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An updated review of the genotoxicity of respirable crystalline silica
Human exposure to (certain forms of) crystalline silica (CS) potentially results in adverse effects on human health. Since 1997 IARC has classified CS as a Group 1 carcinogen [1], which was confirmed in a later review in 2012 [2]. The genotoxic potential and mode of genotoxic action of CS was not co...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5963024/ https://www.ncbi.nlm.nih.gov/pubmed/29783987 http://dx.doi.org/10.1186/s12989-018-0259-z |
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author | Borm, Paul J. A. Fowler, Paul Kirkland, David |
author_facet | Borm, Paul J. A. Fowler, Paul Kirkland, David |
author_sort | Borm, Paul J. A. |
collection | PubMed |
description | Human exposure to (certain forms of) crystalline silica (CS) potentially results in adverse effects on human health. Since 1997 IARC has classified CS as a Group 1 carcinogen [1], which was confirmed in a later review in 2012 [2]. The genotoxic potential and mode of genotoxic action of CS was not conclusive in either of the IARC reviews, although a proposal for mode of actions was made in an extensive review of the genotoxicity of CS by Borm, Tran and Donaldson in 2011 [3]. The present study identified 141 new papers from search strings related to genotoxicity of respirable CS (RCS) since 2011 and, of these, 17 relevant publications with genotoxicity data were included in this detailed review. Studies on in vitro genotoxic endpoints primarily included micronucleus (MN) frequency and % fragmented DNA as measured in the comet assay, and were mostly negative, apart from two studies using primary or cultured macrophages. In vivo studies confirmed the role of persistent inflammation due to quartz surface toxicity leading to anti-oxidant responses in mice and rats, but DNA damage was only seen in rats. The role of surface characteristics was strengthened by in vitro and in vivo studies using aluminium or hydrophobic treatment to quench the silanol groups on the CS surface. In conclusion, the different modes of action of RCS-induced genotoxicity have been evaluated in a series of independent, adequate studies since 2011. Earlier conclusions on the role of inflammation driven by quartz surface in genotoxic and carcinogenic effects after inhalation are confirmed and findings support a practical threshold. Whereas classic in vitro genotoxicity studies confirm an earlier no-observed effect level (NOEL) in cell cultures of 60-70 μg/cm(2), transformation frequency in SHE cells suggests a lower threshold around 5 μg/cm(2). Both levels are only achieved in vivo at doses (2–4 mg) beyond in vivo doses (> 200 μg) that cause persistent inflammation and tissue remodelling in the rat lung. |
format | Online Article Text |
id | pubmed-5963024 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-59630242018-06-25 An updated review of the genotoxicity of respirable crystalline silica Borm, Paul J. A. Fowler, Paul Kirkland, David Part Fibre Toxicol Review Human exposure to (certain forms of) crystalline silica (CS) potentially results in adverse effects on human health. Since 1997 IARC has classified CS as a Group 1 carcinogen [1], which was confirmed in a later review in 2012 [2]. The genotoxic potential and mode of genotoxic action of CS was not conclusive in either of the IARC reviews, although a proposal for mode of actions was made in an extensive review of the genotoxicity of CS by Borm, Tran and Donaldson in 2011 [3]. The present study identified 141 new papers from search strings related to genotoxicity of respirable CS (RCS) since 2011 and, of these, 17 relevant publications with genotoxicity data were included in this detailed review. Studies on in vitro genotoxic endpoints primarily included micronucleus (MN) frequency and % fragmented DNA as measured in the comet assay, and were mostly negative, apart from two studies using primary or cultured macrophages. In vivo studies confirmed the role of persistent inflammation due to quartz surface toxicity leading to anti-oxidant responses in mice and rats, but DNA damage was only seen in rats. The role of surface characteristics was strengthened by in vitro and in vivo studies using aluminium or hydrophobic treatment to quench the silanol groups on the CS surface. In conclusion, the different modes of action of RCS-induced genotoxicity have been evaluated in a series of independent, adequate studies since 2011. Earlier conclusions on the role of inflammation driven by quartz surface in genotoxic and carcinogenic effects after inhalation are confirmed and findings support a practical threshold. Whereas classic in vitro genotoxicity studies confirm an earlier no-observed effect level (NOEL) in cell cultures of 60-70 μg/cm(2), transformation frequency in SHE cells suggests a lower threshold around 5 μg/cm(2). Both levels are only achieved in vivo at doses (2–4 mg) beyond in vivo doses (> 200 μg) that cause persistent inflammation and tissue remodelling in the rat lung. BioMed Central 2018-05-21 /pmc/articles/PMC5963024/ /pubmed/29783987 http://dx.doi.org/10.1186/s12989-018-0259-z 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 | Review Borm, Paul J. A. Fowler, Paul Kirkland, David An updated review of the genotoxicity of respirable crystalline silica |
title | An updated review of the genotoxicity of respirable crystalline silica |
title_full | An updated review of the genotoxicity of respirable crystalline silica |
title_fullStr | An updated review of the genotoxicity of respirable crystalline silica |
title_full_unstemmed | An updated review of the genotoxicity of respirable crystalline silica |
title_short | An updated review of the genotoxicity of respirable crystalline silica |
title_sort | updated review of the genotoxicity of respirable crystalline silica |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5963024/ https://www.ncbi.nlm.nih.gov/pubmed/29783987 http://dx.doi.org/10.1186/s12989-018-0259-z |
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