Original Article

Leukemia (2017) 31, 1398–1407; doi:10.1038/leu.2016.344; published online 9 December 2016

Stem cell biology

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

C Rodman1,6, G Almeida-Porada1,6, S K George1, J Moon1, S Soker1, T Pardee2, M Beaty2, P Guida3, S P Sajuthi4, C D Langefeld4, S J Walker1, P F Wilson3,5 and C D Porada1

  1. 1Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA
  2. 2Department of Hematology/Oncology, Wake Forest University School of Medicine, Winston-Salem, NC, USA
  3. 3Biological, Environmental, and Climate Sciences Department, Brookhaven National Laboratory, Upton, NY, USA
  4. 4Center for Public Health Genomics, Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA
  5. 5Department of Radiation Oncology, University of California Davis Comprehensive Cancer Center, Sacramento, CA, USA

Correspondence: Dr CD Porada, Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, 391 Technology Way, Winston-Salem, NC 27157-1083, USA. E-mail: cporada@wakehealth.edu

6These authors contributed equally to this work.

Received 30 March 2016; Revised 10 October 2016; Accepted 21 October 2016
Accepted article preview online 24 November 2016; Advance online publication 9 December 2016

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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) to extended mission-relevant doses of accelerated high-energy protons and iron 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, of what 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.