Difference in the relative biological effectiveness and DNA damage repair processes in response to proton beam therapy according to the positions of the spread out Bragg peak.
Difference in the relative biological effectiveness and DNA damage repair processes in response to proton beam therapy according to the positions of the spread out Bragg peak.
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DOI：
10.1186/s13014-017-0849-1
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发表时间：
2017-07-03
期刊：
影响因子：
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通讯作者：
Akimoto T
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文献类型：
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作者：
Hojo H;Dohmae T;Hotta K;Kohno R;Motegi A;Yagishita A;Makinoshima H;Tsuchihara K;Akimoto T
细胞对质子束辐照的反应尚不清楚，特别是高能质子束在铺展布拉格峰（SOBP）上位置的相对生物有效性（RBE）差异。为此，我们利用两种具有不同放射敏感性的人食管癌细胞系，研究了高能质子束对放置在SOBP不同位置的靶细胞的生物学效应差异。用235 mev的质子束辐照两株不同放射敏感性的人食管癌细胞系OE21、KYSE450，分别照射于SOBP上的4个不同位置（位置1:SOBP入口处；位置2:SOBP近端；位置3:SOBP中心；位置4:SOBP远端），通过克隆实验评估细胞存活率。靶细胞系在SOBP上各位置的RBE10根据光子束照射后的细胞存活测定结果确定。此外，通过免疫荧光定量分析细胞核中形成的磷酸化组蛋白H2AX （γH2AX）灶的数量，估计DNA双链断裂的数量。质子束的RBE值随SOBP上位置的不同而变化，随着SOBP上位置的远端移动，RBE值有增加的趋势。照射24 h后对两种细胞系的γ - h2ax残灶数量的比较显示，在SOPB远端照射的细胞比在SOBP近端或中心照射的细胞有更多的残灶数量。本研究的结果表明，与细胞系的放射敏感性水平无关，高能质子束的RBE和细胞对高能质子束辐照的反应，包括DNA损伤修复过程，根据SOBP上的位置而不同。本文的在线版本（doi:10.1186/s13014-017-0849-1）包含补充材料，仅供授权用户使用。
Cellular responses to proton beam irradiation are not yet clearly understood, especially differences in the relative biological effectiveness (RBE) of high-energy proton beams depending on the position on the Spread-Out Bragg Peak (SOBP). Towards this end, we investigated the differences in the biological effect of a high-energy proton beam on the target cells placed at different positions on the SOBP, using two human esophageal cancer cell lines with differing radiosensitivities. Two human esophageal cancer cell lines (OE21, KYSE450) with different radiosensitivities were irradiated with a 235-MeV proton beam at 4 different positions on the SOBP (position #1: At entry; position #2: At the proximal end of the SOBP; position #3: Center of the SOBP; position #4: At the distal end of the SOBP), and the cell survivals were assessed by the clonogenic assay. The RBE10 for each position of the target cell lines on the SOBP was determined based on the results of the cell survival assay conducted after photon beam irradiation. In addition, the number of DNA double-strand breaks was estimated by quantitating the number of phospho-histone H2AX (γH2AX) foci formed in the nuclei by immunofluorescence analysis. In regard to differences in the RBE of a proton beam according to the position on the SOBP, the RBE value tended to increase as the position on the SOBP moved distally. Comparison of the residual number of γH2AX foci at the end 24 h after the irradiation revealed, for both cell lines, a higher number of foci in the cells irradiated at the distal end of the SOPB than in those irradiated at the proximal end or center of the SOBP. The results of this study demonstrate that the RBE of a high-energy proton beam and the cellular responses, including the DNA damage repair processes, to high-energy proton beam irradiation, differ according to the position on the SOBP, irrespective of the radiosensitivity levels of the cell lines. The online version of this article (doi:10.1186/s13014-017-0849-1) contains supplementary material, which is available to authorized users.