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

Oncotarget
Andreyan N OsipovIlya Eremin

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,...Continue Reading

References

Sep 1, 1991·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·A I Caplan
Oct 20, 2000·Clinical Orthopaedics and Related Research·A I Caplan
Dec 2, 2000·Nature·B B Zhou, S J Elledge
Sep 26, 2001·The Journal of Biological Chemistry·S BurmaD J Chen
Oct 24, 2001·The Journal of Biological Chemistry·I M Ward, J Chen
Jan 31, 2003·Nature·Christopher J Bakkenist, Michael B Kastan
Apr 8, 2003·Proceedings of the National Academy of Sciences of the United States of America·Kai Rothkamm, Markus Löbrich
Jan 27, 2004·The Journal of Biological Chemistry·Irene M WardJunjie Chen
May 22, 2004·Stem Cells·Joachim OswaldCarsten Werner
Jul 29, 2004·DNA Repair·Ebba U Kurz, Susan P Lees-Miller
Sep 21, 2004·The Journal of Biological Chemistry·Spencer J CollisTheodore L Deweese
Apr 20, 2006·Nature Structural & Molecular Biology·Aude DupréJean Gautier
Dec 18, 2007·Molecular Cell·J Wade Harper, Stephen J Elledge
Apr 10, 2008·Cell Stem Cell·Paolo BiancoPaul J Simmons
Jul 3, 2008·Nature Reviews. Molecular Cell Biology·Karlene A Cimprich, David Cortez
Sep 6, 2008·Nucleic Acids Research·Andrea KinnerGeorge Iliakis
Dec 26, 2008·Haematologica·Muzlifah A HaniffaFrancesco Dazzi
Oct 23, 2009·Nature·Stephen P Jackson, Jiri Bartek
Dec 1, 2009·Cell Cycle·Tatyana V PospelovaMikhail V Blagosklonny
May 11, 2010·Journal of Periodontology·Tomas I MitranoAntonio Sanz
Jul 28, 2010·Proceedings of the National Academy of Sciences of the United States of America·Saskia GrudzenskiMarkus Löbrich
Sep 16, 2010·Nature Reviews. Molecular Cell Biology·Eva Petermann, Thomas Helleday
Mar 23, 2011·Mutation Research·Humberto Rodriguez-RochaRodrigo Franco
Apr 2, 2011·Expert Review of Cardiovascular Therapy·Patricia K Nguyen, Joseph C Wu
Jul 30, 2011·Tissue Engineering. Part B, Reviews·Pamela Gehron Robey
Dec 21, 2011·Proceedings of the National Academy of Sciences of the United States of America·Teresa NeumaierSylvain V Costes
Nov 10, 2012·Journal of Clinical Periodontology·Sandra Treves-ManusevitzSandu Pitaru
Jul 23, 2013·Journal of Dental Research·X XuS Shi
Jul 25, 2013·International Journal of Molecular Sciences·Konstantin V KotenkoAndreyan N Osipov
Aug 16, 2013·Stem Cells and Development·Benjamin P J FournierLari Häkkinen

❮ Previous
Next ❯

Citations

Jan 16, 2018·Radiology and Oncology·Igor PiotrowskiJulian Malicki
May 31, 2019·International Journal of Molecular Sciences·Stepan UlyanenkoAndreyan N Osipov
Sep 17, 2020·International Journal of Molecular Sciences·Usha KabilanDmitry Klokov
Jun 6, 2019·Journal of Radiation Research·Yi QuanBing Deng
Dec 14, 2016·Aging·Margarita PustovalovaAndreyan N Osipov
Apr 12, 2017·Frontiers in Immunology·Tünde SzatmáriKatalin Lumniczky
Jan 1, 2021·Frontiers in Cell and Developmental Biology·Marina KonkovaSvetlana Kostyuk
Jan 3, 2021·International Journal of Hematology·Masaki IwasaYasuo Miura
Dec 18, 2020·International Journal of Molecular Sciences·Nelly BabayanAndreyan Osipov

❮ Previous
Next ❯

Methods Mentioned

BETA
biopsy
X-ray

Software Mentioned

Statistica

Related Concepts

Related Feeds

Ataxia telangiectasia

Ataxia telangiectasia is a rare neurodegenerative diseases caused by defects in the ATM gene, which is involved in DNA damage recognition and repair pathways. Here is the latest research on this autosomal recessive disease.

Ataxia telangiectasia (MDS)

Ataxia telangiectasia is a rare neurodegenerative diseases caused by defects in the ATM gene, which is involved in DNA damage recognition and repair pathways. Here is the latest research on this autosomal recessive disease.