Fractionated low-dose exposure to ionizing radiation leads to DNA damage, epigenetic dysregulation, and behavioral impairment

Environmental Epigenetics
Igor KoturbashOlga Kovalchuk

Abstract

Studies ofFractionatedExposure toLowDoses ofIonizingRadiation (FELDIR) has become of increasing importance to clinical interventions. Its consequences on DNA damage, physical, and mental health have been insufficiently investigated, however. The goal of this study was to determine the effects of FELDIR on the brain using a mouse model. We addressed the levels of DNA damage, global genomic methylation, and DNA methylation machinery in cerebellum, frontal lobe, olfactory bulb and hippocampal tissues, as well as behavioral changes linked to FELDIR exposure. The results reveal increased levels of DNA damage, as reflected by increased occurrence of DNAStrandBreaks (SBs) and dysregulation of stress-response kinase p38. FELDIR also resulted in initial loss of global genomic methylation and altered expression of methyltransferases DNMT1 (down-regulation) and DNMT3a (up-regulation), as well as methyl-binding protein MeCP2 (up-regulation). FELDIR-associated behavioral changes included impaired skilled limb placement on a ladder rung task, increased rearing activity in an open field, and elevated anxiety-like behaviors. The said alterations showed significant dose and tissue specificity. Thus, FELDIR represents a critical impact on DNA in...Continue Reading

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Citations

Mar 19, 2019·Oxidative Medicine and Cellular Longevity·Shashank ShrishrimalRebecca E Oberley-Deegan
Jun 6, 2018·Frontiers in Aging Neuroscience·Neel K SharmaSanchita P Ghosh
Sep 12, 2018·International Journal of Environmental Research and Public Health·Ernesto BurgioLucia Migliore
Jul 5, 2019·International Journal of Radiation Oncology, Biology, Physics·Shubhankar SumanKamal Datta

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