Department of Physics and Materials Science, City University of Hong Kong, Kowloon Tong, Hong Kong.
Mutat Res. 2011 Jan 10;706(1-2):59-64. doi: 10.1016/j.mrfmmm.2010.10.011. Epub 2010 Nov 10.
Mammalian cells respond to ionization radiation by sending out extracellular signals to affect non-irradiated neighboring cells, which is referred to as radiation induced bystander effect. In the present paper, we described a phenomenon entitled the "rescue effects", where the bystander cells rescued the irradiated cells through intercellular signal feedback. The effect was observed in both human primary fibroblast (NHLF) and cancer cells (HeLa) using two-cell co-culture systems. After co-culturing irradiated cells with unirradiated bystander cells for 24h, the numbers of 53BP1 foci, corresponding to the number of DNA double-strand breaks in the irradiated cells were less than those in the irradiated cells that were not co-cultured with the bystander cells (0.78±0.04foci/cell vs. 0.90±0.04foci/cell) at a statistically significant level. Similarly, both micronucleus formation and extent of apoptosis in the irradiated cells were different at statistically significant levels if they were co-cultured with the bystander cells. Furthermore, it was found that unirradiated normal cells would also reduce the micronucleus formation in irradiated cancer cells. These results suggested that the rescue effects could participate in repairing the radiation-induced DNA damages through a media-mediated signaling feedback, thereby mitigating the cytotoxicity and genotoxicity of ionizing radiation.
哺乳动物细胞通过发出细胞外信号来响应电离辐射,从而影响未受照射的邻近细胞,这被称为辐射诱导的旁观者效应。在本文中,我们描述了一种称为“拯救效应”的现象,其中旁观者细胞通过细胞间信号反馈来拯救受照射的细胞。我们使用双细胞共培养系统在人原代成纤维细胞(NHLF)和癌细胞(HeLa)中观察到了这种效应。将照射细胞与未照射的旁观者细胞共培养 24 小时后,与未与旁观者细胞共培养的照射细胞相比,照射细胞中 53BP1 焦点(对应于照射细胞中 DNA 双链断裂的数量)的数量减少(0.78±0.04 焦点/细胞对 0.90±0.04 焦点/细胞),具有统计学意义。同样,如果与旁观者细胞共培养,照射细胞中的微核形成和凋亡程度也存在统计学差异。此外,还发现未照射的正常细胞也会减少照射癌细胞中的微核形成。这些结果表明,拯救效应可以通过介质介导的信号反馈参与修复辐射诱导的 DNA 损伤,从而减轻电离辐射的细胞毒性和遗传毒性。