Decreased DNA repair activity in bone marrow due to low expression of DNA damage repair proteins
Decreased DNA repair activity in bone marrow due to low expression of DNA damage repair proteins
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DOI：
10.4161/cbt.28883
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发表时间：
2014-07-01
影响因子：
3.6
通讯作者：
Ouchi, Toru
中科院分区：
文献类型：
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作者：
So, Eui Young;Ouchi, Toru
骨髓是对电离辐射（IR）急性照射敏感的器官之一，但其对IR高敏感性的机制仍有待阐明。骨髓用粒细胞巨噬细胞集落刺激因子（GM-CSF）诱导分化为树突状细胞（DC）。使用这种体外模型，我们研究了在未分化和分化的BM中放射敏感性是否受到明显调节。我们发现，DNA损伤修复（DDR）蛋白的水平在BM中极低，并且在分化为DC时显著增加。与DC相比，BM中同源重组（HR）和非同源末端连接（NHEJ）介导的DNA双链断裂（DSB）修复的效率要低得多。与此一致，免疫荧光γ H2 AX是高度检测到BM后IR。这些结果表明，增加的放射敏感性BM至少是由于低表达的DNA修复机制。
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 gamma H2AX 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.