Microbeam Irradiation Facilities for Radiobiology in Japan and China

Department of Quantum Biology, Division of Bioregulatory Medicine, Gumma Univ. Graduate School of Medicine, Maebashi, Gumma 371-8511, Japan.
Journal of Radiation Research (Impact Factor: 1.8). 03/2009; 50 Suppl A(Suppl.A):A29-47. DOI: 10.1269/jrr.09009S
Source: OAI


In order to study the radiobiological effects of low dose radiation, microbeam irradiation facilities have been developed in the world. This type of facilities now becomes an essential tool for studying bystander effects and relating signaling phenomena in cells or tissues. This review introduces you available microbeam facilities in Japan and in China, to promote radiobiology using microbeam probe and to encourage collaborative research between radiobiologists interested in using microbeam in Japan and in China.

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Available from: Teruaki Konishi,
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    • "We used a synchrotron X-ray microbeam irradiation system developed at the Photon Factory, High Energy Accelerator Research Organization, KEK [12–15], and found that cell death is more prevalent in cells irradiated with X-ray microbeams when only nuclei, rather than the whole cells, are irradiated [16, 17]. Furthermore, we recently showed that the biphasic increase in bystander cell death was dose-dependent when nuclei of targeted cells were exposed to X-ray microbeams [7, 18]. "
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    ABSTRACT: The potential for carcinogenic risks is increased by radiation-induced bystander responses; these responses are the biological effects in unirradiated cells that receive signals from the neighboring irradiated cells. Bystander responses have attracted attention in modern radiobiology because they are characterized by non-linear responses to low-dose radiation. We used a synchrotron X-ray microbeam irradiation system developed at the Photon Factory, High Energy Accelerator Research Organization, KEK, and showed that nitric oxide (NO)-mediated bystander cell death increased biphasically in a dose-dependent manner. Here, we irradiated five cell nuclei using 10 × 10 µm(2) 5.35 keV X-ray beams and then measured the mutation frequency at the hypoxanthine-guanosine phosphoribosyl transferase (HPRT) locus in bystander cells. The mutation frequency with the null radiation dose was 2.6 × 10(-)(5) (background level), and the frequency decreased to 5.3 × 10(-)(6) with a dose of approximately 1 Gy (absorbed dose in the nucleus of irradiated cells). At high doses, the mutation frequency returned to the background level. A similar biphasic dose-response effect was observed for bystander cell death. Furthermore, we found that incubation with 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO), a specific scavenger of NO, suppressed not only the biphasic increase in bystander cell death but also the biphasic reduction in mutation frequency of bystander cells. These results indicate that the increase in bystander cell death involves mechanisms that suppress mutagenesis. This study has thus shown that radiation-induced bystander responses could affect processes that protect the cell against naturally occurring alterations such as mutations.
    Journal of Radiation Research 05/2013; 54(6). DOI:10.1093/jrr/rrt068 · 1.80 Impact Factor

  • Biological Sciences in Space 01/2009; 23(4):195-201. DOI:10.2187/bss.23.195
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    ABSTRACT: Recent technological advances and new radiobiology challenges are behind the great interest in the use of microirradiation techniques for radiobiological studies. Radiobiological microbeams are facilities able to deliver precise doses of radiation to preselected individual cells (or part of them) in vitro and assess their biological consequences on a single cell base. They are therefore uniquely powerful tools to address specific problems where very precise targeting accuracy and dose delivery are required. The majority of radiobiological microbeams are centred on particle accelerators in order to irradiated biological samples with an exact number of ions. Currently there are only three microbeam facilities in routine use which employ focused X-rays: two are based on laboratory bench X-ray sources (Queen's University Belfast and Nagasaki University) and one developed using synchrotron X-ray beams (Photon Factory in Tsukuba, Japan). While low dose rates limit laboratory bench sources to a few keV, micronsize X-ray probes of a few tens of keV are achievable using synchrotron sources. Each facility has however their own benefits and draw back points. Techniques for focusing X-rays are well established and continuously improving with focal spots down to 50nm achievable for ultrasoft X-rays using circular diffraction gratings known as "zone plates". Re°ection X-ray optics such as Kirkpatrick-Baez mirrors and polycapillary systems are also used to produce micron size X-ray spots. Combined with nano-positioning accuracy of the new generation of stages, improved optics and image analysis algorithms, X-ray microbeams are able to address radiobiological issues in an unprecedented way. Microbeams have contributed significantly to the discovery and characterization of important new findings regarding the mechanisms of interaction of ionizing radiation with cells and tissues. In particular, they have played a fundamental role in the investigation of non-targeted effects where radiation response is induced in samples whose DNA has not been directly exposed. The exquisite resolution offered by focused X-ray probes has allowed important questions regarding the locations and mechanisms of subcellular targets to be precisely addressed. Evidences of the critical role played by the cytoplasm have been collected and radio-sensitivity across the cell nucleus itself is attracting considerable interest. Moreover using the microbeam single cell approach, it has been possible to study the mechanisms underpinning the bystander effect where radiation damage is expressed in cells which have not been directly irradiated but were in contact or shared medium with directly exposed samples. As a result, microbeam facilities are regarded as a main tool for the formulation of a new radiobiological paradigm where direct damage to cellular DNA is not a requirement. Additionally, the implications of the non-targeted effects in in vivo systems and ultimately humans have still to be fully understood. The new generation of X-ray microbeams equipped with 3D image stations and higher X-ray energies offers the perfect approach to extend targeted studies to complex biological models. Finally, the single-cell approach and the high spatial resolution offered by the microbeam provide the perfect tool to study and quantify the dynamic processes associated with the production and repair of DNA damage. Using green fluorescent protein (GFP), it is now possible to follow the spatiooral development of the DNA damage sites which is currently of great interest in order to monitor the remodelling of chromatin structure that the cell undergoes to deal with DNA damage.
    PIERS Online 01/2010; 6(3):207-211. DOI:10.2529/PIERS090825101324
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