Yokota Yuichiro, Funayama Tomoo, Mutou-Yoshihara Yasuko, Ikeda Hiroko, Kobayashi Yasuhiko
Microbeam Radiation Biology Group, Japan Atomic Energy Agency , Takasaki, Gunma , Japan.
Int J Radiat Biol. 2015 May;91(5):383-8. doi: 10.3109/09553002.2015.1021960.
To investigate the dependence of the bystander cell-killing effect on radiation dose and quality, and to elucidate related molecular mechanisms.
Normal human fibroblast WI-38 cells were irradiated with 0.125 - 2 Gy of γ-rays or carbon ions and were co-cultured with non-irradiated cells. Survival rates of bystander cells were investigated using the colony formation assays, and nitrite concentrations in the medium were measured using the modified Saltzman method.
Survival rates of bystander cells decreased with doses of γ-rays and carbon ions of ≤ 0.5 Gy. Treatment of the specific nitric oxide (NO) radical scavenger prevented reductions in survival rates of bystander cells. Moreover, nitrite concentrations increased with doses of less than 0.25 Gy (γ-rays) and 1 Gy (carbon ions). The dose responses of increased nitrite concentrations as well as survival reduction were similar between γ-rays and carbon ions. In addition, negative relationships were observed between survival rates and nitrite concentrations.
The bystander cell-killing effect mediated by NO radicals in normal human fibroblasts depends on irradiation doses of up to 0.5 Gy, but not on radiation quality. NO radical production appears to be an important determinant of γ-ray- and carbon-ion-induced bystander effects.
研究旁观者细胞杀伤效应对辐射剂量和质量的依赖性，并阐明相关分子机制。
用0.125 - 2 Gy的γ射线或碳离子照射正常人成纤维细胞WI-38，并与未照射的细胞共培养。采用集落形成试验研究旁观者细胞的存活率，并用改良的Saltzman法测量培养基中的亚硝酸盐浓度。
当γ射线和碳离子剂量≤0.5 Gy时，旁观者细胞的存活率降低。使用特定的一氧化氮（NO）自由基清除剂处理可防止旁观者细胞存活率降低。此外，当γ射线剂量小于0.25 Gy和碳离子剂量小于1 Gy时，亚硝酸盐浓度升高。γ射线和碳离子之间，亚硝酸盐浓度升高以及存活率降低的剂量反应相似。此外，在存活率和亚硝酸盐浓度之间观察到负相关关系。
正常人成纤维细胞中由NO自由基介导的旁观者细胞杀伤效应取决于高达0.5 Gy的照射剂量，但不取决于辐射质量。NO自由基的产生似乎是γ射线和碳离子诱导的旁观者效应的重要决定因素。
