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MMR Deficiency Does Not Sensitize or Compromise the Function of Hematopoietic Stem Cells to Low and High LET Radiation
dc.contributor.authorPatel, Rutulkumar
dc.contributor.authorQing, Yulan
dc.contributor.authorKennedy, Lucy
dc.contributor.authorYan, Yan
dc.contributor.authorPink, John
dc.contributor.authorAguila, Brittany
dc.contributor.authorDesai, Amar
dc.contributor.authorGerson, Stanton L.
dc.contributor.authorWelford, Scott M.
dc.date.accessioned2018-08-13T18:51:37Z
dc.date.available2019-09-04T20:15:38Zen
dc.date.issued2018-07
dc.identifier.citationPatel, Rutulkumar; Qing, Yulan; Kennedy, Lucy; Yan, Yan; Pink, John; Aguila, Brittany; Desai, Amar; Gerson, Stanton L.; Welford, Scott M. (2018). "MMR Deficiency Does Not Sensitize or Compromise the Function of Hematopoietic Stem Cells to Low and High LET Radiation." STEM CELLS Translational Medicine 7(7): 513-520.
dc.identifier.issn2157-6564
dc.identifier.issn2157-6580
dc.identifier.urihttps://hdl.handle.net/2027.42/145333
dc.description.abstractOne 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. Stem Cells Translational Medicine 2018;7:513–520The hematopoietic system is essential for life, and normally has the capacity to sustain function for the duration of our lifetimes in spite of natural declination, which is associated with loss of DNA repair (including as DNA mismatch repair). Astronauts are exposed to ionizing radiation sources that are not commonly found on earth (such as HZE ions) and thus may display unforseen risks that need accounting in NASA risk models.
dc.publisherWiley Periodicals, Inc.
dc.publisherWolters Kluwer Health/Lippincott Williams & Wilkins
dc.subject.otherMlh1
dc.subject.otherHematopoiesis
dc.subject.otherStem cells
dc.subject.otherIonizing radiation
dc.subject.otherDNA mismatch repair
dc.subject.otherHematopoietic stem cell
dc.titleMMR Deficiency Does Not Sensitize or Compromise the Function of Hematopoietic Stem Cells to Low and High LET Radiation
dc.typeArticleen_US
dc.rights.robotsIndexNoFollow
dc.subject.hlbsecondlevelMolecular, Cellular and Developmental Biology
dc.subject.hlbtoplevelHealth Sciences
dc.description.peerreviewedPeer Reviewed
dc.description.bitstreamurlhttps://deepblue.lib.umich.edu/bitstream/2027.42/145333/1/sct312310.pdf
dc.description.bitstreamurlhttps://deepblue.lib.umich.edu/bitstream/2027.42/145333/2/sct312310_am.pdf
dc.identifier.doi10.1002/sctm.17-0295
dc.identifier.sourceSTEM CELLS Translational Medicine
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dc.owningcollnameInterdisciplinary and Peer-Reviewed


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