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

被引:16
作者
Miousse, Isabelle R. [1 ]
Currie, Richard [2 ]
Datta, Kaushik [3 ]
Ellinger-Ziegelbauer, Heidrun [4 ]
French, John E. [5 ]
Harrill, Alison H. [1 ]
Koturbash, Igor [1 ]
Lawton, Michael [6 ]
Mann, Derek [7 ]
Meehan, Richard R. [8 ]
Moggs, Jonathan G. [9 ]
O'Lone, Raegan [10 ]
Rasoulpour, Reza J. [11 ]
Pera, Renee A. Reijo [12 ]
Thompson, Karol [13 ]
机构
[1] Univ Arkansas Med Sci, Dept Environm & Occupat Hlth, Little Rock, AR 72205 USA
[2] Syngenta Jealotts Hill Int Res Ctr, Bracknell, Berks, England
[3] Celgene Corp, Summit, NJ USA
[4] Bayer Pharma AG, Toxicol, Wuppertal, Germany
[5] NIEHS, Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA
[6] Pfizer Inc, Groton, CT 06340 USA
[7] Newcastle Univ, Inst Cellular Med, Fibrosis Res Grp, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England
[8] Univ Edinburgh, Inst Genet & Mol Med, MRC, Human Genet Unit, Edinburgh, Midlothian, Scotland
[9] Novartis Inst Biomed Res, Preclin Safety, Discovery & Invest Safety, Basel, Switzerland
[10] ILSI Hlth & Environm Sci Inst, Washington, DC 20036 USA
[11] Dow Chem Co USA, Toxicol Environm Res & Consulting, Midland, MI 48674 USA
[12] Montana State Univ, Bozeman, MT 59717 USA
[13] US FDA, Div Appl Regulatory Sci, OCP, CDER, Silver Spring, MD USA
关键词
Epigenetics; Safety assessment; Models; Transgenerational effects; Stem cells; Biomarkers; EPIGENOME-WIDE ASSOCIATION; EPSTEIN-BARR-VIRUS; DNA METHYLATION; STEM-CELLS; NATIONAL-HEALTH; CANCER; 5-HYDROXYMETHYLCYTOSINE; EXPOSURE; INHERITANCE; ZEBRAFISH;
D O I
10.1016/j.tox.2015.06.009
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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. (C) 2015 The Authors. Published by Elsevier Ireland Ltd.
引用
收藏
页码:11 / 19
页数:9
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