Relationship between spontaneous γH2AX foci formation and progenitor functions in circulating hematopoietic stem and progenitor cells among atomic-bomb survivors
Autor: | Marcel R.M. van den Brink, Yoshiko Kubo, Kei Nakachi, Waka Ohishi, Yoichiro Kusunoki, Jae-Hung Shieh, Malcolm A.S. Moore, Munechika Misumi, Kengo Yoshida, Seishi Kyoizumi, Tomonori Hayashi, Lauren F. Young, Junko Kajimura, Kazue Imai, Nan-ping Weng |
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Jazyk: | angličtina |
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
DNA damage Health Toxicology and Mutagenesis Cellular differentiation CD34 Biology Article Histones 03 medical and health sciences 0302 clinical medicine Genetics Humans Peripheral blood cell Progenitor cell Aged Aged 80 and over Stem Cells Age Factors Cell Differentiation Middle Aged Hematopoietic Stem Cells humanities Haematopoiesis 030104 developmental biology 030220 oncology & carcinogenesis Immunology Cancer research Radiation Induced DNA Damage Stem cell DNA Damage |
Popis: | Accumulated DNA damage in hematopoietic stem cells is a primary mechanism of aging-associated dysfunction in human hematopoiesis. About 70 years ago, atomic-bomb (A-bomb) radiation induced DNA damage and functional decreases in the hematopoietic system of A-bomb survivors in a radiation dose-dependent manner. The peripheral blood cell populations then recovered to a normal range, but accompanying cells derived from hematopoietic stem cells still remain that bear molecular changes possibly caused by past radiation exposure and aging. In the present study, we evaluated radiation-related changes in the frequency of phosphorylated (Ser-139) H2AX (γH2AX) foci formation in circulating CD34-positive/lineage marker-negative (CD34 + Lin−) hematopoietic stem and progenitor cells (HSPCs) among 226Hiroshima A-bomb survivors. An association between the frequency of γH2AX foci formation in HSPCs and the radiation dose was observed, but the γH2AX foci frequency was not significantly elevated by past radiation. We found a negative correlation between the frequency of γH2AX foci formation and the length of granulocyte telomeres. A negative interaction effect between the radiation dose and the frequency of γH2AX foci was suggested in a proportion of a subset of HSPCs as assessed by the cobblestone area-forming cell assay (CAFC), indicating that the self-renewability of HSPCs may decrease in survivors who were exposed to a higher radiation dose and who had more DNA damage in their HSPCs. Thus, although many years after radiation exposure and with advancing age, the effect of DNA damage on the self-renewability of HSPCs may be modified by A-bomb radiation exposure. |
Databáze: | OpenAIRE |
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