Research Paper|Volume 9, Issue 11|pp 2397—2410

Residual γH2AX foci induced by low dose x-ray radiation in bone marrow mesenchymal stem cells do not cause accelerated senescence in the progeny of irradiated cells

Margarita Pustovalova^1,², Тatiana A. Astrelina¹, Anna Grekhova^1,^2,³, Natalia Vorobyeva^1,², Anastasia Tsvetkova^1,⁴, Taisia Blokhina^1,², Victoria Nikitina¹, Yulia Suchkova¹, Daria Usupzhanova¹, Vitalyi Brunchukov¹, Irina Kobzeva¹, Тatiana Karaseva¹, Ivan V. Ozerov^1,⁵, Aleksandr Samoylov¹, Andrey Bushmanov¹, Sergey Leonov^4,⁶, Evgeny Izumchenko⁷, Alex Zhavoronkov⁵, Dmitry Klokov^8,⁹, Andreyan N. Osipov^1,^2,^4,⁵

¹State Research Center - Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency, Moscow 123098, Russia
²Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow 119991, Russia
³Emanuel Institute for Biochemical Physics, Russian Academy of Sciences, Moscow 119991, Russia
⁴School of Biological and Medical Physics, Moscow Institute of Physics and Technology, Dolgoprudny, Moscow Region 141700, Russia
⁵Insilico Medicine, Inc, ETC, Johns Hopkins University, Baltimore, MD 21218, USA
⁶Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia
⁷Department of Otolaryngology-Head and Neck Cancer Research, Johns Hopkins University, School of Medicine, Baltimore, MD 21218, USA
⁸Canadian Nuclear Laboratories, Chalk River, Ontario K0J1P0, Canada
⁹University of Ottawa, Ottawa, Ontario K1N6N5, Canada

Received: August 18, 2017Accepted: November 11, 2017Published: November 21, 2017

https://doi.org/10.18632/aging.101327

Copyright: © 2017 Pustovalova et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Mechanisms underlying the effects of low-dose ionizing radiation (IR) exposure (10-100 mGy) remain unknown. Here we present a comparative study of early (less than 24h) and delayed (up to 11 post-irradiation passages) radiation effects caused by low (80 mGy) vs intermediate (1000 mGy) dose X-ray exposure in cultured human bone marrow mesenchymal stem cells (MSCs). We show that γН2АХ foci induced by an intermediate dose returned back to the control value by 24 h post-irradiation. In contrast, low-dose irradiation resulted in residual γН2АХ foci still present at 24 h. Notably, these low dose induced residual γН2АХ foci were not co-localized with рАТМ foci and were observed predominantly in the proliferating Кi67 positive (Кi67+) cells. The number of γН2АХ foci and the fraction of nonproliferating (Кi67-) and senescent (SA-β-gal+) cells measured at passage 11 were increased in cultures exposed to an intermediate dose compared to unirradiated controls. These delayed effects were not seen in the progeny of cells that were irradiated with low-dose X-rays, although such exposure resulted in residual γН2АХ foci in directly irradiated cells. Taken together, our results support the hypothesis that the low-dose IR induced residual γH2AХ foci do not play a role in delayed irradiation consequences, associated with cellular senescence in cultured MSCs.