Journal
ARCHIVES OF TOXICOLOGY
Volume 91, Issue 7, Pages 2577-2597Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s00204-017-1979-9
Keywords
Epigentic changes; Environmental exposures; Epigenetic machinery; Histone modification; Therapy; Nutrition
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Epigenotoxicology is an emerging field of study that investigates the non-genotoxic epigenetic effects of environmental toxicants resulting in alteration of normal gene expression and disruption of cell function. Recent findings on the role of toxicant-induced epigenetic modifications in the development of degenerative diseases have opened up a promising research direction to explore epigenetic therapy approaches and related prognostic biomarkers. In this review, we presented comprehensive data on epigenetic alterations identified in various diseases, including cancer, autoimmune disorders, pulmonary conditions as well as cardiovascular, gastrointestinal and bone disease. Although data on abnormalities of DNA methylation and their role in the development of diseases are abundant, less is known about the impact of histone modifications and microRNA expressions. Further, we discussed the effects of selected common environmental toxicants on epigenetic modifications and their association with particular abnormalities. A number of different environmental toxicants have been identified for their role in aberrant DNA methylation, histone modifications, and microRNA expression. Such epigenetic effects were shown to be tissue-type specific and highly associated with the level and duration of exposure. Finally, we described present and future therapeutic strategies, including medicines and dietary compounds for combating the toxicant-induced epigenetic alterations. There are currently seven histone deacetylase inhibitors and two DNA methyltransferase inhibitors approved for clinical use and many other promising candidates are in preclinical and clinical testing. Dietary compounds are thought to be the effective and safe strategies for treating and prevention of epigenetic pathophysiological conditions. Still more concentrated epigenetic researches are required for evaluation of chemical toxicity and identifying the causal association between key epigenetic alteration and disease.
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