Effects of gamma-ray and high energy carbon ion irradiation on swimming velocity of Euglena gracilis.

The effects of gamma-ray and high energy carbon ion irradiation on the swimming velocity of the photosynthetic flagellate Euglena gracilis strain Z were studied, focusing on a dose-effect relationship. Cells were exposed to 60Co gamma-rays at 6 doses of 10, 15, 20, 40, 100 and 200 Gy for water, and also to 290 MeV/amu carbon ions from the Heavy Ion Medical Accelerator in Chiba at 7 doses (5, 10, 15, 20, 50, 100 and 200 Gy for water). The swimming velocity was measured by a biomonitoring system, called ECOTOX. The swimming velocities of Euglena gracilis cells were significantly decreased by >40 Gy gamma-rays and >5 Gy carbon ions, respectively. The 50% effective doses for inhibition, 34 +/- 4 Gy (gamma-rays) and 13 +/- 1 Gy (290 MeV/amu carbon ions), were estimated from the best fit to data of the logistic model. The relative biological effectiveness (2.6 +/- 0.4) was calculated by the ratio of 50% effective doses. The inhibition of the swimming velocity of the cells irradiated with gamma-rays was still present after 3 days, while recovery of the swimming velocity was shown in the cells exposed to 290 MeV/amu carbon ions. It is suggested that ionizing radiation inhibits ATP production and/or increases frictional drag on beating of the flagellum, thus decreasing swimming velocity.     

Energetic metabolism response in algae and higher plant species from simulation experiments with the clinostat.

Adenylate state is acknowledged to be among the most convenient approaches in the study of physiological changes in plant cells under simulation of altered gravity condition with the clinostat. Adenylate levels and the ATP/ADP ratio in cytoplasmic and mitochondrial extracts of cultivated cells of Haplopappus gracilis and algae cells of Chlorella vulgaris under initial stages of the fast-rotating and slow-rotating clinorotation, as well as the long-term clinorotation, have been investigated. For analysis of ATP and ADP levels in the plant cells under the clinorotation, we applied a high-sensitive bioluminescence method using the luciferase and piruvate kinase enzyme systems. It has been shown that the adenylate ratio is already increased during at the start of clinorotation with the different speed of rotation in the biological material tested. The considerable changes in mitochondrial ultrastructure of Chlorella cells, as well as the rising ATP level and dropping of the ATP/ADP ratio appear after long-duration clinorotation if compared to control material. It is probably connected with the distinctions in ATP-synthetase functioning in mitochondria of the cells under the clinorotation conditions.     

Head and neck tumors after energetic proton irradiation in rats.

This is a two-year progress report on a life span dose-response study of brain tumor risk at moderate to high doses of energetic protons. It was initiated because a joint NASA/USAF life span study of rhesus monkeys that were irradiated with 55-MeV protons (average surface dose, 3.5 Gy) indicated that the incidence of brain tumors per unit surface absorbed dose was over 19 times that of the human tinea capitis patients whose heads were exposed to 100 kv x-rays. Examination of those rats that died in the two-year interval after irradiation of the head revealed a linear dose-response for total head and neck tumor incidence in the dose range of 0-8.5 Gy. The exposed rats had a greater incidence of pituitary chromophobe adenomas, epithelial and mesothelial cell tumors than the unexposed controls but the excessive occurrence of malignant gliomas that was observed in the monkeys was absent in the rats. The estimated dose required to double the number of all types of head and neck tumors was 5.2 Gy. The highest dose, 18 Gy, resulted in high mortality due to obstructive squamous metaplasia at less than 50 weeks, prompting a new study of the relative biological effectiveness of high energy protons in producing this lesion.     

Histologic effects of high energy electron and proton irradiation of rat brain detected with a silver-degeneration stain.

Application of the degeneration sensitive, cupric-silver staining method to brain sections of male Sprague-Dawley rats irradiated 4 days before sacrifice with 155 Mev protons, 2-8 Gy at 1 Gy/min (N=6) or 22-l0lGy at 20 Gy/min (N=16) or with 18.6 Mev electrons, 32-67 Gy at 20 Gy/min (N=20), doses which elicit behavioral changes (accelerod or conditioned taste aversion), resulted in a display of degeneration of astrocyte-like cell profiles which were not uniformly distributed. Plots of 'degeneration scores' (counts of profiles in 29 areas) vs. dose for the proton and electron irradiations displayed a linear dose response for protons in the range of 2-8 Gy. In the 20-100 Gy range, for both electrons and protons the points were distributed in a broad band suggesting a saturation curve. The dose range in which these astrocyte-like profiles becomes maximal corresponds well with the dose range for the X-ray eradication of a subtype of astrocytes, 'beta astrocytes'.     

Effects of carbon ions on primary cultures of mouse brain cells.

Primary mixed cultures of astrocytes and microglia were obtained from neonatal mice, and were irradiated with high-LET carbon ions. Immunohistochemical staining showed astrocytes survived more prominently than microglia. Tagged with specific antibodies, astrocytes and microglia surviving after irradiation were counted by flow cytometry. Decreases in the number of microglia and astrocytes were detected at a dose as small as 2 Gy when Day 5 cultures were irradiated with 13 keV/micrometer carbon ions. When the cultures were irradiated on Day 10, the dose-dependent decrease of microglia was more prominent for 13 keV/micrometer carbon ions than 70 keV/micrometer carbon ions. Astrocytes showed a marginal decrease at Day 10 and Day 14. We concluded that microglia are more sensitive than astrocytes to carbon ions and X-rays, and that the radiosensitivity of microglia depends on both differentiation/proliferation status and radiation quality.     

Radiation-induced apoptosis in scid mice spleen after low dose irradiation.

To assess the radioadaptive response of the whole body system in mice, we examined the temporal effect of low dose priming as an indicator of challenging irradiation-induced apoptosis through a p53 tumor suppressor protein- mediated signal transduction pathway. The p53 protein also plays an important role both in cell cycle control and DNA repair through cellular signal transduction. Using severe combined immunodeficiency mice defective in DNA-dependent protein kinase catalytic subunit, we examined the role of DNA-dependent protein kinase activity in radioadaptation induced by low dose irradiation. Specific pathogen free 5-week-old female severe combined immunodeficiency mice and the parental mice (CB- 17 Icr +/+) were irradiated with X-ray at 3.0 Gy at 1, 2, 3 or 4 weeks after the conditioning irradiation at 0.15, 0.30, 0.45 or 0.60 Gy. The mice spleens were fixed for immunohistochemistry 12 h after the challenging irradiation. The p53-dependent apoptosis related Bax proteins on formalin-fixed paraffin-embedded sections were stained by the avidin-biotin peroxidase complex method. The apoptosis incidence in the sections was measured by hematoxylin-eosin staining. The frequency of Bax- and apoptosis-positive cells increased up to 12 h after the challenging irradiation in the spleen of both mice. However, these cells were not observed after a low dose irradiation at 0.15-0.60 Gy. When pre-irradiation at 0.45 Gy 2 weeks before the challenging irradiation at 3.0 Gy was performed, Bax accumulation and apoptosis induced by challenging irradiation were depressed in the spleens of CB-17 Icr +/+ mice, but not in severe combined immunodeficiency mice. These data suggest that DNA-dependent protein kinase might play a major role in radioadaptation induced by pre-irradiation with a low dose in mice spleen. We expect that the present findings will provide useful information in the health care of space crews.     

Analysis of cytogenetic effects of the secondary radiation resulting from 70 GeV protons of Chinese hamster cells.

The cell culture of a Chinese hamster was irradiated on a Serpuchov proton synchrotron at a dose of 0.5-4 Gy and a dose rate of 1 Gy/min and by gamma-irradiation at dose 1-5 Gy and dose rate 1.2-1.4 Gy/min. The effect of radiation on the cell culture was judged from chromosomal aberrations in G2-stage of cell cycle and micronuclear test. The relative biological efficience of the secondary radiation was approximately 3. Modifying effect of caffeine on the cells irradiated by secondary radiation of synchrotron was not observed. In the presence of caffeine the effect of gamma-irradiation practically is increased up to the level observed upon secondary irradiation. This suggests that secondary radiation inhibits the repair of the cytogenetic damage.     

Late effects from particulate radiations in primate and rabbit tissues.

Optic tissues in groups of New Zealand white rabbits were irradiated locally at different stages throughout the median life span of the species with a single dose (9 Gy) of 425 MeV/amu Ne ions (LET infinity approximately 30 keV/micrometer) and then inspected routinely for the progression of radiation cataracts. The level of early cataracts was found to be highest in the youngest group of animals irradiated (8 weeks old), but both the onset of late cataracts and loss of vision occurred earlier when animals were irradiated during the second half of the median life span. This age response can have serious implications in terms of space radiation hazards to man. Rhesus monkeys that had been subjected to whole-body skin irradiation (2.8 and 5.6 Gy) by 32 MeV protons (range in tissue approximately 1 cm) some twenty years previously were analysed for radiation damage by the propagation of skin fibroblasts in primary cultures. Such propagation from skin biopsies in MEM-alpha medium (serial cultivation) or in supplemented Ham's F-10 medium (cultivation without dilution) revealed late damage in the stem (precursor) cells of the skins of the animals. The proton fluxes employed in this experiment are representative of those occurring in major solar flares.     

Metabolic adaptation to long term changes in gravity environment.

Biochemical analyses of the brain of Cichlid fish larvae, exposed during their very early development for 7 days to an increased acceleration of 3g (hyper-gravity), revealed a decrease in brain nucleoside diphosphate kinase (NDPK) as well as creatine kinase (BB-CK) activity. Using high performance liquid chromatography (HPLC) the concentrations of adenine nucleotides (AMP, ADP, ATP), phospliocreatine (CP), as well as of nicotineamide adenine dinucleotides (NAD, NADP) were analyzed in the brain of hyper-g exposed larvae vs. 1g controls. A slight reduction in the total adenine nucleotides (TAN) as well as the adenylate energy charge (AEC) was found. In parallel a significant increase in the NAD concentration and a corresponding decrease in NADP concentration occurred in larva's hyper-g brains vs. 1 g controls. These results give further evidence for an Influence of gravity on cellular level and furthermore contribute to a clarification of the cellular signal-response chain for gravity perception.     

The effects of proton radiation on UHMWPE material properties for space flight and medical applications

Ultra High Molecular Weight Polyethylene (UHMWPE) is a polymer widely used as a radiation shielding material in space flight applications and as a bearing material in total joint replacements. As a long chain hydrocarbon based polymer, UHMWPE’s material properties are influenced by radiation exposure, and prior studies show that gamma irradiation is effective for both medical sterilization and increased wear resistance in total joint replacement applications. However, the effects of space flight radiation types and doses on UHMWPE material properties are poorly understood. In this study, three clinically relevant grades of UHMWPE (GUR 1020, GUR 1050, and GUR 1020 blended with Vitamin E) were proton irradiated and tested for differences in material properties. Each of the three types of UHMWPE was irradiated at nominal doses of 0 Gy (control), 5 Gy, 10 Gy, 20 Gy, and 35 Gy. Following irradiation, uniaxial tensile testing and thermal testing using Differential Scanning Calorimetry (DSC) and Dynamic Mechanical Analysis (DMA) were performed. Results show small but significant changes in several material properties between the control (0 Gy) and 35 Gy samples, indicating that proton irradiation could have a effect on the long term performance of UHMWPE in both medical and space flight applications.     

Mutagenic effects of heavy ion radiation in plants.

Genetic and developmental effects of heavy ions in maize and rice were investigated. Heavy particles with various charges and energies were accelerated at the BEVALAC. The frequency of occurrence of white-yellow stripes on leaves of plants developed from irradiated maize seeds increased linearly with dose, and high-LET heavy charged particles, e.g., neon, argon, and iron, were 2-12 times as effective as gamma rays in inducing this type of mutation. The effectiveness of high-LET heavy ion in (1) inhibiting rice seedling growth, (2) reducing plant fertility, (3) inducing chromosome aberration and micronuclei in root tip cells and pollen mother cells of the first generation plants developed from exposed seeds, and (4) inducing mutation in the second generation, were greater than that of low-LET gamma rays. All effects observed were dose-dependent; however, there appeared to be an optimal range of doses for inducing certain types of mutation, for example, for argon ions (400 MeV/u) at 90-100 Gy, several valuable mutant lines with favorable characters, such as semidwarf, early maturity and high yield ability, were obtained. Experimental results suggest that the potential application of heavy ions in crop improvement is promising. RFLP analysis of two semidwarf mutants induced by argon particles revealed that large DNA alterations might be involved in these mutants.     

M-FISH analysis of chromosome aberrations in human fibroblasts exposed to energetic iron ions in vitro.

Confluent human fibroblast cells were exposed to 6 Gy gamma-rays or 200 MeV/nucleon Fe ions at 0.7 or 3 Gy. The cells were allowed to repair for 24 hours after exposure and chromosomes were collected using a premature chromosome condensation technique with calyculin-A. Chromosome aberrations were analyzed using the multicolor FISH (mFISH) technique that allows identification of both complex and truly incomplete exchanges. Results showed that both doses of the Fe ions produced higher ratios of complex to simple exchanges and lower ratio of complete to incomplete exchanges than the 6 Gy gamma-exposure. The ratios of aberration yields were similar for the two doses of Fe ions. After 0.7 Gy of Fe ions, most complex aberrations were found to involve three or four chromosomes, indicating this is the maximum number of chromosome domains traversed by a single Fe ion track.     

Low-dose carbon ion irradiation effects on DNA damage and oxidative stress in the mouse testis

To investigate the effects of low-dose carbon ion irradiation on reproductive system of mice, the testes of outbred Kunming strain mice were whole-body irradiated with 0, 0.05, 0.1, 0.5 and 1 Gy, respectively. We measured DNA double-strand breaks (DNA DSBs) and oxidative stress parameters including malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, and testis weight and sperm count at 12 h, 21 d and 35 d after irradiation in mouse testis. At 12 h postirradiation, a significant increase in DNA DSB level but no pronounced alterations in MDA content or SOD activity were observed in 0.5 and 1 Gy groups compared with the control group. At 21 d postirradiation, there was a significant reduction in sperm count and distinct enhancements of DSB level and MDA content in 0.5 and 1 Gy groups in comparison with control. At 35 d postirradiation, the levels of DNA DSBs and MDA, and SOD activity returned to the baseline except for the MDA content in 1 Gy (P < 0.05), while extreme falls of sperm count were still observed in 0.5 (P < 0.01) and 1 Gy (P < 0.01) groups. For the 0.05 or 0.1 Gy group, no differences were found in DNA DSB level and MDA content between control and at 12 h, 21 d and 35 d after irradiation, indicating that lower doses of carbon ion irradiation have no significant influence on spermatogenesis processes. In this study, male germ cells irradiated with over 0.5 Gy of carbon ions are difficult to repair completely marked by the sperm count. Furthermore, these data suggest that the deleterious effects may be chronic or delayed in reproductive system after whole-body exposure to acute high-dose carbon ions.     

Observation of enhanced sub-iron (Sc---Cr) to iron ration in low energy cosmic rays of 50–100 MeV/N in spacelab-3

Relative abundances of sub-iron (Sc-Cr) to iron nuclei in low energy (50–100 MeV/N) galactic cosmic rays have been determined from an analysis of about 100 events of heavy ions (Z = 10−28) recorded in a detector assembly flown in the Anuradha cosmic ray experiment in the Spacelab-3 on a six day mission in April–May 1985. The measured abundance ratio of (Sc-Cr)/Fe nuclei in 50–100 MeV/N energy range is 1.1 ± 0.3, and the present result of enhanced ratio of sub-iron to iron nuclei is in agreement with other experimental results in 200–800 MeV/N range. The over-abundance of iron secondaries at these low energies cannot be explained in the conventional models for propagation of cosmic rays. Available experimental data indicate a very different time history for the low energy iron-group, as compared to those of lighter nuclei in galactic cosmic rays.     

Early and delayed reproductive death in human cells exposed to high energy iron ion beams.

The aim of this research was to determine the biological effectiveness for early and delayed effects of high energy, high linear energy transfer (LET) charged particles. Survival and delayed reproductive death were measured in AG1522 human fibroblast cells exposed to Fe-ion beams of energies between 0.2 and 1 GeV/n, 0.97 GeV/n Ti-ion and 0.49 GeV/n Si-ion beams. The cells were irradiated at the HIMAC accelerator in Chiba, Japan (0.2 and 0.5 GeV/n Fe and 0.49 GeV/n Si) and at the NASA Space Radiation Laboratory in Brookhaven, USA (1 GeV/n Fe and 0.97 GeV/n Ti ions). The dose-effect curves were measured in the dose range between 0.25 and 2 Gy. For comparison cells were exposed to 60Co gamma rays. Analysis of the dose-effect curves show that all the heavy ion beams induce inactivation and delayed reproductive death more effectively than 60Co gamma rays. The only exception is the 0.2 GeV/n Fe-ion beam at low doses. The progeny of the irradiated cells show delayed damage in the form of reproductive death with all the heavy ion beams with the 1 GeV/n Fe-ion beam being the most effective. The relative biological effectiveness at low doses of the iron beams is highest for LET values between 140 and 200 keV/micrometers with values of 1.6 and 3 for early and delayed reproductive death, respectively. Analysis of the fluence-effect curves shows that the cross-sections for early and delayed inactivation increase with increasing LET up to 442 keV/micrometers.     

In vivo and in vitro measurements of complex-type chromosomal exchanges induced by heavy ions.

Heavy ions are more efficient in producing complex-type chromosome exchanges than sparsely ionizing radiation, and this can potentially be used as a biomarker of radiation quality. We measured the induction of complex-type chromosomal aberrations in human peripheral blood lymphocytes exposed in vitro to accelerated H-, He-, C-, Ar-, Fe- and Au-ions in the LET range of approximately 0.4-1400 keV/micrometers. Chromosomes were analyzed either at the first post-irradiation mitosis, or in interphase, following premature condensation by phosphatase inhibitors. Selected chromosomes were then visualized after FISH-painting. The dose-response curve for the induction of complex-type exchanges by heavy ions was linear in the dose-range 0.2-1.5 Gy, while gamma-rays did not produce a significant increase in the yield of complex rearrangements in this dose range. The yield of complex aberrations after 1 Gy of heavy ions increased up to an LET around 100 keV/micrometers, and then declined at higher LET values. When mitotic cells were analyzed, the frequency of complex rearrangements after 1 Gy was about 10 times higher for Ar- or Fe- ions (the most effective ions, with LET around 100 keV/micrometers) than for 250 MeV protons, and values were about 35 times higher in prematurely condensed chromosomes. These results suggest that complex rearrangements may be detected in astronauts' blood lymphocytes after long-term space flight, because crews are exposed to HZE particles from galactic cosmic radiation. However, in a cytogenetic study of ten astronauts after long-term missions on the Mir or International Space Station, we found a very low frequency of complex rearrangements, and a significant post-flight increase was detected in only one out of the ten crewmembers. It appears that the use of complex-type exchanges as biomarker of radiation quality in vivo after low-dose chronic exposure in mixed radiation fields is hampered by statistical uncertainties.     

The effects of heavy particle irradiation on exploration and response to environmental change.

Free radicals produced by exposure to heavy particles have been found to produce motor and cognitive behavioral toxicity effects in rats similar to those found during aging. The present research was designed to investigate the effects of exposure to 56Fe particles on the ability of male Sprague-Dawley rats to detect novel arrangements in a given environment. Using a test of spatial memory previously demonstrated to be sensitive to aging, open field activity and reaction to spatial and non-spatial changes were measured in a group that received a dose of 1.5 Gy (n=10) of 56Fe heavy particle radiation or in non-radiated controls (n=10). Animals irradiated with 1.5 Gy of 56Fe particles exhibited some age-like effects in rats tested, even though they were, for the most part, subtle. Animals took longer to enter, visited less and spent significantly less time in the middle and the center portions of the open field, independently of total frequency and duration of activity of both groups. Likewise, irradiated subjects spend significantly more time exploring novel objects placed in the open field than did controls. However, irradiated subjects did not vary from controls in their exploration patterns when objects in the open field were spatially rearranged. Thus, irradiation with a dose of 1.5 Gy of 56Fe high-energy particle radiation elicited age-like effects in general open field exploratory behavior, but did not elicit age-like effects during the spatial and non-spatial rearrangement tasks.     

Radioprotection by metals: selenium.

The need exists for compounds that will protect individuals from high-dose acute radiation exposure in space and the agents that might be less protective but less toxic and longer acting. Metals and metal derivatives provide a small degree of radioprotection (dose reduction factor < or = 1.2 for animal survival after whole-body irradiation). Emphasis is placed here on the radioprotective potential of selenium (Se). Both the inorganic salt, sodium selenite, and the organic Se compound, selenomethionine, enhance the survival of irradiated mice (60Co, 0.2 Gy/min) when injected IP either before (-24 hr and -1 hr) or shortly after (+15 min) radiation exposure. When administered at equitoxic doses (one-fourth LD10; selenomethionine = 4.0 mg/kg Se, sodium selenite = 0.8 mg/kg Se), both drugs enhanced the 30-day survival of mice irradiated at 9 Gy. Survival after 10-Gy exposure was significantly increased only after selenomethionine treatment. An advantage of selenomethionine is lower lethal and behavioral toxicity (locomotor activity depression) compared to sodium selenite, when they are administered at equivalent doses of Se. Sodium selenite administered in combination with WR-2721, S-2-(3-aminopropylamino)ethylphosphorothioic acid, enhances the radioprotective effect and reduces the lethal toxicity, but not the behavioral toxicity, of WR-2721. Other studies on radioprotection and protection against chemical carcinogens by different forms of Se are reviewed. As additional animal data and results from human chemoprevention trials become available, consideration also can be given to prolonged administration of Se compounds for protection against long-term radiation effects in space.     

Induction of genomic instability after an acute whole-body exposure of mice to Fe ions

The purpose of this study was to evaluate dose–response relationships for the in vivo induction of micronuclei (MN) as a measure of both initial radiation damage and the induction of genomic instability. These measurements were made in mouse blood erythrocytes as a function of radiation dose, radiation quality, time after irradiation, and the genetic background of exposed individuals. Blood samples were collected from two strains of mouse (CBA/CaJ and C57BL/6J) at different times up to 3 months following a whole-body exposure to various doses of 1 GeV/amu ⁵⁶Fe ions (0, 0.1, 0.5 and 1.0 Gy, at the dose rate of a 1 Gy/min) or ¹³⁷Cs gamma rays (0, 0.5, 1.0 and 3.0 Gy, at the dose rate of 0.72 Gy/min). Blood-smear slides were stained with acridine orange (AO). The frequencies of MN were measured in mature normochromatic-erythrocytes (MN-NCEs) and in immature polychromatic-erythrocytes (MN-PCEs). Effects of both types of radiation on erythropoiesis were also evaluated. As a measure of cell progression delay, a dose-dependent decrease in numbers of PCEs was observed at day 2 post-exposure in both strains, regardless of radiation quality. Subsequently, the levels of PCEs increased in all exposed mice, reaching control levels (or higher) by day 7 post-exposure. Further, at day 2 after the exposure, there was no increase in the frequency of MN-PCEs in CBA/CaJ mice exposed to ⁵⁶Fe ions while the frequency of MN-PCEs elevated as a function of dose in the C57BL/6J mice. At day 4, there was no dose related increase in MN-NCEs in either strain of mouse exposed to ¹³⁷Cs gamma rays. Additionally, at the early sacrifice times (days 2 and 4), ⁵⁶Fe ions were slightly more effective (per unit dose) in inducing MN-NCEs than ¹³⁷Cs gamma rays in CBA/CaJ mice. However, there was no increase in the frequency of MN-NCEs at late times after an acute exposure to either type of radiation. In contrast, both types of radiation induced increased MN-PCEs frequencies in irradiated CBA/CaJ mice, but not C57BL/6J mice, at late times post-exposure. This finding indicates the potential induction of genomic instability in hematopoietic cells of CBA/CaJ mice by both types of radiation. The finding also demonstrates the influence of genetic background on radiation-induced genomic instability in vivo.     

Low fluence.

The question of the appropriate extrapolation to low dose has long been a subject of controversy. A linear no-threshold model is favored by regulatory bodies as the basis of RBE assignments and estimates of radiation hazards to the general population. This model is largely supported by extensive application of the linear-quadratic survival formula "fitted" statistically to a wide variety of experimental data obtained at doses typically exceeding 1 Gy, and then extrapolated to mGy for practical applications, and even to the prediction of hazards from single electrons. Such extrapolations are questionable at best, and may even prove hazardous for risk evaluations. Fluence and geometry rather than dose based data are proposed as a basis for a limiting "threshold" for a "low dose" extrapolation. The proposed threshold is one where the fluence of particles is one per square micron, where on average only 2/3 of the 1 micrometers2 pixels covering an irradiated area are traversed by one or more particles. The corresponding dose threshold is determined by the LET of the bombarding radiation. For relativistic electrons this dose is about 0.032 Gy.