MMR Deficiency Does Not Sensitize or Compromise the Function of Hematopoietic Stem Cells to Low and High LET Radiation. 2018

Rutulkumar Patel, and Yulan Qing, and Lucy Kennedy, and Yan Yan, and John Pink, and Brittany Aguila, and Amar Desai, and Stanton L Gerson, and Scott M Welford
Department of Pharmacology.

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 56 Fe 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;7:513-520.

UI MeSH Term Description Entries
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D011829 Radiation Dosage The amount of radiation energy that is deposited in a unit mass of material, such as tissues of plants or animal. In RADIOTHERAPY, radiation dosage is expressed in gray units (Gy). In RADIOLOGIC HEALTH, the dosage is expressed by the product of absorbed dose (Gy) and quality factor (a function of linear energy transfer), and is called radiation dose equivalent in sievert units (Sv). Sievert Units,Dosage, Radiation,Gray Units,Gy Radiation,Sv Radiation Dose Equivalent,Dosages, Radiation,Radiation Dosages,Units, Gray,Units, Sievert
D001772 Blood Cell Count The number of LEUKOCYTES and ERYTHROCYTES per unit volume in a sample of venous BLOOD. A complete blood count (CBC) also includes measurement of the HEMOGLOBIN; HEMATOCRIT; and ERYTHROCYTE INDICES. Blood Cell Number,Blood Count, Complete,Blood Cell Counts,Blood Cell Numbers,Blood Counts, Complete,Complete Blood Count,Complete Blood Counts,Count, Blood Cell,Count, Complete Blood,Counts, Blood Cell,Counts, Complete Blood,Number, Blood Cell,Numbers, Blood Cell
D001854 Bone Marrow Cells Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells. Bone Marrow Cell,Cell, Bone Marrow,Cells, Bone Marrow,Marrow Cell, Bone,Marrow Cells, Bone
D005260 Female Females
D005720 Gamma Rays Penetrating, high-energy electromagnetic radiation emitted from atomic nuclei during NUCLEAR DECAY. The range of wavelengths of emitted radiation is between 0.1 - 100 pm which overlaps the shorter, more energetic hard X-RAYS wavelengths. The distinction between gamma rays and X-rays is based on their radiation source. Gamma Wave,Gamma Radiation,Nuclear X-Rays,Radiation, Gamma,X-Rays, Nuclear,Gamma Radiations,Gamma Ray,Gamma Waves,Nuclear X Rays,Nuclear X-Ray,Ray, Gamma,Wave, Gamma,Waves, Gamma,X Rays, Nuclear,X-Ray, Nuclear
D006410 Hematopoiesis The development and formation of various types of BLOOD CELLS. Hematopoiesis can take place in the BONE MARROW (medullary) or outside the bone marrow (HEMATOPOIESIS, EXTRAMEDULLARY). Hematopoiesis, Medullary,Haematopoiesis,Medullary Hematopoiesis
D006412 Hematopoietic Stem Cells Progenitor cells from which all blood cells derived. They are found primarily in the bone marrow and also in small numbers in the peripheral blood. Colony-Forming Units, Hematopoietic,Progenitor Cells, Hematopoietic,Stem Cells, Hematopoietic,Hematopoietic Progenitor Cells,Cell, Hematopoietic Progenitor,Cell, Hematopoietic Stem,Cells, Hematopoietic Progenitor,Cells, Hematopoietic Stem,Colony Forming Units, Hematopoietic,Colony-Forming Unit, Hematopoietic,Hematopoietic Colony-Forming Unit,Hematopoietic Colony-Forming Units,Hematopoietic Progenitor Cell,Hematopoietic Stem Cell,Progenitor Cell, Hematopoietic,Stem Cell, Hematopoietic,Unit, Hematopoietic Colony-Forming,Units, Hematopoietic Colony-Forming
D000070957 MutL Protein Homolog 1 Eukaryotic homolog of the bacterial MutL DNA MISMATCH REPAIR protein. It heterodimerizes with MISMATCH REPAIR ENDONUCLEASE PMS2 to form MutL alpha, which is recruited to DNA mismatch sites by the MUTS DNA MISMATCH-BINDING PROTEIN. Mutations in the human MLH1 gene are associated with COLORECTAL NEOPLASMS, HEREDITARY NONPOLYPOSIS. COCA2 Protein,Colon Cancer, Nonpolyposis Type 2 Protein,MLH1 Protein,MutL Homolog 1

Related Publications

Rutulkumar Patel, and Yulan Qing, and Lucy Kennedy, and Yan Yan, and John Pink, and Brittany Aguila, and Amar Desai, and Stanton L Gerson, and Scott M Welford
December 2021, Scientific reports,
Rutulkumar Patel, and Yulan Qing, and Lucy Kennedy, and Yan Yan, and John Pink, and Brittany Aguila, and Amar Desai, and Stanton L Gerson, and Scott M Welford
July 2016, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation,
Rutulkumar Patel, and Yulan Qing, and Lucy Kennedy, and Yan Yan, and John Pink, and Brittany Aguila, and Amar Desai, and Stanton L Gerson, and Scott M Welford
January 1987, Radiobiologia, radiotherapia,
Rutulkumar Patel, and Yulan Qing, and Lucy Kennedy, and Yan Yan, and John Pink, and Brittany Aguila, and Amar Desai, and Stanton L Gerson, and Scott M Welford
October 2013, Nature reviews. Urology,
Rutulkumar Patel, and Yulan Qing, and Lucy Kennedy, and Yan Yan, and John Pink, and Brittany Aguila, and Amar Desai, and Stanton L Gerson, and Scott M Welford
October 2009, Cancer biology & therapy,
Rutulkumar Patel, and Yulan Qing, and Lucy Kennedy, and Yan Yan, and John Pink, and Brittany Aguila, and Amar Desai, and Stanton L Gerson, and Scott M Welford
April 1999, The American journal of physiology,
Rutulkumar Patel, and Yulan Qing, and Lucy Kennedy, and Yan Yan, and John Pink, and Brittany Aguila, and Amar Desai, and Stanton L Gerson, and Scott M Welford
April 2007, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology,
Rutulkumar Patel, and Yulan Qing, and Lucy Kennedy, and Yan Yan, and John Pink, and Brittany Aguila, and Amar Desai, and Stanton L Gerson, and Scott M Welford
December 2005, NMR in biomedicine,
Rutulkumar Patel, and Yulan Qing, and Lucy Kennedy, and Yan Yan, and John Pink, and Brittany Aguila, and Amar Desai, and Stanton L Gerson, and Scott M Welford
July 2004, Oncogene,
Rutulkumar Patel, and Yulan Qing, and Lucy Kennedy, and Yan Yan, and John Pink, and Brittany Aguila, and Amar Desai, and Stanton L Gerson, and Scott M Welford
July 2018, International journal of molecular sciences,
Copied contents to your clipboard!