Low doses of X-rays induce prolonged and ATM-independent persistence of γH2AX foci in human gingival mesenchymal stem cells

Oncotarget. 2015 Sep 29;6(29):27275-87. doi: 10.18632/oncotarget.4739.


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.

Keywords: DNA double-strand breaks; DNA repair; X-rays; low doses; mesenchymal stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Ataxia Telangiectasia Mutated Proteins / genetics
  • Ataxia Telangiectasia Mutated Proteins / metabolism*
  • DNA Breaks, Double-Stranded
  • DNA Repair
  • Dose-Response Relationship, Radiation
  • Female
  • Gingiva / metabolism
  • Gingiva / radiation effects*
  • Healthy Volunteers
  • Histones / metabolism*
  • Humans
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / radiation effects*
  • Microscopy, Fluorescence
  • Phosphorylation
  • Signal Transduction
  • X-Rays


  • H2AX protein, human
  • Histones
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins