DNA damage response of haematopoietic stem and progenitor cells to high-LET neutron irradiation

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(+)CD38(+) cells) were isolated from umbilical cord blood and irradiated with Co-60 gamma-rays (photons) and high energy p(66)/Be(40) neutrons. At 2 h post-irradiation, a significantly higher number of 1.28 +/- 0.12 gamma-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 h. However, a significant difference in late apoptosis was observed with Annexin-V+/PI+ assay between photon and neutron irradiation at 18 h, 43.17 +/- 6.10% versus 55.55 +/- 4.87%, respectively. A significant increase in MN frequency was observed after both 0.5 and 1 Gy neutron irradiation compared to photons illustrating higher levels of neutron-induced cytogenetic damage, 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.

Automated summary

The study showed that HSPCs exhibit higher DNA damage induction after neutron irradiation, leading to increased apoptosis rate and levels of cytogenetic damage, which contribute to a higher risk of leukemogenesis.