Abstract
One of the major health risks to astronauts is radiation on long-duration space missions. Space radiation from sun and galactic cosmic rays consists primarily of 85% protons, 14% helium nuclei and 1% high-energy high-charge (HZE) particles, such as oxygen (16O), carbon, silicon, and iron ions. HZE particles exhibit dense linear tracks of ionization associated with clustered DNA damage and often high relative biological effectiveness (RBE). Therefore, new knowledge of risks from HZE particle exposures must be obtained. In the present study, we investigated the acute effects of low doses of 16O irradiation on the hematopoietic system. Specifically, we exposed C57BL/6J mice to 0.1, 0.25 and 1.0 Gy whole body 16O (600 MeV/n) irradiation and examined the effects on peripheral blood (PB) cells, and bone marrow (BM) hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) at two weeks after the exposure. The results showed that the numbers of white blood cells, lymphocytes, monocytes, neutrophils and platelets were significantly decreased in PB after exposure to 1.0 Gy, but not to 0.1 or 0.25 Gy. However, both the frequency and number of HPCs and HSCs were reduced in a radiation dose-dependent manner in comparison to un-irradiated controls. Furthermore, HPCs and HSCs from irradiated mice exhibited a significant reduction in clonogenic function determined by the colony-forming and cobblestone area-forming cell assays. These acute adverse effects of 16O irradiation on HSCs coincided with an increased production of reactive oxygen species (ROS), enhanced cell cycle entry of quiescent HSCs, and increased DNA damage. However, none of the 16O exposures induced apoptosis in HSCs. These data suggest that exposure to low doses of 16O irradiation induces acute BM injury in a dose-dependent manner primarily via increasing ROS production, cell cycling, and DNA damage in HSCs. This finding may aid in developing novel strategies in the protection of the hematopoietic system from space radiation.
Highlights
Radiation is considered to be one of the major risk factors during space activities and has emerged as a critical issue to be resolved for the completion of safe long-duration space missions
The counts of white blood cells (WBCs), lymphocytes, monocytes, neutrophils and platelets showed significant decrease after 1.0 Gy 16O-TBI compared to 0.25 Gy radiation (Fig 1A and 1C, p
Fig 6. 16O TBI causes persistent increases in DNA damage in hematopoietic stem cells (HSCs) but not in hematopoietic progenitor cells (HPCs) two weeks after the exposure. (A) Representative analysis of DNA damage measured in Lin- cells by flow cytometry using γH2AX staining in bone marrow (BM) HPCs and HSCs from control and 1.0 Gy16O TBI mice
Summary
Radiation is considered to be one of the major risk factors during space activities and has emerged as a critical issue to be resolved for the completion of safe long-duration space missions. The primary components of the space radiation environment are galactic cosmic rays (GCR) and radiation from solar particle events. These space radiation sources consist mainly of protons, helium nuclei and nuclei of elements of atomic number >2 (high-energy high charge particles, HZE), of which 56Fe, 28Si, 16O, and 12C are major contributors to dose equivalent in free space. While 56Fe may be the single largest contributor to GCR dose equivalent in free space[1], space craft material will lead to fragmentation of heavy ions, such that the radiation environment inside a space craft will contain a larger proportion of hydrogen, helium, and ions with smaller masses[2]. We have chosen to investigate the biological effects of 16O on cells and tissues in relation to long-duration space missions
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