Microscopic track structure of equal-LET heavy ions.

The spatial distributions of ionization and energy deposition produced by high-velocity heavy ions are crucial to an understanding of their radiation quality as exhibited eg., in track segment experiments of cell survival and chromosome aberrations of mammalian cells. The stopping power (or LET) of a high velocity ion is proportional to the ratio z2/v2, apart from a slowly varying logarithmic factor. The maximum delta-ray energy that an ion can produce is proportional to v2 (non-relativistically). Therefore, two HZE ions having the same LET, but in general differing z and v will have different maximum delta-ray energies and consequently will produce different spatial patterns of energy deposition along their paths. To begin to explore the implications of this fact for the microscopic dosimetry of heavy ions, we have calculated radial distributions in energy imparted and ionization for iron and neon ions of approximately equal LET in order to make a direct comparison of their delta-ray track structure. Monte Carlo techniques are used for the charged particle radiation transport simulation.     

Biological effects of heavy ions from the standpoint of target theory.

The biological effect of heavy ions is best described through the action cross section, as a function of the end-point of interest and the charge and speed of the ion. In track theory this is called the "ion-kill" cross section, for it is the effect produced by a single heavy ion and its delta rays. As with nuclear emulsions the biological track structure passes from the grain count regime to the track width regime to the thindown region with an increase in LET. With biological cells, as with any detector capable of storing sublethal damage, with low LET irradiation the action cross section (in the ion-kill mode) is increasingly obscured by the effect of "gamma-kill", by the influence of overlapping delta rays from neighboring heavy ions. Thus at low LET response is dominated by the gamma-kill mode, so that the RBE approaches 1. The theory requires 4 radiosensitivity parameters for biological detectors, extracted from survival curves at several high LET bombardments passing through the grain count regime, and at high doses. Once these are known the systematic response of biological detectors to all high LET bombardments can be unfolded separating ion kill from gamma kill, predicting the response to a mixed radiation environment, and predicting low dose response even at the level of a single heavy ion. Cell killing parameters are now available for a variety of cell lines. Newly added is a set of parameters for cell transformation.     

HZE effects on mammalian cells.

In track segment experiments cell survival and chromosome aberrations of mammalian cells have been measured for various heavy ion beams between helium and uranium in the energy range between 0.5 and 960 MeV/u, corresponding to a velocity range of 0.03 to 0.87 C, and an LET spectrum from 10 to 15 000 keV/micrometers. At low LET, the cross section (sigma) for cell killing increases with increasing LET and shows a common curve for all ions regardless of the atomic number. This indicates that in this region the track structure of the different ions is of only a minor influence, and it is rather the total energy transfer, which is important for cell killing. At higher LET values, deviations from a common sigma-LET curve can be observed which indicate a saturation effect. The saturation of the lighter ions occurs at lower LET values than for the heavier ions. These findings are also confirmed by the chromosome data, where the efficiency for the induction of chromosomal aberrations for high LET particles depends on the track structure and is nearly independent of LET. In the heavier beams (Z > or = 10) individual particles cause multiple chromosome breaks in mitotic cells.     

Mutation induction in yeast by very heavy ions.

Resistance to canavanine was studied in haploid yeast after exposure to heavy ions (argon to uranium) of energies between 1 and 10 MeV/u covering a LET-range up to about 10000 keV/micrometer. Mutations were found in all instances but the induction cross sections increased with ion energy. This is taken to mean that the contribution of penumbra electrons plays an important role. The probability to recover surviving mutants is highest if the cell is not directly hit by the particle. The experiments demonstrate that the geometrical dimensions of the target cell nucleus as well as its sensitivity in terms of survival have a critical influence on mutation induction with very heavy ions.     

空间重粒子击中卤虫卵的定位技术及其生物效应

为了能够估价空间重粒子对单个生物细胞的放射生物学效应,我们设计、制成了卤虫卵-核乳胶夹层式生物包.经搭载我国“8885”卫星飞行数天后回收.用图象分析仪研究了空间重离子在核乳胶上留下的径迹及其分布;并实验观察了卤虫卵的前期发育情况.看到:随星飞行过的卤虫卵与地面对照组相比,其发育能力明显降低,表现为孵化率低且发育时间推迟.实验表明:生物样品板-核乳胶影象定位技术能清楚而比较准确地给出卤虫卵(或其他生物细胞)受重离子作用的信息,是重离子生物效应及其作用机理研究的可行实验手段及分析方法之一.     

An assessment of galactic cosmic radiation quality considering heavy ion track structures within the cellular environment.

Beyond the magnetic influence of the Earth, the flux of galactic cosmic radiation (GCR) represents a radiological concern for long-term manned space missions. Current concepts of radiation quality and equivalent dose are inadequate for accurately specifying the relative biological "efficiency" of low doses of such heavily ionising radiations, based as they are on the single parameter of Linear Energy Transfer (LET). Such methods take no account of the mechanisms, nor of the highly inhomogeneous spatial structure, of energy deposition in radiation tracks. DNA damage in the cell nucleus, which ultimately leads to the death or transformation of the cell, is usually initiated by electrons liberated from surrounding molecules by the incident projectile ion. The characteristics of these emitted "delta-rays", dependent primarily upon the charge and velocity of the ion, are considered in relation to an idealised representation of the cellular environment. Theoretically calculated delta-ray energy spectra are multiplied by a series of weighting algorithms designed to represent the potential for DNA insult in this environment, both in terms of the quantity and quality of damage. By evaluating the resulting curves, and taking into account the energy spectra of heavy ions in space, a relative measure of the biological relevance of the most abundant GCR species is obtained, behind several shielding configurations. It is hoped that this method of assessing the radiation quality of galactic cosmic rays will be of value when considering the safety of long-term manned space missions.     

A comparison of total reaction cross section models used in particle and heavy ion transport codes

Understanding the interactions and propagations of high energy protons and heavy ions are essential when trying to estimate the biological effects of Galactic Cosmic Rays (GCR) and Solar Particle Events (SPE) on personnel in space. To be able to calculate the shielding properties of different materials and radiation risks, particle and heavy ion transport codes are needed. In all particle and heavy ion transport codes, the probability function that a projectile particle will collide within a certain distance x in the matter depends on the total reaction cross sections, and the calculated partial fragmentation cross sections scale with the total reaction cross sections. It is therefore crucial that accurate total reaction cross section models are used in the transport calculations. In this paper, different models for calculating nucleon–nucleus and nucleus–nucleus total reaction cross sections are compared with each other and with measurements. The uncertainties in the calculations with the different models are discussed, as well as their overall performances with respect to the available experimental data. Finally, a new compilation of experimental data is briefly presented.     

Cellular parameters for track structure modeling of radiation hazard in space.

Based on irradiation with 45 MeV/u N and B ions and with Co-60 gamma rays, cellular parameters of Katz's track structure model have been fitted for the survival of V79-379A Chinese hamster lung fibroblasts. Cellular parameters representing neoplastic transformations in C3H10T/1/2 cells after their irradiation with heavy ion beams, taken from earlier work, were also used to model the radiation hazard in deep space, following the system for evaluating, summing and reporting occupational exposures proposed in 1967 by a subcommittee of NCRP. We have performed model calculations of the number of transformations in surviving cells, after a given fluence of heavy charged particles of initial energy 500 MeV/u, penetrating thick layers of cells. We take the product of cell transformation and survival probabilities, calculated along the path lengths of charged particles using cellular survival and transformation parameters, to represent a quantity proportional to the "radiation risk factor" discussed in the NCRP document. The "synergistic" effect of simultaneous charged particle transfers is accounted for by the "track overlap" mode inherent in the model of Katz.     

DNA fragmentation induced by Fe ions in human cells: shielding influence on spatially correlated damage.

Outside the magnetic field of the Earth, high energy heavy ions constitute a relevant part of the biologically significant dose to astronauts during the very long travels through space. The typical pattern of energy deposition in the matter by heavy ions on the microscopic scale is believed to produce spatially correlated damage in the DNA which is critical for radiobiological effects. We have investigated the influence of a lucite shielding on the initial production of very small DNA fragments in human fibroblasts irradiated with 1 GeV/u iron (Fe) ions. We also used gamma rays as reference radiation. Our results show: (1) a lower effect per incident ion when the shielding is used; (2) an higher DNA Double Strand Breaks (DSB) induction by Fe ions than by gamma rays in the size range 1-23 kbp; (3) a non-random DNA DSB induction by Fe ions.     

Quantitative interpretation of heavy ions effects: models for the biological effects of heavy ions.

Heavy ions are an important part of space radiation. Although they contribute only about 1 percent in number the fraction in terms of energy deposited is much higher. Also the quality of radiation is different from the other components since the LET is generally quite high. This poses the problem of Relative Biological Effectiveness (RBE). It is considerably more important in space than on earth because shielding measures are costly and sometimes not even feasible. Radiation hazards appear to be the limiting factor In long term space flights and their evaluation constitutes a major task. There is still no general agreement about RBE of earthbound radiation, and even less concerning the biological weighting of very heavy and very energetic ions in space. Because of the lack of experimental data--particularly for risk estimates in humans-- theoretical approaches may be very helpful in this respect and provide the only means to judge the radiation protection situation in outer space. In order to be useful careful checks of their consistency are necessary. This paper summarizes some of the more common approaches in a critical manner. The unhappy conclusion at the end will be that at present it is not possible to understand even heavy ion action on survival quantitatively with an acceptable precision.     

Analysis of secondary electron emission spectra of equal-LET protons and alpha particles for purposes of radiation quality and spaceflight hazard assessment.

Amongst the great variety of heavy particles present in the galactic and solar cosmic ray spectra, hydrogen and helium nuclei are significantly more abundant than all other heavier ions and, as such, represent a major radiation hazard to humans in space. Experimental data have suggested that differences in relative biological effectiveness (RBE) exist between the two species at the same value of linear energy transfer (LET). This has consequences for heavily ionising radiation protection procedures, which currently still assume a simple dependence of radiation quality on LET. By analysing the secondary electron (delta-ray) emission spectra of protons and alpha particles, in terms of the spatial characteristics of energy deposition in cellular targets and the likelihood of complex lesion formation, a numerical quantity representing biological effectiveness is generated. When expressed relative to a reference radiation, this quantity is found to differ for protons and a particles of the same LET, demonstrating not only the ion-specific nature of RBE but also the inadequacy of specifying radiation quality as a function of LET only. Such a method for numerically assessing radiation quality may have implications for procedures for heavy ion protection in space at low doses and for understanding the initial mechanisms of radiation action.     

Mutagenic effects of heavy ions in bacteria.

Various mutagenic effects by heavy ions were studied in bacteria, irradiated at accelerators in Dubna, Prague, Berkeley or Darmstadt. Endpoints investigated are histidine reversion (B. subtilis, S. typhimurium), azide resistance (B. subtilis), mutation in the lactose operon (E. coli), SOS chromotest (E. coli) and lambda-prophage induction (E. coli). It was found that the cross sections of the different endpoints show a similar dependence on energy. For light ions (Z < or = 4) the cross section decreases with increasing energy. For ions of Z = 10, it is nearly independent of energy. For heavier ions (Z > or = 26) it increases with energy up to a maximum or saturation. The increment becomes steeper with increasing Z. This dependence on energy suggests a "mutagenic belt" inside the track that is restricted to an area where the density of departed energy is low enough not to kill the cell, but high enough to induce mutations.     

Quantitative interpretation of heavy ion effects: comparison of different systems and endpoints.

For a quantitative interpretation of biological heavy ion action the following parameters have to be taken into account: variations of energy depositions in microscopical sites, the dependence of primary lesion formation on local energy density and changes in reparability. They can be studied in objects of different size and with different sensitivities. Results on survival and mutation induction in yeast and in mammalian cells will be compared with theoretical predictions. It is shown that shouldered survival curves of diploid yeast can be adequately described if the final slope is adjusted according to the varying production of primary lesions. This is not the case for mammalian cells where the experiments show a rapid loss of the shoulder with LET, contrary to theoretical expectations. This behaviour is interpreted to mean that the reparability of heavy ion lesions is different in the two systems. Mutation induction is theoretically expected to decrease with higher LET. This is found in yeast but not in mammalian cells where it actually increases. These results suggest a higher rate of misrepair in mammalian cells.     

Early and late damages induced by heavy charged particle irradiation in embryonic tissue of Arabidopsis seeds.

Early and late effects of accelerated heavy ions (HZE) on the embryonic tissue of Arabidopsis thaliana seeds were investigated seeing that initial cells of the plant eumeristems resemble the original cells of animal and human tissues with continuous cell proliferation. The endpoints measured were lethality and tumorization in the M1-generation for early effects and embryonic lethality in the M2-generation for late effects. The biological endpoints are plotted as functions of the physical parameters of the irradiation i.e. ion fluence (p/cm2), dose (Gray), charge Z and linear energy transfer (LET). The results presented contribute to the estimation of the principles of biological HZE effects and thus may help to develop a unified theory which could explain the whole sequence from physical and chemical reactions to biological responses connected with heavy ion radiation. Additionally, the data of this paper may be used for the discussion of the quality factor for heavy ion irradiation needed for space missions and for HZE-application in radio-therapy by use of accelerators (UNILAC, (SIS/ESR), BEVALAC).     

Induction of chromosome aberrations in mammalian cells after heavy ion exposure.

The induction of chromosome aberrations by heavy charged particles was studied in V79 Chinese hamster cells over a wide range of energies (3-100 MeV/u) and LET (20-16000 keV/micrometer). For comparison, X-ray experiments were performed. Our data indicate quantitative and qualitative differences in the response of cells to particle and x-ray irradiation. For the same level of cell survival the amount of damaged cells which can be observed is smaller in heavy ion (11.4 MeV/u Ar) irradiated samples. The highest yield of damaged cells is found 8 to 12 hours after particle irradiation and 4 hours after x-irradiation. Differences in the amount of damaged cells are attributed to cell cycle perturbations which interfere with the expression of damage. After heavy ion exposure the amount of cells reaching mitosis (mitotic index) decreases drastically and not all damaged cells reach mitosis within 48 hours after exposure. A portion of cells die in interphase. Cell cycle delays induced by x-ray irradiation are less pronounced and all cells reach the first post-irradiation mitosis within 24 hours after irradiation. Additionally, the damage produced by charged particles seems to be more severe. The disintegration of chromosomes was only observed after high LET radiation: an indication of the high and local energy deposition in the particle track. Only cross sections for the induction of chromosome aberrations in mitotic cells were reported in this paper because of the problems arising from the drastic cell cycle perturbations. In this case, cells were irradiated in mitosis and assayed immediately.     

Microdosimetric considerations of effects of heavy ions on E. coli K-12 mutants.

The inactivation cross sections of E. coli K-12 recombination-deficient mutants, JC1553 (recA) and AB2470 (recB), for several MeV/u alpha-particles and N ions have been successfully analyzed by Katz's target theory in which radiosensitivity parameter E0 is assumed to be LET independent and equal to D37 for gamma-rays. For E. coli K-12 wild type, AB1157 (rec+, uvr+), however, it is impossible to interpret the inactivation cross section data by an LET-independent E0-value. In the latter case, as in the case of B. subtilis spore, it is necessary to assume that the radiosensitivity of the target for the core of a heavy ion is higher than that for delta-electrons. As well as Waligorski, Hamm and Katz's dose, the dose around the trajectory of an ion based on Tabata and Ito's energy deposition algorithm for electrons has been used in the course of analysis.     

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.     

Heavy ion-induced chromosomal damage and repair.

We have been using the "premature chromosome condensation (PCC)" technique to investigate chromosomal breakage, rejoining and misrepair induced by accelerated heavy ions. With the presentation of new Fe experiments, we now review the available PCC data to summarize our current understanding of the action of high velocity charged particles on mammalian chromosomes. Implications for the survival RBE/LET relationship are also discussed.     

A model of the effects of heavy ion radiation on human tissue

In heavy ion radiotherapy and space travel humans are exposed to energetic heavy ions (C, Si, Fe and others). This type of irradiation often produces more severe biological effects per unit dose than more common X-rays. A new Monte Carlo model generates a physical space with the complex geometry of human tissue or a cell culture based model of tissue, which is affected by the passage of ionizing radiation. For irradiation, the model relies on a physical code for the ion track structure; for tissues, cellular maps are derived from two- or three-dimensional confocal microscopy images using image segmentation algorithm, which defines cells as pixilated volumes. The model is used to study tissue-specific statistics of direct ion hits and the remote ion action on cells. As an application of the technique, we considered the spatial pattern of apoptotic cells after heavy ion irradiation. The pattern of apoptosis is modeled as a stochastic process, which is defined by the action cross section taken from available experimental data. To characterize the degree of apoptosis, an autocorrelation function that describes the spatial correlation of apoptotic cells is introduced. The values of the autocorrelation function demonstrate the effect of the directionality of the radiation track on the spatial arrangements of inactivated cells in tissue. This effect is intrinsic only to high linear-energy-transfer radiation.     

高能重离子径迹结构对单粒子翻转的影响

利用解析法计算了高能重离子的径迹结构,通过MonteCarlo方法研究了径迹结构对微电子芯片单粒子翻转的影响.结果表明,考虑了径迹结构的影响后,当离子能量较高时,具有小尺寸灵敏单元、低翻转阈值的芯片的翻转截面较传统的LET描述结果小许多;当离子更重时,这种差别对灵敏单元尺寸较大、翻转阈值较高的芯片也变得较明显.即离子径迹结构的影响是通过其有效地沉积到灵敏单元中的能量与翻转阈值相比较而表现出来的.还研究了作用距离较深、结构宽大的径迹造成的相邻多个灵敏单元的同时翻转,即多位翻转现象,这是用LET所不能反映的.