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Integration of Epigenetic Mechanisms into Non-Genotoxic Carcinogenicity Hazard Assessment: Focus on DNA Methylation and Histone Modifications
Epigenetics involves a series of mechanisms that entail histone and DNA covalent modifications and non-coding RNAs, and that collectively contribute to programing cell functions and differentiation. Epigenetic anomalies and DNA mutations are co-drivers of cellular dysfunctions, including carcinogene...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8535778/ https://www.ncbi.nlm.nih.gov/pubmed/34681626 http://dx.doi.org/10.3390/ijms222010969 |
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author | Desaulniers, Daniel Vasseur, Paule Jacobs, Abigail Aguila, M. Cecilia Ertych, Norman Jacobs, Miriam N. |
author_facet | Desaulniers, Daniel Vasseur, Paule Jacobs, Abigail Aguila, M. Cecilia Ertych, Norman Jacobs, Miriam N. |
author_sort | Desaulniers, Daniel |
collection | PubMed |
description | Epigenetics involves a series of mechanisms that entail histone and DNA covalent modifications and non-coding RNAs, and that collectively contribute to programing cell functions and differentiation. Epigenetic anomalies and DNA mutations are co-drivers of cellular dysfunctions, including carcinogenesis. Alterations of the epigenetic system occur in cancers whether the initial carcinogenic events are from genotoxic (GTxC) or non-genotoxic (NGTxC) carcinogens. NGTxC are not inherently DNA reactive, they do not have a unifying mode of action and as yet there are no regulatory test guidelines addressing mechanisms of NGTxC. To fil this gap, the Test Guideline Programme of the Organisation for Economic Cooperation and Development is developing a framework for an integrated approach for the testing and assessment (IATA) of NGTxC and is considering assays that address key events of cancer hallmarks. Here, with the intent of better understanding the applicability of epigenetic assays in chemical carcinogenicity assessment, we focus on DNA methylation and histone modifications and review: (1) epigenetic mechanisms contributing to carcinogenesis, (2) epigenetic mechanisms altered following exposure to arsenic, nickel, or phenobarbital in order to identify common carcinogen-specific mechanisms, (3) characteristics of a series of epigenetic assay types, and (4) epigenetic assay validation needs in the context of chemical hazard assessment. As a key component of numerous NGTxC mechanisms of action, epigenetic assays included in IATA assay combinations can contribute to improved chemical carcinogen identification for the better protection of public health. |
format | Online Article Text |
id | pubmed-8535778 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-85357782021-10-23 Integration of Epigenetic Mechanisms into Non-Genotoxic Carcinogenicity Hazard Assessment: Focus on DNA Methylation and Histone Modifications Desaulniers, Daniel Vasseur, Paule Jacobs, Abigail Aguila, M. Cecilia Ertych, Norman Jacobs, Miriam N. Int J Mol Sci Review Epigenetics involves a series of mechanisms that entail histone and DNA covalent modifications and non-coding RNAs, and that collectively contribute to programing cell functions and differentiation. Epigenetic anomalies and DNA mutations are co-drivers of cellular dysfunctions, including carcinogenesis. Alterations of the epigenetic system occur in cancers whether the initial carcinogenic events are from genotoxic (GTxC) or non-genotoxic (NGTxC) carcinogens. NGTxC are not inherently DNA reactive, they do not have a unifying mode of action and as yet there are no regulatory test guidelines addressing mechanisms of NGTxC. To fil this gap, the Test Guideline Programme of the Organisation for Economic Cooperation and Development is developing a framework for an integrated approach for the testing and assessment (IATA) of NGTxC and is considering assays that address key events of cancer hallmarks. Here, with the intent of better understanding the applicability of epigenetic assays in chemical carcinogenicity assessment, we focus on DNA methylation and histone modifications and review: (1) epigenetic mechanisms contributing to carcinogenesis, (2) epigenetic mechanisms altered following exposure to arsenic, nickel, or phenobarbital in order to identify common carcinogen-specific mechanisms, (3) characteristics of a series of epigenetic assay types, and (4) epigenetic assay validation needs in the context of chemical hazard assessment. As a key component of numerous NGTxC mechanisms of action, epigenetic assays included in IATA assay combinations can contribute to improved chemical carcinogen identification for the better protection of public health. MDPI 2021-10-11 /pmc/articles/PMC8535778/ /pubmed/34681626 http://dx.doi.org/10.3390/ijms222010969 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Desaulniers, Daniel Vasseur, Paule Jacobs, Abigail Aguila, M. Cecilia Ertych, Norman Jacobs, Miriam N. Integration of Epigenetic Mechanisms into Non-Genotoxic Carcinogenicity Hazard Assessment: Focus on DNA Methylation and Histone Modifications |
title | Integration of Epigenetic Mechanisms into Non-Genotoxic Carcinogenicity Hazard Assessment: Focus on DNA Methylation and Histone Modifications |
title_full | Integration of Epigenetic Mechanisms into Non-Genotoxic Carcinogenicity Hazard Assessment: Focus on DNA Methylation and Histone Modifications |
title_fullStr | Integration of Epigenetic Mechanisms into Non-Genotoxic Carcinogenicity Hazard Assessment: Focus on DNA Methylation and Histone Modifications |
title_full_unstemmed | Integration of Epigenetic Mechanisms into Non-Genotoxic Carcinogenicity Hazard Assessment: Focus on DNA Methylation and Histone Modifications |
title_short | Integration of Epigenetic Mechanisms into Non-Genotoxic Carcinogenicity Hazard Assessment: Focus on DNA Methylation and Histone Modifications |
title_sort | integration of epigenetic mechanisms into non-genotoxic carcinogenicity hazard assessment: focus on dna methylation and histone modifications |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8535778/ https://www.ncbi.nlm.nih.gov/pubmed/34681626 http://dx.doi.org/10.3390/ijms222010969 |
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