Open AccessLow doses of oxygen ion irradiation cause long-term damage to bone marrow hematopoietic progenitor and stem cells in mice
Author(s) -
Yingying Wang,
Jianhui Chang,
Xin Li,
Rupak Pathak,
Vijayalakshmi Sridharan,
Tamako Jones,
Xiao Wen Mao,
Gregory A. Nelson,
Marjan Boerma,
Martin HauerJensen,
Daohong Zhou,
Longquan Shao
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0189466
Subject(s) - haematopoiesis , irradiation , bone marrow , progenitor cell , stem cell , total body irradiation , andrology , medicine , immunology , biology , microbiology and biotechnology , chemotherapy , physics , nuclear physics , cyclophosphamide
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 ( 16 O) 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 16 O irradiation remain undefined. In the current study, we investigated the long-term effects of low dose 16 O 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 16 O (600 MeV/n) irradiation. The effects of 16 O 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 16 O 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 16 O 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 16 O 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 16 O irradiation induces long-term hematopoietic injury, primarily via increased ROS production in HSCs.