Effects of Defined Mixtures of Persistent Organic Pollutants (POPs) on Pre-lethal Cytotoxicity in the Human A-498 Kidney Cell Line In Vitro

Mazia Amber, Yuling Xie, Hanne Friis Berntsen, Karin Elizabeth Zimmer, Erik Ropstad, Steven Verhaegen, Lisa Connolly*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

A total mixture of 29 persistent organic pollutants (POPs) modelled from Scandinavian blood concentrations was used to expose human A-498 kidney cells for 24 h over a concentration range spanning below to above blood level (1/10x, 1x, 50x, 100x, 500x). Its constituent submixtures (PFAA, Br, Cl) and co-mixtures (PFAA + Br, PFAA + Cl, Br + Cl) were also tested. Valinomycin (12 µM) was used as a cytotoxic comparative compound. Cell number (CN), nuclear area (NA), nuclear intensity (NI), mitochondrial membrane potential (MMP), and mitochondrial mass (MM) were assessed using high content analysis (HCA). Only the co-mixtures (PFAA + Cl, PFAA + Br) at 50x and 50x, 500x decreased CN, respectively. NI was increased by the total mixture at 500x and Cl mixture at all concentrations tested. MMP was increased by the total mixture at 100x and 500x, PFAA at 1x, Br + Cl and PFAA + Cl at 100x and 500x, respectively. MM was decreased by the total mixture at 500x. In contrast, valinomycin decreased CN and surviving cells showed a decrease in MMP and an increase in MM. In conclusion, POP exposure altered mitochondrial metabolism and induced cell death via an alternative mechanism to valinomycin. Only specific combinations of individual chemical classes, but not the total mixture, affected cell number.

Original languageEnglish
JournalExposure and Health
Early online date10 May 2021
DOIs
Publication statusEarly online date - 10 May 2021

Bibliographical note

Funding Information:
The POP mixtures used in this study were constructed under projects funded by the Norwegian Research Council (NFR), project 213076/H10 and project 204361/H10.

Funding Information:
This project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Grant Agreement No. 722634 ( http://protected.eu.com/ ).

Publisher Copyright:
© 2021, The Author(s).

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

Keywords

  • Brominated flame retardants
  • Cytotoxicity
  • High content analysis
  • Organochlorinated pesticides
  • Perfluorinated alkylating agents
  • Polychlorinated biphenyls

ASJC Scopus subject areas

  • Water Science and Technology
  • Pollution
  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

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