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Peer-reviewedCC BY 4.0International Journal of Molecular Sciences

Disentangling Dose and Radiation Quality Effects on Late DNA Damage Response in Human Mesenchymal Stromal Cells

  • Sofia A. Korneva1,2
  • Alexander P. Chernyaev1,3
  • Oleg V. Belov4,5
  • Anna Chigasova2,6,7
  • Andrey А. Osipov6
  • Maxim Ignatov2,6
  • Elizaveta Yashkina2,6
  • Vyacheslav Saburov8
  • Natalia Vorobyeva2,6
  • Nikolay Zyuzikov9
  • Andreyan N. Osipov2,4,6,10
10 affiliations
  1. 1Faculty of Physics, Lomonosov Moscow State University, 119991 Moscow, Russia
  2. 2State Research Center—Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency (SRC—FMBC), 123098 Moscow, Russia
  3. 3Skobeltsyn Institute of Nuclear Physics, Lomonosov Moscow State University, 119991 Moscow, Russia
  4. 4Veksler and Baldin Laboratory of High Energy Physics, Joint Institute for Nuclear Research, 141980 Dubna, Russia
  5. 5Institute of Biomedical Problems, Russian Academy of Sciences, 123007 Moscow, Russia
  6. 6N.N. Semenov Federal Research Center for Chemical Physics, Russian Academy of Sciences, 119991 Moscow, Russia
  7. 7Emanuel Institute for Biochemical Physics, Russian Academy of Sciences, 119334 Moscow, Russia
  8. 8A. Tsyb Medical Radiological Research Center, Branch of the National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, 249031 Obninsk, Russia
  9. 9Department of Physics, Faculty of Science and Technology, The University of the West Indies, St. Augustine 999183, Trinidad and Tobago
  10. 10CANDLE Synchrotron Research Institute, 31 Acharyan, Yerevan 0040, Armenia
Open at sourceDOICite

Abstract

Although ionizing radiation quality shapes the spatial structure and complexity of primary DNA lesions, its contribution relative to absorbed dose in the late DNA damage response (DDR) remains poorly quantified. We analyzed γH2AX and pATM foci kinetics in human mesenchymal stromal/stem cells exposed to 60Co γ-rays, 150 MeV protons, and 14.1 MeV neutrons at doses of 0.25, 0.5, 1.0, and 2.0 Gy, delivered at dose rates of 0.5 Gy/min for γ-rays, 1 Gy/min for protons, and 46 mGy/min for neutrons, respectively. An effective kinetic model was used to describe the time course of the DDR and incorporated an ultraslow component as a model-based index of long-lasting repair burden. Radiation types differed less in early signal amplitude than in decay rate and late persistence. At every investigated dose, the normalized ultraslow fraction followed the order γ-rays < protons < neutrons. This ordering was preserved in per-dose fits, while parametric bootstrapping supported the γ–neutron separation, although the absolute values of the internal fractions were only partially identifiable. RAD51, analyzed independently from model fitting, showed the same qualitative ordering at late time points, supporting the interpretation that radiation quality is more associated with persistent DDR signaling than absorbed dose within the investigated range. These findings suggest that absorbed dose alone may not fully characterize the late cellular response to different radiation qualities and highlight the importance of radiation quality in comparative radiobiology, radiation protection, and the interpretation of normal-tissue responses to therapeutic irradiation.

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Cite

BibTeXRIS
BibTeX
@article{korneva2026disentangling,
  title = {{Disentangling Dose and Radiation Quality Effects on Late DNA Damage Response in Human Mesenchymal Stromal Cells}},
  author = {Sofia A. Korneva and Alexander P. Chernyaev and Oleg V. Belov and Anna Chigasova and Andrey А. Osipov and Maxim Ignatov and Elizaveta Yashkina and Vyacheslav Saburov and Natalia Vorobyeva and Nikolay Zyuzikov and Andreyan N. Osipov},
  journal = {International Journal of Molecular Sciences},
  year = {2026},
  month = oct,
  doi = {10.3390/ijms27219423},
  url = {https://www.mdpi.com/1422-0067/27/21/9423},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Disentangling Dose and Radiation Quality Effects on Late DNA Damage Response in Human Mesenchymal Stromal Cells
AU  - Sofia A. Korneva
AU  - Alexander P. Chernyaev
AU  - Oleg V. Belov
AU  - Anna Chigasova
AU  - Andrey А. Osipov
AU  - Maxim Ignatov
AU  - Elizaveta Yashkina
AU  - Vyacheslav Saburov
AU  - Natalia Vorobyeva
AU  - Nikolay Zyuzikov
AU  - Andreyan N. Osipov
PY  - 2026
DA  - 2026/10/22
JO  - International Journal of Molecular Sciences
DO  - 10.3390/ijms27219423
UR  - https://www.mdpi.com/1422-0067/27/21/9423
AB  - Although ionizing radiation quality shapes the spatial structure and complexity of primary DNA lesions, its contribution relative to absorbed dose in the late DNA damage response (DDR) remains poorly quantified. We analyzed γH2AX and pATM foci kinetics in human mesenchymal stromal/stem cells exposed to 60Co γ-rays, 150 MeV protons, and 14.1 MeV neutrons at doses of 0.25, 0.5, 1.0, and 2.0 Gy, delivered at dose rates of 0.5 Gy/min for γ-rays, 1 Gy/min for protons, and 46 mGy/min for neutrons, respectively. An effective kinetic model was used to describe the time course of the DDR and incorporated an ultraslow component as a model-based index of long-lasting repair burden. Radiation types differed less in early signal amplitude than in decay rate and late persistence. At every investigated dose, the normalized ultraslow fraction followed the order γ-rays < protons < neutrons. This ordering was preserved in per-dose fits, while parametric bootstrapping supported the γ–neutron separation, although the absolute values of the internal fractions were only partially identifiable. RAD51, analyzed independently from model fitting, showed the same qualitative ordering at late time points, supporting the interpretation that radiation quality is more associated with persistent DDR signaling than absorbed dose within the investigated range. These findings suggest that absorbed dose alone may not fully characterize the late cellular response to different radiation qualities and highlight the importance of radiation quality in comparative radiobiology, radiation protection, and the interpretation of normal-tissue responses to therapeutic irradiation.
SN  - 1422-0067
ER  -