Residual γH2AX foci induced by low dose x-ray radiation in bone marrow mesenchymal stem cells do not cause accelerated senescence in the progeny of irradiated cells

Margarita Pustovalova, Tatiana A. Astrelina, Anna Grekhova, Natalia Vorobyeva, Anastasia Tsvetkova, Taisia Blokhina, Victoria Nikitina, Yulia Suchkova, Daria Usupzhanova, Vitalyi Brunchukov, Irina Kobzeva, Tatiana Karaseva, Ivan V. Ozerov, Aleksandr Samoylov, Andrey Bushmanov, Sergey Leonov, Evgeny Izumchenko, Alex Zhavoronkov, Dmitry Klokov, Andreyan N. Osipov

Research output: Contribution to journalArticle

Abstract

Mechanisms underlying the effects of low-dose ionizing radiation (IR) exposure (10-100 mGy) remain unknown. Here we present a comparative study of early (less than 24h) and delayed (up to 11 post-irradiation passages) radiation effects caused by low (80 mGy) vs intermediate (1000 mGy) dose X-ray exposure in cultured human bone marrow mesenchymal stem cells (MSCs). We show that γH2AX foci induced by an intermediate dose returned back to the control value by 24 h post-irradiation. In contrast, low-dose irradiation resulted in residual γH2AX foci still present at 24 h. Notably, these low dose induced residual γH2AX foci were not co-localized with ρATM foci and were observed predominantly in the proliferating Ki67 positive (Ki67+) cells. The number of γH2AX foci and the fraction of nonproliferating (Ki67-) and senescent (SA-β-gal+) cells measured at passage 11 were increased in cultures exposed to an intermediate dose compared to unirradiated controls. These delayed effects were not seen in the progeny of cells that were irradiated with low-dose X-rays, although such exposure resulted in residual γH2AX foci in directly irradiated cells. Taken together, our results support the hypothesis that the low-dose IR induced residual γH2AX foci do not play a role in delayed irradiation consequences, associated with cellular senescence in cultured MSCs.

Original languageEnglish (US)
Pages (from-to)2397-2410
Number of pages14
JournalAging
Volume9
Issue number11
DOIs
StatePublished - Jan 1 2017

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Mesenchymal Stromal Cells
Bone Marrow
X-Rays
Radiation
Ionizing Radiation
Cell Aging
Radiation Effects

Keywords

  • Cellular proliferation
  • Cellular senescence
  • Delayed radiation effects
  • Low-dose radiation effects
  • γH2AX foci

ASJC Scopus subject areas

  • Aging
  • Cell Biology

Cite this

Pustovalova, M., Astrelina, T. A., Grekhova, A., Vorobyeva, N., Tsvetkova, A., Blokhina, T., ... Osipov, A. N. (2017). Residual γH2AX foci induced by low dose x-ray radiation in bone marrow mesenchymal stem cells do not cause accelerated senescence in the progeny of irradiated cells. Aging, 9(11), 2397-2410. https://doi.org/10.18632/aging.101327

Residual γH2AX foci induced by low dose x-ray radiation in bone marrow mesenchymal stem cells do not cause accelerated senescence in the progeny of irradiated cells. / Pustovalova, Margarita; Astrelina, Tatiana A.; Grekhova, Anna; Vorobyeva, Natalia; Tsvetkova, Anastasia; Blokhina, Taisia; Nikitina, Victoria; Suchkova, Yulia; Usupzhanova, Daria; Brunchukov, Vitalyi; Kobzeva, Irina; Karaseva, Tatiana; Ozerov, Ivan V.; Samoylov, Aleksandr; Bushmanov, Andrey; Leonov, Sergey; Izumchenko, Evgeny; Zhavoronkov, Alex; Klokov, Dmitry; Osipov, Andreyan N.

In: Aging, Vol. 9, No. 11, 01.01.2017, p. 2397-2410.

Research output: Contribution to journalArticle

Pustovalova, M, Astrelina, TA, Grekhova, A, Vorobyeva, N, Tsvetkova, A, Blokhina, T, Nikitina, V, Suchkova, Y, Usupzhanova, D, Brunchukov, V, Kobzeva, I, Karaseva, T, Ozerov, IV, Samoylov, A, Bushmanov, A, Leonov, S, Izumchenko, E, Zhavoronkov, A, Klokov, D & Osipov, AN 2017, 'Residual γH2AX foci induced by low dose x-ray radiation in bone marrow mesenchymal stem cells do not cause accelerated senescence in the progeny of irradiated cells', Aging, vol. 9, no. 11, pp. 2397-2410. https://doi.org/10.18632/aging.101327
Pustovalova, Margarita ; Astrelina, Tatiana A. ; Grekhova, Anna ; Vorobyeva, Natalia ; Tsvetkova, Anastasia ; Blokhina, Taisia ; Nikitina, Victoria ; Suchkova, Yulia ; Usupzhanova, Daria ; Brunchukov, Vitalyi ; Kobzeva, Irina ; Karaseva, Tatiana ; Ozerov, Ivan V. ; Samoylov, Aleksandr ; Bushmanov, Andrey ; Leonov, Sergey ; Izumchenko, Evgeny ; Zhavoronkov, Alex ; Klokov, Dmitry ; Osipov, Andreyan N. / Residual γH2AX foci induced by low dose x-ray radiation in bone marrow mesenchymal stem cells do not cause accelerated senescence in the progeny of irradiated cells. In: Aging. 2017 ; Vol. 9, No. 11. pp. 2397-2410.
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T1 - Residual γH2AX foci induced by low dose x-ray radiation in bone marrow mesenchymal stem cells do not cause accelerated senescence in the progeny of irradiated cells

AU - Pustovalova, Margarita

AU - Astrelina, Tatiana A.

AU - Grekhova, Anna

AU - Vorobyeva, Natalia

AU - Tsvetkova, Anastasia

AU - Blokhina, Taisia

AU - Nikitina, Victoria

AU - Suchkova, Yulia

AU - Usupzhanova, Daria

AU - Brunchukov, Vitalyi

AU - Kobzeva, Irina

AU - Karaseva, Tatiana

AU - Ozerov, Ivan V.

AU - Samoylov, Aleksandr

AU - Bushmanov, Andrey

AU - Leonov, Sergey

AU - Izumchenko, Evgeny

AU - Zhavoronkov, Alex

AU - Klokov, Dmitry

AU - Osipov, Andreyan N.

PY - 2017/1/1

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N2 - Mechanisms underlying the effects of low-dose ionizing radiation (IR) exposure (10-100 mGy) remain unknown. Here we present a comparative study of early (less than 24h) and delayed (up to 11 post-irradiation passages) radiation effects caused by low (80 mGy) vs intermediate (1000 mGy) dose X-ray exposure in cultured human bone marrow mesenchymal stem cells (MSCs). We show that γH2AX foci induced by an intermediate dose returned back to the control value by 24 h post-irradiation. In contrast, low-dose irradiation resulted in residual γH2AX foci still present at 24 h. Notably, these low dose induced residual γH2AX foci were not co-localized with ρATM foci and were observed predominantly in the proliferating Ki67 positive (Ki67+) cells. The number of γH2AX foci and the fraction of nonproliferating (Ki67-) and senescent (SA-β-gal+) cells measured at passage 11 were increased in cultures exposed to an intermediate dose compared to unirradiated controls. These delayed effects were not seen in the progeny of cells that were irradiated with low-dose X-rays, although such exposure resulted in residual γH2AX foci in directly irradiated cells. Taken together, our results support the hypothesis that the low-dose IR induced residual γH2AX foci do not play a role in delayed irradiation consequences, associated with cellular senescence in cultured MSCs.

AB - Mechanisms underlying the effects of low-dose ionizing radiation (IR) exposure (10-100 mGy) remain unknown. Here we present a comparative study of early (less than 24h) and delayed (up to 11 post-irradiation passages) radiation effects caused by low (80 mGy) vs intermediate (1000 mGy) dose X-ray exposure in cultured human bone marrow mesenchymal stem cells (MSCs). We show that γH2AX foci induced by an intermediate dose returned back to the control value by 24 h post-irradiation. In contrast, low-dose irradiation resulted in residual γH2AX foci still present at 24 h. Notably, these low dose induced residual γH2AX foci were not co-localized with ρATM foci and were observed predominantly in the proliferating Ki67 positive (Ki67+) cells. The number of γH2AX foci and the fraction of nonproliferating (Ki67-) and senescent (SA-β-gal+) cells measured at passage 11 were increased in cultures exposed to an intermediate dose compared to unirradiated controls. These delayed effects were not seen in the progeny of cells that were irradiated with low-dose X-rays, although such exposure resulted in residual γH2AX foci in directly irradiated cells. Taken together, our results support the hypothesis that the low-dose IR induced residual γH2AX foci do not play a role in delayed irradiation consequences, associated with cellular senescence in cultured MSCs.

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