Heavy Ion Particle Research Articles

Irradiation with heavy-ion particles changes the cellular distribution of human histone acetyltransferase HAT1

Hat1 was the first histone acetyltransferase identified; however, its biological function is still unclear. In this report, it is shown for the first time that human Hat1 has two isoforms. Isoform a has 418 amino acids (aa) and is localized exclusively in the nuclear matrix of normal human keratinocytes (NHKs). Isoform b has 334 aa and is located in the cytoplasm, the nucleoplasm, attached to the chromatin and to the nuclear matrix. Immunohistochemical analyses revealed that the bulk of Hat1 is confined to the nucleus, with much lesser amounts in the cytoplasm. Cells undergoing mitotic division have an elevated amount of Hat1 compared to those that are non-mitotic. Senescent cells, however, exhibit a higher concentration of Hat1 in the cytoplasm compare to proliferating cells and the amount of Hat1 in the nucleus decreases with the progression of senescence. NHKs exposed to hydrogen peroxide (H(2)O(2)) or to a beam of high mass and energy ion particles displayed bright nuclear staining for Hat1, a phenotype that was not observed in NHKs exposed to gamma-rays. We established that the enhanced nuclear staining for Hat1 in response to these treatments is regulated by the PI3K and the mitogen-activated protein kinase signaling pathways. Our observations clearly implicate Hat1 in the cellular response assuring the survival of the treated cells.

Prematurely condensed chromosome fragments in human lymphocytes induced by high doses of high-linear-energy-transfer irradiation

This study provides a useful biodosimetry protocol for radiation accidents that involve high doses of heavy particle radiation. Human peripheral blood lymphocytes (PBLs) were irradiated in vitro with high doses (5–50 Gy) of charged heavy-ion particles (carbon ions, at an effective linear-energy-transfer (LET) of 34.6 keV/μm), and were then stimulated to obtain dividing cells. PBLs were treated with 100 nM calyculin A to force chromosomes to condense prematurely, and chromosome spreads were obtained and stained with Giemsa. The G2 prematurely condensed chromosome (G2-PCC) index and the number of G2-PCC including fragments (G2-PCC-Fs) per cell for each radiation dose point were scored. Dose-effect relationships were obtained by plotting the G2-PCC indices or G2-PCC-Fs numbers against radiation doses. The G2-PCC index was greater than 5% up to doses of 15 Gy; even after a 30 Gy radiation dose, the index was 1 to 2%. At doses higher than 30 Gy, however, the G2-PCC indices were close to zero. The number of G2-PCC-Fs increased steeply for radiation doses up to 30 Gy at a rate of 1.07 Gy −1. At doses higher than 30 Gy, the numbers of G2-PCC-Fs could not be accurately indexed because of the limited numbers of cells for analysis. Therefore, the number of G2-PCC-Fs could be used to estimate radiation doses up to 30 Gy. In addition, a G2-PCC index close to zero could be used as an indicator for radiation doses greater than 40 Gy.

EPR and UV spectroscopic investigations of sucrose irradiated with heavy-ion particles

Crystalline sucrose irradiated with C and Si ions is investigated with EPR and UV spectroscopy. Samples are treated at different doses of radiation in the region 20–300 Gy and linear energy transfer (LET) values of 39.6, 49 and 58 keV μm −1 for C ions and 60 keV μm −1 for Si ions. All samples exhibit identical EPR spectra due to radiation-induced stable sucrose radicals. At given constant LET the EPR signal responses are linear to the absorbed doses of Si and C ions. Water solutions of irradiated sucrose exhibit UV absorption maximum at 267 nm due to the product of radical recombination. The intensity of this band is stronger at irradiation with Si than with C ions. UV absorption is more sensitive to heavy-ion species irradiation than the EPR signals.

Introduction to The Proposed Space Experiments Aboard The ISS Using The Silkworm, Bombyx mori

The authors have a plan to examine the biological effects of cosmic rays by loading the eggs of the silkworm, Bombyx mori, in the International Space Station (ISS) for 3 months. In advance of the project, several ground experiments have been performed. In order to investigate the biological effects of radiation, heavy ion particles were used instead of cosmic rays. Heterozygous eggs of the black-striped strain (pS/p) were irradiated with Carbon (C), Neon (Ne) or Ferrous (Fe) ion particles. At the fifth instar stage, larvae that hatched from these eggs showed white spots on their backs against the black or dark brown of their integument. These are somatic mutations which seem to be caused by the effects of radiation on the pS gene. The incidence of this somatic mutation increased in proportion to dose and linear energy transfer of C and Ne ion particles, and it was higher after resumption of embryogenesis in eggs that had been irradiated after diapause termination as compared with eggs irradiated while still in diapause. Irradiation by more than 0.04 Gy of Fe ion particles to diapause-terminated eggs induced a significant incidence of somatic mutation compared with controls (P

EXPERIMENTAL STUDY AND SPICE SIMULATION OF CMOS INVERTERS LATCH-UP EFFECTS DUE TO HIGH POWER MICROWAVE INTERFERENCE

Experimental study and SPICE simulation of CMOS digital circuits latch-up effects due to high power microwave interference are reported in this paper. As a traditional inherent destruction phenomenon, latch-up effect may jeopardize the correct function of the circuits, and could be triggered in various ways such as ESD pulse, cosmic ray, heavy ion particles etc. Through the directly injected experimental investigation of CMOS inverters, it is shown that the single short high power RF pulse not only could disturb and upset the inverters output logic voltage, but also might trigger CMOS latch-up effects. It is observed that the RF pulse leading to inverters latch-up effects have energy threshold characteristics, which means that the injected RF pulse power is inversely proportional to the pulse width. SPICE simulations indicated that the inverters maximum static consumption current in latch-up state will increase up to 6600 multiples compared to the normal value when input logic state is high. With the device scaling down, higher integration and higher working frequency, the power consumption problem plays a significant role, which makes CMOS logic circuits more vulnerable due to the latch-up effects under high power microwave threats.

The Effects of Heavy Ion Particles on Human Megakaryocytopoiesis and Thrombopoiesis.

Heavy ion particles provide unique properties in radiotherapy. However, they have also been shown to pose high risks for both work at nuclear facilities and astronauts participating in space missions. In a previous study, we demonstrated that in radio-sensitive megakaryocyte progenitor cells, namely colony-forming unit megakaryocytes (CFU-Meg), a degree of X-ray-induced damage was prevented by post-treatment with several cytokines. In this study, we analyzed the effects of heavy ion particles on megakaryocytopoiesis and thrombopoiesis.The CD34+ CFU-Meg were isolated from human placental and umbilical cord blood using a magnetic isolation kit and then were exposed to a carbon ion beam (LET=50 KeV/mm). They were cultured in a serum free medium supplemented with a thrombopoietin (TPO) alone or a combination of TPO plus other cytokines including stem cell factor, interleukin-3 (IL-3) and Flt3-ligand. The number of CFU-Meg was calculated by a plasma clot technique. The differentiation into megakaryocytes (CD41+) and the release of platelets (CD42a+) in a liquid culture were both analyzed by flow cytometry. The increase of gamma-H2AX, a marker of DNA double-strand breaks (DSBs) was also detected by flow cytometry.The sensitivity of CFU-Meg to a carbon ion beam was found to be extremely high and could not be lowered by any type of cytokines unlike X-rays. However, treatment with TPO plus IL-3 potentially induced megakaryocytopoiesis and thrombopoiesis at 14 days after the exposure to a carbon ion beam at 2 Gy. The cytokine treatment enhanced the induction of gamma-H2AX in X-ray-irradiated CD34+ CFU-Meg but not in a carbon ion beam-irradiated one.These results show that not only the downregulation of death signals, but also the repair of DSBs was less strongly promoted by cytokines in CFU-Meg exposed to a carbon ion beam than X-rays. Different treatments therefore are required to protect against megakaryocytopoiesis and thrombopoiesis damage by heavy ion particles.

LET-Dependent Survival of Irradiated Normal Human Fibroblasts and Their Descendents

Evidence has accumulated showing that ionizing radiations persistently perturb genomic stability and induce delayed reproductive death in the progeny of survivors; however, the linear energy transfer (LET) dependence of these inductions has not been fully characterized. We have investigated the cell killing effectiveness of gamma rays (0.2 keV/microm) and six different beams of heavy-ion particles with LETs ranging from 16.2 to 1610 keV/microm in normal human fibroblasts. First, irradiated confluent density-inhibited cultures were plated for primary colony formation, revealing that the relative biological effectiveness (RBE) based on the primary 10% survival dose peaked at 108 keV/microm and that the inactivation cross section increased proportionally up to 437 keV/microm. Second, cells harvested from primary colonies were plated for secondary colony formation, showing that delayed reproductive death occurred in a dose-dependent fashion. While the RBE based on the secondary 80% survival dose peaked at 108 keV/microm, very little difference in LET was observed in the RBE based on secondary survival at the primary 10% survival dose. Our present results indicate that delayed reproductive death arising only during secondary colony formation is independent of LET and is more likely to be dependent on initial damages having been fixed during primary colony formation.

Past and future application of solid-state detectors in manned spaceflight

The radiation exposure in space missions can be reduced by careful mission planning and appropriate measures, such as provision of a radiation shelter, but it cannot be eliminated. The reason for that is the high penetration capability of the radiation components owing to their high energies. Radiation is therefore an acknowledged primary concern for manned spaceflight and is a potentially limiting factor for long-term orbital and interplanetary missions. The radiation environment is a complex mixture of charged particles of solar and galactic origin and of the radiation belts, as well as of secondary particles produced in interactions of the galactic cosmic particles with the nuclei of atmosphere of the earth. The complexity even increases by placing a spacecraft into this environment owing to the interaction of the radiation components with the shielding material. Therefore it is a challenge to provide for appropriate measurements in this radiation field, coping with the limited resources on experiment power and mass. Solid-state dosemeters were already chosen for measurements in the first manned flights. Thermoluminescence dosemeters (TLDs) and plastic nuclear track detectors (PNTD) especially found a preferred application because they are light-weighted, need no power supply and they are tissue-equivalent. Most of the data available until 1996 were gathered by using these passive detectors; this especially holds for heavy ion particle spectra. The systems, supplemented by converter foils or fission detectors and bubble detectors, provide information on dose, particle flux-, energy- and linear energy transfer spectra of the ionising radiation and neutron fluxes and doses. From 1989, silicon detectors were used for dose and flux measurements and later on for particle spectrometry. Silicon detectors were demonstrated as a powerful tool for the description of space radiation environment. Optical simulated luminescence (OSL) detectors have now been introduced as a new system in space research. Both, OSL and superheated drop detectors are candidates for personal dosimetry systems. The article will summarise past results, and results of measurements performed recently on the ISS, and conclude with future aspects.

Heteroepitaxial diamond detectors for heavy ion beam tracking

Heteroepitaxy has been shown to produce uniform crystals of single crystal diamond. An advantage of heteroepitaxy is its potential for creating materials suitable for energetic particle detectors that require large-area plates. At this point, there is little information on the electronic properties of heteroepitaxial material and its suitability for detector use is an open question. To address this issue, a heteroepitaxially grown single crystal was used for high-temperature DC transport measurements and for evaluation as a heavy ion particle detector. Using a transverse geometry with an as-grown Ir film as one electrode and a diffused Ti–Au top electrode, the sample showed no detectable current leakage at room temperature up to 100 V bias. At temperatures between 250 and 600 °C, the DC electrical conductivity exhibited thermally activated behavior with an activation energy of 1.4 eV. A 76Ge beam with an energy of 100 MeV/u produced at the Coupled Cyclotron Facility at Michigan State University was used to test detector performance. At typical beam fluences, single events were recorded with instrumentally limited rise times of 0.5 ns and pulse width 1 ns. Single pulses corresponded to an energy loss Δ E = 46 MeV. A pulse-height resolution of the energy loss signal of Δ E / E = 18% was measured. Of particular importance is the fast performance at high beam intensities. No degradation of timing properties and energy resolution could be observed with count rates up to 10 6 particles/s. These measurements reflect the properties of the as-grown heteroepitaxial diamond crystal to which no subsequent processing was applied. It is anticipated that by using thicker crystals that allow the defective initial growth region to be removed mechanically, greatly improved energy resolution can be observed.

Characterization of clustered DNA damage induced by heavy ion particles

Characterization of clustered DNA damage induced by heavy ion particles

A long-term effects of heavy ion particle irradiation to whole body in mature female rats

A long-term effects of heavy ion particle irradiation to whole body in mature female rats

Cytokines and their receptors in gastrointestinal malignancies and their relationship to metastases and local recurrences in patients treated with heavy–ion particle therapy

Cytokines and their receptors in gastrointestinal malignancies and their relationship to metastases and local recurrences in patients treated with heavy–ion particle therapy

Comprehensive Cross-Section Database Development for Generalized Three-Dimensional Radiation Transport Codes

To correctly specify the composition and spectra of transmitted heavy-ion radiation fields, such as those encountered in space radiation protection studies, accurate values of the total, elastic scattering, reaction cross sections, and spectral and angular distributions of all emitted particles (nucleons, light ions, and heavy ions) from the nuclear interactions of propagating high-energy heavy-ion particles with target nuclei are required. For space radiation protection studies, this means that double-differential (energy and angle) isotope production cross sections must be known for all stable nuclear isotopes with mass numbers from 1 to about 60 colliding with any target nucleus at energies from tens of mega-electron-volts per nucleon up to several giga-electron-volts per nucleon. Currently there are several radiation transport codes that transport high-energy nucleons, light ions, heavy ions, or some combination of them. None, however, transport all of these particles in more than one dimension. In order to make a comprehensive tool for space applications that transports all of these particles, with a wide range of energies and in three dimensions, the database described above is needed, particularly for light and heavy ions. This paper discusses the creation of this comprehensive cross-section database.

Clustered DNA damage induced by heavy ion particles

Clustered DNA damage (locally multiply damaged site) is thought to be a critical lesion caused by ionizing radiation, and high LET radiation such as heavy ion particles is believed to produce high yields of such damage. Since heavy ion particles are major components of ionizing radiation in a space environment, it is important to clarify the chemical nature and biological consequences of clustered DNA damage and its relationship to the health effects of exposure to high LET particles in humans. The concept of clustered DNA damage emerged around 1980, but only recently has become the subject of experimental studies. In this article, we review methods used to detect clustered DNA damage, and the current status of our understanding of the chemical nature and repair of clustered DNA damage.

Evaluation of quantity and quality of DNA damage induced by heavy ion particles

Evaluation of quantity and quality of DNA damage induced by heavy ion particles

Radiation effects of heavy ion particles on bone metabolism

Radiation effects of heavy ion particles on bone metabolism

Contamination dose from photoneutron processes in bodily tissues during therapeutic radiation delivery.

Dose to the total body from induced radiation resulting from primary exposure to radiotherapeutic beams is not detailed in routine treatment planning though this information is potentially important for better estimates of health risks including secondary cancers. This information can also allow better management of patient treatment logistics, suggesting better timing, sequencing, and conduct of treatment. Monte Carlo simulations capable of taking into account all interactions contributing to the dose to the total body, including neutron scattering and induced radioactivity, provide the most versatile and accurate tool for investigating these effects. MCNPX code version 2.2.6 with full IAEA library of photoneutron cross sections is particularly suited to trace not only photoneutrons but also protons and heavy ion particles that result from photoneutron interactions. Specifically, the MCNPX code is applied here to the problem of dose calculations in traditional (non-IMRT) photon beam therapy. Points of calculation are located in the head, where the primary irradiation has been directed, but also in the superior portion of the torso of the ORNL Mathematical Human Phantom. We calculated dose contributions from neutrons, protons, deutrons, tritons and He-3 that are produced at the time of photoneutron interactions in the body and that would not have been accounted for by conventional radiation oncology dosimetry.

The Effects of Heavy Ion Particles on the Developing Murine Cerebellum, with Special Reference to Cell Death

We report here the effects of heavy ion beams on postnatal mouse cerebellar development, with reference to cell death. Eight-day-old B6C3F1 mice were irradiated with single doses of 0.1, 0.25, 0.5, 1.0, and 2.0 Gy, using a carbon beam of 290 MeV delivered from a heavy ion medical accelerator in Chiba (HIMAC). To compare the effects of X-rays with those of accelerated carbon ions, 8-day-old mice were exposed to X-rays single doses of 0.1, 0.25, 0.5, 1.0, and 2.0 Gy, respectively. Pups were fixed at 1, 6, 12 and 24 hr after exposure to HIMAC beams or X-rays. Four-μm-thick parasagittal sections of the cerebella were processed for hematoxylin-eosin staining as well as for staining with the TUNEL (terminal dUTP nick-end labeling) technique. The density of fragmented nuclei in the external granular layer increased with time, peaking at 6 hr after exposure, in both the HIMAC and X-irradiated groups. In the HIMAC groups, the density was significantly higher in those animals exposed to 0.25 Gy or more compared to 0 Gy, whereas in the X-irradiated groups it was significantly higher in those mice exposed to 0.5 Gy or more. Electron microscopic examinations revealed chromatin condensation in the cell nuclei in the HIMAC groups. This is the first in vivo evidence that apoptotic cell death is induced in developing mouse cerebellum after exposure to heavy ion particles. The difference in the frequency of dying cells between exposure to heavy ion particles and to X-rays may reflect the high linear energy transfer (LET) associated with a heavy ion beam.

A low-pressure gas detector for heavy-ion tracking and particle identification

A low-pressure gas tracker for heavy ions is described. It is based on a drift chamber with four series of multiplying wires for energy loss measurement and underlying strips for position and angle determination. Results of tests with an α-source and with low-energy heavy-ion beams are presented. They indicate the suitability of such a detector in a wide range of experiments with heavy ions where a low energy threshold, a large solid angle, together with a precise measurement of ion trajectories and identification is needed. In particular, the application as a prototype of the focal plane detector for the large-acceptance spectrometer MAGNEX is discussed.

A theoretical model for the microdosimetry of discontinuous distributions of heavy particle tracks.

A novel approach to solving microdosimetry problems using conditional probabilities and geometric concepts has been developed. This approach is valid for cases where a convex site is immersed in uniform or discontinuous distributions of heavy charged particle tracks and assumes no restrictions in site geometry or the kind of randomness. These conditions are relevant to the study of microdosimetry in applications such as neutron capture therapy (NCT), irradiation experiments using heavy ion particle beams, environmental radon, or occupational exposure to radioactive materials. Expressions applicable to the case of surface-distributed sources of tracks are presented that may represent situations such as NCT, where boron compounds are bound to the membranes of cellular nuclei. Microdosimetric spectra, specific energy averages, and mean number of 10B capture reactions for cell inactivation are calculated, showing their dependence on 10B localisation.