TY - JOUR
T1 - MMR Deficiency Does Not Sensitize or Compromise the Function of Hematopoietic Stem Cells to Low and High LET Radiation
AU - Patel, Rutulkumar
AU - Qing, Yulan
AU - Kennedy, Lucy
AU - Yan, Yan
AU - Pink, John
AU - Aguila, Brittany
AU - Desai, Amar
AU - Gerson, Stanton L.
AU - Welford, Scott M.
N1 - Funding Information:
This study was supported by NASA NNX14AC95G, and the Cytometry & Microscopy and Radiation Resources Shared Resources of the Case Comprehensive Cancer Center (P30CA043703). We thank members of NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory for help and support of our studies. We further thank Thomas F. Peter-son, Jr., for his generosity.
Publisher Copyright:
© 2018 The Authors
PY - 2018
Y1 - 2018
N2 - One of the major health concerns on long-duration space missions will be radiation exposure to the astronauts. Outside the earth's magnetosphere, astronauts will be exposed to galactic cosmic rays (GCR) and solar particle events that are principally composed of protons and He, Ca, O, Ne, Si, Ca, and Fe nuclei. Protons are by far the most common species, but the higher atomic number particles are thought to be more damaging to biological systems. Evaluation and amelioration of risks from GCR exposure will be important for deep space travel. The hematopoietic system is one of the most radiation-sensitive organ systems, and is highly dependent on functional DNA repair pathways for survival. Recent results from our group have demonstrated an acquired deficiency in mismatch repair (MMR) in human hematopoietic stem cells (HSCs) with age due to functional loss of the MLH1 protein, suggesting an additional risk to astronauts who may have significant numbers of MMR deficient HSCs at the time of space travel. In the present study, we investigated the effects gamma radiation, proton radiation, and 56Fe radiation on HSC function in Mlh1+/+ and Mlh1-/-marrow from mice in a variety of assays and have determined that while cosmic radiation is a major risk to the hematopoietic system, there is no dependence on MMR capacity.
AB - One of the major health concerns on long-duration space missions will be radiation exposure to the astronauts. Outside the earth's magnetosphere, astronauts will be exposed to galactic cosmic rays (GCR) and solar particle events that are principally composed of protons and He, Ca, O, Ne, Si, Ca, and Fe nuclei. Protons are by far the most common species, but the higher atomic number particles are thought to be more damaging to biological systems. Evaluation and amelioration of risks from GCR exposure will be important for deep space travel. The hematopoietic system is one of the most radiation-sensitive organ systems, and is highly dependent on functional DNA repair pathways for survival. Recent results from our group have demonstrated an acquired deficiency in mismatch repair (MMR) in human hematopoietic stem cells (HSCs) with age due to functional loss of the MLH1 protein, suggesting an additional risk to astronauts who may have significant numbers of MMR deficient HSCs at the time of space travel. In the present study, we investigated the effects gamma radiation, proton radiation, and 56Fe radiation on HSC function in Mlh1+/+ and Mlh1-/-marrow from mice in a variety of assays and have determined that while cosmic radiation is a major risk to the hematopoietic system, there is no dependence on MMR capacity.
KW - DNA mismatch repair
KW - Hematopoiesis
KW - Hematopoietic stem cell
KW - Ionizing radiation
KW - Mlh1
KW - Stem cells
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U2 - 10.1002/sctm.17-0295
DO - 10.1002/sctm.17-0295
M3 - Article
C2 - 29656536
AN - SCOPUS:85045405054
VL - 7
SP - 513
EP - 520
JO - Stem cells translational medicine
JF - Stem cells translational medicine
SN - 2157-6564
IS - 7
ER -