Importance of investigating epigenetic alterations for industry and regulators: An appraisal of current efforts by the Health and Environmental Sciences Institute. (1st September 2015)

• Record Type: Journal Article
• Authors: Miousse, Isabelle R.; Currie, Richard; Datta, Kaushik; Ellinger-Ziegelbauer, Heidrun; French, John E.; Harrill, Alison H.; Koturbash, Igor; Lawton, Michael; Mann, Derek; Meehan, Richard R.; Moggs, Jonathan G.; O'Lone, Raegan; Rasoulpour, Reza J.; Pera, Renee A. Reijo; Thompson, Karol
• Is Part Of: Toxicology. Volume 335(2015)
• Page Start: 11
• Page End: 19
• Publication Date: 2015-09-01
• Subjects: 5-caC 5-carboxylcytosine -- 5-fC 5-formylcytosine -- 5-hmC 5-hydroxymethylcytosine -- 5-mC 5-methylcytosine -- DNMT DNA methyltransferase -- EWAS Epigenome-Wide Association Study -- HDAC histone deacetylase -- hESC human embryonic stem cell -- iPSC induced pluripotent stem cell -- NOAEL no-observed-adverse-effect level -- PGC primordial germ cells -- TCDD 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin; Epigenetics -- Safety assessment -- Models -- Transgenerational effects -- Stem cells -- Biomarkers; Toxicology -- Periodicals; Chemicals -- Physiological effect -- Periodicals; 615.9005
• DOI: 10.1016/j.tox.2015.06.009
• Languages: English
• ISSNs: 0300-483X

Abstract

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.