Activation of homologous recombination DNA repair in human skin fibroblasts continuously exposed to X-ray radiation
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Andreyan N. Osipov1,2,3,4, Anna Grekhova1,5, Margarita Pustovalova1,2, Ivan V. Ozerov1, Petr Eremin1, Natalia Vorobyeva1,3, Natalia Lazareva1, Andrey Pulin1, Alex Zhavoronkov4,6,7, Sergey Roumiantsev3,4,8, Dmitry Klokov9, Ilya Eremin1
1State Research Center - Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency (SRC-FMBC), Moscow 123098, Russia
2Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow 119991, Russia
3Dmitry Rogachev Federal Research Center of Pediatric Hematology, Oncology and Immunology, Moscow 117997, Russia
4Moscow Institute of Physics and Technology, Dolgoprudny, Moscow Region 141700, Russia
5Emanuel Institute for Biochemical Physics, Russian Academy of Sciences, Moscow 119991, Russia
6Insilico Medicine, Inc, ETC, Johns Hopkins University, Baltimore, MD 21218, USA
7The Biogerontology Research Foundation, BGRF, London W1J 5NE, UK
8N.I. Pirogov Russian National Research Medical University, Moscow 117997, Russia
9Canadian Nuclear Laboratories, Chalk River, ON K0J1P0, Canada
Andreyan N. Osipov, e-mail: email@example.com
Keywords: DNA DSB repair, homologous recombination, human fibroblasts, X-rays, continuous irradiation
Received: April 08, 2015 Accepted: July 31, 2015 Published: August 13, 2015
Molecular and cellular responses to protracted ionizing radiation exposures are poorly understood. Using immunofluorescence microscopy, we studied the kinetics of DNA repair foci formation in normal human fibroblasts exposed to X-rays at a dose rate of 4.5 mGy/min for up to 6 h. We showed that both the number of γH2AX foci and their integral fluorescence intensity grew linearly with time of irradiation up to 2 h. A plateau was observed between 2 and 6 h of exposure, indicating a state of balance between formation and repair of DNA double-strand breaks. In contrast, the number and intensity of foci formed by homologous recombination protein RAD51 demonstrated a continuous increase during 6 h of irradiation. We further showed that the enhancement of the homologous recombination repair was not due to redistribution of cell cycle phases. Our results indicate that continuous irradiation of normal human cells triggers DNA repair responses that are different from those elicited after acute irradiation. The observed activation of the error-free homologous recombination DNA double-strand break repair pathway suggests compensatory adaptive mechanisms that may help alleviate long-term biological consequences and could potentially be utilized both in radiation protection and medical practices.
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