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

نویسندگان

  • Andreyan N. Osipov
  • Anna Grekhova
  • Margarita Pustovalova
  • Ivan V. Ozerov
  • Petr Eremin
  • Natalia Vorobyeva
  • Natalia Lazareva
  • Andrey Pulin
  • Alex Zhavoronkov
  • Sergey Roumiantsev
  • Dmitry Klokov
  • Ilya Eremin
چکیده

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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عنوان ژورنال:

دوره 6  شماره 

صفحات  -

تاریخ انتشار 2015