Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Desaulniers, Daniel, Vasseur, Paule, Jacobs, Abigail, Aguila, M. Cecilia, Ertych, Norman, Jacobs, Miriam N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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
_version_ 1784587866042531840
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
work_keys_str_mv AT desaulniersdaniel integrationofepigeneticmechanismsintonongenotoxiccarcinogenicityhazardassessmentfocusondnamethylationandhistonemodifications
AT vasseurpaule integrationofepigeneticmechanismsintonongenotoxiccarcinogenicityhazardassessmentfocusondnamethylationandhistonemodifications
AT jacobsabigail integrationofepigeneticmechanismsintonongenotoxiccarcinogenicityhazardassessmentfocusondnamethylationandhistonemodifications
AT aguilamcecilia integrationofepigeneticmechanismsintonongenotoxiccarcinogenicityhazardassessmentfocusondnamethylationandhistonemodifications
AT ertychnorman integrationofepigeneticmechanismsintonongenotoxiccarcinogenicityhazardassessmentfocusondnamethylationandhistonemodifications
AT jacobsmiriamn integrationofepigeneticmechanismsintonongenotoxiccarcinogenicityhazardassessmentfocusondnamethylationandhistonemodifications