Relationship between spontaneous ?H2AX foci formation and progenitor functions in circulating hematopoietic stem and progenitor cells among atomic-bomb survivors

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-depende...

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Published in:Mutation research. Genetic toxicology and environmental mutagenesis 2016-05, Vol.802, p.59
Main Authors: Kajimura, Junko, Kyoizumi, Seishi, Kubo, Yoshiko, Misumi, Munechika, Yoshida, Kengo, Hayashi, Tomonori, Imai, Kazue, Ohishi, Waka, Nakachi, Kei, Weng, Nan-ping, Young, Lauren F, Shieh, Jae-Hung, Moore, Malcolm A, vandenBrink, Marcel RM, Kusunoki, Yoichiro
Format: Article
Language:English
Subjects:
Bombs
DNA damage
Nuclear energy
Radiation
Stem cells
Survivor
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Summary: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 (...H2AX) foci formation in circulating CD34-positive/lineage marker-negative (CD34 + Lin-) hematopoietic stem and progenitor cells (HSPCs) among 226 Hiroshima A-bomb survivors. An association between the frequency of ...H2AX foci formation in HSPCs and the radiation dose was observed, but the ...H2AX foci frequency was not significantly elevated by past radiation. We found a negative correlation between the frequency of ...H2AX foci formation and the length of granulocyte telomeres. A negative interaction effect between the radiation dose and the frequency of ...H2AX 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. (ProQuest: ... denotes formulae/symbols omitted.)
ISSN:1383-5718
1879-3592