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超短激光驱动电子束团的放射生物学效应:微核频率、端粒缩短与细胞活力

Radiobiological Effectiveness of Ultrashort Laser-Driven Electron Bunches: Micronucleus Frequency, Telomere Shortening and Cell Viability.

作者信息

Andreassi Maria Grazia, Borghini Andrea, Pulignani Silvia, Baffigi Federica, Fulgentini Lorenzo, Koester Petra, Cresci Monica, Vecoli Cecilia, Lamia Debora, Russo Giorgio, Panetta Daniele, Tripodi Maria, Gizzi Leonida A, Labate Luca

机构信息

a   Genetics Unit, CNR Institute of Clinical Physiology, Pisa, Italy;

b   Intense Laser Irradiation Laboratory, CNR National Institute of Optics, Pisa, Italy; and.

出版信息

Radiat Res. 2016 Sep;186(3):245-53. doi: 10.1667/RR14266.1. Epub 2016 Jul 19.

Abstract

Laser-driven electron accelerators are capable of producing high-energy electron bunches in shorter distances than conventional radiofrequency accelerators. To date, our knowledge of the radiobiological effects in cells exposed to electrons using a laser-plasma accelerator is still very limited. In this study, we compared the dose-response curves for micronucleus (MN) frequency and telomere length in peripheral blood lymphocytes exposed to laser-driven electron pulse and X-ray radiations. Additionally, we evaluated the effects on cell survival of in vitro tumor cells after exposure to laser-driven electron pulse compared to electron beams produced by a conventional radiofrequency accelerator used for intraoperative radiation therapy. Blood samples from two different donors were exposed to six radiation doses ranging from 0 to 2 Gy. Relative biological effectiveness (RBE) for micronucleus induction was calculated from the alpha coefficients for electrons compared to X rays (RBE = alpha laser/alpha X rays). Cell viability was monitored in the OVCAR-3 ovarian cancer cell line using trypan blue exclusion assay at day 3, 5 and 7 postirradiation (2, 4, 6, 8 and 10 Gy). The RBE values obtained by comparing the alpha values were 1.3 and 1.2 for the two donors. Mean telomere length was also found to be reduced in a significant dose-dependent manner after irradiation with both electrons and X rays in both donors studied. Our findings showed a radiobiological response as mirrored by the induction of micronuclei and shortening of telomere as well as by the reduction of cell survival in blood samples and cancer cells exposed in vitro to laser-generated electron bunches. Additional studies are needed to improve preclinical validation of the radiobiological characteristics and efficacy of laser-driven electron accelerators in the future.

摘要

与传统射频加速器相比,激光驱动电子加速器能够在更短的距离内产生高能电子束。迄今为止,我们对于使用激光等离子体加速器产生的电子照射细胞后的放射生物学效应的了解仍然非常有限。在本研究中,我们比较了外周血淋巴细胞暴露于激光驱动电子脉冲和X射线辐射后微核(MN)频率和端粒长度的剂量反应曲线。此外,与用于术中放射治疗的传统射频加速器产生的电子束相比,我们评估了激光驱动电子脉冲照射后对体外肿瘤细胞存活的影响。来自两名不同供体的血样暴露于0至2 Gy的六种辐射剂量下。微核诱导的相对生物学效应(RBE)由电子与X射线的α系数计算得出(RBE = α激光/αX射线)。在照射后第3、5和7天(2、4、6、8和10 Gy),使用台盼蓝排斥试验在OVCAR-3卵巢癌细胞系中监测细胞活力。通过比较α值获得的两名供体的RBE值分别为1.3和1.2。在研究的两名供体中,电子和X射线照射后,平均端粒长度也均以显著的剂量依赖性方式缩短。我们的研究结果表明,在体外暴露于激光产生的电子束的血样和癌细胞中,微核诱导、端粒缩短以及细胞存活减少反映了放射生物学反应。未来需要进行更多研究以改善激光驱动电子加速器放射生物学特性和疗效的临床前验证。

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