The response of tissue-equivalent proportional counters to heavy ions

The paper presents a theoretical model for the response of a tissue-equivalent proportional counter (TEPC) irradiated with charged particles. Heavy ions and iron ions in particular constitute a significant part of radiation in space. TEPCs are used for all space shuttle and International Space Station (ISS) missions to estimate the dose and radiation quality (in terms of lineal energy) inside spacecraft. The response of the tissue-equivalent proportional counters shows distortions at the wall/cavity interface. In this paper, we present microdosimetric investigation using Monte Carlo track structure calculations to simulate the response of a TEPC to charged particles of various LET (1 MeV protons, 2.4 MeV alpha particles, 46 MeV/nucleon 20Ne, 55 MeV/nucleon 20Ne, 45 MeV/nucleon 40Ar, and 1.05 GeV/nucleon 56Fe). Data are presented for energy lost and energy absorbed in the counter cavity and wall. The model calculations are in good agreement with the results of Rademacher et al. (Radiat. Res. 149, 387-389, 1998), including the study of the interface between the wall and the sensitive region of the counter. It is shown that the anomalous response observed at large event sizes in the experiment is due to an enhanced entry of secondary electrons from the wall into the gas cavity.     

Modeling the effects of low-LET cosmic rays on electronic components

The effects of cosmic radiation in single cells, organic tissues and electronics are a major concern for space exploration and manned missions. Standard heavy ions radiation tests employ ion cocktails with energy of the order of 10 MeV per nucleon and with a linear energy transfer ranging from a few MeV cm(2) mg(-1) to hundreds of MeV cm(2) mg(-1). In space, cosmic rays show significant fluxes at energies up to the order of GeV per nucleon. The present work aims at investigating single event damage due to low-, high- and very-high-energy ions. The European Space Agency reference single event upset monitor data are used to support the discussion. Finally, the effect of ionization induced directly by primary particles and ionization induced by recoils produced in an electronic device is investigated for different types of devices.     

Yield of OH radicals in water under high-density energy deposition by heavy-ion irradiation

The purpose of the present study was to evaluate the dependence of the OH radical yield on the atomic number and the energy of the heavy ions to understand chemical reactions of aqueous solutions. The total yields of oxidized products from phenol in water increased superlinearly as the incident energy increased from 5 MeV/nucleon to 18 MeV/nucleon for carbon and neon ions. The radiolytic yields of OH radicals produced by the ions were determined by analyzing the relationships of the oxidation yields of phenol to the incident energies up to 18 MeV/nucleon for ions in the range of LET from 110 eV/nm to 550 eV/nm and from 320 eV/nm to 1100 eV/nm for carbon and neon ions, respectively. The yields of the OH radicals increased with the specific energy for the same kind of ion and decreased with the atomic number for different ions used at the same specific energy.     

FLUKA capabilities for microdosimetric analysis

Delta-ray transport is important in microdosimetric studies, and how Monte Carlo models handle delta electrons using condensed histories is important for accurate simulation. The purpose of this study was to determine how well FLUKA can simulate energy deposition spectra in a tissue-equivalent proportional counter (TEPC) and produce a reliable estimate of delta-ray events produced when a TEPC is exposed to high-energy heavy ions (HZE) like those in the galactic cosmic-ray (GCR) environment. A 1.27-cm spherical TEPC with a low-pressure gas simulating a 1-μm site, typical of the one flown on the ISS, was constructed in FLUKA, and its response was compared to experimental data for an (56)Fe-ion beam at 360 MeV/nucleon. Several narrow beams at different impact parameters were used to explain the response of the same detector exposed to a uniform field of radiation. Additionally, the effect that wall thickness had on the response of the TEPC and the range of delta rays in the tissue-equivalent (TE) wall material was investigated, and FLUKA produced the expected wall effect for primary particles passing outside the sensitive volume. A final comparison to experimental data was made for the simulated TEPCs exposed to various broad beams in the energy range of 200-1000 MeV/nucleon. FLUKA overestimated energy deposition in the gas volume in all cases. The FLUKA results differed from the experimental data by an average of 25.2% for y(F) and 12.4% for y(D). It is suggested that this difference can be reduced by adjusting the FLUKA default ionization potential and density correction factors. Accurate transport codes are desirable because of the high cost of beam time for experimental evaluation of energy deposition spectra produced by HZE ions and the flexibility that calculations offer in the TEPC engineering and design process.     

Relative biological effectiveness of 12C and 28Si radiation in C57BL/6J mice

Study of heavy ion radiation-induced effects on mice could provide insight into the human health risks of space radiation exposure. The purpose of the present study is to assess the relative biological effectiveness (RBE) of (12)C and (28)Si ion radiation, which has not been reported previously in the literature. Female C57BL/6J mice (n = 15) were irradiated using 4-8 Gy of (28)Si (300 MeV/nucleon energy; LET 70 keV/μm) and 5-8 Gy of (12)C (290 MeV/nucleon energy; LET 13 keV/μm) ions. Post-exposure, mice were monitored regularly, and their survival observed for 30 days. The LD(50/30) dose (the dose at which 50 % lethality occurred by 30-day post-exposure) was calculated from the survival curve and was used to determine the RBE of (28)Si and (12)C in relation to γ radiation. The LD(50/30) for (28)Si and (12)C ion is 5.17 and 7.34 Gy, respectively, and the RBE in relation to γ radiation (LD(50/30)-7.25 Gy) is 1.4 for (28)Si and 0.99 for (12)C. Determination of RBE of (28)Si and (12)C for survival in mice is not only important for space radiation risk estimate studies, but it also has implications for HZE radiation in cancer therapy.     

The absence of an early calcium response to heavy-ion radiation in Mammalian cells

Du, G., Fischer, B. E., Voss, K.-O., Becker, G., Taucher-Scholz, G., Kraft, G. and Thiel, G. The Absence of an Early Calcium Response to Heavy-Ion Radiation in Mammalian Cells. Radiat. Res. 170, 316-326 (2008).Intracellular calcium is an important second messenger that regulates many cell functions. Recent studies have shown that calcium ions can also regulate the cellular responses to ionizing radiation. However, previous data are restricted to cells treated with low-LET radiations (X rays, gamma rays and beta particles). In this work, we investigated the calcium levels in cells exposed to heavy-ion radiation of high LET. The experiments were performed at the single ion hit facility of the GSI heavy-ion microprobe. Using a built-in online calcium imaging system, the intracellular calcium concentrations were examined in HeLa cells and human foreskin fibroblast AG1522-D cells before and after irradiation with 4.8 MeV/nucleon carbon or argon ions. Although the experiment was sensitive enough to detect the calcium response to other known stimuli, no response to heavy-ion radiation was found in these two cell types. We also found that heavy-ion radiation has no impact on calcium oscillation induced by hypoxia stress in fibroblast cells.     

The response of a spherical tissue-equivalent proportional counter to iron particles from 200-1000 MeV/nucleon

The radiation environment on board the space shuttle and the International Space Station includes high-Z and high-energy (HZE) particles that are part of the galactic cosmic radiation (GCR) spectrum. Iron-56 particles are considered to be one of the most biologically important parts of the GCR spectrum. Tissue-equivalent proportional counters (TEPCs) are used as active dosimeters on manned space flights. These TEPCs are further used to determine the average quality factor for each space mission. A TEPC simulating a 1-microm-diameter sphere of tissue was exposed as part of a particle spectrometer to (56)Fe particles at energies from 200-1000 MeV/nucleon. The response of TEPCs in terms of mean lineal energy, y(F), and dose mean lineal energy, y(D), as well as the energy deposited at different impact parameters through the detector was determined for six different incident energies of (56)Fe particles in this energy range. Calculations determined that charged-particle equilibrium was achieved for each of the six experiments. Energy depositions at different impact parameters were calculated using a radial dose distribution model, and the results were compared to experimental data.     

Induction of micronuclei in human fibroblasts across the Bragg curve of energetic heavy ions

The space environment consists of a varying field of radiation particles including high-energy ions, with spacecraft shielding material providing the major protection to astronauts from harmful exposure. Unlike low-LEpsilonTau gamma or X rays, the presence of shielding does not always reduce the radiation risks for energetic charged-particle exposure. The dose delivered by the charged particle increases sharply as the particle approaches the end of its range, a position known as the Bragg peak. However, the Bragg curve does not necessarily represent the biological damage along the particle path since biological effects are influenced by the track structures of both primary and secondary particles. Therefore, the "biological Bragg curve" is dependent on the energy and the type of the primary particle and may vary for different biological end points. Here we report measurements of the biological response across the Bragg curve in human fibroblasts exposed to energetic silicon and iron ions in vitro at two different energies, 300 MeV/nucleon and 1 GeV/nucleon. A quantitative biological response curve generated for micronuclei per binucleated cell across the Bragg curve did not reveal an increased yield of micronuclei at the location of the Bragg peak. However, the ratio of mono- to binucleated cells, which indicates inhibition of cell progression, increased at the Bragg peak location. These results confirm the hypothesis that severely damaged cells at the Bragg peak are more likely to go through reproductive death and not be evaluated for micronuclei.     

Interaction of ion tracks in spatial and temporal proximity

In the present work, a systematic analysis of the impact of spatial and temporal proximity of ion tracks on the yield of higher-order radiolytic species as well as of DNA damage patterns is presented. This potential impact may be of concern when laser-driven particle accelerators are used for ion radiation therapy. The biophysical Monte Carlo track structure code PARTRAC was used and, to this end, extended in two aspects: first, the temporal information about track evolution has been included in the track structure module and, second, the simulation code has been modified to enable parallel multiple track processing during simulation of subsequent modelling stages. Depending on the spatial and temporal separation between ion-track pairs, the yield of chemical species has been calculated for incident protons with start energies of 20 MeV, for He²⁺ ions with start energies of 1 and 20 MeV, and for 60 MeV C⁶⁺ ions. Provided the overlap of the considered ion tracks is sufficient in all four dimensions (space and time), the yield of hydroxyl radicals was found to be reduced compared to that of single tracks, for all considered ion types. The biological endpoints investigated were base damages, single-strand breaks, double-strand breaks, and clustered lesions for incident pairs of protons and He²⁺ ions, each with start energies of 20 MeV. The yield of clustered lesions produced by 20 MeV protons turned out to be influenced by the spatial separation of the proton pair; in contrast, no influence was found for different start times of the protons. The yield of single-strand breaks and base hits was found neither to depend on the spatial separation nor on the temporal separation between the incident protons. For incident 20 MeV He²⁺ ions, however, a dependence on the spatial and temporal separation of the ion pair was found for all considered biological endpoints. Nevertheless, spatial proximity conditions where such intertrack effects were obtained are not met in the case of tumour radiation therapy; thus, no impact on radiation effects due to short pulse duration of laser-driven accelerators can be expected from alterations during the chemical stage.     

Spectrum of complex DNA damages depends on the incident radiation

Ionizing radiation induces bistranded clustered damages--two or more abasic sites, oxidized bases and strand breaks on opposite DNA strands within a few helical turns. Since clusters are refractory to repair and are potential sources of double-strand breaks (DSBs), they are potentially lethal and mutagenic. Although induction of single-strand breaks (SSBs) and isolated lesions has been studied extensively, little is known about the factors affecting induction of clusters other than DSBs. To determine whether the type of incident radiation could affect the yields or spectra of specific clusters, we irradiated genomic T7 DNA, a simple 40-kbp linear, blunt-ended molecule, with ion beams [iron (970 MeV/nucleon), carbon (293 MeV/nucleon), titanium (980 MeV/nucleon), silicon (586 MeV/nucleon), protons (1 GeV/nucleon)] or 100 kVp X rays and then quantified DSBs, Fpg-oxypurine clusters and Nfo-abasic clusters using gel electrophoresis, electronic imaging and number average length analysis. The yields (damages/Mbp Gy(-1)) of all damages decreased with increasing linear energy transfer (LET) of the radiation. The relative frequencies of DSBs compared to abasic and oxybase clusters were higher for the charged particles-including the high-energy, low-LET protons-than for the ionizing photons.     

Relative biological effectiveness of high-energy iron ions for micronucleus formation at low doses

Dose-response curves for micronucleus (MN) formation were measured in Chinese hamster V79 and xrs6 (Ku80(-)) cells and in human mammary epithelial MCF10A cells in the dose range of 0.05-1 Gy. The Chinese hamster cells were exposed to 1 GeV/nucleon iron ions, 600 MeV/nucleon iron ions, and 300 MeV/nucleon iron ions (LETs of 151, 176 and 235 keV/microm, respectively) as well as with 320 kVp X rays as reference. Second-order polynomials were fitted to the induction curves, and the initial slopes (the alpha values) were used to calculate RBE. For the repair-proficient V79 cells, the RBE at these low doses increased with LET. The values obtained were 3.1 +/- 0.8 (LET = 151 keV/microm), 4.3 +/- 0.5 (LET = 176 keV/microm), and 5.7 +/- 0.6 (LET = 235 keV/microm), while the RBE was close to 1 for the repair-deficient xrs6 cells regardless of LET. For the MCF10A cells, the RBE was determined for 1 GeV/nucleon iron ions and was found to be 5.5 +/- 0.9, slightly higher than for V79 cells. To test the effect of shielding, the 1 GeV/nucleon iron-ion beam was intercepted by various thicknesses of high-density polyethylene plastic absorbers, which resulted in energy loss and fragmentation. It was found that the MN yield for V79 cells placed behind the absorbers decreased in proportion to the decrease in dose both before and after the iron-ion Bragg peak, indicating that RBE did not change significantly due to shielding except in the Bragg peak region. At the Bragg peak itself with an entrance dose of 0.5 Gy, where the LET is very high from stopping low-energy iron ions, the effectiveness for MN formation per unit dose was decreased compared to non-Bragg peak areas.     

The fragmentation of 670A MeV neon-20 as a function of depth in water. II. One-generation transport theory

The results of an experiment to study the interaction of a beam of 670A MeV neon ions incident on a water column set to different thicknesses were compared with a "first principles" transport calculation in the straight-ahead approximation. This calculation assumes that the nuclear interactions of the incident particles lead to a secondary particle with the velocity of the incident projectile at the interaction point moving in the direction of the incident projectile. Subsequent nuclear interactions of the fragments were taken into account partially, by calculating the nuclear attenuation of the fragments in the residual material, but were not taken into account as a source of further nuclear interaction products. Fluence spectra were calculated per unit incident neon fluence for 14 absorber thicknesses. The acceptance for each fragment was calculated based on a knowledge of the material in the beam and of the beam extraction energy. The theoretical spectra were multiplied by the calculated acceptance and convoluted with the LET resolution associated with the experiment. The stopping power used in the transport calculation was found to predict a range approximately 1.6% shorter than that given by experiment; this small difference resulted in significant discrepancies between theory and experiment in the stopping region. For particles not stopping in the absorber, the transport calculation was accurate to within 30% for depths less than approximately 15 cm; the effects of tertiary particles become significant at greater depth.     

Irradiation of mammalian cultured cells with a collimated heavy-ion microbeam

As the first step for the analysis of the biological effect of heavy charged-particle radiation, we established a method for the irradiation of individual cells with a heavy-ion microbeam apparatus at JAERI-Takasaki. CHO-K1 cells attached on a thin film of an ion track detector, CR-39, were automatically detected under a fluorescence microscope and irradiated individually with an 40Ar13+ ion (11.5 MeV/nucleon, LET 1260 keV/microm) microbeam. Without killing the irradiated cells, trajectories of irradiated ions were visualized as etch pits by treatment of the CR-39 with an alkaline-ethanol solution at 37 degrees C. The exact positions of ion hits were determined by overlaying images of both cells and etch pits. The cells that were irradiated with argon ions showed a reduced growth in postirradiation observations. Moreover, a single hit of an argon ion to the cell nucleus resulted in strong growth inhibition. These results tell us that our verified irradiation method enables us to start a precise study of the effects of high-LET radiation on cells.     

Physical and biological organ dosimetry analysis for international space station astronauts

In this study, we analyzed the biological and physical organ dose equivalents for International Space Station (ISS) astronauts. Individual physical dosimetry is difficult in space due to the complexity of the space radiation environment, which consists of protons, heavy ions and secondary neutrons, and the modification of these radiation types in tissue as well as limitations in dosimeter devices that can be worn for several months in outer space. Astronauts returning from missions to the ISS undergo biodosimetry assessment of chromosomal damage in lymphocyte cells using the multicolor fluorescence in situ hybridization (FISH) technique. Individual-based pre-flight dose responses for lymphocyte exposure in vitro to gamma rays were compared to those exposed to space radiation in vivo to determine an equivalent biological dose. We compared the ISS biodosimetry results, NASA's space radiation transport models of organ dose equivalents, and results from ISS and space shuttle phantom torso experiments. Physical and biological doses for 19 ISS astronauts yielded average effective doses and individual or population-based biological doses for the approximately 6-month missions of 72 mSv and 85 or 81 mGy-Eq, respectively. Analyses showed that 80% or more of organ dose equivalents on the ISS are from galactic cosmic rays and only a small contribution is from trapped protons and that GCR doses were decreased by the high level of solar activity in recent years. Comparisons of models to data showed that space radiation effective doses can be predicted to within about a +/-10% accuracy by space radiation transport models. Finally, effective dose estimates for all previous NASA missions are summarized.     

Effects of nuclear cross sections at different energies on the radiation hazard from galactic cosmic rays

The radiation hazard for astronauts from galactic cosmic rays (GCR) is a major obstacle to long-duration human space exploration. Space radiation transport codes have been developed to calculate the radiation environment on missions to the Moon, Mars, and beyond. We have studied how uncertainties in fragmentation cross sections at different energies affect the accuracy of predictions from such radiation transport calculations. We find that, in deep space, cross sections at energies between 0.3 and 0.85 GeV/nucleon have the largest effect in solar maximum GCR environments. At the International Space Station, cross sections at higher energies have the largest effect due to the geomagnetic cutoff.     

DNA fragmentation induced in human fibroblasts by accelerated (56)fe ions of differing energies

DNA fragmentation was studied in the fragment size range 0.023-5.7 Mbp after irradiation of human fibroblasts with iron-ion beams of four different energies, i.e., 200 MeV/nucleon, 500 MeV/nucleon, 1 GeV/nucleon and 5 GeV/nucleon, with gamma rays used as the reference radiation. The double-strand break (DSB) yield (and thus the RBE for DNA DSB induction) of the four iron-ion beams, which have LETs ranging from 135 to 442 keV/mum, does not vary greatly as a function of LET. As a consequence, the variation of the cross section for DSB induction mainly reflects the variation in LET. However, when the fragmentation spectra were analyzed with a simple theoretical tool that we recently introduced, the results showed that spatially correlated DSBs, which are absent after gamma irradiation, increased markedly with LET for the iron-ion beams. This occurred because iron ions produce DNA fragments smaller than 0.75 Mbp with a higher probability than gamma rays (a probability that increases with LET). These sizes include those expected from fragmentation of the chromatin loops with Mbp dimensions. This result does not exclude a correlation at distances smaller than the lower size analyzed here, i.e. 23 kbp. Moreover, the DSB correlation is dependent on dose, decreasing when dose increases; this can be explained with the argument that at increasing dose there is an increasing fraction of fragments produced by DSBs caused by separate, uncorrelated tracks.     

Effects of protons and HZE particles on glutamate transport in astrocytes, neurons and mixed cultures

Radiation-induced neurotoxicity is a well-characterized phenomenon. However, the underlying mechanism of this toxicity is poorly understood. In the central nervous system (CNS), excitotoxic mechanisms are implicated in many neurodegenerative disease processes. Pivotal to the excitotoxic pathway is dysfunction of glutamate signaling. We reported previously that exposure to low-LET γ radiation results in altered glutamate transport in neurons and astrocytes. In the present study, we sought to investigate the effects of various particle radiations of differing LET on glutamate transport as a measure of the neurochemical vulnerability of the CNS. NTera2-derived neurons and astrocytes isolated as pure and mixed cultures were exposed to doses of 10 cGy, 50 cGy or 2 Gy of 250 MeV protons, 290 MeV/nucleon carbon ions, or 1000 MeV/nucleon iron ions. Transporter function was assessed at 3 h, 2 days and 7days after exposure. Functional assessment of glutamate transport revealed that neurons and astrocytes respond in a reciprocal manner after exposure to particle radiation. Uptake activity in neurons increased after particle irradiation. This effect was evident as late as our last time (7 days) after exposure (P < 0.05). In astrocytes, transporter activity decreased after exposure. The decrease in uptake observed in astrocytes was evident 7 days after exposure to carbon and iron ions. Uptake in mixed cultures after exposure to all three forms of radiation revealed a muted interactive response suggestive of the individual responses of each cellular phenotype acting in opposition.     

Activation of thick targets by energetic heavy ions and the resultant radiation levels

This study completes data collected for thick targets exposed to carbon and oxygen ions accelerated at 86 MeV/u. The radioactivity induced in carbon and tungsten targets bombarded by argon projectiles at 95 MeV/u has been studied in order to assess the relative contributions of the incoming heavy ion and the mass number of the bombarded nuclei to the consequent radiation hazards related to the production of radioactive ion beams. Induced radioactivity measurements are only rarely made under controlled irradiation conditions, in order to derive from the measured activites the dose rates after beam bombardment and a prediction of radiation protection constraints.Submitted paper presented at the International Symposium on Heavy Ion Research: Space, Radiation Protection and Therapy, Sophia-Antipolis, France, 21–24 March 1994     

Alterations in dose and lineal energy spectra under different shieldings in the Los Alamos high-energy neutron field

Nuclear interactions of space radiation with shielding materials result in alterations in dose and lineal energy spectra that depend on the specific elemental composition, density and thickness of the material. The shielding characteristics of materials have been studied using charged-particle beams and radiation transport models by examining the risk reduction using the conventional dose-equivalent approach. Secondary neutrons contribute a significant fraction of the total radiation exposure in space. An experiment to study the changes in dose and lineal energy spectra by shielding materials was carried out at the Los Alamos Nuclear Science Center neutron facility. In the energy range of about 2 to 200 MeV, this neutron spectrum is similar in shape within a factor of about 2 to the spectrum expected in the International Space Station habitable modules. It is shown that with a shielding thickness of about 5 g cm(-2), the conventional radiation risk increases, in some cases by as much as a factor of 2, but decreases with thicknesses of about of 20 g cm(-2). This suggests that care must be taken in evaluating the shielding effectiveness of a given material by including both the charged-particle and neutron components of space radiation.     

Cataractogenic action of accelerated carbon ions with energies of 300 MeV/nucleon

The influence of carbon ions of 300 MeV/nucleon on the incidence of lenticular opacity has been studied on mice. The cataractogenic efficiency of low carbon ion doses (0.003 to 0.5 Gy) is higher than that of gamma-radiation. The threshold dose of carbon ions is 0.05 Gy. The RBE ratios vary from 30.4 to 11.1 as the period of the postirradiation observation increases from 20 to 50 weeks.