Low Doses of X-rays Induce Prolonged and ATM-independent Persistence of γH2AX Foci in Human Gingival Mesenchymal Stem Cells

Overview

Journal Oncotarget

Specialty Oncology

Date 2015 Aug 29

PMID 26314960

Citations 31

Authors

Andreyan N Osipov

Margarita Pustovalova

Anna Grekhova

Petr Eremin

Natalia Vorobyova

Andrey Pulin

Alex Zhavoronkov

Sergey Roumiantsev

Dmitry Y Klokov

Ilya Eremin

Affiliations

Soon will be listed here.

Abstract

Diagnostic imaging delivering low doses of radiation often accompany human mesenchymal stem cells (MSCs)-based therapies. However, effects of low dose radiation on MSCs are poorly characterized. Here we examine patterns of phosphorylated histone H2AX (γH2AX) and phospho-S1981 ATM (pATM) foci formation in human gingiva-derived MSCs exposed to X-rays in time-course and dose-response experiments. Both γH2AX and pATM foci accumulated linearly with dose early after irradiation (5-60 min), with a maximum induction observed at 30-60 min (37 ± 3 and 32 ± 3 foci/cell/Gy for γH2AX and pATM, respectively). The number of γH2AX foci produced by intermediate doses (160 and 250 mGy) significantly decreased (40-60%) between 60 and 240 min post-irradiation, indicating rejoining of DNA double-strand breaks. In contrast, γH2AX foci produced by low doses (20-80 mGy) did not change after 60 min. The number of pATM foci between 60 and 240 min decreased down to control values in a dose-independent manner. Similar kinetics was observed for pATM foci co-localized with γH2AX foci. Collectively, our results suggest differential DNA double-strand break signaling and processing in response to low vs. intermediate doses of X-rays in human MSCs. Furthermore, mechanisms governing the prolonged persistence of γH2AX foci in these cells appear to be ATM-independent.

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