²⁸ Si total body irradiation injures bone marrow hematopoietic stem cells via induction of cellular apoptosis

Long-term space mission exposes astronauts to a radiation environment with potential health hazards. High-energy charged particles (HZE), including ²⁸ Si nuclei in space, have deleterious effects on cells due to their characteristics with high linear energy transfer and dense ionization. The influence of ²⁸ Si ions contributes more than 10% to the radiation dose equivalent in the space environment. Understanding the biological effects of ²⁸ Si irradiation is important to assess the potential health hazards of long-term space missions. The hematopoietic system is highly sensitive to radiation injury and bone marrow (BM) suppression is the primary life‐threatening injuries after exposure to a moderate dose of radiation. Therefore, in the present study we investigated the acute effects of low doses of ²⁸ Si irradiation on the hematopoietic system in a mouse model. Specifically, 6-month-old C57BL/6 J mice were exposed to 0.3, 0.6 and 0.9 Gy ²⁸ Si (600 MeV) total body irradiation (TBI). The effects of ²⁸ Si TBI on BM hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) were examined four weeks after the exposure. The results showed that exposure to ²⁸ Si TBI dramatically reduced the frequencies and numbers of HSCs in irradiated mice, compared to non-irradiated controls, in a radiation dose-dependent manner. In contrast, no significant changes were observed in BM HPCs regardless of radiation doses. Furthermore, irradiated HSCs exhibited a significant impairment in clonogenic ability. These acute effects of ²⁸ Si irradiation on HSCs may be attributable to radiation-induced apoptosis of HSCs, because HSCs, but not HPCs, from irradiated mice exhibited a significant increase in apoptosis in a radiation dose-dependent manner. However, exposure to low doses of ²⁸ Si did not result in an increased production of reactive oxygen species and DNA damage in HSCs and HPCs. These findings indicate that exposure to ²⁸ Si irradiation leads to acute HSC damage.