Open AccessLow Doses of Oxygen Ion Irradiation Cause Acute Damage to Hematopoietic Cells in Mice
Author(s) -
Jianhui Chang,
Yi Luo,
Yingying Wang,
Rupak Pathak,
Vijayalakshmi Sridharan,
Tamako Jones,
Xiao Wen Mao,
Gregory A. Nelson,
Marjan Boerma,
Martin HauerJensen,
Daohong Zhou,
Longquan Shao
Publication year - 2016
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.0158097
Subject(s) - haematopoiesis , irradiation , clonogenic assay , relative biological effectiveness , bone marrow , stem cell , white blood cell , dna damage , progenitor cell , reactive oxygen species , ionizing radiation , peripheral blood cell , linear energy transfer , microbiology and biotechnology , chemistry , immunology , cancer research , cell , biology , biochemistry , physics , dna , nuclear physics
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 ( 16 O), 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 16 O irradiation on the hematopoietic system. Specifically, we exposed C57BL/6J mice to 0.1, 0.25 and 1.0 Gy whole body 16 O (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 16 O 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 16 O exposures induced apoptosis in HSCs. These data suggest that exposure to low doses of 16 O 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.