Wu Jinhua, Hei Tom K
a Center for Radiological Research, College of Physicians and Surgeons, Columbia University , New York , NY , USA.
b Department of Environmental Health Sciences, Mailman School of Public Health , Columbia University , New York , NY , USA.
Int J Radiat Biol. 2018 Aug;94(8):782-788. doi: 10.1080/09553002.2017.1364801. Epub 2017 Aug 29.
Even though the first ultraviolet microbeam was described by S. Tschachotin back in 1912, the development of sophisticated micro-irradiation facilities only began to flourish in the late 1980s. In this article, we highlight significant microbeam experiments, describe the latest microbeam irradiator configurations and critical discoveries made by using the microbeam apparatus.
Modern radiological microbeams facilities are capable of producing a beam size of a few micrometers, or even tens of nanometers in size, and can deposit radiation with high precision within a cellular target. In the past three decades, a variety of microbeams has been developed to deliver a range of radiations including charged particles, X-rays, and electrons. Despite the original intention for their development to measure the effects of a single radiation track, the ability to target radiation with microbeams at sub-cellular targets has been extensively used to investigate radiation-induced biological responses within cells.
Studies conducted using microbeams to target specific cells in a tissue have elucidated bystander responses, and further studies have shown reactive oxygen species (ROS) and reactive nitrogen species (RNS) play critical roles in the process. The radiation-induced abscopal effect, which has a profound impact on cancer radiotherapy, further reaffirmed the importance of bystander effects. Finally, by targeting sub-cellular compartments with a microbeam, we have reported cytoplasmic-specific biological responses. Despite the common dogma that nuclear DNA is the primary target for radiation-induced cell death and carcinogenesis, studies conducted using microbeam suggested that targeted cytoplasmic irradiation induces mitochondrial dysfunction, cellular stress, and genomic instability. A more recent development in microbeam technology includes application of mouse models to visualize in vivo DNA double-strand breaks.
Microbeams are making important contributions towards our understanding of radiation responses in cells and tissue models.
尽管早在1912年S. Tschachotin就描述了第一台紫外线微束,但精密微辐照设备的发展直到20世纪80年代末才开始蓬勃兴起。在本文中,我们重点介绍了重要的微束实验,描述了最新的微束辐照器配置以及使用微束设备所取得的关键发现。
现代放射微束设备能够产生尺寸为几微米甚至几十纳米的束斑,并能将辐射高精度地沉积在细胞靶点内。在过去三十年中,已开发出多种微束来传递包括带电粒子、X射线和电子在内的一系列辐射。尽管其最初的开发目的是测量单个辐射径迹的效应,但利用微束将辐射靶向亚细胞靶点的能力已被广泛用于研究细胞内辐射诱导的生物学反应。
使用微束靶向组织中特定细胞进行的研究阐明了旁效应,进一步的研究表明活性氧(ROS)和活性氮(RNS)在这一过程中起关键作用。对癌症放疗有深远影响的辐射诱导远隔效应进一步证实了旁效应的重要性。最后,通过用微束靶向亚细胞区室,我们报道了细胞质特异性生物学反应。尽管普遍认为核DNA是辐射诱导细胞死亡和致癌的主要靶点,但使用微束进行的研究表明,靶向细胞质辐照会诱导线粒体功能障碍、细胞应激和基因组不稳定。微束技术的一项最新进展包括应用小鼠模型来可视化体内DNA双链断裂。
微束在增进我们对细胞和组织模型中辐射反应的理解方面正发挥着重要作用。