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

doi:10.1007/s12403-021-00396-7

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

School of Biological Sciences

Research output: Contribution to journal › Article › peer-review

5 Citations (Scopus)

113 Downloads (Pure)

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 language	English
Pages (from-to)	465–475
Journal	Exposure and Health
Volume	13
Early online date	10 May 2021
DOIs	https://doi.org/10.1007/s12403-021-00396-7
Publication status	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1007/s12403-021-00396-7Licence: CC BY

Effects of defined mixtures of persistent organic pollutants (pops) on pre-lethal cytotoxicity in the human A-498 kidney cell line in vitro
Copyright 2021 the authors. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Final published version, 767 KBLicence: CC BY

Effects of endocrine disrupting chemicals and their human-relevant mixtures on cellular health and hormone receptor function
Amber, M. (Author), Connolly, L. (Supervisor), Verhaegen, S. (Supervisor), Ropstad, E. (Supervisor) & Green, B. (Supervisor), Jul 2023
Student thesis: Doctoral Thesis › Doctor of Philosophy
Endocrine disrupting chemicals : impact on obesity/diabetes pathways and intervention via dietary nutrients
Xie, Y. (Author), Connolly, L. (Supervisor) & Green, B. (Supervisor), Dec 2019
Student thesis: Doctoral Thesis › Doctor of Philosophy

File

Cite this

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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.",

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author = "Mazia Amber and Yuling Xie and Berntsen, {Hanne Friis} and Zimmer, {Karin Elizabeth} and Erik Ropstad and Steven Verhaegen and Lisa Connolly",

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{\textquoteright}s Horizon 2020 research and innovation program under the Marie Sk{\l}odowska-Curie Grant Agreement No. 722634 ( http://protected.eu.com/ ). Publisher Copyright: {\textcopyright} 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

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AU - Amber, Mazia

AU - Xie, Yuling

AU - Berntsen, Hanne Friis

AU - Zimmer, Karin Elizabeth

AU - Ropstad, Erik

AU - Verhaegen, Steven

AU - Connolly, Lisa

N1 - 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.

PY - 2021/5/10

Y1 - 2021/5/10

N2 - 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.

AB - 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.

KW - Brominated flame retardants

KW - Cytotoxicity

KW - High content analysis

KW - Organochlorinated pesticides

KW - Perfluorinated alkylating agents

KW - Polychlorinated biphenyls

U2 - 10.1007/s12403-021-00396-7

DO - 10.1007/s12403-021-00396-7

M3 - Article

AN - SCOPUS:85105565978

SN - 2451-9766

VL - 13

SP - 465

EP - 475

JO - Exposure and Health

JF - Exposure and Health

ER -

Effects of defined mixtures of persistent organic pollutants (pops) on pre-lethal cytotoxicity in the human A-498 kidney cell line in vitro

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Fingerprint

Student theses

Effects of endocrine disrupting chemicals and their human-relevant mixtures on cellular health and hormone receptor function

Endocrine disrupting chemicals : impact on obesity/diabetes pathways and intervention via dietary nutrients

Cite this