title: Low Doses of Oxygen Ion Irradiation Cause Acute Damage to Hematopoietic Cells in Mice.
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.
authors.affiliation: Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Chang
authors.affiliation: Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
authors.forename: Yi
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
authors.forename: Rupak
authors.initials: R
authors.lastname: Pathak
authors.affiliation: Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
authors.forename: Vijayalakshmi
authors.initials: V
authors.lastname: Sridharan
authors.affiliation: Department of Basic Sciences, Division of Radiation Research, School of Medicine, Loma Linda University, Loma Linda, California, United States of America.
authors.forename: Tamako
authors.initials: T
authors.lastname: Jones
authors.affiliation: Department of Basic Sciences, Division of Radiation Research, School of Medicine, Loma Linda University, Loma Linda, California, United States of America.
authors.forename: Xiao Wen
authors.initials: XW
authors.lastname: Mao
authors.affiliation: Department of Basic Sciences, Division of Radiation Research, School of Medicine, Loma Linda University, Loma Linda, California, United States of America.
authors.forename: Gregory
authors.initials: G
authors.lastname: Nelson
authors.affiliation: Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
authors.forename: Marjan
authors.initials: M
authors.lastname: Boerma
authors.affiliation: Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
authors.forename: Martin
authors.initials: M
authors.lastname: Hauer-Jensen
authors.affiliation: Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
authors.forename: Daohong
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
authors.forename: Lijian
authors.initials: L
authors.lastname: Shao
mesh_terms: D000818:Animals; D001772:Blood Cell Count; D002453:Cell Cycle / Q000528:radiation effects; D004249:DNA Damage; D004307:Dose-Response Relationship, Radiation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000528:radiation effects; D010100:Oxygen / Q000009:adverse effects*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D010100:Oxygen