Low doses of oxygen ion irradiation cause long-term damage to bone marrow hematopoietic progenitor and stem cells in mice.

Yingying Wang,Daohong Zhou,Lijian Shao,Gregory Nelson,Jianhui Chang,Tamako Jones,Xin Li,Marjan Boerma,Martin Hauer-Jensen,Rupak Pathak,Vijayalakshmi Sridharan,Xiao Wen Mao,Roberto Amendola

doi:10.1371/journal.pone.0189466

Yingying Wang, Daohong Zhou + Show 11 more

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https://doi.org/10.1371/journal.pone.0189466

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Abstract

During deep space missions, astronauts will be exposed to low doses of charged particle irradiation. The long-term health effects of these exposures are largely unknown. We previously showed that low doses of oxygen ion (16O) irradiation induced acute damage to the hematopoietic system, including hematopoietic progenitor and stem cells in a mouse model. However, the chronic effects of low dose 16O irradiation remain undefined. In the current study, we investigated the long-term effects of low dose 16O irradiation on the mouse hematopoietic system. Male C57BL/6J mice were exposed to 0.05 Gy, 0.1 Gy, 0.25 Gy and 1.0 Gy whole body 16O (600 MeV/n) irradiation. The effects of 16O irradiation on bone marrow (BM) hematopoietic progenitor cells (HPCs) and hematopoietic stem cells (HSCs) were examined three months after the exposure. The results showed that the frequencies and numbers of BM HPCs and HSCs were significantly reduced in 0.1 Gy, 0.25 Gy and 1.0 Gy irradiated mice compared to 0.05 Gy irradiated and non-irradiated mice. Exposure of mice to low dose 16O irradiation also significantly reduced the clongenic function of BM HPCs determined by the colony-forming unit assay. The functional defect of irradiated HSCs was detected by cobblestone area-forming cell assay after exposure of mice to 0.1 Gy, 0.25 Gy and 1.0 Gy of 16O irradiation, while it was not seen at three months after 0.5 Gy and 1.0 Gy of γ-ray irradiation. These adverse effects of 16O irradiation on HSCs coincided with an increased intracellular production of reactive oxygen species (ROS). However, there were comparable levels of cellular apoptosis and DNA damage between irradiated and non-irradiated HPCs and HSCs. These data suggest that exposure to low doses of 16O irradiation induces long-term hematopoietic injury, primarily via increased ROS production in HSCs.

Highlights

Deep space missions are associated with several risk factors, including the exposure to space radiation
We have previously shown that 1.0 Gy of 16O total body irradiation (TBI) significantly decreased peripheral blood cell counts, those of white blood cells (WBC) and platelets (PLT), in mice two weeks after TBI[21]
The results showed that the frequencies of burst-forming unit-erythroid (BFU-E), Colony-forming unit (CFU)-GMs, and CFU-GEMMs in bone marrow (BM) cells were significantly reduced, regardless of radiation doses (Fig 3A, p

Summary

Introduction

Deep space missions are associated with several risk factors, including the exposure to space radiation. Two main sources of space radiation are solar particle events (SPE) and galactic cosmic rays (GCR)[1]. High atomic number and energy (HZE) particles from GCR, such as 56Fe, 28Si, 16O, and 12C, have higher energy and stronger toxicities to normal tissues than photon and proton radiation[2, 3]. Exposure to space radiation usually occurs at low doses and dose rates, an extended exposure of the body to space radiation, to HZE radiation, during long-term space missions might result in a dose accumulation of HZE radiation sufficient to cause health hazards[4, 5]. There is limited knowledge of the RBE of 16O ion exposure, especially regarding the long-term health effects, which limits the development of mitigating strategies against space radiation

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