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In vitro-in vivo correlations of pulmonary inflammogenicity and genotoxicity of MWCNT

BACKGROUND: Multi-walled carbon nanotubes (MWCNT) have received attention due to extraordinary properties, resulting in concerns for occupational health and safety. Costs and ethical concerns of animal testing drive a need for in vitro models with predictive power in respiratory toxicity. The aim of...

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Autores principales: Di Ianni, Emilio, Erdem, Johanna Samulin, Møller, Peter, Sahlgren, Nicklas Mønster, Poulsen, Sarah Søs, Knudsen, Kristina Bram, Zienolddiny, Shan, Saber, Anne Thoustrup, Wallin, Håkan, Vogel, Ulla, Jacobsen, Nicklas Raun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299626/
https://www.ncbi.nlm.nih.gov/pubmed/34301283
http://dx.doi.org/10.1186/s12989-021-00413-2
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author Di Ianni, Emilio
Erdem, Johanna Samulin
Møller, Peter
Sahlgren, Nicklas Mønster
Poulsen, Sarah Søs
Knudsen, Kristina Bram
Zienolddiny, Shan
Saber, Anne Thoustrup
Wallin, Håkan
Vogel, Ulla
Jacobsen, Nicklas Raun
author_facet Di Ianni, Emilio
Erdem, Johanna Samulin
Møller, Peter
Sahlgren, Nicklas Mønster
Poulsen, Sarah Søs
Knudsen, Kristina Bram
Zienolddiny, Shan
Saber, Anne Thoustrup
Wallin, Håkan
Vogel, Ulla
Jacobsen, Nicklas Raun
author_sort Di Ianni, Emilio
collection PubMed
description BACKGROUND: Multi-walled carbon nanotubes (MWCNT) have received attention due to extraordinary properties, resulting in concerns for occupational health and safety. Costs and ethical concerns of animal testing drive a need for in vitro models with predictive power in respiratory toxicity. The aim of this study was to assess pro-inflammatory response (Interleukin-8 expression, IL-8) and genotoxicity (DNA strand breaks) caused by MWCNT with different physicochemical properties in different pulmonary cell models and correlate these to previously published in vivo data. Seven MWCNT were selected; two long/thick (NRCWE-006/Mitsui-7 and NM-401), two short/thin (NM-400 and NM-403), a pristine (NRCWE-040) and two surface modified; hydroxylated (NRCWE-041) and carboxylated (NRCWE-042). Carbon black Printex90 (CB) was included as benchmark material. Human alveolar epithelial cells (A549) and monocyte-derived macrophages (THP-1a) were exposed to nanomaterials (NM) in submerged conditions, and two materials (NM-400 and NM-401) in co-cultures of A549/THP-1a and lung fibroblasts (WI-38) in an air-liquid interface (ALI) system. Effective doses were quantified by thermo-gravimetric-mass spectrometry analysis (TGA-MS). To compare genotoxicity in vitro and in vivo, we developed a scoring system based on a categorization of effects into standard deviation (SD) units (< 1, 1, 2, 3 or 4 standard deviation increases) for the increasing genotoxicity. RESULTS: Effective doses were shown to be 25 to 53%, and 21 to 57% of the doses administered to A549 and THP-1a, respectively. In submerged conditions (A549 and THP-1a cells), all NM induced dose-dependent IL-8 expression. NM-401 and NRCWE-006 caused the strongest pro-inflammatory response. In the ALI-exposed co-culture, only NM-401 caused increased IL-8 expression, and no DNA strand breaks were observed. Strong correlations were found between in vitro and in vivo inflammation when doses were normalized by surface area (also proxy for diameter and length). Significantly increased DNA damage was found for all MWCNT in THP-1a cells, and for short MWCNT in A549 cells. A concordance in genotoxicity of 83% was obtained between THP-1a cells and broncho-alveolar lavaged (BAL) cells. CONCLUSION: This study shows correlations of pro-inflammatory potential in A549 and THP-1a cells with neutrophil influx in mice, and concordance in genotoxic response between THP-1a cells and BAL cells, for seven MWCNT. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12989-021-00413-2.
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spelling pubmed-82996262021-07-28 In vitro-in vivo correlations of pulmonary inflammogenicity and genotoxicity of MWCNT Di Ianni, Emilio Erdem, Johanna Samulin Møller, Peter Sahlgren, Nicklas Mønster Poulsen, Sarah Søs Knudsen, Kristina Bram Zienolddiny, Shan Saber, Anne Thoustrup Wallin, Håkan Vogel, Ulla Jacobsen, Nicklas Raun Part Fibre Toxicol Research BACKGROUND: Multi-walled carbon nanotubes (MWCNT) have received attention due to extraordinary properties, resulting in concerns for occupational health and safety. Costs and ethical concerns of animal testing drive a need for in vitro models with predictive power in respiratory toxicity. The aim of this study was to assess pro-inflammatory response (Interleukin-8 expression, IL-8) and genotoxicity (DNA strand breaks) caused by MWCNT with different physicochemical properties in different pulmonary cell models and correlate these to previously published in vivo data. Seven MWCNT were selected; two long/thick (NRCWE-006/Mitsui-7 and NM-401), two short/thin (NM-400 and NM-403), a pristine (NRCWE-040) and two surface modified; hydroxylated (NRCWE-041) and carboxylated (NRCWE-042). Carbon black Printex90 (CB) was included as benchmark material. Human alveolar epithelial cells (A549) and monocyte-derived macrophages (THP-1a) were exposed to nanomaterials (NM) in submerged conditions, and two materials (NM-400 and NM-401) in co-cultures of A549/THP-1a and lung fibroblasts (WI-38) in an air-liquid interface (ALI) system. Effective doses were quantified by thermo-gravimetric-mass spectrometry analysis (TGA-MS). To compare genotoxicity in vitro and in vivo, we developed a scoring system based on a categorization of effects into standard deviation (SD) units (< 1, 1, 2, 3 or 4 standard deviation increases) for the increasing genotoxicity. RESULTS: Effective doses were shown to be 25 to 53%, and 21 to 57% of the doses administered to A549 and THP-1a, respectively. In submerged conditions (A549 and THP-1a cells), all NM induced dose-dependent IL-8 expression. NM-401 and NRCWE-006 caused the strongest pro-inflammatory response. In the ALI-exposed co-culture, only NM-401 caused increased IL-8 expression, and no DNA strand breaks were observed. Strong correlations were found between in vitro and in vivo inflammation when doses were normalized by surface area (also proxy for diameter and length). Significantly increased DNA damage was found for all MWCNT in THP-1a cells, and for short MWCNT in A549 cells. A concordance in genotoxicity of 83% was obtained between THP-1a cells and broncho-alveolar lavaged (BAL) cells. CONCLUSION: This study shows correlations of pro-inflammatory potential in A549 and THP-1a cells with neutrophil influx in mice, and concordance in genotoxic response between THP-1a cells and BAL cells, for seven MWCNT. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12989-021-00413-2. BioMed Central 2021-07-23 /pmc/articles/PMC8299626/ /pubmed/34301283 http://dx.doi.org/10.1186/s12989-021-00413-2 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Di Ianni, Emilio
Erdem, Johanna Samulin
Møller, Peter
Sahlgren, Nicklas Mønster
Poulsen, Sarah Søs
Knudsen, Kristina Bram
Zienolddiny, Shan
Saber, Anne Thoustrup
Wallin, Håkan
Vogel, Ulla
Jacobsen, Nicklas Raun
In vitro-in vivo correlations of pulmonary inflammogenicity and genotoxicity of MWCNT
title In vitro-in vivo correlations of pulmonary inflammogenicity and genotoxicity of MWCNT
title_full In vitro-in vivo correlations of pulmonary inflammogenicity and genotoxicity of MWCNT
title_fullStr In vitro-in vivo correlations of pulmonary inflammogenicity and genotoxicity of MWCNT
title_full_unstemmed In vitro-in vivo correlations of pulmonary inflammogenicity and genotoxicity of MWCNT
title_short In vitro-in vivo correlations of pulmonary inflammogenicity and genotoxicity of MWCNT
title_sort in vitro-in vivo correlations of pulmonary inflammogenicity and genotoxicity of mwcnt
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299626/
https://www.ncbi.nlm.nih.gov/pubmed/34301283
http://dx.doi.org/10.1186/s12989-021-00413-2
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