Abstract

X-ray microbeams have been used to explore radiobiological effects induced by targeting a specific site in living systems. Synchrotron radiation from the Photon Factory, Japan, with high brilliance and highly parallel directionality is a source suitable for delivering a particular beam size or shape, which can be changed according to target morphology by using a simple metal slit system (beam size from 5 μm to several millimeters). Studies have examined the non-targeted effects, called bystander cellular responses, which are thought to be fundamental mechanisms of low-dose or low-dose-rate effects in practical radiation risk research. Narrow microbeams several tens of micrometers or less in their size targeted both the cell nucleus and the cytoplasm. Our method combined with live-cell imaging techniques has challenged the traditional radiobiological dogma that DNA damage is the only major cause of radiation-induced genetic alterations and is gradually revealing the role of organelles, such as mitochondria, in these biological effects. Furthermore, three-dimensionally cultured cell systems have been used as microbeam targets to mimic organs. Combining the spatial fractionation of X-ray microbeams and a unique ex vivo testes organ culture technique revealed that the tissue-sparing effect was induced in response to the non-uniform radiation fields. Spatially fractionated X-ray beams may be a promising tool in clinical radiation therapy.

Highlights

  • Cells in multicellular systems have been targeted by irradiation with ionizing radiation or UV lasers in mechanistic studies of radiobiological phenomena

  • Experimental evidence has shown that cell-to-cell communications between exposed and unexposed cells surrounding the exposed cells play an important role in inducing certain kinds of genetically critical effects in the unexposed cells, known as the bystander response

  • We have investigated the mitochondrial effects by using a deformational synchrotron X-ray microbeam from the Photon Factory (KEK, Japan) (Figure 4) to expose cell nuclei or cytoplasm uniformly

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Summary

Introduction

Cells in multicellular systems have been targeted by irradiation with ionizing radiation or UV lasers in mechanistic studies of radiobiological phenomena. Nagasawa and Little [4] performed pioneering work in which they exposed 1% of Chinese hamster ovary cells in a culture dish to alpha particles and measured the induction of sister chromatid exchanges (SCE). A similar enhancement of SCE induction by alpha-particle irradiation of a small percentage of cells was reported by Deshpande et al [5] These studies challenged the radiobiological dogma that radiation damage to DNA is the only major cause of genomic alteration. The synchrotron X-ray microbeam provides a uniformly exposed small area in a wide range of biological targets, from DNA to animals This is a specific advantage of this microbeam compared with ion particle irradiation or focused laser beams. The use of the X-ray microbeam combined with live-cell imaging techniques is highlighted in relation to investigating the risks of low-dose radiation exposure, as well as radiation therapy for cancer treatment

Early Studies of Bystander Effects using X-Ray Microbeams
Synchrotron X-Ray Microbeams in Radiation Biology
Cytoplasmic Irradiation with X-Ray Microbeams
Microbeam Exposure to Cell Population Systems Including 3-D Cultured Cells
Clinical Appreciations of X-Ray Microbeams
Findings
Summary

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