Yoshiya Furusawa

High energy ion beams are effective physical mutagens for mutation induction in plants. Due to their high linear energy transfer (LET) property, they are known to generate single nucleotide variations (SNVs) and insertion/deletions (InDels, <50 bp) as well as structural variations (SVs). However, due to the technical difficulties to identify SVs, s...

We examined lethal damages of X rays induced by direct and indirect actions, in terms of double-strand break (DSB) repair susceptibility using two kinds of repair-deficient Chinese hamster ovary (CHO) cell lines. These CHO mutants (51D1 and xrs6) are genetically deficient in one of the two important DNA repair pathways after genotoxic injury [homol...

We have been studying the effectiveness of direct action, which induces clustered DNA damage leading to cell killing, relative to indirect action. Here a new criterion Direct Ation-Based Biological Effectiveness (DABBLE) is proposed to understand the contribution of direct action for cell killing induced by C ions. DABBLE is defined as the ratio of...

High-energy ion beams are known to be an effective and unique type of physical mutagen in plants. However, no study on the mutagenic effect of argon (Ar) ion beam radiation on rice has been reported. Genome-wide studies on induced mutations are important to comprehend their characteristics for establishing knowledge-based protocols for mutation ind...

Purpose: A study is presented of the irradiation of cancerous cervical cell line HeLa loaded with a platinum salt, betamethasone and deoxyglucose. The presence of the platinum increases the free-radical concentration and augments the cell death rate, whereas betamethasone or deoxyglucose induces radiosensitization by the alteration of metabolic pat...

HIMAC, a therapeutic accelerator, has also been used for basic research, including various types of biological studies. Some of these studies, have attempted to expand the applications of heavy particle beams (ion beams) to other than cancer treatment; research on disease treatment other than cancer and breeding research can be cited. These project...

Biological effects caused by ionizing radiation have been investigated mainly using photons due to restrictions on available radiation sources. While HIMAC is the first synchrotron in the world specifically constructed for medical use, NIRS accepted and promoted basic sciences proposed by domestic and international researchers. Research at HIMAC pr...

Single Particle Irradiation system to Cell (SPICE) facility at the National Institute of Radiological Sciences (NIRS) provides a magnetically focused 3.4 MeV proton microbeam. Throughout the radiobiological studies using SPICE over the years, we have realized that biological effect can be affected by the highly localized dose distribution of the mi...

Radioresistance is the major obstacle in the radiotherapy of the malignant melanoma. Thus, it is of importance to increase the radiosensitivity of melanoma cells. In the present study, the radioresistant melanoma cell line OCM-1 with inducible overexpression of Ras-related C3 botulinum toxin substrate 2 was established based on a radiation-inducibl...

Hypofractionated carbon-ion therapy has been applied to treatment of several tumours. In this case, relative biological effectiveness (RBE) at high dose region must be considered, however, the RBE calculated physically has been not verified biologically. In this study, spheroid technique was adopted to estimate RBE in wide dose range. Cells were ir...

It is believed that the dose-rate of radiation will have an influence on cell sensitivity. The dose-rate effects on cell survival can be expressed by the change of the β term in the linear quadratic model. The value at a high-dose-rate decreases below 60 Gy/h and reaches zero at 0.2 Gy/h or less for photons. However, the effect for a high-LET ion-b...

Bi-directional signaling involved in radiation-induced bystander effect (RIBE) between irradiated carcinoma cells and their surrounding non-irradiated normal cells is relevant to radiation cancer therapy. Using the SPICE-NIRS microbeam, we delivered 500 protons to A549-GFP lung carcinoma cells, stably expressing H2B-GFP, which were co-cultured with...

The development of new varieties of perennial plants generally requires lengthy and laborious procedures. In this study, we used ion beam irradiation mutagenesis in an attempt to accelerate the breeding process for perennial plants. We evaluated the biological effects of five ion beam sources (carbon, neon, argon, silicon, and iron) and neutron irr...

It has been known that heart disease-such as myocardial infarction (MI), cardiac hypertrophy, or heart failure-alters the molecular structure and function of the gap junction, which can lead to an abnormal heart rhythm. Radiation has been shown to modulate intercellular communication in the skin and lungs by increasing connexin43 (Cx43) expression....

The goal of this work was to clarify the effect of carbon-ion beams on reduction of the metastatic potential of malignant melanoma using in vitro and in vivo techniques. We utilized a 290 MeV/u carbon beam with a 6-cm spread-out Bragg-peak (SOBP), 137Cs γ rays or 200 kVp X rays for irradiation, and in vitro murine melanoma B16/BL6 cells that were i...

2016): RAC2-P38 MAPK-dependent NADPH oxidase activity is associated with the resistance of quiescent cells to ionizing radiation, Cell Cycle To link to this article: http://dx. ABSTRACT Our recent study showed that quiescent G0 cells are more resistant to ionizing radiation than G1 cells; however, the underlying mechanism for this increased radiore...

It has been established that irradiation with higher linear energy transfer (LET) increases lethality and mutagenicity more than that with lower LET. However, the characteristics specific to carbon ion beam have not yet been elucidated. Yeast cells were irradiated with carbon ions with an LET of 13 or 50keV/μm, and cell survival and mutation freque...

The quality of the sublethal damage (SLD) after irradiation with high–linear energy transfer (LET) ion beams was investigated with low-LET photons. Chinese hamster V79 cells and human squamous carcinoma SAS cells were first exposed to a priming dose of different ion beams at different LETs at the Heavy Ion Medical Accelerator in the Chiba facility....

Introduction: Carbon-ion irradiation of rabbit hearts has improved left ventricular conduction abnormalities through upregulation of gap junctions. However, to date, there has been no investigation on the effect of carbon-ion irradiation on electrophysiological properties in human. We investigated this effect in patients with mediastinum extra-car...

Ionizing radiations have been used for medical care more than 100 years. The types of radiations begin in the X-ray spread to a variety of radiation. Quantum beams such as photon, neutron, pion, proton, and heavy-ion have their each own physical characteristic, especially in the energy distribution in matter. Charged particle beam show a Bragg's pe...

L-[methyl-¹¹C]Methionine (¹¹C-Met) is useful for estimating the therapeutic efficacy of particle radiotherapy at early stages of the treatment. Given the short half-life of ¹¹C, the development of longer-lived ¹⁸F- and ¹²³I-labeled probes that afford diagnostic information similar to ¹¹C-Met, are being sought. Tumor uptake of ¹¹C-Met is involved in...

Background: Targeted external heavy ion irradiation (THIR) of rabbit hearts 2 weeks after myocardial infarction (MI) reduced the vulnerability of fatal ventricular tachyarrhythmias (VT/VF) in association with the increased connexin43 (Cx43). Increased Cx43 was maintained for at least 1 year in normal rabbits, but the long-term antiarrhythmic effec...

Our recent study showed that quiescent G0 cells are more resistant to ionizing radiation than G1 cells; however, the underlying mechanism for this increased radioresistance is unknown. Based on the relatively lower DNA damage induced in G0 cells, we hypothesize that these cells are exposed to less oxidative stress during exposure. As a catalytic su...

The purpose of this study was to investigate the effect of metformin on the responses of hepatocellular carcinoma (HCC) cells to γ-rays (low-linear energy transfer (LET) radiation) and carbon-ion beams (high-LET radiation). HCC cells were pretreated with metformin and exposed to a single dose of γ-rays or carbon ion beams. Metformin treatment incre...

PU-H71, a heat shock protein 90 (Hsp90) inhibitor, has yielded therapeutic efficacy in many preclinical models and is currently in clinical trials. Carbon-ion radiotherapy (CIRT) has provided successful tumor control; however, there is still room for improvement, particularly in terms of tumor-specific radiosensitization. The Hsp90 inhibitor PU-H71...

This chapter is dedicated to the possibility of augmenting the radiobiological effects when irradiated tissues are loaded with high-Z atoms contained in molecules or nanoparticles by fast atomic ions. A preliminary quantitative study of DNA break induction by monochromatic photons tuned to the resonant photoabsorption energy of LIII shell of platin...

Solid tumours often present regions with severe oxygen deprivation (hypoxia), which are resistant to both chemotherapy and radiotherapy. Increased radiosensitivity as a function of the oxygen concentration is well described for X-rays. It has also been demonstrated that radioresistance in anoxia is reduced using high-LET radiation rather than conve...

Common cancer therapies employ chemicals or radiation that damage DNA. Cancer and normal cells respond to DNA damage by activating complex networks of DNA damage sensor, signal transducer, and effector proteins that arrest cell cycle progression, and repair damaged DNA. If damage is severe enough, the DNA damage response (DDR) triggers programmed c...

Accumulated evidence has shown that radiation-induced bystander effect (RIBE) may have significant implications to the efficiency of radiotherapy. Although cellular radiosensitivity relies on cell cycle status, it is largely unknown how about the relationship between RIBE and cell cycle distribution, much less the underlying mechanism. In the prese...

Ionising radiation-induced bystander effects are well recognised, but its dependence on dose or linear energy transfer (LET) is still a matter of debate. To test this, 49 sites in confluent cultures of AG01522D normal human fibroblasts were targeted with microbeams of carbon (103 keV µm(-1)), neon (375 keV µm(-1)) and argon ions (1260 keV µm(-1)) a...

The microbeam irradiation system is designed to deliver a defined number of charged particles on to a single cell and it has become a powerful tool in radiobiological studies. The SPICE-NIRS microbeam can target cell nuclei, cytoplasm, or both, automatically with a defined number of protons. The approximately 2 μm diameter proton beam is focused wi...

Little work has been done on the mechanism of low dose hyper-radiosensitivity (HRS) and later appeared radioresistance (termed induced radioresistance (IRR)) after irradiation with medium and high linear energy transfer (LET) particles. The aim of this study was to find out whether ATR pathway is involved in the mechanism of HRS induced by high LET...

Most cause of death of ischemic heart disease or cardiomyopathy is a lethal ventricular arrhythmia. In recent years, catheter ablation is established for treatment of tachyarrhythmia. Drug therapy is focused on arrhythmia therapy under consideration of the patient characteristics. However, there is no curative treatment in lethal ventricular arrhyt...

In this article, the in vivo study performed to evaluate the uniformity of biological doses within an hypothetical target volume and calculate the values of relative biological effectiveness (RBE) at different depths in the spread-out Bragg peak (SOBP) of the new CNAO (National Centre for Oncological Hadrontherapy) carbon beams is presented, in the...

Comparison of the efficiency of photon and carbon ion radiotherapy (RT) administered with the same number of fractions might be of limited clinical interest, since a wide range of fractionation patterns are used clinically today. Due to advanced photon treatment techniques, hypofractionation is becoming increasingly accepted for prostate and lung t...

Comparison of the efficiency of photon and carbon ion radiotherapy (RT) administered with the same number of fractions might be of limited clinical interest, since a wide range of fractionation patterns are used clinically today. Due to advanced photon treatment techniques, hypofractionation is becoming increasingly accepted for prostate and lung t...

In the clinic, the relative biological effectiveness (RBE) value of 1.1 has usually been used in relation to the whole depth of the spread-out Bragg-peak (SOBP) of proton beams. The aim of this study was to confirm the actual biological effect in the SOBP at the very distal end of clinical proton beams using an in vitro cell system. A human salivar...

Clustered DNA damage is a specific type of DNA damage induced by ionizing radiation. Any type of ionizing radiation traverses the target DNA molecule as a beam, inducing damage along its track. Our previous study showed that clustered DNA damage yields decreased with increased linear energy transfer (LET), leading us to investigate the importance o...

In biological processes after energy deposition of radiation in cells, DNA damage occurs at first to produce chromosomal breaks and then appear many cell responses. Reproductive and interphase cell death causes inactivation of cancer tissue. Traditional target theory and linear quadratic model are used to explain mechanism and treatment prediction....

The geometric locations of ion traversals in mammalian cells constitute important information in the study of heavy ion-induced biological effect. Single ion traversal through a cellular nucleus produces complex and massive DNA damage at a nanometer level, leading to cell inactivation, mutations and transformation. We present a novel approach that...

DNA double-strand breaks (DSBs) induced by ionizing radiation pose a major threat to cell survival. The cell can respond to the presence of DSBs through two major repair pathways: homologous recombination (HR) and non-homologous end joining (NHEJ). Higher levels of cell death are induced by high-linear energy transfer (LET) radiation when compared...

There are few reports on the biological homogeneity within the spread-out Bragg peak (SOBP) of proton beams. Therefore, to evaluate the relative biological effectiveness (RBE) and the oxygen enhancement ratio (OER), human salivary gland tumor (HSG) cells were irradiated at the plateau position (position A) and three different positions within a 6-c...

Fig. S2. Clonogenic survival of hepG2, HSG, and SHG44 cells following combined treatment with 3-methyladenine (3-MA) or rapamycin and carbon ion irradiation.

Fig. S1. Clonogenic survival of various tumor cells following treatment with different reagents alone.

Fig. S3. Apoptotic rates of HeLa cells treated with different reagents alone.

Table S1. Survival fraction at 2 Gy for cells cotreated with high- linear energy transfer radiation and reagents.

In the clinic, the relative biological effectiveness (RBE) value of 1.1 has usually been used in relation to the whole depth of the spread-out Bragg-peak (SOBP) of proton beams. The aim of this study was to confirm the actual biological effect in the SOBP at the very distal end of clinical proton beams using an in vitro cell system. A human salivar...