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Primary genotoxicity in the liver following pulmonary exposure to carbon black nanoparticles in mice
BACKGROUND: Little is known about the mechanism underlying the genotoxicity observed in the liver following pulmonary exposure to carbon black (CB) nanoparticles (NPs). The genotoxicity could be caused by the presence of translocated particles or by circulating inflammatory mediators released during...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5753473/ https://www.ncbi.nlm.nih.gov/pubmed/29298701 http://dx.doi.org/10.1186/s12989-017-0238-9 |
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author | Modrzynska, Justyna Berthing, Trine Ravn-Haren, Gitte Jacobsen, Nicklas Raun Weydahl, Ingrid Konow Loeschner, Katrin Mortensen, Alicja Saber, Anne Thoustrup Vogel, Ulla |
author_facet | Modrzynska, Justyna Berthing, Trine Ravn-Haren, Gitte Jacobsen, Nicklas Raun Weydahl, Ingrid Konow Loeschner, Katrin Mortensen, Alicja Saber, Anne Thoustrup Vogel, Ulla |
author_sort | Modrzynska, Justyna |
collection | PubMed |
description | BACKGROUND: Little is known about the mechanism underlying the genotoxicity observed in the liver following pulmonary exposure to carbon black (CB) nanoparticles (NPs). The genotoxicity could be caused by the presence of translocated particles or by circulating inflammatory mediators released during pulmonary inflammation and acute-phase response. To address this, we evaluated induction of pulmonary inflammation, pulmonary and hepatic acute-phase response and genotoxicity following exposure to titanium dioxide (TiO(2)), cerium oxide (CeO(2)) or CB NPs. Female C57BL/6 mice were exposed by intratracheal instillation, intravenous injection or oral gavage to a single dose of 162 μg NPs/mouse and terminated 1, 28 or 180 days post-exposure alongside vehicle control. RESULTS: Liver DNA damage assessed by the Comet Assay was observed after intravenous injection and intratracheal instillation of CB NPs but not after exposure to TiO(2) or CeO(2). Intratracheal exposure to NPs resulted in pulmonary inflammation in terms of increased neutrophils influx for all NPs 1 and 28 days post-exposure. Persistent pulmonary acute phase response was detected for all NPs at all three time points while only a transient induction of hepatic acute phase response was observed. All 3 materials were detected in the liver by enhanced darkfield microscopy up to 180 days post-exposure. In contrast to TiO(2) and CeO(2) NPs, CB NPs generated ROS in an acellular assay. CONCLUSIONS: Our results suggest that the observed hepatic DNA damage following intravenous and intratracheal dosing with CB NPs was caused by the presence of translocated, ROS-generating, particles detected in the liver rather than by the secondary effects of pulmonary inflammation or hepatic acute phase response. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12989-017-0238-9) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5753473 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-57534732018-01-05 Primary genotoxicity in the liver following pulmonary exposure to carbon black nanoparticles in mice Modrzynska, Justyna Berthing, Trine Ravn-Haren, Gitte Jacobsen, Nicklas Raun Weydahl, Ingrid Konow Loeschner, Katrin Mortensen, Alicja Saber, Anne Thoustrup Vogel, Ulla Part Fibre Toxicol Research BACKGROUND: Little is known about the mechanism underlying the genotoxicity observed in the liver following pulmonary exposure to carbon black (CB) nanoparticles (NPs). The genotoxicity could be caused by the presence of translocated particles or by circulating inflammatory mediators released during pulmonary inflammation and acute-phase response. To address this, we evaluated induction of pulmonary inflammation, pulmonary and hepatic acute-phase response and genotoxicity following exposure to titanium dioxide (TiO(2)), cerium oxide (CeO(2)) or CB NPs. Female C57BL/6 mice were exposed by intratracheal instillation, intravenous injection or oral gavage to a single dose of 162 μg NPs/mouse and terminated 1, 28 or 180 days post-exposure alongside vehicle control. RESULTS: Liver DNA damage assessed by the Comet Assay was observed after intravenous injection and intratracheal instillation of CB NPs but not after exposure to TiO(2) or CeO(2). Intratracheal exposure to NPs resulted in pulmonary inflammation in terms of increased neutrophils influx for all NPs 1 and 28 days post-exposure. Persistent pulmonary acute phase response was detected for all NPs at all three time points while only a transient induction of hepatic acute phase response was observed. All 3 materials were detected in the liver by enhanced darkfield microscopy up to 180 days post-exposure. In contrast to TiO(2) and CeO(2) NPs, CB NPs generated ROS in an acellular assay. CONCLUSIONS: Our results suggest that the observed hepatic DNA damage following intravenous and intratracheal dosing with CB NPs was caused by the presence of translocated, ROS-generating, particles detected in the liver rather than by the secondary effects of pulmonary inflammation or hepatic acute phase response. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12989-017-0238-9) contains supplementary material, which is available to authorized users. BioMed Central 2018-01-03 /pmc/articles/PMC5753473/ /pubmed/29298701 http://dx.doi.org/10.1186/s12989-017-0238-9 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Modrzynska, Justyna Berthing, Trine Ravn-Haren, Gitte Jacobsen, Nicklas Raun Weydahl, Ingrid Konow Loeschner, Katrin Mortensen, Alicja Saber, Anne Thoustrup Vogel, Ulla Primary genotoxicity in the liver following pulmonary exposure to carbon black nanoparticles in mice |
title | Primary genotoxicity in the liver following pulmonary exposure to carbon black nanoparticles in mice |
title_full | Primary genotoxicity in the liver following pulmonary exposure to carbon black nanoparticles in mice |
title_fullStr | Primary genotoxicity in the liver following pulmonary exposure to carbon black nanoparticles in mice |
title_full_unstemmed | Primary genotoxicity in the liver following pulmonary exposure to carbon black nanoparticles in mice |
title_short | Primary genotoxicity in the liver following pulmonary exposure to carbon black nanoparticles in mice |
title_sort | primary genotoxicity in the liver following pulmonary exposure to carbon black nanoparticles in mice |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5753473/ https://www.ncbi.nlm.nih.gov/pubmed/29298701 http://dx.doi.org/10.1186/s12989-017-0238-9 |
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