Decreased repair of radiation-induced DNA double-strand breaks with cellular differentiation.
Decreased repair of radiation-induced DNA double-strand breaks with cellular differentiation.
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DOI：
10.2307/3578534
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发表时间：
1992-11
影响因子：
3.4
通讯作者：
C. A. Bill;B. M. Grochan;E. Vrdoljak;E. A. Mendoza;P. Tofilon
中科院分区：
文献类型：
--
作者：
C. A. Bill;B. M. Grochan;E. Vrdoljak;E. A. Mendoza;P. Tofilon
虽然大多数原位哺乳动物细胞是终末分化的，但大多数DNA修复研究都使用了增殖细胞。为了更好地了解分化和DNA修复之间的关系，我们使用了小鼠3T3-T前体脂肪细胞系。在这个模型系统中，增殖(干细胞)细胞经历生长停滞(GD细胞)，然后当暴露于含有血小板耗尽的人血浆的介质中时，最终分化为脂肪细胞。用脉冲场凝胶电泳法检测电离辐射对DNA双链断裂的诱导和修复作用。在GD和终末分化细胞中，辐射诱导的DSB水平相似，但在这两种情况下，在每种辐射剂量(0-40GY)下，都高于干细胞中的DSB水平；这些差异似乎是由于G1期生长停滞所致。对每种细胞类型的DNA双链断裂进行双相动力学修复。在终末分化的细胞中，25%的DNADSB在4h的修复时间后保持不连接，而在GD和干细胞中只有10%。这些数据表明，3T3-T细胞的终末分化与电离辐射诱导的DNADSBs修复的减少有关。
Although the majority of mammalian cells in situ are terminally differentiated, most DNA repair studies have used proliferating cells. In an attempt to understand better the relationship between differentiation and DNA repair, we have used the murine 3T3-T proadipocyte cell line. In this model system, proliferating (stem) cells undergo growth arrest (GD cells) and subsequently terminally differentiate into adipocytes when exposed to media containing platelet-depleted human plasma. Pulsed-field gel electrophoresis was used to evaluate the induction and repair of DNA double-strand breaks (DSBs) after ionizing radiation. The levels of radiation-induced DSBs in GD and terminally differentiated cells were similar, but in both cases greater than those found in stem cells at each radiation dose tested (0 to 40 Gy); these differences appear to be due to growth arrest in G1 phase. DNA DSBs were repaired with biphasic kinetics for each cell type. For terminally differentiated cells 25% of DNA DSBs remained unrejoined compared with < 10% for GD and stem cells after a repair time of 4 h. These data indicate that terminal differentiation of 3T3-T cells is associated with a reduction in the repair of ionizing radiation-induced DNA DSBs.