Epigenetic Effects of Ionizing Radiation
Over the past decade, research efforts have focused on elucidating the cellular and molecular mechanisms of ionizing radiation (IR)-induced effects in eukaryotic and, most importantly, mammalian cells. The primary sources of radiation exposure stem from d
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Epigenetic Effects of Ionizing Radiation Olga Kovalchuk
Abstract Over the past decade, research efforts have focused on elucidating the cellular and molecular mechanisms of ionizing radiation (IR)-induced effects in eukaryotic and, most importantly, mammalian cells. The primary sources of radiation exposure stem from diagnostic tests, therapeutic treatments, occupational exposures, nuclear tests, nuclear accidents, as well as the growing production of radioactive waste. It is now well accepted that the effects of IR exposure can be noticed far beyond the borders of the directly irradiated tissue. IR can affect neighboring cells, giving rise to a bystander effect. IR effects can also span several generations and influence the progeny of exposed parents, leading to transgenerational effects. Bystander and transgenerational IR effects are linked to the phenomenon of the IR-induced genome instability that manifests itself as chromosome aberrations, gene mutations, late cell death, and aneuploidy. While the occurrence of these phenomena is well documented, the mechanisms that lead to their development are still being defined. Mounting evidence suggests that IRinduced genome instability and bystander and transgenerational effects may be epigenetically mediated. The epigenetic alterations include DNA methylation, histone modification, and RNA-associated silencing. Recent studies show that IR exposure alters epigenetic parameters not only in the directly exposed tissues but also in the distant bystander tissues. Furthermore, transgenerational radiation effects are proposed to be of an epigenetic nature. In this chapter, I will discuss the role of the epigenetics in IR-induced direct responses, as well as in bystander and transgenerational effects.
O. Kovalchuk (*) Department of Biological Sciences, University of Lethbridge, 4401 University Drive, Alberta T1K 3M4, Canada e-mail: [email protected] R.L. Jirtle and F.L. Tyson (eds.), Environmental Epigenomics in Health and Disease, Epigenetics and Human Health, DOI 10.1007/978-3-642-23380-7_5, # Springer-Verlag Berlin Heidelberg 2013
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O. Kovalchuk
Keywords Bystander effects • Direct effects • DNA methylation • Epigenetics • Genome instability • Histone modifications • MicroRNAs • Radiation • Small RNAs • Transgenerational genome instability
Abbreviations 3D ATR BORIS DNA DNMT ESTR DSBs IR LSH MBD mRNA miRNA piRNA RB RISC RNA UTR
5.1
Three-dimensional Ataxia telangiectasia and Rad3 related Brother of the regulator of imprinted sites Deoxyribonucleic acid DNA methyltransferase Expanded simple tandem repeat Double-strand breaks Ionizing radiation Lymphoid-specific helicase Methyl CpG-binding domain Messenger RNA MicroRNA Piwi-interacting RNA Retinoblastoma RNA-induced silencing complex Ribonucleic acid Untranslated region
Introduction
All living organisms are exposed daily to radiation. In addition to diagnostic and therapeutic medical exposures, we are exposed chronically to background radiation from cosmic rays, radioactive waste, radon decay, nuclear te
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