Teruaki Konishi - Academia.edu (original) (raw)

Papers by Teruaki Konishi

Radiation research, Jan 21, 2015

Cancer stem-like cells (CSCs) have been suggested to be the principal cause of tumor radioresista... more Cancer stem-like cells (CSCs) have been suggested to be the principal cause of tumor radioresistance, dormancy and recurrence after radiotherapy. However, little is known about CSC behavior in response to clinical radiotherapy, particularly with regard to CSC communication with bulk cancer cells. In this study, CSCs and nonstem-like cancer cells (NSCCs) were co-cultured, and defined cell types were chosen and irradiated, respectively, with proton microbeam. The bidirectional rescue effect in the combinations of the two cell types was then investigated. The results showed that out of all four combinations, only the targeted, proton irradiated NSCCs were protected by bystander CSCs and showed less accumulation of 53BP1, which is a widely used indicator for DNA double-strand breaks. In addition, supplementation with c-PTIO, a specific nitric oxide scavenger, can show a similar effect on targeted NSCCs. These results, showed that the rescue effect of CSCs on targeted NSCCs involves nitr...

International Journal of PIXE, 2008

ABSTRACT We originally developed a preparation method for samples of automobile engine lubricatin... more ABSTRACT We originally developed a preparation method for samples of automobile engine lubricating oil (liquid sample) specifically designed for in-air particle induced X-ray emission (PIXE) analysis with Helium ions. In the developed preparation method, target samples were fixed by making the oil sample sandwiches with 1% collodion solution based ethanol. With this analytical method, elements such as Al, Si, P, S, Cl, Ca and Zn can be detected from the oil samples, while Si, P, S, Ca and Zn were the elemental components of the oil additives.

Cancer letters, Jan 17, 2015

The abscopal effect could be an underlying factor in evaluating prognosis of radiotherapy. This s... more The abscopal effect could be an underlying factor in evaluating prognosis of radiotherapy. This study established an in vitro system to examine whether tumor-generated bystander signals could be transmitted by macrophages to further trigger secondary cellular responses after different irradiations, where human lung cancer NCI-H446 cells were irradiated with either γ-rays or carbon ions and co-cultured with human macrophage U937 cells, then these U937 cells were used as a bystander signal transmitter and co-cultured with human bronchial epithelial cells BEAS-2B. Results showed that U937 cells were only activated by γ-irradiated NCI-H446 cells so that the secondary injuries in BEAS-2B cells under carbon ion irradiation were weaker than γ-rays. Both TNF-α and IL-1α were involved in γ-irradiation induced secondary bystander effect but only TNF-α contributed to the carbon ion induced response. Further assay disclosed that IL-1α but not TNF-α was largely responsible for the activation of ...

Journal of applied toxicology : JAT, Jan 13, 2015

Renal toxicity is a hallmark of uranium exposure, with uranium accumulating specifically in the S... more Renal toxicity is a hallmark of uranium exposure, with uranium accumulating specifically in the S3 segment of the proximal tubules causing tubular damage. As the distribution, concentration and dynamics of accumulated uranium at the cellular level is not well understood, here, we report on high-resolution quantitative in situ measurements by high-energy synchrotron radiation X-ray fluorescence analysis in renal sections from a rat model of uranium-induced acute renal toxicity. One day after subcutaneous administration of uranium acetate to male Wistar rats at a dose of 0.5 mg uranium kg(-1) body weight, uranium concentration in the S3 segment of the proximal tubules was 64.9 ± 18.2 µg g(-1) , sevenfold higher than the mean renal uranium concentration (9.7 ± 2.4 µg g(-1) ). Uranium distributed into the epithelium of the S3 segment of the proximal tubules and highly concentrated uranium (50-fold above mean renal concentration) in micro-regions was found near the nuclei. These uranium ...

Mutation research. Fundamental and molecular mechanisms of mutagenesis, Jan 28, 2014

Most of the studies of radiation-induced bystander effects (RIBE) have been focused on understand... more Most of the studies of radiation-induced bystander effects (RIBE) have been focused on understanding the radiobiological changes observed in bystander cells in response to the signals from irradiated cells in a normal cell population with implications to radiation risk assessment. However, reports on RIBE with relevance to cancer radiotherapy especially investigating the bidirectional and criss-cross bystander communications between cancer and normal cells are limited. Hence, in present study employing co-culture approach, we have investigated the bystander cross-talk between lung cancer (A549) and normal (WI38) cells after proton-microbeam irradiation using γ-H2AX foci fluorescence as a measure of DNA double-strand breaks (DSBs). We observed that in A549-A549 co-cultures, irradiated A549 cells exert damaging effects in bystander A549 cells, which were found to be mediated through gap junctional intercellular communication (GJIC). However, in A549-WI38 co-cultures, irradiated A549 d...

Radiation Physics and Chemistry, 2009

ABSTRACT Times Cited: 0 2nd Asia-Pacific Symposium on Radiation Chemistry AUG 29-SEP 01, 2008 Was... more ABSTRACT Times Cited: 0 2nd Asia-Pacific Symposium on Radiation Chemistry AUG 29-SEP 01, 2008 Waseda Univ, Int Conf Ctr, Tokyo, JAPAN

Radiation Measurements, 2011

Chemical modification along ion tracks in PADC films has been studied by means of FT-IR spectrome... more Chemical modification along ion tracks in PADC films has been studied by means of FT-IR spectrometry, which was exposed to proton and heavy ions of He, C, Ne, Ar, Fe, Kr and Xe with energies around the Bragg peaks. This study covers a wide region of the stopping power ranging from 10 to 10,000 keV/μm. Removal cross sections for the loss

Radiation Measurements, 2013

ABSTRACT We studied the track response of CR-39 plastic nuclear track detectors (PNTD) for low (&... more ABSTRACT We studied the track response of CR-39 plastic nuclear track detectors (PNTD) for low (<6 MeV/n) and high (>100 MeV/n) energy heavy ions using the atomic force microscope (AFM). CR-39 PNTD was exposed to several heavy ion beams of different energy at HIMAC (Heavy Ion Medical Accelerator in Chiba). For AFM measurement, the amount of bulk etch was controlled to be ∼2 μm in order to avoid etching away of short range tracks. The response data obtained by AFM for ∼2 μm bulk etch was in good agreement with data obtained by the conventional optical microscope analysis for larger bulk etch. The response data from low energy beams (stopping near the surface) was also consistent with the data from high energy beams (penetrating the detector) as a function of REL (restricted energy loss) with the δ-ray cut off energy of ω0 = 200 eV. We experimentally verified that REL (ω0 = 200 eV) gives a universal function for wide energy range in CR-39 PNTD. This work has been done as part of a basic study in the measurement of secondary short range tracks produced by target fragmentation reactions in proton cancer therapy fields.

Radiation Measurements, 2005

A system to expose biological specimens to medium-energy (2.6-6.0 MeV/u) irradiation has been dev... more A system to expose biological specimens to medium-energy (2.6-6.0 MeV/u) irradiation has been developed at the NIRS-HIMAC. In order to determine the beam energy or LET at the irradiation position in air, the dose distribution for 6.0 MeV/u carbon beam has been obtained using a secondary electron monitor and a flat-type ionization chamber by using air as the energy absorber. Imaging plates were applied to assess the beam profile distribution. The intensity of photo-stimulated luminescence (PSL) was found to be almost proportional to the energy deposited within the sensitive layer of the imaging plate. It has been confirmed that a uniform irradiation field can be produced (about ±5% within 20 mm in diameter) at low-intensity exposure from 10 1 to 10 4 ions/cm 2 /s. Long-term beam stability in the low-intensity condition has also been demonstrated. As a consequence, the methodology for uniform, stable and low-intensity beam exposure has been established, and the continuously variable linear energy transfer (LET) values have also been obtained by changing the distance from the endcap of beamport, for biological studies.

Life Sciences in Space Research, 2014

LET Bystander effect p53 Mitochondria ROS High LET particle irradiation has several potential adv... more LET Bystander effect p53 Mitochondria ROS High LET particle irradiation has several potential advantages over γ -rays such as p53-independent response. The purpose of this work is to disclose the effect of p53 on the bystander effect induced by different LET irradiations and underlying mechanism. Lymphocyte cells of TK6 (wild type p53) and HMy2.CIR (mutated p53) were exposed to either low or high LET irradiation, then their mitochondrial dysfunction and ROS generation were detected. The micronuclei (MN) induction in HL-7702 hepatocytes co-cultured with irradiated lymphocytes was also measured. It was found that the mitochondrial dysfunction, p66 Shc activation, and intracellular ROS were enhanced in TK6 but not in HMy2.CIR cells after γ -ray irradiation, but all of them were increased in both cell lines after carbon and iron irradiation. Consistently, the bystander effect of MN formation in HL-7702 cells was only triggered by γ -irradiated TK6 cells but not by γ -irradiated HMy2.CIR cells. But this bystander effect was induced by both lymphocyte cell lines after heavy ion irradiation. PFT-μ, an inhibitor of p53, only partly inhibited ROS generation and bystander effect induced by 30 keV/μm carbon-irradiated TK6 cells but failed to suppress the bystander effect induced by the TK6 cells irradiated with either 70 keV/μm carbon or 180 keV/μm iron. The mitochondrial inhibitors of rotenone and oligomycin eliminated heavy ion induced ROS generation in TK6 and HMy2.CIR cells and hence diminished the bystander effect on HL-7702 cells. These results clearly demonstrate that the bystander effect is p53-dependent for low LET irradiation, but it is p53-independent for high LET irradiation which may be because of p53-independent ROS generation due to mitochondrial dysfunction.

In order to study the radiobiological effects of low dose radiation, microbeam irradiation facili... more 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.

Polymeric micelles loaded with cis-diamminedichloroplatinum(II), CDDP, (cisplatin micelles) enabl... more Polymeric micelles loaded with cis-diamminedichloroplatinum(II), CDDP, (cisplatin micelles) enable higher accumulation in solid tumors and lower toxicities compared with CDDP alone. The combined use of cisplatin micelles with radiation is expected to enhance therapeutic effects and reduce side effects. The kinetics of cisplatin micelle uptake, however, have not been fully understood. Particle Induced X-Ray Emission has been employed in this study to measure the time transients of platinum in Chinese Hamster ovary cells. The results show that the platinum content of cells treated with cisplatin micelles increased more slowly than with CDDP alone, suggesting that cellular uptake could be controlled using micelles. The CDDP released from micelles was predominantly incorporated into the cells by diffusion. The uptake characteristics were further analyzed using micelles with different collapse rates. The results and techniques used in this study will be useful for designing an optimum treatment plan combining platinum-containing polymeric micelles and radiation in clinical applications.

HeLa and CHO-K1 cells were irradiated with Fe ions (1.14 MeV/nucleon) near the Bragg peak to dete... more HeLa and CHO-K1 cells were irradiated with Fe ions (1.14 MeV/nucleon) near the Bragg peak to determine how many ion traversals through a cell nucleus are necessary to induce cell inactivation. The ion traversals through a cell nucleus were visualized by immunostaining the phosphorylated histone H2AX (gamma-H2AX), as an indicator of DNA double strand breaks (DSBs), to confirm that DSBs are actually induced along every Fe ion traversal through the nucleus. The survival curves after irradiation with Fe ions decreased exponentially with the ion fluence without a shoulder. The inactivation cross sections calculated from the slope of the survival curves and the standard errors were 96.9 +/- 1.8 and 57.9 +/- 5.4 microm2 for HeLa and CHO-K1 cells, respectively, corresponding to 0.442 and 0.456 of the mean value of each cell nucleus area. Taking the distribution of the cell nucleus area into consideration with an equation proposed by Goodhead et al. (1980), which calculates the average number of lesions per single ion track through the average area of a sensitive organelle (mainly nucleus), these two ratios were converted to 0.705 and 0.659 for HeLa and CHO-K1 cells, respectively. These ratios were less than one, suggesting that the average numbers of lethal hits per cell produced by a single ion traversal were less than one. We thus considered two possible explanations for ion traversals of more than one, necessary for cell inactivation.

African green monkey kidney cells, CV-1, were irradiated with Carbon ions (LET: 735 keV/µm Argon ... more African green monkey kidney cells, CV-1, were irradiated with Carbon ions (LET: 735 keV/µm Argon ions (LET: 3,000 keV/µm) to visualize ion tracks through the cell nucleus by labeling the 3'-OH termini result of DNA strand breaks. The 3'-OH termini of DNA were labeled with BrdU-triphosphate catalyzed by TdT. This method of TUNEL (TdT-mediated dUTP Nick End labeling) is based on the specific binding of TdT to 3'-OH termini of DNA. Subsequent immuno-fluorescent staining with the primary monoclonal antibody against BrdU, followed by a secondary antibody of Alexa Fluor 488, was performed to visualize the BrdU labeled DNA termini. Images of the cell nuclei were acquired by confocal laser microscopy. When cell monolayers were irradiated perpendicularly with argon ions, induced DSBs in cell nuclei were identifiable as fluorescent spots. In another irradiation setup, when cells were irradiated at a small angle with incident argon ions, DNA strand breaks were detected as fluorescent stripes across the cell nucleus. These results demonstrate the induction of 3'-OH termini at sites of DNA strand breaks along Argon ion tracks.

In the studies reported here, a high-linear-energy-transfer (high-LET)-radiation dose was used to... more In the studies reported here, a high-linear-energy-transfer (high-LET)-radiation dose was used to induce adaptive response in zebrafish embryos in vivo. Microbeam protons were used to provide the priming dose and X-ray photons were employed to provide the challenging dose. The microbeam irradiation system (Single-Particle Irradiation System to Cell, acronym as SPICE) at the National Institute of Radiological Sciences (NIRS), Japan, was employed to control and accurately quantify the number of protons at very low doses, viz., about 100 µGy. The embryos were dechorionated at 4 h post fertilization (hpf) and irradiated at 5 hpf by microbeam protons. For each embryo, ten irradiation points were arbitrarily chosen without overlapping with one another. To each irradiation point, 5, 10 or 20 protons each with an energy of 3.4 MeV were delivered. The embryos were returned back to the incubator until 10 hpf to further receive the challenging exposure, which was achieved using 2 Gy of X-ray irradiation, and then again returned to the incubator until 24 hpf for analyses. The levels of apoptosis in zebrafish embryos at 25 hpf were quantified through terminal dUTP transferase-mediated nick end-labeling (TUNEL) assay, with the apoptotic signals captured by a confocal microscope. The results revealed that 5 to 20 protons delivered at 10 points each on the embryos, or equivalently 110 to 430 µGy, could induce radioadaptive response in the zebrafish embryos in vivo.

The Single Particle Irradiation system to Cell (SPICE) facility at the National Institute of Radi... more The Single Particle Irradiation system to Cell (SPICE) facility at the National Institute of Radiological Sciences (NIRS) is a focused vertical microbeam system designed to irradiate the nuclei of adhesive mammalian cells with a defined number of 3.4 MeV protons. The approximately 2-μm diameter proton beam is focused with a magnetic quadrupole triplet lens and traverses the cells contained in dishes from bottom to top. All procedures for irradiation, such as cell image capturing, cell recognition and position calculation, are automated. The most distinctive characteristic of the system is its stability and high throughput; i.e. 3000 cells in a 5 mm 5 mm area in a single dish can be routinely irradiated by the 2-μm beam within 15 min (the maximum irradiation speed is 400 cells/min). The number of protons can be set as low as one, at a precision measured by CR-39 detectors to be 99.0%. A variety of targeting modes such as fractional population targeting mode, multi-position targeting mode for nucleus irradiation and cytoplasm targeting mode are available. As an example of multi-position targeting irradiation of mammalian cells, five fluorescent spots in a cell nucleus were demonstrated using the γ-H2AX immune-staining technique. The SPICE performance modes described in this paper are in routine use. SPICE is a joint-use research facility of NIRS and its beam times are distributed for collaborative research.

Rifampicin-resistant mutants were collected from the spores of three B. subtilis strains, HA101 (... more Rifampicin-resistant mutants were collected from the spores of three B. subtilis strains, HA101 (HA, repair proficient), TKJ6312 (US, UV-repair defective) and TKJ6412 (RF, recombination deficient) grown after exposure to various radiations and simulated space environments. All of 563 mutations analyzed carried sequence changes in the N-terminal region of the rpoB gene cod-ing for the subunit beta of RNA polymerase II and belonged to 56 alleles. (1) Most of spontaneous mutants from the three strains belonged to 13 single-base substitution (SBS) alleles, exceptions (50%) of TDS. In HA spores, the al-lele r201 (CA to TT at 1460) was the most frequent, while in US spores, another allele r210 (TC to AA at 1404) was the most frequent. In conclusion, some of the conditions encountered in space environments, such as space vacuum and ionizing radiations, could produce unique mutational signatures in the rpoB gene of B. subtilis spores.

Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms, 2003

Selective irradiation by an ionizing particle of a targeted cell organelle may disclose such mech... more Selective irradiation by an ionizing particle of a targeted cell organelle may disclose such mechanisms as signal transaction among cell organelles and cell-to-cell communication in the processes toward an endpoint observed. Bystander effect, existence of which has been clearly evidenced by application of the particle microbeam to biological experiments, suggests potential deviation from the conventional risk estimation at low particle fluence rates, such as in an environment of space radiation in International Space Station. To promote these studies we started the construction of a microbeam facility (named as SPICE) by using our HVEE Tandem accelerator (3.4 MeV proton and 5.1 MeV 4 He 2þ ). For our primary goal, ''irradiation of cell organelle with a single particle with a position resolution of 2 lm in a reasonable irradiation time'', special features are considered. Usage of a triplet Q-magnet for focussing the beam to micrometer levels is an outstanding feature compared to facilities of other institutes. Other features are almost similar to those of other institutes. Those are precise position control of a cell dish holder, design of the cell dish, data acquisition of microscopic image of a cell organelle (cell nucleus), data processing, reliable particle detection, soft and hard wares to integrate all these related data and system to control and irradiate a targeted spot with exactly determined number of particles.

Journal of radiation research, Jan 16, 2014

The geometric locations of ion traversals in mammalian cells constitute important information in ... more 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 uses a fluorescent nuclear track detector (FNTD) for the simultaneous detection of the geometrical images of ion traversals and DNA damage in single cells using confocal microscopy. HT1080 or HT1080-53BP1-GFP cells were cultured on the surface of a FNTD and exposed to 5.1-MeV/n neon ions. The positions of the ion traversals were obtained as fluorescent images of a FNTD. Localized DNA damage in cells was identified as fluorescent spots of γ-H2AX or 53BP1-GFP. These track images and images of damaged DNA were obtained in a short time using a confocal laser scanning microscope. The geometrical distribution of DNA damage indicated by fluoresce...