Cellular and subcellular effect of heavy ions: a comparison of the induction of strand breaks and chromosomal aberration with the incidence of inactivation and mutation.

Radiobiological effects of heavy charged particles are compared for a large variety of ions from Helium to Uranium and energies between 1 and 1000 MeV/u which correspond to LET values between 10 and 16000 keV/micrometers. The different cross section for the induction of strand breaks and chromosomal aberrations as well as for inactivation and mutation induction exhibit striking similarities when compared as function of the linear energy transfer (LET). At LET values below 100 keV/micrometers all data points of one specific effect form one single curve as a function of LET, independent of the atomic number of the ion. In this LET range, the biological effects are independ from the particle energy or track structure and depend only on the energy transfer. Therefore, LET is a good parameter in this regime. For LET values greater than 100 keV/micrometers, the curves for the different ions separate from the common curve in order of increasing atomic numbers. In this regime LET is no longer a good parameter and the physical parameters of the formation of particle tracks are important. The similarity of the sigma-LET curves for different endpoints indicates that the 'hook-structure' is produced by physical and chemical effects which occur before the biologically relevant lesions are formed. However, from the existing data of biological effects, it can be concluded that the efficiencies for cell killing are always smaller than those extrapolated from X-ray data on the basis of the energy deposition only. Therefore, cells which are directly hit by an HZE particle are not killed and undergo a finite risk of mutation and transformation.     

The influence of radiation quality on the formation of DNA breaks.

We have aimed to present a comprehensive review of our understanding to date of the formation of DNA strand breaks induced by high LET radiation. We have discussed data obtained from DNA in solution as well as from the formation and "repair" of strand breaks in cell DNA. There is good agreement, qualitatively, between these two systems. Results were evaluated for two parameters: (1) effectivity per particle, the cross section (sigma) in micrometers 2/particle; and (2) the strand break induction frequency as number of breaks per Gy per unit DNA (bp or dalton). A series of biological effects curves (one for each Z-number) is obtained in effectivity versus LET plots. The relationships between induction frequencies of single-strand breaks, or double-strand breaks, or the residual "irrepairable" breaks and LET-values have been evaluated and discussed for a wide spectrum of heavy ions, both for DNA in solution and for DNA in the cell. For radiation induced total breaks in cell DNA, the RBE is less than one, while the RBE for the induction of DSBs can be greater than one in the 100-200 keV/micrometers range. The level of irrepairable strand breaks is highest in this same LET range and may reach 25 percent of the initial break yield. The data presented cover results obtained for helium to uranium particles, covering a particle incident energy range of about 2 to 900 MeV/u with a corresponding LET range of near 16 to 16000 keV/micrometers.     

Analysis of radiation risk from alpha particle component of solar particle events.

The solar particle events (SPE) will contain a primary alpha particle component, representing a possible increase in the potential risk to astronauts during an SPE over the often studied proton component. We discuss the physical interactions of alpha particles important in describing the transport of these particles through spacecraft and body shielding. Models of light ion reactions are presented and their effects on energy and linear energy transfer (LET) spectra in shielding discussed. We present predictions of particle spectra, dose, and dose equivalent in organs of interest for SPE spectra typical of those occurring in recent solar cycles. The large events of solar cycle 19 are found to have substantial increase in biological risk from alpha particles, including a large increase in secondary neutron production from alpha particle breakup.     

Charged-particle mutagenesis II. Mutagenic effects of high energy charged particles in normal human fibroblasts.

The biological effects of high LET charged particles are a subject of great concern with regard to the prediction of radiation risk in space. In this report, mutagenic effects of high LET charged particles are quantitatively measured using primary cultures of human skin fibroblasts, and the spectrum of induced mutations are analyzed. The LET of the charged particles ranged from 25 KeV/micrometer to 975 KeV/micrometer with particle energy (on the cells) between 94-603 MeV/u. The X-chromosome linked hypoxanthine guanine phosphoribosyl transferase (hprt) locus was used as the target gene. Exposure to these high LET charged particles resulted in exponential survival curves; whereas, mutation induction was fitted by a linear model. The Relative Biological Effect (RBE) for cell-killing ranged from 3.73 to 1.25, while that for mutant induction ranged from 5.74 to 0.48. Maximum RBE values were obtained at the LET of 150 keV/micrometer. The inactivation cross-section (alpha i) and the action cross-section for mutant induction (alpha m) ranged from 2.2 to 92.0 micrometer2 and 0.09 to 5.56 x 10(-3) micrometer2, respectively. The maximum values were obtained by 56Fe with an LET of 200 keV/micrometer. The mutagenicity (alpha m/alpha i) ranged from 2.05 to 7.99 x 10(-5) with the maximum value at 150 keV/micrometer. Furthermore, molecular analysis of mutants induced by charged particles indicates that higher LET beams are more likely to cause larger deletions in the hprt locus.     

Cytogenetic effects of energetic ions with shielding

In order to understand the effects of shielding on the induction of biological damages by charged particles, we conducted experiments with accelerated protons (250 MeV) and iron particles (1 GeV/u). Human lymphocytes in vitro were exposed to particle beams through polyethylene with various thickness, and chromosomal aberrations were determined using FISH technique. Dose response curves for chromosome aberrations were obtained and compared for various particle types. Experimental results indicated that for a given absorbed dose at the cell, the effectiveness of protons and iron particles in the induction of chromosomal aberrations was not significantly altered by polyethylene with thickness up to 30-cm and 15-cm respectively. Comparing with gamma rays, charged particles were very effective in producing complex chromosomal damages, which may be an important mechanism in alterating functions in nondividing tissues, such as nervous systems.     

Investigation of PMSE dependence on high energy particle precipitation during their simultaneous occurrence

This paper is based on the observations of Polar Mesosphere Summer Echoes (PMSE) with the EISCAT VHF 224?MHz radar during the summer month 08–12 July 2013. The effect of high energy particle precipitation on PMSE intensity, particularly during their simultaneous occurrence for longer time interval (longer than or equal to 3-h) has been investigated. The correlation between the two phenomena has been computed using the Spearman rank and Pearson linear correlation coefficient. The variations in high energy particle precipitation reaching down to altitude of 91?km and PMSE intensity in the altitude range of 80–90?km are positively correlated. The electron density irregularity due to ionization caused by precipitating particles might be one of the possible reasons for this positive correlation. Moreover, some other background parameters i.e. K-indices (proxy of high energy particle precipitation) and electron fluxes during the simultaneous occurrence of the two phenomena also support one of the possible reasons given for explanation of the observed positive correlation. The X-rays and proton fluxes have no noticeable effect on PMSE echoes in this study.     

Galactic cosmic rays and cell-hit frequencies outside the magnetosphere.

An evaluation of the exposure of space travelers to galactic cosmic radiation outside the earth's magnetosphere is made by calculating fluences of high-energy primary and secondary particles with various charges traversing a sphere of area 100 microns2. Calculations relating to two shielding configurations are presented: the center of a spherical aluminum shell of thickness 1 g/cm2, and the center of a 4 g/cm2 thick aluminum spherical shell within which there is a 30 g/cm2 diameter spherical water phantom with the point of interest 5 g/cm2 from the surface. The area of 100 microns2 was chosen to simulate the nucleus of a cell in the body. The frequencies as a function of charge component in both shielding configurations reflects the odd-even disparity of the incident particle abundances. For a three-year mission, 33% of the cells in the more heavily shielded configuration would be hit by at least one particle with Z greater than 10. Six percent would be hit by at least two such particles. This emphasizes the importance of studying single high-Z particle effects both on cells which might be "at risk" for cancer induction and on critical neural cells or networks which might be vulnerable to inactivation by heavy charged particle tracks. Synergistic effects with the more numerous high-energy protons and helium ions cannot be ruled out. In terms of more conventional radiation risk assessment, the dose equivalent decreased by a factor of 2.85 from free space to that in the more heavily shielded configuration. Roughly half of this was due to the decrease in energy deposition (absorbed dose) and half to the decrease in biological effectiveness (quality factor).     

Physical events in the track structure of heavy ions and their relation to alterations of biomolecules.

Heavy charged particles interacting with biological cells can produce a wide variety of different physical, chemical and biological consequences. A rigorous identification of relevant chemical and biological alterations of biomolecules in cells, however, is still lacking and, thus, it is difficult to identify the potential biological importance of different early physical events. In addition, due to experimental and theoretical problems also little is known about the details of energy transfer, -absorption and -decay from projectiles to atoms/molecules in condensed targets; this is particularly true for not completely stripped heavy ions. Nevertheless, one might conclude from available data that higher densities of physical energy absorption events have a significantly higher probability to lead to qualitatively more severe biochemical alterations as regards the induction of DNA double strand breaks and of chromatin damage. It is not very likely that energy migration along the DNA molecule in biological cells over long distances plays a significant role as contributor to these biological radiation effects.     

Results of measurements of the response of a delta-doped CCD to neutral and charged particle beams

We report the measurements of the response of a delta-doped Charge Coupled Device (CCD) in imaging mode to beams of charged and neutral particles. That is, the detector imaged the incident beam over its 1024 × 1024 pixels, integrating the number of particles counted in each pixel during the exposure period. In order to count individual particles the exposure time would have had to be reduced considerably compared to the typical ?5 s used in these studies. Our CCD thus operated in a different manner than do conventional particle detectors such as the CEM and MCP that normally are used in a particle counting mode. The measurements were carried out over an energy range from 0.8 to 30 keV. The species investigated include H, H⁺, He⁺, N⁺, N₂⁺, and Ar⁺. The energy and ion mass covered wider ranges than previous measurements for the CCD. The results of these measurements show, as in the case of the previous measurement, for a given ion the CCD response increases with energy and for a given particle energy the response decreases with increasing mass of the particle. These results are in agreement with predictions of the theory of the range of ions in solids. The results also show the possibility for the application of the delta doped CCD as a detector for low energy particle measurements for space plasma physics applications.     

Unique biological aspects of radiation hazards--an overview.

Low orbit, geostationary, and deep-space flights differ from one another with respect to particle radiation environment, participating population size, mission duration, and biological risks other than radiation. It is proposed that all of these factors be considered in the setting of safety standards and, in particular, that the rem-dose concept is applicable only to radiations having low and intermediate linear energy transfer (electrons, protons, and helium ions), whereas the incidence of microlesions is a more meaningful indicator of the hazard due to higher-Z, high energy (HZE) particles. A microlesion is the biological injury inflicted in a specific tissue by a single HZE particle, and it is still in need of quantitative biological definition for specific mammalian tissues. If for example, a microlesion is taken as due to a HZE particle track 10 cell diameters long with LET > 200 KeV/micrometer in its core and > 25 rad dose in its penumbra at a distance of 10 micrometers, then the microlesion dose rate in geostationary orbit, for example, is about 9,000 microlesions per cm3 of tissue per month.     

Effect of HZE particles and space hadrons on bacteriophages.

The effect of high energy (HZE) particles and high energy hadrons on T4Br+ bacteriophage was analyzed. The experiments were done in orbital flight, on high mountains, on an accelerator, and with an alpha particle source. We studied the survival rate of the bacteriophage, the mutation frequency, the mutation spectrum and the revertability under the action of chemical mutagens with a known mechanism of action on DNA. It was found that the biological efficiency of HZE particles and high energy hadrons is greater than that of gamma radiation. The spectra of mutations produced by these mutations and the mechanisms of their action are also different. These effects were local, because of the mode of interaction of the radiant energy with biological objects, and depended on the linear energy transfer (LET). The modes have now been experimentally defined.     

Operant responding following exposure to HZE particles and its relationship to particle energy and linear energy transfer

On exploratory class missions astronauts will be exposed to a variety of heavy particles (HZE particles) which differ in terms of particle energy and particle linear energy transfer. The present experiments were designed to evaluate how these physical characteristics of different particles affect cognitive performance, specifically operant responding. Following exposure to ²⁸Si, ⁴⁸Ti, ¹²C and ¹⁶O particles at the NASA Space Radiation Laboratory rats were tested for their ability to respond appropriately to changes in reinforcement schedules using an operant task. The results showed that the effectiveness of different particles in disrupting cognitive performance, defined as the lowest dose that produced a performance decrement, varied as a function of the energy of the specific particle: for comparisons between different energies of the same particle (e.g., ⁵⁶Fe) the effectiveness of the particle was directly proportional to particle linear energy transfer, whereas for comparisons between different particles (e.g., ⁵⁶Fe and ¹⁶O) effectiveness was inversely proportional to particle linear energy transfer. The results are discussed in terms of the mechanisms that influence the effectiveness of different particles and energies and in terms of their implications for analyzing the possible risks to astronauts of decrements in cognitive performance following exposure to HZE particles on long-duration exploratory class missions.     

Induction and repair of DNA double-strand breaks in human fibroblasts after particle irradiation.

Two assay were employed to study the induction and repair of DNA double-strand breaks (dsbs) in normal human fibroblasts after exposure to particle radiation covering an LET range from 1 to 350 keV/micrometer. The hybridization assay allows measurement of absolute induction frequencies in defined regions of the genome and quantitates rejoining of correct DNA ends while the FAR assay determines all rejoining events, correct and incorrect. Assuming Poisson statistics for the number of breaks per DNA fragment investigated, and thus neglecting any clustering of breaks, we found the induction rate to decrease with increasing LET of the particles. RBE values compared to 225 kVp X-rays dropped to 0.48 for the highest LETs. Repair studies of X-ray-induced dsbs showed that almost all breaks (>95%) are rejoined after incubation times of 24 h while the frequency for correct rejoining is only 70%. Thus about 25% of the initially induced breaks are rejoined by the connection of incorrect DNA ends. Postirradiation incubation after particle irradiation showed less efficient total rejoining with increasing LET and an impaired ability for correct rejoining. The frequency for rejoining of incorrect DNA ends was found to be independent of LET. The possible biological significance of the different rejoining events is discussed.     

GEANT程序在空间粒子探测器优化设计中的应用

在众多的蒙特卡罗模拟程序中,介绍了其中的一种程序——GEANT程序．首先对蒙特卡罗方法的产生和基本思想作了解释,对GEANT程序的主要模块和基本结构以及粒子在程序中的传输过程作了描述．在程序中,GEANT程序应用了先进的ZEBRA存储管理器,使各个模块之间的联系更为方便．在空间粒子探测中,利用GEANT程序,可以计算空间粒子在探测器中的能量损失,在不同材料中的射程以及产生的次级粒子的数量,最后利用GEANT程序可以模拟出各种粒子在不同材料中的LET值,本文还进一步表明了蒙特卡罗方法对空间粒子探测的重要意义．     

Estimates of HZE particle contributions to SPE radiation exposures on interplanetary missions.

Estimates of radiation doses resulting from possible HZE (high energy heavy ion) components of solar particle events (SPEs) are presented for crews of manned interplanetary missions. The calculations assume a model spectrum obtained by folding measured solar flare HZE particle abundances with the measured energy spectra of SPE alpha particles. These hypothetical spectra are then transported through aluminum spacecraft shielding. The results, presented as estimates of absorbed dose and dose equivalent, indicate that HZE components by themselves are not a major concern for crew protection but should be included in any overall risk assessment. The predictions are found to be sensitive to the assumed spectral hardness parameters.     

Induction and rejoining of DNA double-strand breaks in CHO cells after heavy ion irradiation.

DNA double-strand breaks (DSBs) are the crucial events ultimately leading to cell inactivation. Aimed at understanding the biological action of the charged particle component of cosmic radiation, the induction of DSBs and their repairability was evaluated in Chinese hamster ovary (CHO-K1) cells after exposure to accelerated particles. Irradiations were performed with various ion species including O, Ni and Ca, covering a LET range from 20 to 2000 keV/micrometer. DSBs were determined for plateau-phase cells using the electrophoretic elution of radiation-induced DNA fragments in a static electric field combined with fluorescence scanning of ethidium bromide stained gels. Assuming a DSB yield of 22 DSB per Gy per cell, as derived from X-irradiation, cross-sections for DSB production were calculated from the corresponding fluence-effect curves at a fraction of 0.7 of DNA retained. The same ordinate was used as a reference for the calculation of relative biological efficiency (RBE) for DSB induction. At low LETs (< or = 20 keV/micrometer) RBE values slightly above unity were obtained, but a decrease of RBE was observed with increasing LET. In the region of 100-200 keV/micrometer the RBE for initial DSB induction was clearly below unity. Rejoining of DSBs was assessed by measuring the fraction of DNA retained following post-irradiation incubation of cells under culture conditions. After exposure to Ca ions, DSB rejoining was considerably impaired compared to X-rays.     

Track structure and DNA damage.

Heavy particles like protons or heavier ions are different in their biological efficiency when compared to sparsely ionizing radiation. These differences have been attributed to the different pattern of energy deposition in the track of the particles. In radiobiological models two different approaches are used for the characterization of the radiation quality: the continuous dose distribution of the various track structure models and the separation in small compartments inside the track which are used in microdosimetry. In a recent Monte Carlo calculation using the binary encounter approximation as input for the electron emission process, the radial distribution of the dose is calculated for heavy ions. The result of this calculation is compared to other models and used for a qualitative interpretation of the induction of DNA damage by particles.     

Effects of prolonged exposure of lettuce seeds to HZE particles on orbital stations.

In a study of the biological effects of cosmic HZE particles, lettuce (Lactuca sativa) seeds were flown on the orbital stations Salyut 6 and 7 for varying periods of time (from 40 to 457 days). The dependence of the biological damage on flight duration, physical parameters and the fact of passage of an HZE particle through the seed was estimated using the criterion of the frequency of aberrant cells. The arrangement of the flight biological container Biobloc made it possible to trace the location of tracks of individual HZE particles with Z > or = 6 and LET 200 keV/um. In seeds hit by HZE particles, for all exposure times, a statistically significant much higher yield of aberrant cells and also of cells containing multiple chromosome aberrations was observed than in the control material. The frequency of aberrant cells is markedly higher (by a factor of 1,5) in seeds hit than in non-hit ones. The changes of the yield of aberrant cells as a function of the absorbed dose (3.2-63.4 mGy) and the fluence (4.8-44.2 particles/cm2) are linear for the exposure duration ranging from 40 to 457 days.     

On the parameterization of the biological effect in a mixed radiation field.

The exposure of astronauts and electronics to the cosmic radiation especially to the particle component pose a major risk to all space flights. Up to now it is not possible to quantify this risk within acceptable limits of accuracy. This uncertainty is not only caused by difficulties in the more or less exact prediction of the incidence of the cosmic radiation but depends also on the problem of the quantification of the radiation field and the correlation of the biological effect. Usually the biological action of a mixed radiation field is estimated as product of the measured dose with an average quality factor, the relative biological efficiency. Because of the large variation in energy and atomic number of the cosmic particles, average values of the quality factor are not precise for risk estimation. A more appropriate way to treat the biological effects of mixed radiation is the concept of particle fluence and action cross section.