title: Decreased DNA repair activity in bone marrow due to low expression of DNA damage repair proteins.
abstract: The bone marrow (BM) is one of the organs that is sensitive to acute exposure of ionizing radiation (IR); however, the mechanism of its high sensitivity to IR remains to be elucidated. BM is differentiated into dendritic cells (DC) with granulocyte macrophage-colony stimulating factor (GM-CSF). Using this in vitro model, we studied whether radiosensitivity is distinctly regulated in undifferentiated and differentiated BM. We discovered that levels of DNA damage repair (DDR) proteins are extremely low in BM, and they are markedly increased upon differentiation to DC. Efficiency of both homologous recombination (HR)- and non-homologous end joining (NHEJ)-mediated repair of DNA double strand breaks (DSBs) is much lower in BM compared with that of DC. Consistent with this, immunofluorescent γH2AX is highly detected in BM after IR. These results indicate that increased radiosensitivity of BM is at least due to low expression of the DNA repair machinery.
authors.affiliation: Department of Cancer Genetics; Roswell Park Cancer Institute; Buffalo, NY USA.
authors.forename: Eui Young
authors.initials: EY
authors.lastname: So
authors.affiliation: Department of Cancer Genetics; Roswell Park Cancer Institute; Buffalo, NY USA.
authors.forename: Toru
authors.initials: T
authors.lastname: Ouchi
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D002454:Cell Differentiation; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D059766:DNA End-Joining Repair; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D008297:Male; D051379:Mice; D011836:Radiation Tolerance; D059767:Recombinational DNA Repair
chemical_list: C468783:H2AX protein, human; D006657:Histones; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D045643:DNA Repair Enzymes
keywords: DNA damage; DNA double strand breaks; homologous recombination repair; ionizing radiation; non-homologous end joining
references.citation: EMBO J. 1996 Sep 16;15(18):5093-103
references.pmid: 8890183
references.citation: Nature. 2004 Nov 18;432(7015):316-23
references.pmid: 15549093
references.citation: Cell. 2007 Oct 19;131(2):223-5
references.pmid: 17956720
references.citation: Nature. 2003 Jan 30;421(6922):499-506
references.pmid: 12556884
references.citation: Science. 1998 Apr 24;280(5363):590-2
references.pmid: 9554850
references.citation: Proc Natl Acad Sci U S A. 2007 Aug 7;104(32):13068-73
references.pmid: 17670947
references.citation: J Exp Med. 1987 Nov 1;166(5):1484-98
references.pmid: 2445889
references.citation: J Exp Med. 1922 Jan 31;35(2):203-11
references.pmid: 19868599
references.citation: Nature. 1992 Nov 19;360(6401):258-61
references.pmid: 1279441
references.citation: Oncogene. 2007 Dec 10;26(56):7731-40
references.pmid: 18066085
references.citation: J Exp Med. 1992 May 1;175(5):1157-67
references.pmid: 1569392
references.citation: J Exp Med. 1973 May 1;137(5):1142-62
references.pmid: 4573839
references.citation: Nat Rev Mol Cell Biol. 2002 May;3(5):317-27
references.pmid: 11988766
references.citation: J Immunol Methods. 1999 Feb 1;223(1):77-92
references.pmid: 10037236
references.citation: Nat Rev Immunol. 2007 Jan;7(1):19-30
references.pmid: 17170756
references.citation: J Biol Chem. 1996 Jun 14;271(24):14405-11
references.pmid: 8662903
references.citation: Nature. 1979 Nov 15;282(5736):324-6
references.pmid: 503208
references.citation: Mol Cell. 2004 Dec 3;16(5):715-24
references.pmid: 15574327