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Title: In vitro and in vivo assessment of direct effects of simulated solar and galactic cosmic radiation on human hematopoietic stem/progenitor cells

Abstract

Future deep space missions to Mars and near-Earth asteroids will expose astronauts to chronic solar energetic particles (SEP) and galactic cosmic ray (GCR) radiation,and likely one or more solar particle events (SPEs).Given the inherent radiosensitivity of hematopoietic cells and short latency period of leukemias, space radiation-induced hematopoietic damage poses a particular threat to astronauts on extended missions.We show that exposing human hematopoietic stem/progenitor cells(HSC) toextended mission-relevant doses of accelerated high-energyprotons andiron ions leads to the following: (1) introduces mutations that are frequently located within genes involved in hematopoiesis and are distinct from those induced by γ-radiation; (2) markedly reduces in vitro colony formation; (3)markedly alters engraftment and lineage commitment in vivo; and (4) leads to the development, in vivo, ofwhat appears to be T-ALL. Sequential exposure to protons and iron ions (as typically occurs in deep space) proved far more deleterious to HSC genome integrity and function than either particle species alone.Our results represent a critical step for more accurately estimating risks to the human hematopoietic system from space radiation, identifying and better defining molecular mechanisms by which space radiation impairs hematopoiesis and induces leukemogenesis, as well as for developing appropriately targeted countermeasures.

Authors:
 [1];  [1];  [1];  [1];  [1];  [1];  [1];  [2];  [1];  [1];  [1];  [3];  [1]
  1. Wake Forest Univ. of School of Medicine, Winston-Salem, NC (United States)
  2. Brookhaven National Lab. (BNL), Upton, NY (United States)
  3. Brookhaven National Lab. (BNL), Upton, NY (United States); Univ. of California, Davis, CA (United States)
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL), Upton, NY (United States)
Sponsoring Org.:
National Aeronautics and Space Administration (NASA)
OSTI Identifier:
1389216
Report Number(s):
BNL-114101-2017-JA
Journal ID: ISSN 0887-6924
Grant/Contract Number:  
SC0012704
Resource Type:
Accepted Manuscript
Journal Name:
Leukemia
Additional Journal Information:
Journal Volume: 31; Journal Issue: 6; Journal ID: ISSN 0887-6924
Publisher:
Nature Publishing Group (NPG)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Rodman, C., Almeida-Porada, G., George, S. K., Moon, J., Soker, S., Pardee, T., Beaty, M., Guida, P., Sajuthi, S. P., Langefeld, C. D., Walker, S. J., Wilson, PF., and Porada, C. D. In vitro and in vivo assessment of direct effects of simulated solar and galactic cosmic radiation on human hematopoietic stem/progenitor cells. United States: N. p., 2016. Web. doi:10.1038/leu.2016.344.
Rodman, C., Almeida-Porada, G., George, S. K., Moon, J., Soker, S., Pardee, T., Beaty, M., Guida, P., Sajuthi, S. P., Langefeld, C. D., Walker, S. J., Wilson, PF., & Porada, C. D. In vitro and in vivo assessment of direct effects of simulated solar and galactic cosmic radiation on human hematopoietic stem/progenitor cells. United States. doi:10.1038/leu.2016.344.
Rodman, C., Almeida-Porada, G., George, S. K., Moon, J., Soker, S., Pardee, T., Beaty, M., Guida, P., Sajuthi, S. P., Langefeld, C. D., Walker, S. J., Wilson, PF., and Porada, C. D. Thu . "In vitro and in vivo assessment of direct effects of simulated solar and galactic cosmic radiation on human hematopoietic stem/progenitor cells". United States. doi:10.1038/leu.2016.344. https://www.osti.gov/servlets/purl/1389216.
@article{osti_1389216,
title = {In vitro and in vivo assessment of direct effects of simulated solar and galactic cosmic radiation on human hematopoietic stem/progenitor cells},
author = {Rodman, C. and Almeida-Porada, G. and George, S. K. and Moon, J. and Soker, S. and Pardee, T. and Beaty, M. and Guida, P. and Sajuthi, S. P. and Langefeld, C. D. and Walker, S. J. and Wilson, PF. and Porada, C. D.},
abstractNote = {Future deep space missions to Mars and near-Earth asteroids will expose astronauts to chronic solar energetic particles (SEP) and galactic cosmic ray (GCR) radiation,and likely one or more solar particle events (SPEs).Given the inherent radiosensitivity of hematopoietic cells and short latency period of leukemias, space radiation-induced hematopoietic damage poses a particular threat to astronauts on extended missions.We show that exposing human hematopoietic stem/progenitor cells(HSC) toextended mission-relevant doses of accelerated high-energyprotons andiron ions leads to the following: (1) introduces mutations that are frequently located within genes involved in hematopoiesis and are distinct from those induced by γ-radiation; (2) markedly reduces in vitro colony formation; (3)markedly alters engraftment and lineage commitment in vivo; and (4) leads to the development, in vivo, ofwhat appears to be T-ALL. Sequential exposure to protons and iron ions (as typically occurs in deep space) proved far more deleterious to HSC genome integrity and function than either particle species alone.Our results represent a critical step for more accurately estimating risks to the human hematopoietic system from space radiation, identifying and better defining molecular mechanisms by which space radiation impairs hematopoiesis and induces leukemogenesis, as well as for developing appropriately targeted countermeasures.},
doi = {10.1038/leu.2016.344},
journal = {Leukemia},
number = 6,
volume = 31,
place = {United States},
year = {2016},
month = {11}
}

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