Nuclear Science and Engineering Center, Research Group for Radiation Transport Analysis, Japan Atomic Energy Agency (JAEA), 2-4 Shirakata, Tokai, Ibaraki, 319-1195, Japan.
Faculty of Health Sciences, Hokkaido University, Kita-12 Nishi-5, Kita-ku, Sapporo, Hokkaido, 060-0812, Japan.
Phys Med Biol. 2021 Apr 6;66(7). doi: 10.1088/1361-6560/abf011.
Hypoxic cancer cells within solid tumours show radio-resistance, leading to malignant progression in fractionated radiotherapy. When prescribing dose to tumours under heterogeneous oxygen pressure with intensity-modulated radiation fields, intercellular signalling could have an impact on radiosensitivity between in-field and out-of-field (OF) cells. However, the impact of hypoxia on radio-sensitivity under modulated radiation intensity remains to be fully clarified. Here, we investigate the impact of hypoxia on in-field and OF radio-sensitivities using two types of cancer cells, DU145 and H1299. Using a nBIONIX hypoxic culture kit and a shielding technique to irradiate 50% of a cell culture flask, oxygen enhancement ratios for double-strand breaks (DSB) and cell death endpoints were determined. Thesemeasurements indicate that hypoxia impacts OF cells, although the hypoxic impacts on OF cells for cell survival were dose-dependent and smaller compared to those for in-field and uniformly irradiated cells. These decreased radio-sensitivities of OF cells were shown as a consistent tendency for both DSB and cell death endpoints, suggesting that radiation-induced intercellular communication is of importance in advanced radiotherapy dose-distributions such as with intensity-modulated radiotherapy.
实体瘤中的缺氧癌细胞表现出放射抵抗性，导致分割放疗中的恶性进展。当在异质氧压下使用强度调制辐射场为肿瘤规定剂量时，细胞间信号可能会影响场内和场外（OF）细胞的放射敏感性。然而，缺氧对调制辐射强度下的放射敏感性的影响仍有待充分阐明。在这里，我们使用两种癌细胞 DU145 和 H1299 研究了缺氧对场内和 OF 放射敏感性的影响。使用 nBIONIX 缺氧培养试剂盒和屏蔽技术辐照细胞培养瓶的 50%，确定了双链断裂（DSB）和细胞死亡终点的氧增强比。这些测量表明，缺氧会影响 OF 细胞，尽管与场内和均匀辐照细胞相比，缺氧对 OF 细胞的存活影响具有剂量依赖性且较小。对于 DSB 和细胞死亡终点，这些 OF 细胞放射敏感性的降低表现出一致的趋势，表明辐射诱导的细胞间通讯在强度调制放疗等先进放疗剂量分布中很重要。
