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September 29, 2015

Activation of homologous recombination DNA repair in human skin fibroblasts continuously exposed to X-ray radiation. Oncotarget.

Written and published by Biogerontology Research Foundation staff in collaboration with Canadian Nuclear Laboratories, Insilico Medicine Inc., Emanuel Institute for Biochemical Physics (Russian Academy of Sciences), Moscow Institute of Physics and Technology, Dmitry Rogachev Federal Research Center of Pediatric Hematology, Oncology and Immunology, Semenov Institute of Chemical Physics (Russian Academy of Sciences) and State Research Center - Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency (SRC-FMBC).

Activation of homologous recombination DNA repair in human skin fibroblasts continuously exposed to X-ray radiation. Oncotarget. 2015 Sep 29;6(29):26876-85.

Osipov AN(1,2,3,4), Grekhova A(1,5), Pustovalova M(1,2), Ozerov IV(1), Eremin P(1), Vorobyeva N(1,3), Lazareva N(1), Pulin A(1), Zhavoronkov A(4,6,7), Roumiantsev S(3,4,8), Klokov D(9), Eremin I(1).

(1) State Research Center - Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency (SRC-FMBC), Moscow 123098, Russia.

(2) Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow 119991, Russia.

(3) Dmitry Rogachev Federal Research Center of Pediatric Hematology, Oncology and Immunology, Moscow 117997, Russia.

(4) Moscow Institute of Physics and Technology, Dolgoprudny, Moscow Region 141700, Russia.

(5) Emanuel Institute for Biochemical Physics, Russian Academy of Sciences, Moscow 119991, Russia.

(6) Insilico Medicine, Inc, ETC, Johns Hopkins University, Baltimore, MD 21218, USA.

(7) The Biogerontology Research Foundation, BGRF, London W1J 5NE, UK.

(8) N.I. Pirogov Russian National Research Medical University, Moscow 117997, Russia.

(9) Canadian Nuclear Laboratories, Chalk River, ON K0J1P0, Canada.

Abstract: 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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