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DNA Damage Response of Haematopoietic Stem and Progenitor Cells to High-LET Neutron Irradiation

Article scientifique 2021 Anglais

Résumé

Abstract The radiosensitivity of haematopoietic stem and progenitor cells (HSPCs) to neutron radiation remains largely underexplored, notwithstanding their potential role as target cells for radiation-induced leukemogenesis. New insights are required for radiation protection purposes, particularly for aviation, space missions, nuclear accidents and even particle therapy. In this study, HSPCs (CD34+ cells) were isolated from umbilical cord blood and irradiated with 60Co γ-rays (photons) and high energy p(66)/Be(40) neutrons. At 2 hours post-irradiation, a significantly higher number of 1.28 ± 0.12 γ-H2AX foci/cell was observed after 0.5 Gy neutrons compared to 0.84 ± 0.14 foci/cell for photons, but this decreased to similar levels for both radiation qualities after 18 hours. However, a signficant difference in late apoptosis was observed between photon and neutron irradiation at 18 hours, 43.17 ± 6.10 % versus 55.55 ± 4.87 %, respectively. A significant increase in cytogenetic damage was observed after both 0.5 and 1 Gy neutron irradiation compared to photons, while there was no difference in the nuclear division index between both radiation qualities. The results point towards a higher induction of DNA damage after neutron irradiation in HSPCs followed by error-prone DNA repair, which contributes to genomic instability and a higher risk of leukemogenesis.

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Engelbrecht, M., Ndimba, R., Kock, M., Miles, X., Nair, S., Fisher, R., Plessis, P., Bolcaen, J., Botha, M., Zwanepoel, E., Sioen, S., Baeyens, A., Nieto-Camero, J., Kock, E., Vandevoorde, C. (2021). DNA Damage Response of Haematopoietic Stem and Progenitor Cells to High-LET Neutron Irradiation. https://doi.org/10.21203/rs.3.rs-753713/v1

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Auteur(s)

Monique Engelbrecht Roya Ndimba Maryna de Kock Xanthene Miles Shankari Nair Randall Fisher Peter du Plessis Julie Bolcaen Matthys H. Botha Elbie Zwanepoel Simon Sioen Ans Baeyens Jaime Nieto-Camero Evan de Kock Charlot Vandevoorde

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