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Toxicology. 2015 Sep 1;335:11-9. doi: 10.1016/j.tox.2015.06.009. Epub 2015 Jun 29.

Importance of investigating epigenetic alterations for industry and regulators: An appraisal of current efforts by the Health and Environmental Sciences Institute.

Author information

1
Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
2
Syngenta Jealotts Hill International Research Centre, Bracknell, Berkshire, UK.
3
Celgene Corporation, Summit, NJ, USA.
4
Toxicology, Bayer Pharma AG, Wuppertal, Germany; Member of the Innovative Medicines Initiative (IMI) BioMARkers & molecular tumor classification for non-genotoxic CARcinogenesis (MARCAR) consortium www.imi-marcar.eu.
5
National Institute for Environmental Health Sciences, Division of the National Toxicology Program, Research Triangle Park, NC, USA.
6
Pfizer, Groton, CT, USA.
7
Fibrosis Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, UK.
8
MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK; Member of the Innovative Medicines Initiative (IMI) BioMARkers & molecular tumor classification for non-genotoxic CARcinogenesis (MARCAR) consortium www.imi-marcar.eu.
9
Discovery and Investigative Safety, Preclinical Safety, Novartis Institutes for Biomedical Research, Basel, Switzerland; Member of the Innovative Medicines Initiative (IMI) BioMARkers & molecular tumor classification for non-genotoxic CARcinogenesis (MARCAR) consortium www.imi-marcar.eu.
10
ILSI Health and Environmental Sciences Institute, Washington, D.C., USA.
11
Toxicology Environmental Research and Consulting, The Dow Chemical Company, Midland, MI, USA.
12
Montana State University, Bozeman, MT, USA.
13
Division of Applied Regulatory Science, OCP, CDER, US FDA, Silver Spring, MD, USA.

Abstract

Recent technological advances have led to rapid progress in the characterization of epigenetic modifications that control gene expression in a generally heritable way, and are likely involved in defining cellular phenotypes, developmental stages and disease status from one generation to the next. On November 18, 2013, the International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) held a symposium entitled "Advances in Assessing Adverse Epigenetic Effects of Drugs and Chemicals" in Washington, D.C. The goal of the symposium was to identify gaps in knowledge and highlight promising areas of progress that represent opportunities to utilize epigenomic profiling for risk assessment of drugs and chemicals. Epigenomic profiling has the potential to provide mechanistic information in toxicological safety assessments; this is especially relevant for the evaluation of carcinogenic or teratogenic potential and also for drugs that directly target epigenetic modifiers, like DNA methyltransferases or histone modifying enzymes. Furthermore, it can serve as an endpoint or marker for hazard characterization in chemical safety assessment. The assessment of epigenetic effects may also be approached with new model systems that could directly assess transgenerational effects or potentially sensitive stem cell populations. These would enhance the range of safety assessment tools for evaluating xenobiotics that perturb the epigenome. Here we provide a brief synopsis of the symposium, update findings since that time and then highlight potential directions for future collaborative efforts to incorporate epigenetic profiling into risk assessment.

KEYWORDS:

Biomarkers; Epigenetics; Models; Safety assessment; Stem cells; Transgenerational effects

PMID:
26134581
DOI:
10.1016/j.tox.2015.06.009
[Indexed for MEDLINE]
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