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Compromised hematopoiesis and increased DNA damage following non-lethal ionizing radiation of a human hematopoietic system reconstituted in immunodeficient mice.
MedLine Citation:
PMID:  23020858     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Abstract Purpose: Precise understanding of radiation effects is critical to development of new modalities for the prevention and treatment of radiation-induced damage. In this study, we evaluated the effects of non-lethal doses of X-ray irradiation on human hematopoietic stem and progenitor cells (HSPCs) reconstituted in NOD/Shi-scid, IL2Rγ(null) (NOG) immunodeficient mice. Materials and methods: We transplanted cord blood CD34(+) HSPCs into NOG mice irradiated with 2.0 Gy via tail veins. At the twelfth week after transplantation, the NOG mice were irradiated with 0, 0.5, 1.0, 2.0, or 4.0 Gy, and the radiation effects on human HSPCs in vivo were evaluated. Results: Although a majority of the mice irradiated with 2.0 Gy or more died in 12 weeks after irradiation, the mice that were exposed to 0.5 or 1.0 Gy of irradiation survived and were subjected to analysis. The chimerism of human CD45(+) hematopoietic cells in peripheral blood and bone marrow (BM) of the recipient mice was reduced in an X-ray dose-dependent manner after irradiation. Percentages of human CD34(+) HSPCs as well as human CD34(+)CD38- HSCs in BM similarly declined. CD34(+)CD38- HSCs purified from the humanized mice at the twelfth week after irradiation showed significantly increased numbers of phosphorylated H2AX (γH2AX) foci, a marker of DNA breaks, in an X-ray dose-dependent manner. Expression of p16(INK4A), a hallmark of aging of HSCs, was also detected only in HSPCs from irradiated mice. Conclusions: With further refinement, the humanized mouse model might be effectively used to study the biological effects of non-lethal radiation in vivo.
Authors:
Changshan Wang; Shunsuke Nakamura; Motohiko Oshima; Makiko Mochizuki-Kashio; Yaeko Nakajima-Takagi; Mitsujiro Osawa; Yoichiro Kusunoki; Seishi Kyoizumi; Kazue Imai; Kei Nakachi; Atsushi Iwama
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-1
Journal Detail:
Title:  International journal of radiation biology     Volume:  -     ISSN:  1362-3095     ISO Abbreviation:  Int. J. Radiat. Biol.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-1     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8809243     Medline TA:  Int J Radiat Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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