Abstract Background Nanomaterials have been applied as radiosensitizer in an effort to improve the effectiveness of radiotherapy in killing cancer cells while simultaneously sparing the healthy normal tissue. Increase in radiotoxicity to the cancerous region might also influence the non-targeted cells through radiation-induced bystander effect (RIBE) mechanism. In this study, we implemented Bi2O3 NPs as radiosensitizer in combination with megavoltage radiotherapy and probe into the RIBE consequences in the non-targeted cells. Aim To investigate the effects of bismuth oxide nanoparticles (Bi2O3 NPs) on RIBE triggered in MCF-7 and hFOB 1.19 after irradiation with 10 MV clinical photon beam. Materials and methods The MCF-7 (human breast cancer) and hFOB 1.19 (human fetal osteoblast) cell lines were incubated with and without Bi2O3 NPs prior to irradiation. The treated cells were irradiated with radiation doses of 0 to 12 Gy using 10 MV photon beam in a single exposure. The irradiated-cell conditioned medium (ICCM) were collected from the targeted cells and transferred into the non-targeted cells. Reactive oxygen species (ROS), cell viability and colony forming assay was employed to evaluate the effect. Results The present study demonstrated that the MCF-7 and hFOB 1.19 bystander cells are able to maintain their cell viability for more than 80% after 48 h incubation with ICCM treated with Bi2O3 NPs at 2 Gy radiation dose. The percentage of cell survival fraction of hFOB 1.19 cells which received ICCM with Bi2O3 NPs decreased to 86.8%, in contrast to MCF-7 bystander cells which show an increment in their cells survival after treatment with Bi2O3 NPs. Our results show that the ROS level was increased in the bystander cells, but the addition of Bi2O3 NPs did not significantly increase the ROS level. Conclusions The application of nanoparticles for radiosensitization during radiotherapy must also considered the RIBE responses in the non-irradiated cells. These findings provide evidence that the use Bi2O3 NPs as radiosensitizer in radiotherapy is safe and do not significantly increase the RIBE responses in non-targeted cells.

中文翻译：

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在 10 MV 光子束照射下氧化铋纳米颗粒对 MCF-7 和 hFOB 1.19 细胞旁观者效应的影响

摘要背景纳米材料已被用作放射增敏剂，以努力提高放射疗法在杀死癌细胞的同时保护健康正常组织的有效性。对癌变区域的放射毒性增加也可能通过辐射诱导的旁观者效应 (RIBE) 机制影响非靶向细胞。在这项研究中，我们将 Bi2O3 NPs 作为放射增敏剂与兆压放疗相结合，并探讨了非靶向细胞中的 RIBE 后果。目的 研究氧化铋纳米颗粒 (Bi2O3 NPs) 对 10 MV 临床光子束照射后 MCF-7 和 hFOB 1.19 中触发的 RIBE 的影响。材料和方法 MCF-7（人乳腺癌）和 hFOB 1。19 个（人胎儿成骨细胞）细胞系在辐照前用和不用 Bi2O3 NPs 孵育。在单次曝光中使用 10 MV 光子束以 0 至 12 Gy 的辐射剂量照射处理过的细胞。从靶细胞中收集辐照细胞条件培养基 (ICCM) 并转移到非靶细胞中。采用活性氧 (ROS)、细胞活力和集落形成试验来评估效果。结果 本研究表明，MCF-7 和 hFOB 1.19 旁观者细胞在与用 Bi2O3 NPs 以 2 Gy 辐射剂量处理的 ICCM 孵育 48 小时后能够保持其细胞活力超过 80%。接受 ICCM 和 Bi2O3 NPs 的 hFOB 1.19 细胞的细胞存活率百分比降低至 86.8%，与 MCF-7 旁观者细胞相反，MCF-7 旁观者细胞在用 Bi2O3 NPs 处理后细胞存活率增加。我们的结果表明，旁观者细胞中的 ROS 水平增加，但 Bi2O3 NPs 的添加并未显着增加 ROS 水平。结论 在放射治疗期间应用纳米粒子进行放射增敏还必须考虑未照射细胞中的 RIBE 反应。这些发现证明在放射治疗中使用 Bi2O3 NPs 作为放射增敏剂是安全的，并且不会显着增加非靶向细胞的 RIBE 反应。结论 在放射治疗期间应用纳米粒子进行放射增敏还必须考虑未照射细胞中的 RIBE 反应。这些发现证明在放射治疗中使用 Bi2O3 NPs 作为放射增敏剂是安全的，并且不会显着增加非靶向细胞的 RIBE 反应。结论 在放射治疗期间应用纳米粒子进行放射增敏还必须考虑未照射细胞中的 RIBE 反应。这些发现证明在放射治疗中使用 Bi2O3 NPs 作为放射增敏剂是安全的，并且不会显着增加非靶向细胞的 RIBE 反应。