Kobayashi Alisa, Konishi Teruaki
SPICE-BIO research core, International Open Laboratory, National Institute of Radiological Sciences (NIRS), National Institutes for Quantum and Radiological Science and Technology (QST), 4-9-1 Anagawa, Inageku, Chiba, Japan.
Department of Accelerator and Medical Physics, National Institute of Radiological Sciences (NIRS), National Institutes for Quantum and Radiological Science and Technology (QST), 4-9-1 Anagawa, Inageku, Chiba, Japan.
J Radiat Res. 2018 Nov 1;59(6):754-759. doi: 10.1093/jrr/rry065.
This study aimed to determine whether the radiation-induced bystander effect (RIBE) is affected by radiation quality. To mimic the different radiation qualities of the direct action (D)/indirect action (ID) ratio, A549 cells were exposed to X-rays, with either 100 mM of the radical scavenger, thio-urea (TU+), or null (TU-). Biological responses in irradiated and bystander cells were compared at equal lethal effects of a 6% survival dose, which was estimated from the survival curves to be 8 Gy and 5 Gy for TU+ and TU-, respectively. Cyclooxygenase-2 (COX-2) expression in TU- irradiated cells increased up to 8 h post-irradiation, before decreasing towards 24 h. The concentration of prostaglandin E2 (PGE2), a primary product of COX-2 and known as a secreted inducible factor in RIBE, increased over 3-fold compared with that in the control at 8 h post-irradiation. Conversely, COX-2 expression and PGE2 production of TU+ irradiated cells were drastically suppressed. These results show that the larger D/ID suppressed COX-2 expression and PGE2 production in irradiated cells. However, in contrast to the case in the irradiated cells, COX-2 expression was equally observed in the TU- and TU+ co-cultured bystander cells, which showed the highest expression levels at 24 h post-irradiation. Taken together, these findings demonstrate that radiation quality, such as the D/ID ratio, may be an important factor in the alteration of signalling pathways involved in RIBE.
本研究旨在确定辐射诱导旁观者效应（RIBE）是否受辐射品质影响。为模拟直接作用（D）/间接作用（ID）比率的不同辐射品质，将A549细胞暴露于X射线下，一组添加100 mM自由基清除剂硫脲（TU+），另一组不添加（TU-）。在6%存活剂量的同等致死效应下比较受照射细胞和旁观者细胞的生物学反应，根据存活曲线估计TU+和TU-的该剂量分别为8 Gy和5 Gy。TU-照射细胞中的环氧合酶-2（COX-2）表达在照射后8小时内升高，之后在24小时时下降。前列腺素E2（PGE2）是COX-2的主要产物，也是RIBE中一种分泌诱导因子，其浓度在照射后8小时比对照增加了3倍多。相反，TU+照射细胞的COX-2表达和PGE2产生受到显著抑制。这些结果表明，较大的D/ID抑制了照射细胞中COX-2的表达和PGE2的产生。然而，与照射细胞的情况相反，在TU-和TU+共培养的旁观者细胞中均观察到COX-2表达，且在照射后24小时显示出最高表达水平。综上所述，这些发现表明，诸如D/ID比率等辐射品质可能是RIBE中信号通路改变的一个重要因素。
