Desai Sejal, Kobayashi Alisa, Konishi Teruaki, Oikawa Masakazu, Pandey Badri N
Radiation Signalling and Cancer Biology Section, Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400 085, India.
Radiation System and Engineering Section, Department of Technical Support and Development, Research, Development and Support Center, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
Mutat Res. 2014 May-Jun;763-764:39-44. doi: 10.1016/j.mrfmmm.2014.03.004. Epub 2014 Mar 28.
Most of the studies of radiation-induced bystander effects (RIBE) have been focused on understanding the radiobiological changes observed in bystander cells in response to the signals from irradiated cells in a normal cell population with implications to radiation risk assessment. However, reports on RIBE with relevance to cancer radiotherapy especially investigating the bidirectional and criss-cross bystander communications between cancer and normal cells are limited. Hence, in present study employing co-culture approach, we have investigated the bystander cross-talk between lung cancer (A549) and normal (WI38) cells after proton-microbeam irradiation using γ-H2AX foci fluorescence as a measure of DNA double-strand breaks (DSBs). We observed that in A549-A549 co-cultures, irradiated A549 cells exert damaging effects in bystander A549 cells, which were found to be mediated through gap junctional intercellular communication (GJIC). However, in A549-WI38 co-cultures, irradiated A549 did not affect bystander WI38 cells. Rather, bystander WI38 cells induced inverse protective signalling (rescue effect) in irradiated A549 cells, which was independent of GJIC. On the other hand, in response to irradiated WI38 cells neither of the bystander cells (A549 or WI38) showed significant increase in γ-H2AX foci. The observed bystander signalling between tumour and normal cells may have potential implications in therapeutic outcome of cancer radiotherapy.
大多数关于辐射诱导旁观者效应（RIBE）的研究都集中在理解正常细胞群体中旁观者细胞对来自受辐照细胞的信号所产生的放射生物学变化，这对辐射风险评估具有重要意义。然而，与癌症放疗相关的RIBE报告，特别是关于癌症细胞与正常细胞之间双向和交叉旁观者通讯的研究却很有限。因此，在本研究中，我们采用共培养方法，以γ-H2AX焦点荧光作为DNA双链断裂（DSB）的测量指标，研究了质子微束辐照后肺癌（A549）细胞与正常（WI38）细胞之间的旁观者串扰。我们观察到，在A549-A549共培养体系中，受辐照的A549细胞对旁观者A549细胞产生了损伤作用，发现这是通过间隙连接细胞间通讯（GJIC）介导的。然而，在A549-WI38共培养体系中，受辐照的A549细胞并未影响旁观者WI38细胞。相反，旁观者WI38细胞在受辐照的A549细胞中诱导了反向保护信号（拯救效应），这与GJIC无关。另一方面，对于受辐照的WI38细胞，旁观者细胞（A549或WI38）均未显示γ-H2AX焦点有显著增加。肿瘤细胞与正常细胞之间观察到的旁观者信号可能对癌症放疗的治疗结果具有潜在影响。
