Cancer risk above 1 Gy and the impact for space radiation protection

Analyses of the epidemiological data on the Japanese A-bomb survivors, who were exposed to γ-rays and neutrons, provide most current information on the dose–response of radiation-induced cancer. Since the dose span of main interest is usually between 0 and 1 Gy, for radiation protection purposes, the analysis of the A-bomb survivors is often focused on this range. However, estimates of cancer risk for doses larger than 1 Gy are becoming more important for long-term manned space missions. Therefore in this work, emphasis is placed on doses larger than 1 Gy with respect to radiation-induced solid cancer and leukemia mortality. The present analysis of the A-bomb survivors data was extended by including two extra high-dose categories and applying organ-averaged dose instead of the colon-weighted dose. In addition, since there are some recent indications for a high neutron dose contribution, the data were fitted separately for three different values for the relative biological effectiveness (RBE) of the neutrons (10, 35 and 100) and a variable RBE as a function of dose. The data were fitted using a linear and a linear-exponential dose–response relationship using a dose and dose-rate effectiveness factor (DDREF) of both one and two. The work presented here implies that the use of organ-averaged dose, a dose-dependent neutron RBE and the bending-over of the dose–response relationship for radiation-induced cancer could result in a reduction of radiation risk by around 50% above 1 Gy. This could impact radiation risk estimates for space crews on long-term mission above 500 days who might be exposed to doses above 1 Gy. The consequence of using a DDREF of one instead of two increases cancer risk by about 40% and would therefore balance the risk decrease described above.     

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.     

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.     

Depth dose measurements with the Liulin-5 experiment inside the spherical phantom of the MATROSHKA-R project onboard the International Space Station

The Liulin-5 experiment is a part of the international project MATROSHKA-R on the Russian segment of the ISS, which uses a tissue-equivalent spherical phantom equipped with a set of radiation detectors. The objective of the MATROSHKA-R project is to provide depth dose distribution of the radiation field inside the sphere in order to get more information on the distribution of dose in a human body. Liulin-5 is a charged particle telescope using three silicon detectors. It measures time resolved energy deposition spectra, linear energy transfer (LET) spectra, particle flux, and absorbed doses of electrons, protons and heavy ions, simultaneously at three depths along the radius of the phantom. Measurements during the minimum of the solar activity in cycle 23 show that the average absorbed daily doses at 40 mm depth in the phantom are between 180 μGy/day and 220 μGy/day. The absorbed doses at 165 mm depth in the phantom decrease by a factor of 1.6–1.8 compared to the doses at 40 mm depth due to the self-shielding of the phantom from trapped protons. The average dose equivalent at 40 mm depth is 590 ± 32 μSV/day and the galactic cosmic rays (GCR) contribute at least 70% of the total dose equivalent at that depth. Shown is that due to the South Atlantic Anomaly (SAA) trapped protons asymmetry and the direction of Liulin-5 lowest shielding zone the dose rates on ascending and descending nodes in SAA are different. The data obtained are compared to data from other radiation detectors on ISS.     

Verification of shielding effect by the water-filled materials for space radiation in the International Space Station using passive dosimeters

The dose reduction effects for space radiation by installation of water shielding material (“protective curtain”) of a stack board consisting of the hygienic wipes and towels have been experimentally evaluated in the International Space Station by using passive dosimeters. The averaged water thickness of the protective curtain was 6.3 g/cm². The passive dosimeters consisted of a combination of thermoluminescent detectors (TLDs) and plastic nuclear track detectors (PNTDs). Totally 12 passive dosimeter packages were installed in the Russian Service Module during late 2010. Half of the packages were located at the protective curtain surface and the other half were at the crew cabin wall behind or aside the protective curtain. The mean absorbed dose and dose equivalent rates are measured to be 327 μGy/day and 821 μSv/day for the unprotected packages and 224 μGy/day and 575 μSv/day for the protected packages, respectively. The observed dose reduction rate with protective curtain was found to be 37 ± 7% in dose equivalent, which was consistent with the calculation in the spherical water phantom by PHITS. The contributions due to low and high LET particles were found to be comparable in observed dose reduction rate. The protective curtain would be effective shielding material for not only trapped particles (several 10 MeV) but also for low energy galactic cosmic rays (several 100 MeV/n). The properly utilized protective curtain will effectively reduce the radiation dose for crew living in space station and prolong long-term mission in the future.     

Early effects of low dose C ion or X-ray irradiation on human peripheral blood lymphocytes

The aim of this study was to estimate the acute effects of low dose ¹²C⁶⁺ ions or X-ray radiation on human immune function. The human peripheral blood lymphocytes (HPBL) of seven healthy donors were exposed to 0.05 Gy ¹²C⁶⁺ ions or X-ray radiation and cell responses were measured at 24 h after exposure. The cytotoxic activities of HPBL were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT); the percentages of T and NK cells subsets were detected by flow cytometry; mRNA expression of interleukin (IL)-2, tumor necrosis factor (TNF)-α and interferon (IFN)-γ were examined by real time quantitative RT-PCR (qRT-PCR); and these cytokines protein levels in supernatant of cultured cells were assayed by enzyme-linked immunosorbent assays (ELISA). The results showed that the cytotoxic activity of HPBL, mRNA expression of IL-2, IFN-γ and TNF-α in HPBL and their protein levels in supernatant were significantly increased at 24 h after exposure to 0.05 Gy ¹²C⁶⁺ ions radiation and the effects were stronger than observed for X-ray exposure. However, there was no significant change in the percentage of T and NK cells subsets of HPBL. These results suggested that 0.05 Gy high linear energy transfer (LET) ¹²C⁶⁺ radiation was a more effective approach to host immune enhancement than that of low LET X-ray. We conclude that cytokines production might be used as sensitive indicators of acute response to LDI.     

Relativistic electron fluxes and dose rate variations during April–May 2010 geomagnetic disturbances in the R3DR data on ISS

Space radiation has been monitored successfully using the Radiation Risks Radiometer-Dosimeter (R3D) installed at the ESA EXPOSE-R (R3DR) facility outside of the Russian Zvezda module of the International Space Station (ISS) between March 2009 and January 2011. R3DR is a Liulin type spectrometer–dosimeter with a single Si PIN detector 2 cm² of area and 0.3 mm thick. The R3DR instrument accumulated about 2 million measurements of the absorbed dose rate and flux of 10 s resolution. The total external and internal shielding before the detector of R3DR device is 0.41 g cm⁻². The calculated stopping energy of normally incident particles to the detector is 0.78 MeV for electrons and 15.8 MeV for protons. After the Coronal Mass Ejection (CME) at 09:54 UTC on 3 April 2010, a shock was observed at the ACE spacecraft at 0756 UTC on 5 April, which led to a sudden impulse on Earth at 08:26 UTC. Nevertheless, while the magnetic substorms on 5 and 6 of April were moderate; the second largest in history of GOES fluence of electrons with energy >2 MeV was measured. The R3DR data show a relatively small amount of relativistic electrons on 5 April. The maximum dose rate of 2323 μGy day⁻¹ was reached on 7 April; by 9 April, a dose of 6600 μGy was accumulated. By the end of the period on 7 May 2010 a total dose of 11,587 μGy was absorbed. Our data were compared with AE-8 MIN, CRESS and ESA-SEE1 models using SPENVIS and with similar observations on American, Japanese and Russian satellites.     

R3D-B2 – Measurement of ionizing and solar radiation in open space in the BIOPAN 5 facility outside the FOTON M2 satellite

Solar and space radiation have been monitored using the R3D-B2 radiation risks radiometer-dosimeter on board a recent space flight on the Russian satellite Foton M2 within the ESA Biopan 5 facility mounted on the outside of the satellite exposed to space conditions. The solar radiation has been assayed in four wavelength bands (UV-C, 170–280 nm, UV-B, 280–315 nm), UV-A (315–400 nm) and PAR (photosynthetic active radiation, 400–700 nm). The data show an increasing tumbling rotation of the satellite during the mission. The photodiodes do not show a cosine response to the incident light which has been corrected. After calibration of the signals using the extraterrestrial spectrum, doses have been calculated for each orbit, for each day and for the total mission as basic data for the biological material which has been exposed in parallel in the Biopan facility. Cosmic ionizing radiation has been monitored and separated in 256 deposited energy spectra, which were further used for determination of the absorbed dose rate and flux. Basic data tables were prepared to be used by other Biopan 5 experiments. The paper summarizes the results for the Earth radiation environment at the altitude (262–304 km) of the Foton M2 spacecraft. Comparisons with the predictions of NASA Earth radiation environment experimental models AE-8 and AP-8, and the PSB97 model are also presented, which calculate the fluxes of ionizing radiation from a simulation. AP-8 is a model for trapped radiation.     

Depth dose distribution measurement on the Foton-M2 bio-satellite by TLD technique

In the framework of “Biology and Physics in Space” project of the European Space Agency (ESA), a returning satellite, Foton-M2, carried an open-to-space sample holder outside of the satellite body, called as BIOPAN-5, loaded with exo-biological experiments and dosemeters for RAdiation DOsimetry (RADO). One of the RADO experiments (Teflon – TLD) was dedicated to dose distribution measurements of the cosmic radiation by thermo-luminescent (TL) technique. It was found that the maximum surface absorbed dose rate, averaged over the first ∼8 mg/cm² thickness, was ∼2 Gy/d and showed a location dependence due the shading effect of the satellite construction elements. The dose rate decreased nearly by 3 orders of magnitude below 500 mg/cm².     

γ-H2AX as a biomarker of DNA damage induced by ionizing radiation in human peripheral blood lymphocytes and artificial skin

Ionizing radiation (IR) exposure is inevitable in our modern society and can lead to a variety of deleterious effects including cancer and birth defects. A reliable, reproducible and sensitive assessment of exposure to IR and the individual response to that exposure would provide much needed information for the optimal treatment of each donor examined. We have developed a diagnostic test for IR exposure based on detection of the phosphorylated form of variant histone H2AX (γ-H2AX), which occurs specifically at sites of DNA double-strand breaks (DSBs). The cell responds to a nascent DSB through the phosphorylation of thousands of H2AX molecules flanking the damaged site. This highly amplified response can be visualized as a γ-H2AX focus in the chromatin that can be detected in situ with the appropriate antibody. Here we assess the usability of γ-H2AX focus formation as a possible biodosimeter for human exposure to IR using peripheral blood lymphocytes irradiated ex vivo and three-dimensional artificial models of human skin biopsies. In both systems, the tissues were exposed to 0.2–5 Gy, doses of IR that might be realistically encountered in various scenarios such as cancer radiotherapies or accidental exposure to radiation. Since the γ-H2AX response is maximal 30 min after exposure and declines over a period of hours as the cells repair the damage, we examined the time limitations of the useful detectability of γ-H2AX foci. We report that a linear response proportional to the initial radiation dose was obtained 48 and 24 h after exposure in blood samples and skin cells respectively. Thus, detection of γ-H2AX formation to monitor DNA damage in minimally invasive blood and skin tests could be useful tools to determine radiation dose exposure and analyze its effects on humans.     

Human response to high-background radiation environments on Earth and in space

The main long-term objective of the space exploration program is the colonization of the planets of the Solar System. The high cosmic radiation equivalent dose rate represents an inescapable problem for the safe establishment of permanent human settlements on these planets. The unshielded equivalent dose rate on Mars ranges between 100 and 200 mSv/year, depending on the Solar cycle and altitude, and can reach values as high as 360 mSv/year on the Moon. The average annual effective dose on Earth is about 3 mSv, nearly 85% of which comes from natural background radiation, reduced to less than 1 mSv if man-made sources and the internal exposure to Rn daughters are excluded. However, some areas on Earth display anomalously high levels of background radiation, as is the case with thorium-rich monazite bearing sand deposits where values 200–400 times higher than the world average can be found. About 2% of the world’s population live above 3 km and receive a disproportionate 10% of the annual effective collective dose due to cosmic radiation, with a net contribution to effective dose by the neutron component which is 3–4 fold that at sea level. Thus far, epidemiological studies have failed to show any adverse health effects in the populations living in these terrestrial high-background radiation areas (HBRA), which provide an unique opportunity to study the health implications of an environment that, as closely as possibly achievable on Earth, resembles the chronic exposure of future space colonists to higher-than-normal levels of ionizing radiation. Chromosomal aberrations in the peripheral blood lymphocytes from the HBRA residents have been measured in several studies because chromosomal damage represents an early biomarker of cancer risk. Similar cytogenetic studies have been recently performed in a cohort of astronauts involved in single or repeated space flights over many years. The cytogenetic findings in populations exposed to high dose-rate background radiation on Earth or in space will be discussed.     

Neuroimmune response and sleep studies after whole body irradiation with high-LET particles

In order to investigate the biological effects of galactic rays on astronaut cerebral functions after space flight, mice were exposed to different heavy ions (HZE) in whole-body conditions at doses comparable to the galactic flux: ¹²C, ¹⁶O and ²⁰Ne (95 MeV/u, at 42–76 mGy). Animals were also exposed to 42 mGy of ⁶⁰Co radiation for comparison with HZE. The neuroimmune response, evaluated by interleukin-1 (IL-1) measurement, showed that this cytokine was produced 3 h after irradiation by ¹⁶O or ⁶⁰Co. In contrast, neither ¹²C (56.7 mGy) nor ²⁰Ne (76 mGy) induced IL-1 production. However, immunohistochemical staining of ¹²C-irradiated mouse brain tissue showed 2 months later a marked inflammatory reaction in the hippocampus and a diffuse response in parenchyma. Sleep studies were realized before and after exposure to 42 mGy of ¹⁶O and 76 mGy of ²⁰Ne: only the ²⁰Ne radiation displayed a small effect. A slight decrease in paradoxical sleep, corresponding to a reduction in the number of episodes of paradoxical sleep, was manifested between 8 and 22 days after exposure. Exposure to ¹²C and ¹⁶O induced no changes either in cellularity of spleen or thymus, or in caspase 3 activity (as much as four months after irradiation). Taken together, these data indicate that the CNS could be sensitive to heavy ions and that responses to HZE impact depend on the nature of the particle, the dose threshold and the time delay to develop biological processes. Differences in responses to different HZE highlight the complex biological phenomena to which astronauts are submitted during space flight.     

Protective effects of melatonin against C beam irradiation-induced oxidative stress and DNA injury in the mouse brain

The purpose of this experiment was to estimate the protective effects of melatonin against radiation-induced brain damages in mice induced by heavy ion beams. Kun-Ming mice were randomly divided into five groups: normal control group, irradiation control group, and three different doses of melatonin (5, 10, and 20 mg/kg, i.p.) treated groups. Apart from the normal control group, the other four groups were exposed to whole-body 4.0 Gy carbon ion beam irradiation (approximately 0.5 Gy/min) after i.p. administration of normal saline or melatonin 1 h before irradiation. The oxidative redox status of brain tissue was assessed by measurement of malondiadehyde (MDA) levels, total superoxide dismutase (T-SOD), cytosolic superoxide dismutase (Cu/ZnSOD, SOD1) and mitochondrial superoxide dismutase (MnSOD, SOD2) activities at 8 h after irradiation. DNA damages were determined using the Comet assay and apoptosis and cell cycle distribution were detected by flow cytometric analyses. A dramatic dose-dependent decrease in MDA levels, tail moment, rates of tailing cells, and apoptosis, and a dose-dependent increase in T-SOD and SOD2 activities, in brain tissues in the melatonin-treated groups were detected compared with the irradiation only group. Furthermore, flow cytometric analysis demonstrated that the percentage of brain cells in the G0/G1 phase decreased significantly, while those in the S and G2/M stage increased dramatically, with mice pretreated with melatonin compared to the irradiation control group. These data indicate that melatonin has protective effects against irradiation-induced brain injury, and that its underlying protective mechanisms may relate to modulation of oxidative stress induced by heavy ionirradiation.     

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.     

Comparison of the transport codes HZETRN,HETC and FLUKA for a solar particle event

The protection of astronauts and instrumentation from galactic cosmic rays and solar particle events is one of the primary constraints associated with mission planning in low earth orbit or deep space. To help satisfy this constraint, several computational tools have been developed to analyze the effectiveness of various shielding materials and structures exposed to space radiation. These tools are now being carefully scrutinized through a systematic effort of verification, validation, and uncertainty quantification. In this benchmark study, the deterministic transport code HZETRN is compared to the Monte Carlo transport codes HETC-HEDS and FLUKA for a 30 g/cm² water target protected by a 20 g/cm² aluminum shield exposed to a parameterization of the February 1956 solar particle event. Neutron and proton fluences as well as dose and dose equivalent are compared at various depths in the water target. The regions of agreement and disagreement between the three codes are quantified and discussed, and recommendations for future work are given.     

Tolerance of chufa (Cyperus esculentus L.) plants,representing the higher plant compartment in bioregenerative life support systems,to super-optimal air temperatures

Plants intended to be included in the photosynthesizing compartment of the bioregenerative life support system (BLSS) need to be studied in terms of both their production parameters under optimal conditions and their tolerance to stress factors that might be caused by emergency situations. The purpose of this study was to investigate tolerance of chufa (Cyperus esculentus L.) plants to the super-optimal air temperature of 45 ± 1 °C as dependent upon PAR (photosynthetically active radiation) intensity and the duration of the exposure to the stress factor. Chufa plants were grown hydroponically, on expanded clay, under artificial light. The nutrient solution was Knop’s mineral medium. Until the plants were 30 days old, they had been grown at 690 μmol m⁻² s⁻¹ PAR and air temperature 25 °C. Thirty-day-old plants were exposed to the temperature 45 °C for 6 h, 20 h, and 44 h at PAR intensities 690 μmol m⁻² s⁻¹ and 1150 μmol m⁻² s⁻¹. The exposure to the damaging air temperature for 44 h at 690 μmol m⁻² s⁻¹ PAR caused irreversible damage to PSA, resulting in leaf mortality. In chufa plants exposed to heat shock treatment at 690 μmol m⁻² s⁻¹ PAR for 6 h and 20 h, respiration exceeded photosynthesis, and CO₂ release in the light was recorded. Functional activity of photosynthetic apparatus, estimated from parameters of pulse-modulated chlorophyll fluorescence in Photosystem 2 (PS 2), decreased 40% to 50%. After the exposure to the stress factor was finished, functional activity of PSA recovered its initial values, and apparent photosynthesis (P_apparent) rate after a 20-h exposure to the stress factor was 2.6 times lower than before the elevation of the temperature. During the first hours of plant exposure to the temperature 45 °C at 1150 μmol m⁻² s⁻¹ PAR, respiration rate was higher than photosynthesis rate, but after 3–4 h of the exposure, photosynthetic processes exceeded oxidative ones and CO₂ absorption in the light was recorded. At the end of the 6-h exposure, P_apparent rate was close to that recorded prior to the exposure, and no significant changes were observed in the functional activity of PSA. At the end of the 20-h exposure, P_apparent rate was close to its initial value, but certain parameters of the functional activity of PSA decreased 25% vs. their initial values. During the repair period, the parameters of external gas exchange recovered their initial values, and parameters of pulse-modulated chlorophyll fluorescence were 20–30% higher than their initial values. Thus, exposure of chufa plants to the damaging temperature of the air for 20 h did not cause any irreversible damage to the photosynthetic apparatus of plants at either 690 μmol m⁻² s⁻¹ or 1150 μmol m⁻² s⁻¹ PAR, and higher PAR intensity during the heat shock treatment enhanced heat tolerance of the plants.     

Spaceflight-relevant types of ionizing radiation and cortical bone: Potential LET effect?

Extended exposure to microgravity conditions results in significant bone loss. Coupled with radiation exposure, this phenomenon may place astronauts at a greater risk for mission-critical fractures. In a previous study, we identified a profound and prolonged loss of trabecular bone (29–39%) in mice following exposure to an acute, 2 Gy dose of radiation simulating both solar and cosmic sources. However, because skeletal strength depends on trabecular and cortical bone, accurate assessment of strength requires analysis of both bone compartments. The objective of the present study was to examine various properties of cortical bone in mice following exposure to multiple types of spaceflight-relevant radiation. Nine-week old, female C57BL/6 mice were sacrificed 110 days after exposure to a single, whole body, 2 Gy dose of gamma, proton, carbon, or iron radiation. Femora were evaluated with biomechanical testing, microcomputed tomography, quantitative histomorphometry, percent mineral content, and micro-hardness analysis. Compared to non-irradiated controls, there were significant differences compared to carbon or iron radiation for only fracture force, medullary area and mineral content. A greater differential effect based on linear energy transfer (LET) level may be present: high-LET (carbon or iron) particle irradiation was associated with a decline in structural properties (maximum force, fracture force, medullary area, and cortical porosity) and mineral composition compared to low-LET radiation (gamma and proton). Bone loss following irradiation appears to be largely specific to trabecular bone and may indicate unique biological microenvironments and microdosimetry conditions. However, the limited time points examined and non-haversian skeletal structure of the mice employed highlight the need for further investigation.     

Protein expression profile changes in human fibroblasts induced by low dose energetic protons

Extrapolation of known radiation risks to the risks from low dose and low dose-rate exposures of human population, especially prolonged exposures of astronauts in the space radiation environment, relies in part on the mechanistic understanding of radiation induced biological consequences at the molecular level. While some genomic data at the mRNA level are available for cells or animals exposed to radiation, the data at the protein level are still lacking. Here, we studied protein expression profile changes using Panorama antibody microarray chips that contain antibodies to 224 proteins (or their phosphorylated forms) involved in cell signaling that included mostly apoptosis, cytoskeleton, cell cycle and signal transduction. Normal human fibroblasts were cultured until fully confluent and then exposed to 2 cGy of 150 MeV protons at high-dose rate. The proteins were isolated at 2 or 6 h after exposure and labeled with Cy3 for the irradiated cells and with Cy5 for the control samples before loading onto the protein microarray chips. The intensities of the protein spots were analyzed using ScanAlyze software and normalized by the summed fluorescence intensities and the housekeeping proteins. The results showed that low dose protons altered the expression of more than 10% of the proteins listed in the microarray analysis in various protein functional groups. Cell cycle (24%) related proteins were induced by protons and most of them were regulators of G1/S-transition phase. Comparison of the overall protein expression profiles, cell cycle related proteins, cytoskeleton and signal transduction protein groups showed significantly more changes induced by protons compared with other protein functional groups.     

Chromosomal aberrations induced by high-energy iron ions with shielding.

Biophysical models are commonly used to evaluate the effectiveness of shielding in reducing the biological damage caused by cosmic radiation in space flights. To improve and validate these codes biophysical experiments are needed. We have measured the induction of chromosomal aberrations in human peripheral blood lymphocytes exposed in vitro to 500 MeV/n iron ion beams (dose range 0.1-1 Gy) after traversing shields of different material (lucite, aluminium, or lead) and thickness (0-11.3 g/cm2). For comparison, cells were exposed to 200 MeV/n iron ions and to X-rays. Chromosomes were prematurely condensed by a phosphatase inhibitor (calyculin A) to avoid cell-cycle selection produced by the exposure to high-LET heavy-ion beams. Aberrations were scored in chromosomes 1, 2, and 4 following fluorescence in situ hybridization. The fraction of aberrant lymphocytes has been evaluated as a function of the dose at the sample position, and of the fluence of primary 56Fe ions hitting the shield. The influence of shield thickness on the action cross-section for the induction of exchange-type aberrations has been analyzed, and the dose average-LET measured as a function of the shield thickness. These preliminary results prove that the effectiveness of heavy ions is modified by shielding, and the biological damage is dependent upon shield thickness and material.     

Cosmic ray detection on the Foton-M2 satellite by a track etch detector stack

In the frame of the European Space Agency (ESA) project called “Biology and Physics in Space”, the returning satellite, Foton-M2, carried an open-to-space exposure platform outside of the satellite body, called as BIOPAN-5, loaded with exo-biological experiments and facilities for radiation dosimetry (RADO). One of the RADO experiments was dedicated to the detection of the primary galactic cosmic rays (GCR) and secondary neutrons by a track etch detector stack. The daily absorbed dose (D) and dose equivalent (H) were calculated from the experimental LET spectra (LET > 10 keV/μm). Under a shielding of ∼2.8 g/cm² the averaged H was found to be 658 ± 8 μSv/d, with a quality factor (Q) of 6.2 ± 1.2. The LET spectra showed a local peak at ∼105 keV/μm suggesting that the majority of tracks were created by trapped protons as it has been predicted by calculations. The low LET dose of the cosmic radiation was determined by 4 TLD stacks, and the total dose was found to be 795 ± 14 μSv/d.