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The influence of exposure approaches to <i>in vitro</i> lung epithelial barrier models to assess engineered nanomaterial hazard

Kirsty Meldrum, Stephen Evans Orcid Logo, Ulla Vogel Orcid Logo, Lang Tran, Shareen Doak Orcid Logo, Martin Clift Orcid Logo

Nanotoxicology, Volume: 16, Issue: 1, Pages: 114 - 134

Swansea University Authors: Kirsty Meldrum, Stephen Evans Orcid Logo, Shareen Doak Orcid Logo, Martin Clift Orcid Logo

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DOI (Published version): 10.1080/17435390.2022.2051627

Abstract

Exposure to engineered nanomaterials (ENM) poses a potential health risk to humans through long-term, repetitive low-dose exposures. Currently, this is not commonplace within in vitro lung cell cultures. Therefore, the purpose of this study was to consider the optimal exposure approach toward determ...

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Published in: Nanotoxicology
ISSN: 1743-5390 1743-5404
Published: Informa UK Limited 2022
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URI: https://cronfa.swan.ac.uk/Record/cronfa59667
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spelling 2022-10-26T14:55:44.3853510 v2 59667 2022-03-18 The influence of exposure approaches to <i>in vitro</i> lung epithelial barrier models to assess engineered nanomaterial hazard bbb7bd27bfa3c6ffc73da8facfebc793 Kirsty Meldrum Kirsty Meldrum true false cfca981bdfb8492873a48cc1629def9a 0000-0002-5352-9800 Stephen Evans Stephen Evans true false 8f70286908f67238a527a98cbf66d387 0000-0002-6753-1987 Shareen Doak Shareen Doak true false 71bf49b157691e541950f5c3f49c9169 0000-0001-6133-3368 Martin Clift Martin Clift true false 2022-03-18 BMS Exposure to engineered nanomaterials (ENM) poses a potential health risk to humans through long-term, repetitive low-dose exposures. Currently, this is not commonplace within in vitro lung cell cultures. Therefore, the purpose of this study was to consider the optimal exposure approach toward determining the stability, sensitivity and validity of using in vitro lung cell mono- and co-cultures to determine ENM hazard. A range of exposure scenarios were conducted with DQ12 (previously established as a positive particle control) (historic and re-activated), TiO2 (JRC NM–105) and BaSO4 (JRC NM–220) on both monocultures of A549 cells as well as co-cultures of A549 cells and differentiated T HP-1 cells. Cell cultures were exposed to either a single, or a repeated exposure over 24, 48- or 72-hours at in vivo extrapolated concentrations of 0–5.2 μg/cm2, 0-6 μg/cm2 and 0-1μg/cm2. The focus of this study was the pro-inflammatory, cytotoxic and genotoxic response elicited by these ENMs. Exposure to DQ12 caused pro-inflammatory responses after 48 hours repeat exposures, as well as increases in micronucleus frequency. Neither TiO2 nor BaSO4 elicited a pro-inflammatory response at this time point. However, there was induction of IL-6 after 24 hours TiO2 exposure. In conclusion, it is important to consider the appropriateness of the positive control implemented, the cell culture model, the time of exposure as well as the type of exposure (bolus or fractionated) before establishing if an in vitro model is appropriate to determine the level of response to the specific ENM of interest. Journal Article Nanotoxicology 16 1 114 134 Informa UK Limited 1743-5390 1743-5404 In vitro; epithelial cells; co-culture; lung; nanoparticles 27 3 2022 2022-03-27 10.1080/17435390.2022.2051627 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University SU Library paid the OA fee (TA Institutional Deal) This study was supported by the PATROLS project, European Union’s Horizon 2020 Research and Innovation Programme under grant agreement No: 760813. 2022-10-26T14:55:44.3853510 2022-03-18T09:02:24.0228759 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Kirsty Meldrum 1 Stephen Evans 0000-0002-5352-9800 2 Ulla Vogel 0000-0001-6807-1524 3 Lang Tran 4 Shareen Doak 0000-0002-6753-1987 5 Martin Clift 0000-0001-6133-3368 6 59667__23677__f87c8f2179d04507b94b41f6a5f1edd4.pdf 59667.pdf 2022-03-28T10:20:33.2232567 Output 3682691 application/pdf Version of Record true © 2022 The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution License true eng http://creativecommons.org/licenses/by/4.0/
title The influence of exposure approaches to <i>in vitro</i> lung epithelial barrier models to assess engineered nanomaterial hazard
spellingShingle The influence of exposure approaches to <i>in vitro</i> lung epithelial barrier models to assess engineered nanomaterial hazard
Kirsty Meldrum
Stephen Evans
Shareen Doak
Martin Clift
title_short The influence of exposure approaches to <i>in vitro</i> lung epithelial barrier models to assess engineered nanomaterial hazard
title_full The influence of exposure approaches to <i>in vitro</i> lung epithelial barrier models to assess engineered nanomaterial hazard
title_fullStr The influence of exposure approaches to <i>in vitro</i> lung epithelial barrier models to assess engineered nanomaterial hazard
title_full_unstemmed The influence of exposure approaches to <i>in vitro</i> lung epithelial barrier models to assess engineered nanomaterial hazard
title_sort The influence of exposure approaches to <i>in vitro</i> lung epithelial barrier models to assess engineered nanomaterial hazard
author_id_str_mv bbb7bd27bfa3c6ffc73da8facfebc793
cfca981bdfb8492873a48cc1629def9a
8f70286908f67238a527a98cbf66d387
71bf49b157691e541950f5c3f49c9169
author_id_fullname_str_mv bbb7bd27bfa3c6ffc73da8facfebc793_***_Kirsty Meldrum
cfca981bdfb8492873a48cc1629def9a_***_Stephen Evans
8f70286908f67238a527a98cbf66d387_***_Shareen Doak
71bf49b157691e541950f5c3f49c9169_***_Martin Clift
author Kirsty Meldrum
Stephen Evans
Shareen Doak
Martin Clift
author2 Kirsty Meldrum
Stephen Evans
Ulla Vogel
Lang Tran
Shareen Doak
Martin Clift
format Journal article
container_title Nanotoxicology
container_volume 16
container_issue 1
container_start_page 114
publishDate 2022
institution Swansea University
issn 1743-5390
1743-5404
doi_str_mv 10.1080/17435390.2022.2051627
publisher Informa UK Limited
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 1
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description Exposure to engineered nanomaterials (ENM) poses a potential health risk to humans through long-term, repetitive low-dose exposures. Currently, this is not commonplace within in vitro lung cell cultures. Therefore, the purpose of this study was to consider the optimal exposure approach toward determining the stability, sensitivity and validity of using in vitro lung cell mono- and co-cultures to determine ENM hazard. A range of exposure scenarios were conducted with DQ12 (previously established as a positive particle control) (historic and re-activated), TiO2 (JRC NM–105) and BaSO4 (JRC NM–220) on both monocultures of A549 cells as well as co-cultures of A549 cells and differentiated T HP-1 cells. Cell cultures were exposed to either a single, or a repeated exposure over 24, 48- or 72-hours at in vivo extrapolated concentrations of 0–5.2 μg/cm2, 0-6 μg/cm2 and 0-1μg/cm2. The focus of this study was the pro-inflammatory, cytotoxic and genotoxic response elicited by these ENMs. Exposure to DQ12 caused pro-inflammatory responses after 48 hours repeat exposures, as well as increases in micronucleus frequency. Neither TiO2 nor BaSO4 elicited a pro-inflammatory response at this time point. However, there was induction of IL-6 after 24 hours TiO2 exposure. In conclusion, it is important to consider the appropriateness of the positive control implemented, the cell culture model, the time of exposure as well as the type of exposure (bolus or fractionated) before establishing if an in vitro model is appropriate to determine the level of response to the specific ENM of interest.
published_date 2022-03-27T04:17:09Z
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