An irradiation device for biological targets using focused microbeams of cyclotron-accelerated heavy ion

Funayama, Tomoo; Sakashita, Tetsuya; Suzuki, Michiyo; Yokota, Yuichiro; Miyawaki, Nobumasa; Kashiwagi, H.; Satoh, Takahiro; Kurashima, Satoshi

doi:10.1016/j.nimb.2019.12.028

Cited by 7 publications

(12 citation statements)

References 56 publications

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“…To better understand CNS involvement in the effects of radiation on the motility of C. elegans, we need a more precise microbeam device that can target specific tissue or cells. We could not clearly distinguish whether the reduction of motility after irradiation of a 60-µm-diameter area was caused by effects on specific CNS cells because of the present technical limitations; however, we are developing a novel microbeam device [37] that can irradiate specific neurons and/or muscle cells in the near future.…”

Section: Remaining Issues On the Targeted Irradiation And Analysis Ofmentioning

confidence: 95%

Targeted Central Nervous System Irradiation of Caenorhabditis elegans Induces a Limited Effect on Motility

Suzuki

Soh

Yamashita

et al. 2020

Biology

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To clarify the tissue responsible for a biological function, that function can be experimentally perturbed by an external stimulus, such as radiation. Radiation can be precisely and finely administered and any subsequent change in function examined. To investigate the involvement of the central nervous system (CNS) in Caenorhabditis elegans’ locomotion, we irradiated a limited 20-µm-diameter area of the CNS with a single dose and evaluated the resulting effects on motility. However, whether irradiated area (beam size)-dependent or dose-dependent effects on motility occur via targeted irradiation remain unknown. In the present study, we examined the irradiated area- and dose-dependent effects of CNS-targeted irradiation on the motility of C. elegans using a collimating microbeam system and confirmed the involvement of the CNS and body-wall muscle cells around the CNS in motility. After CNS-targeted microbeam irradiation, C. elegans’ motility was assayed. The results demonstrated a dose-dependent effect of CNS-targeted irradiation on motility reflecting direct effects on the irradiated CNS. In addition, when irradiated with 1000-Gy irradiation, irradiated area (beam size)-dependent effects were observed. This method has two technical advantages: Performing a series of on-chip imaging analyses before and after irradiation and targeted irradiation using a distinct ion-beam size.

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Section: Remaining Issues On the Targeted Irradiation And Analysis Ofmentioning

confidence: 95%

Targeted Central Nervous System Irradiation of Caenorhabditis elegans Induces a Limited Effect on Motility

Suzuki

Soh

Yamashita

et al. 2020

Biology

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“…Therefore, this facility has contributed to the analysis of radiation effects of HZE to cultured cells from the viewpoint of single-ion-hit effects [62] and bystander effects [63][64][65], as well as analyzed the effects of local HZE radiation on the whole body using the nematode Caenorhabditis elegans [66,67] and Medaka fish [68]. Moreover, at QST-Takasaki, the development of a new microbeam beamline that generates a finer beam spot than the current system is taking place [69]. In summary, heavy-ion microbeams will contribute more in future research examining the effect of HZE radiation, which is a significant health risk for astronauts undertaking long-term projects in space.…”

Section: High-energy Particle Irradiationmentioning

confidence: 99%

“…BioMed Research International functions are important for space missions. The effects of high-LET radiation exposure on several behaviors including muscle movements have been investigated using the nematode C. elegans [66,67,69,153,154], which is an experimental model organism and a powerful tool to study the effects of radiation. In this animal, locomotion, including forward and backward movements and turns, is carried out by 95 body wall muscle cells, for which the fate of each cell from its birth to death can be easily determined.…”

Section: Genome Instabilitymentioning

confidence: 99%

“…To label S-G2-M-phase nuclei green, the Fucci probe has a greenemitting FP fused to the APC Cdh1 -mediated ubiquitylation domain (1-110) of human Geminin (hGem) (Fucci-S/G2/M-Green); this chimeric protein is the direct substrate of APC Cdh1 E3 ligase. To label G1-phase nuclei red, the probe has a red-emitting FP fused to residues 30-120 of human Cdt1 (hCdt1) (Fucci-G1-Red); it contains the Cy motif (amino acids [68][69][70], which binds to the SCF Skp2 E3 ligase. The combination of the RFP-labeled hCdt1(30/120) and GFP-labeled hGem(1/110) can be called Fucci(SA) because they monitor the balance between SCF Skp2 and APC Cdh1 E3 ligase activities.…”

Section: Visualization Of Adverse Eventsmentioning

confidence: 99%

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Space Radiation Biology for “Living in Space”

Furukawa

Nagamatsu

Nenoi

et al. 2020

BioMed Research International

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Space travel has advanced significantly over the last six decades with astronauts spending up to 6 months at the International Space Station. Nonetheless, the living environment while in outer space is extremely challenging to astronauts. In particular, exposure to space radiation represents a serious potential long-term threat to the health of astronauts because the amount of radiation exposure accumulates during their time in space. Therefore, health risks associated with exposure to space radiation are an important topic in space travel, and characterizing space radiation in detail is essential for improving the safety of space missions. In the first part of this review, we provide an overview of the space radiation environment and briefly present current and future endeavors that monitor different space radiation environments. We then present research evaluating adverse biological effects caused by exposure to various space radiation environments and how these can be reduced. We especially consider the deleterious effects on cellular DNA and how cells activate DNA repair mechanisms. The latest technologies being developed, e.g., a fluorescent ubiquitination-based cell cycle indicator, to measure real-time cell cycle progression and DNA damage caused by exposure to ultraviolet radiation are presented. Progress in examining the combined effects of microgravity and radiation to animals and plants are summarized, and our current understanding of the relationship between psychological stress and radiation is presented. Finally, we provide details about protective agents and the study of organisms that are highly resistant to radiation and how their biological mechanisms may aid developing novel technologies that alleviate biological damage caused by radiation. Future research that furthers our understanding of the effects of space radiation on human health will facilitate risk-mitigating strategies to enable long-term space and planetary exploration.

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“…Notably, real-time imaging of cells that express modified, fluorescent fusion proteins has revealed important insights into the functioning of DNA repair in response to various lesions, primarily those induced by visible and UV light 16 , 17 . Such imaging techniques have also been applied to study the accumulation of repair proteins at sites of DSBs induced by a wide range of IR types and energies 18 – 40 . Most of these studies are performed at complex particle accelerator facilities and rely on sophisticated microscopy setups, integrated with the beamline hardware.…”

Section: Introductionmentioning

confidence: 99%

A simple microscopy setup for visualizing cellular responses to DNA damage at particle accelerator facilities

Qian

Hoebe

Faas

et al. 2021

Sci Rep

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Cellular responses to DNA double-strand breaks (DSBs) not only promote genomic integrity in healthy tissues, but also largely determine the efficacy of many DNA-damaging cancer treatments, including X-ray and particle therapies. A growing body of evidence suggests that activation of the mechanisms that detect, signal and repair DSBs may depend on the complexity of the initiating DNA lesions. Studies focusing on this, as well as on many other radiobiological questions, require reliable methods to induce DSBs of varying complexity, and to visualize the ensuing cellular responses. Accelerated particles of different energies and masses are exceptionally well suited for this task, due to the nature of their physical interactions with the intracellular environment, but visualizing cellular responses to particle-induced damage - especially in their early stages - at particle accelerator facilities, remains challenging. Here we describe a straightforward approach for real-time imaging of early response to particle-induced DNA damage. We rely on a transportable setup with an inverted fluorescence confocal microscope, tilted at a small angle relative to the particle beam, such that cells can be irradiated and imaged without any microscope or beamline modifications. Using this setup, we image and analyze the accumulation of fluorescently-tagged MDC1, RNF168 and 53BP1—key factors involved in DSB signalling—at DNA lesions induced by 254 MeV α-particles. Our results provide a demonstration of technical feasibility and reveal asynchronous initiation of accumulation of these proteins at different individual DSBs.

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An irradiation device for biological targets using focused microbeams of cyclotron-accelerated heavy ion

Cited by 7 publications

References 56 publications

Targeted Central Nervous System Irradiation of Caenorhabditis elegans Induces a Limited Effect on Motility

Targeted Central Nervous System Irradiation of Caenorhabditis elegans Induces a Limited Effect on Motility

Space Radiation Biology for “Living in Space”

A simple microscopy setup for visualizing cellular responses to DNA damage at particle accelerator facilities

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