Effect of a hypoxic cell sensitizer doranidazole on the radiation-induced apoptosis of mouse L5178Y lymphoma cells
Effect of a hypoxic cell sensitizer doranidazole on the radiation-induced apoptosis of mouse L5178Y lymphoma cells
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DOI：
10.1269/jrr.43.161
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发表时间：
2002-06-01
影响因子：
2
通讯作者：
Tsujitani, M
中科院分区：
文献类型：
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作者：
Aoki, M;Furusawa, Y;Tsujitani, M
我们研究了一种新的低氧放射增敏剂- 2-硝基咪唑类似物多硝唑对辐射诱导的L5178Y细胞凋亡的增敏作用。通过检测DNA阶梯形成、流式细胞术中亚g1峰的存在和染色质凝聚来评估细胞凋亡。对存活细胞进行软琼脂集落试验也证实了多硝唑的放射增敏作用。在DNA阶梯形成的测定中，观察了在有或没有多硝唑的有氧或缺氧条件下照射后的DNA片段。5 Gy有氧、15 Gy缺氧、10 Gy多硝唑缺氧照射下，流式细胞术检测的亚g1峰细胞比例差异不大。在低氧照射下，当多硝唑浓度达到3 mM时，染色质凝结的细胞比例显著增加，但即使在10 mM时也没有增加。在浓度为1 mM时，增敏剂的增强比估计为1.7左右。这一增强比与测定细胞存活率的结果没有差异。另一方面，在有氧条件下，多硝唑对I mM无放射增敏作用。综上所述，在缺氧条件下，多硝唑可增强辐射诱导的L5178Y细胞凋亡。
We investigated the sensitizing effect of the 2-nitroimidazole analogue doranidazole, a new hypoxic radiosensitizer, on radiation-induced apoptosis in L5178Y cells. Apoptosis was assessed by checking DNA ladder formation, the presence of sub-G1 peaks in flow cytometry, and chromatin condensation. A radiosensitizing effect of doranidazole was also confirmed by a soft-agar colony assay of surviving cells. In the assay of DNA ladder formation, DNA fragmentation was observed following irradiation under an aerobic or hypoxic condition with or without doranidazole. The proportions of the cells at the sub-G1 peak in a flow cytometric measurement was not very different among the irradiations at 5 Gy under the aerobic condition, 15 Gy under hypoxia, and 10 Gy with I mM doranidazole under hypoxia. The fraction of cells with chromatin condensation was found to be significantly increased with doranidazole up to 3 mM when applied under hypoxic irradiation, but did not increase even at 10 mM. The sensitizer enhancement ratio was estimated to be about 1.7 with a concentration of I mM. This enhancement ratio was not different from that observed by assaying cell survivals. On the other hand, doranidazole showed no radiosensitizing effect under aerobic conditions with I mM. In conclusion, the radiation-induced apoptosis of L5178Y cells was enhanced by doranidazole under hypoxia.