a Division of Radiation Oncology and Particle Therapy , National Cancer Center Hospital East, Kashiwa , Chiba , Japan.
b High Energy Accelerator Research Organization , Tsukuba , Japan.
Acta Oncol. 2019 Apr;58(4):475-482. doi: 10.1080/0284186X.2018.1555373. Epub 2019 Jan 11.
To investigate enhancement by 5-fluorouracil (5-FU) of the sensitivity of cancer cells to proton beam irradiation and clarify the differences in the responses of the 5-FU-treated cells to proton beam irradiation according to the position of the cells on the spread-out Bragg peak (SOBP).
OE21 human esophageal squamous cells were irradiated with a 235-MeV proton beam at four different positions on the SOBP. The effects of the irradiation plus 5-FU treatment on the cell survival were assessed by clonogenic assays and determination of the sensitizer enhancement ratio (SER). In addition, DNA double-strand breaks were estimated by measuring phospho-histone H2AX (γH2AX) foci formation in the cells at 0.5 and 24 h after irradiation.
The relative biological effectiveness (RBE) of proton beam irradiation against vehicle-control cells tended to increase with an increase in the depth of the cells on the SOBP. On the other hand, the degree of enhancement of the cellular sensitivity to proton beam irradiation by 5-FU was similar across all the positions on the SOBP. Furthermore, a marked increase in the number of residual γH2AX foci at 24 h post-irradiation was observed in the cells at the distal end of the SOBP.
Our data indicated that the degree of enhancement by 5-FU of the sensitivity of OE21 cells to 235-MeV proton beam irradiation did not differ significantly depending on the position of the cells on the SOBP. Furthermore, the degree of increase in the number of γH2AX foci at 24 h after proton beam irradiation with or without 5-FU exposure did not differ significantly according to the position on the SOBP. The effect of 5-FU in enhancing the effect of proton beam irradiation on cancer cells may be constant for all positions on the SOBP.
研究 5-氟尿嘧啶（5-FU）增强癌细胞对质子束照射敏感性的作用，并根据细胞在扩展布拉格峰（SOBP）上的位置，阐明经 5-FU 处理的细胞对质子束照射反应的差异。
采用 235-MeV 质子束在 SOBP 的四个不同位置照射 OE21 人食管鳞状细胞。通过集落形成实验和确定增敏比（SER）评估照射加 5-FU 处理对细胞存活的影响。此外，通过测量照射后 0.5 和 24 小时细胞中磷酸组蛋白 H2AX（γH2AX）焦点的形成来估计 DNA 双链断裂。
与对照组相比，质子束照射对细胞的相对生物效应（RBE）随 SOBP 上细胞深度的增加而增加。另一方面，5-FU 对质子束照射诱导的细胞敏感性的增强程度在 SOBP 的所有位置都相似。此外，在 SOBP 末端的细胞中，照射后 24 小时残留的 γH2AX 焦点数量明显增加。
我们的数据表明，5-FU 对 OE21 细胞对 235-MeV 质子束照射敏感性的增强程度不因细胞在 SOBP 上的位置而异。此外，在 SOBP 上，无论是否暴露于 5-FU，照射后 24 小时 γH2AX 焦点数量的增加程度没有明显差异。5-FU 增强质子束照射对癌细胞的效果的影响可能在 SOBP 的所有位置都保持不变。
