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

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.