-mixtures of 29 persistent compounds (Cl, Br, and PFAA). The mixtures were based on compounds prominent in blood, breast milk, and/or food. All mixture combinations induced ROS production in one or several of the cell models, and in some cases even at concentrations corresponding to human blood levels (compound range 1 pM - 16 nM). Whilst some interactions were detected (assessed using a mixed linear model), halogenated subgroups mainly acted additively. Mechanistic studies in neutrophils at 500× human levels (0.5 nM - 8 µM) indicated similar mechanisms of action for the Cl, PFAA, the combined PFAA + Cl and total (PFAA + Br + Cl) mixtures, and ROS responses appeared to involve β2-adrenergic receptor (β2AR) and Ca

Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Keywords: Human leucocytes; Immunotoxicity; Mixture toxicity; Persistent organic pollutants; Reactive oxygen species; β2-adrenergic receptor

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