Relationship between spontaneous γH2AX foci formation and progenitor functions in circulating hematopoietic stem and progenitor cells among atomic-bomb survivors.
Relationship between spontaneous γH2AX foci formation and progenitor functions in circulating hematopoietic stem and progenitor cells among atomic-bomb survivors.
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DOI：
10.1016/j.mrgentox.2016.04.006
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发表时间：
2016-05
影响因子：
1.9
通讯作者：
Kusunoki, Yoichiro
中科院分区：
文献类型：
--
作者：
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.;van den Brink, Marcel R. M.;Kusunoki, Yoichiro
关键词：
造血干细胞累积的DNA损伤是人类造血衰老相关功能障碍的主要机制。大约70年前，原子弹（a -bomb）辐射以辐射剂量依赖的方式诱导原子弹幸存者造血系统的DNA损伤和功能下降。外周血细胞数量随后恢复到正常范围，但来自造血干细胞的伴随细胞仍然存在，这些细胞可能因过去的辐射暴露和衰老而发生分子变化。在本研究中，我们评估了226名广岛原子弹幸存者在循环CD34阳性/谱系标记阴性（CD34 + Lin -）造血干细胞和祖细胞（HSPCs）中磷酸化（Ser-139） H2AX （γH2AX）灶形成频率的辐射相关变化。观察到HSPCs中γ - h2ax灶的形成频率与辐射剂量之间存在相关性，但γ - h2ax灶频率未因既往辐射而显著升高。我们发现γ - h2ax灶形成频率与粒细胞端粒长度呈负相关。鹅卵石面积形成细胞试验（CAFC）表明，辐射剂量与γ - h2ax灶频率之间存在负相互作用，表明暴露于较高辐射剂量和HSPCs中DNA损伤较多的幸存者的HSPCs的自我再生能力可能下降。因此，尽管辐射暴露多年后，随着年龄的增长，DNA损伤对HSPCs自我再生能力的影响可能会被原子弹辐射照射所改变。
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.
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DOI：
10.4049/jimmunol.1203189
发表时间：
2013-06-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kyoizumi S;Kubo Y;Kajimura J;Yoshida K;Imai K;Hayashi T;Nakachi K;Young LF;Moore MA;van den Brink MR;Kusunoki Y
通讯作者：
Kusunoki Y
DOI：
10.4049/jimmunol.1303260
发表时间：
2014-06-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kyoizumi S;Kubo Y;Kajimura J;Yoshida K;Hayashi T;Nakachi K;Young LF;Moore MA;van den Brink MR;Kusunoki Y
通讯作者：
Kusunoki Y
影响因子：
3.4
作者：
KYOIZUMI, S;MCCUNE, JM;NAMIKAWA, R
通讯作者：
NAMIKAWA, R
影响因子：
20.3
作者：
KUSUNOKI, Y;KODAMA, Y;AKIYAMA, M
通讯作者：
AKIYAMA, M
DOI：
10.1016/j.mrfmmm.2011.04.008
发表时间：
2012-02-01
影响因子：
2.3
作者：
Murnane, John P.
通讯作者：
Murnane, John P.