Cancer Cells Can Exhibit a Sparing FLASH Effect at Low Doses Under Normoxic In Vitro-Conditions.
Cancer Cells Can Exhibit a Sparing FLASH Effect at Low Doses Under Normoxic In Vitro-Conditions.
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DOI：
10.3389/fonc.2021.686142
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发表时间：
2021
影响因子：
4.7
通讯作者：
Ceberg C
中科院分区：
文献类型：
--
作者：
Adrian G;Konradsson E;Beyer S;Wittrup A;Butterworth KT;McMahon SJ;Ghita M;Petersson K;Ceberg C
在几项体内研究中，超高剂量率（FLASH）照射已被证明可以保护正常组织，而不会妨碍肿瘤控制。很少有细胞系在体外进行了研究，以前的结果是不一致的。假设氧消耗占闪光节约效应，没有节约应出现低剂量照射的细胞在常氧。使用FLASH（≥800戈伊/s）或常规剂量率（CONV，14戈伊/min），使用来自临床直线加速器的10 MeV电子束，以0 - 12戈伊的剂量照射7种癌细胞系（MDA-MB-231、MCF 7、WiDr、LU-HNSCC 4、HeLa [早期传代和亚克隆]）和正常肺成纤维细胞（MRC-5）。用克隆形成试验测定存活分数（SF）。进一步研究了三个细胞系的辐射诱导的DNA损伤灶使用53 BP 1标记和辐射后的细胞周期同步。与CONV相比，FLASH后所有细胞系的存活率均有增加的趋势，其中4/7细胞系存在显著差异。在SF=0.1时，6/7细胞系的FLASH保留幅度表示为剂量修饰因子，约为1.1，HeLassubclone约为1.3。比较FLASH和CONV，发现相似的细胞周期分布和53 BP 1-灶数。我们已经发现，FLASH效应出现在低剂量下常氧条件下的几个细胞系在体外。FLASH效应的大小在细胞系之间不同，表明遗传的生物相容性为FLASH照射。
Irradiation with ultra-high dose rate (FLASH) has been shown to spare normal tissue without hampering tumor control in several in vivo studies. Few cell lines have been investigated in vitro, and previous results are inconsistent. Assuming that oxygen depletion accounts for the FLASH sparing effect, no sparing should appear for cells irradiated with low doses in normoxia. Seven cancer cell lines (MDA-MB-231, MCF7, WiDr, LU-HNSCC4, HeLa [early passage and subclone]) and normal lung fibroblasts (MRC-5) were irradiated with doses ranging from 0 to 12 Gy using FLASH (≥800 Gy/s) or conventional dose rates (CONV, 14 Gy/min), with a 10 MeV electron beam from a clinical linear accelerator. Surviving fraction (SF) was determined with clonogenic assays. Three cell lines were further studied for radiation-induced DNA-damage foci using a 53BP1-marker and for cell cycle synchronization after irradiation. A tendency of increased survival following FLASH compared with CONV was suggested for all cell lines, with significant differences for 4/7 cell lines. The magnitude of the FLASH-sparing expressed as a dose-modifying factor at SF=0.1 was around 1.1 for 6/7 cell lines and around 1.3 for the HeLasubclone. Similar cell cycle distributions and 53BP1-foci numbers were found comparing FLASH to CONV. We have found a FLASH effect appearing at low doses under normoxic conditions for several cell lines in vitro. The magnitude of the FLASH effect differed between the cell lines, suggesting inherited biological susceptibilities for FLASH irradiation.
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影响因子：
3.4
作者：
CYGLER, J;KLASSEN, NV;RAAPHORST, GP
通讯作者：
RAAPHORST, GP
影响因子：
5.7
作者：
Montay-Gruel, Pierre;Petersson, Kristoffer;Vozenin, Marie-Catherine
通讯作者：
Vozenin, Marie-Catherine
影响因子：
3.4
作者：
MICHAELS, HB;EPP, ER;PETERSON, EC
通讯作者：
PETERSON, EC
影响因子：
1.3
作者：
Manti, L.;Perozziello, F. M.;Tramontana, A.
通讯作者：
Tramontana, A.
DOI：
10.1158/1078-0432.ccr-20-0894
发表时间：
2021-02-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Montay-Gruel P;Acharya MM;Gonçalves Jorge P;Petit B;Petridis IG;Fuchs P;Leavitt R;Petersson K;Gondré M;Ollivier J;Moeckli R;Bochud F;Bailat C;Bourhis J;Germond JF;Limoli CL;Vozenin MC
通讯作者：
Vozenin MC