Heavy-ion-induced bystander killing of human lung cancer cells: Role of gap junctional intercellular communication
Heavy-ion-induced bystander killing of human lung cancer cells: Role of gap junctional intercellular communication
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DOI：
10.1111/j.1349-7006.2009.01093.x
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发表时间：
2009-04-01
期刊：
影响因子：
5.7
通讯作者：
Nakano, Takashi
中科院分区：
文献类型：
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作者：
Harada, Kosaku;Nonaka, Tetsuo;Nakano, Takashi
本研究旨在从旁观者效应的角度探讨重离子照射诱导人肺癌A549细胞死亡的机制。在微束照射中，在融合细胞条件下，分别用1、5和10个碳离子粒子(220 MeV)照射1、5和25个细胞，然后用克隆形成实验测定细胞存活率，以研究重离子的旁观者效应。在本实验中，在5或10个碳离子照射的融合细胞条件下，有限数量的细胞(0.0001-0.002%，5-25个细胞)通过克隆形成实验夸大地增加了8-14%的细胞死亡率。然而，在指数生长的细胞条件下，没有观察到这些超调反应。此外，在用缝隙连接细胞间通讯(GJIC)抑制剂处理的细胞中，这些反应被抑制，而在GJIC刺激剂的添加下，这些反应显著增强。结果提示，重离子对旁观者细胞的杀伤主要由细胞间的直接通讯诱导，如GJIC，这可能在旁观者反应中起重要作用。(癌症科学2009；100：684-688)
The aim of the present study was to clarify the mechanisms of cell death induced by heavy-ion irradiation focusing on the bystander effect in human lung cancer A549 cells. In microbeam irradiation, each of 1, 5, and 25 cells under confluent cell conditions was irradiated with 1, 5, or 10 particles of carbon ions (220 MeV), and then the surviving fraction of the population was measured by a clonogenic assay in order to investigate the bystander effect of heavy-ions. In this experiment, the limited number of cells (0.0001-0.002%, 5-25 cells) under confluent cell conditions irradiated with 5 or 10 carbon ions resulted in an exaggerated 8-14% increase in cell death by clonogenic assay. However, these overshooting responses were not observed under exponentially growing cell conditions. Furthermore, these responses were inhibited in cells treated with an inhibitor of gap junctional intercellular communication (GJIC), whereas they were markedly enhanced by the addition of a stimulator of GJIC. The present results suggest that bystander cell killing by heavy-ions was induced mainly by direct cell-to-cell communication, such as GJIC, which might play important roles in bystander responses. (Cancer Sci 2009; 100: 684-688)