**4. Oxygen radiation and hematopoietic stem cells**

As we discussed above, GCR contains various HZE particles including 56Fe, 28Si, 16O, and 12C, which have more detrimental effects on normal tissues than do photon and proton radiations during spaceflight. Oxygen (16O) radiation has relatively high-charge and high-linear energy transfer (LET), leading to a high relative biological effectiveness. In this section, we will mainly discuss the biological negative effects of 16O on hematopoietic stem cells in long-duration space missions.

**87**

**Table 3.**

*Acute and long-term effects of oxygen irradiation on hematopoietic cells.*

*Space Radiation-Induced Hematopoietic Stem Cell Injury*

Hematopoietic cells in the body are the most radiosensitive cells to radiation [73, 74]. Exposure to γ-irradiation causes both acute and long-term damage in hematopoietic stem and progenitor cells (HSPCs), which is due primarily to radiation-induced cellular apoptosis and senescence in HSPCs [37–39, 65]. Using porcine and mice model, it has documented that proton radiation induced both acute and long-term hematopoietic damage. We have described the acute and residual effects of proton radiation on hematopoietic stem cells showing that numbers and function of bone marrow HSCs in mice were detrimentally affected. The negative effects of proton radiation mainly contribute to increasing the production of oxidative stress and DNA damage in irradiated HSCs [53]. 56Fe radiation causes significant alterations in the expression of repetitive elements and DNA methylation, and 0.1-0.4 Gy of 56Fe radiation resulted in significant epigenetic changes in hematopoietic stem and progenitor cells in a mouse model [75]. Using cultured human hematopoietic stem and progenitor cells, it was found that 12C radiation induced chromosome aberrations and cellular apoptosis [76]. 0.3–0.9 Gy of 28Si radiation triggers a significant increase of cellular apoptosis in irradiated mice HSCs at 4 weeks after the exposure, which results in the deficiency of numbers and clonogenic function of irradiated HSCs [77]. These findings indicate that GCR, including different forms of ionizing radiation, induces acute and residual injury in hematopoietic stem cells. However, it remains elusive whether 16O radiation induces acute and long-term hematopoietic effects and what main factors are involved in the negative effects on

In one of our experiments, C57BL/6 J mice were exposed to 0.1, 0.25, and 1.0 Gy 16O (600 MeV/n) total-body irradiation (TBI) and analyzed the effects of 16O radiation on peripheral blood and BM 2 weeks after the exposure [51] (**Table 3**). Since hematopoietic cells are known to be radiosensitive, it is not surprising that a significant decrease was observed in peripheral WBC and platelet counts in mice exposed to 1.0 Gy of 16O. In comparison to 16O radiation, peripheral blood cell counts, including numbers of WBCs and platelets, were almost recovered to normal levels at 2 weeks after 1.0 Gy of γ-ray radiation in BALB/c mice [78]. This might due to (1) different animal species used and (2) different biological effectiveness of 16O and γ-ray radiation along with high LET properties of 16O. 16O TBI causes cellular apoptosis in hematopoietic progenitors but not hematopoietic stem cells at 2 weeks postexposure. To monitor how fast HPCs recover from 16O TBI, apoptotic assay was performed at 3 months after 0.1, 0.25, and 1.0 Gy of 16O TBI, showing that the apoptotic levels in HPCs and HSCs after the exposure are similar to those in nonirradiated mice. These data suggest that HPCs have a slower recovery than HSCs after 16O TBI.

*DOI: http://dx.doi.org/10.5772/intechopen.88914*

HSCs under 16O exposure.
