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Oxidative Medicine and Cellular Longevity
Volume 2017 (2017), Article ID 9515809, 22 pages
https://doi.org/10.1155/2017/9515809
Research Article

Low-Dose Ionizing Radiation Affects Mesenchymal Stem Cells via Extracellular Oxidized Cell-Free DNA: A Possible Mediator of Bystander Effect and Adaptive Response

1Research Centre for Medical Genetics (RCMG), Moscow 115478, Russia
2V. A. Negovsky Research Institute of General Reanimatology, Moscow 107031, Russia
3Bach Institute of Biochemistry and Russian Academy of Sciences, 33 Leninskii Ave., Moscow 119071, Russia
4N. I. Pirogov Russian National Research Medical University, Moscow 117997, Russia

Correspondence should be addressed to V. A. Sergeeva; moc.liamg@enalpehtycart

Received 20 January 2017; Revised 17 April 2017; Accepted 18 May 2017; Published 22 August 2017

Academic Editor: Magdalena Skonieczna

Copyright © 2017 V. A. Sergeeva et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

We have hypothesized that the adaptive response to low doses of ionizing radiation (IR) is mediated by oxidized cell-free DNA (cfDNA) fragments. Here, we summarize our experimental evidence for this model. Studies involving measurements of ROS, expression of the NOX (superoxide radical production), induction of apoptosis and DNA double-strand breaks, antiapoptotic gene expression and cell cycle inhibition confirm this hypothesis. We have demonstrated that treatment of mesenchymal stem cells (MSCs) with low doses of IR (10 cGy) leads to cell death of part of cell population and release of oxidized cfDNA. cfDNA has the ability to penetrate into the cytoplasm of other cells. Oxidized cfDNA, like low doses of IR, induces oxidative stress, ROS production, ROS-induced oxidative modifications of nuclear DNA, DNA breaks, arrest of the cell cycle, activation of DNA reparation and antioxidant response, and inhibition of apoptosis. The MSCs pretreated with low dose of irradiation or oxidized cfDNA were equally effective in induction of adaptive response to challenge further dose of radiation. Our studies suggest that oxidized cfDNA is a signaling molecule in the stress signaling that mediates radiation-induced bystander effects and that it is an important component of the development of radioadaptive responses to low doses of IR.