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.     

Korean space food development: Ready-to-eat Kimchi, a traditional Korean fermented vegetable,sterilized with high-dose gamma irradiation

Addition of calcium lactate and vitamin C, a mild heating, deep-freezing, and gamma irradiation at 25 kGy were conducted to prepare Kimchi as a ready-to-eat space food. It was confirmed that the space food was sterilized by an irradiation at 25 kGy through incubation at 37 °C for 30 days. The hardness of the Space Kimchi (SK) was lower than the untreated Kimchi (CON), but higher than the irradiated Kimchi (IR). Also, this result was supported by the scanning electron microscopic observation. Sensory attributes of the SK were similar to CON, and maintained during preservation at 35 °C for 30 days. According to the Ames test, Kimchi sterilized with a high-dose irradiation exerted no mutagenic activity in the bacterial strains of Salmonella typhimurium. And, the SK was certificated for use in space flight conditions during 30 days by the Russian Institute of Biomedical Problems.     

Design and performance of a vacuum-UV simulator for material testing under space conditions

This paper describes the construction and performance of a VUV-simulator that has been designed to study degradation of materials under space conditions. It is part of the Complex Irradiation Facility at DLR in Bremen, Germany, that has been built for testing of material under irradiation in the complete UV-range as well as under proton and electron irradiation. Presently available UV-sources used for material tests do not allow the irradiation with wavelengths smaller than about 115 nm where common Deuterium lamps show an intensity cut-off. The VUV-simulator generates radiation by excitation of a gas-flow with an electron beam. The intensity of the radiation can be varied by manipulating the gas-flow and/or the electron beam.     

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.     

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.     

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.     

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.     

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.     

Cytogenetic examination of cosmonauts for space radiation exposure estimation

Purpose

To evaluate radiation induced chromosome aberration frequency in peripheral blood lymphocytes of cosmonauts who participated in flights on Mir Orbital Station and ISS (International Space Station).

Materials and methods

Cytogenetic examination which has been performed in the period 1992–2008 included the analysis of chromosome aberrations using conventional Giemsa staining method in 202 blood samples from 48 cosmonauts who participated in flights on Mir Orbital Station and ISS.

Results

Space flights led to an increase of chromosome aberration frequency. Frequency of dicentrics plus centric rings (Dic+Rc) depend on the space flight duration and accumulated dose value. After the change of space stations (from Mir Orbital Station to ISS) the radiation load of cosmonauts based on data of cytogenetic examination decreased. Extravehicular activity also adds to chromosome aberration frequency in cosmonauts’ blood lymphocytes. Average doses after the first flight, estimated by the frequency of Dic+Rc, were 227 and 113 mGy Eq for long-term flights (LTF) and 107 and 53 mGy Eq for short-term flights (STF).

Conclusion

Cytogenetic examination of cosmonauts can be applied to assess equivalent doses.     

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.     

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.     

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.     

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.     

Comparative study of spermatogonial survival after x-ray exposure, high LET (HZE) irradiation or spaceflight.

Spermatogonial cell loss has been observed in rats flown on Space Lab 3, Cosmos 1887, Cosmos 2044 and in mice following irradiation with X-ray or with high energy (HZE) particle beams. Spermatogonial loss is determined by cell counting in maturation stage 6 seminiferous [correction of seminferous] tubules. With the exception of Iron, laboratory irradiation experiments (with mice) revealed a similar pattern of spermatogonial loss proportional to the radiation dose at levels less than 0.1 Gy. Helium and Argon irradiation resulted in a 5% loss of spermatogonia after only 0.01 Gy exposure. However, significant spermatogonial loss (45%) occured at this radiation level with Iron particle beams. The loss of spermatogonia during each space flight was less than 10% when compared to control (non-flight) animals. This loss, although small, was significant. Although radiation may be a contributing factor in the loss of spermatogonia during space flight, exposure levels, as determined by dosimetry, were not significant to account for the total cell loss observed.     

A sample collector for robotic sample return missions II: Radiation tests

Sample return from small solar system objects is playing an increasingly important part in solar system exploration. Critical to such missions is a robust, simple, and economic sample collector. We have developed a collector such as this for near-Earth asteroid sample return missions that we have termed the Touch-and-Go Impregnable Pad (TGIP). The collector utilizes a silicone substrate that is pushed into the dust and gravel surface layer of the asteroid. As part of a systematic evaluation of the TGIP, we have investigated the resilience of this substrate to ionizing radiations. Several miniature versions of the collector, containing typically ∼3 g of the collection substrate, were exposed to 0.564 MeV beta particles from a ⁹⁰Sr source and a 6 MeV electron beam in a linear accelerator to simulate the wide range of energies of solar and galactic ionizing radiation. Various radiation levels up to eight times greater than expected on a six-year asteroid mission (in the case of beta radiation) and 50 times greater than expected (in the case of the 6 MeV electron radiation) were administered to the substrate. After irradiation, the efficiency of the substrate in collecting samples of mock regolith was compared with that of collectors that had not been irradiated. No difference beyond experimental uncertainty was observed and we suggest that the operational TGIP will not be affected adversely by radiation doses expected during a typical six-year inner solar system mission.     

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.     

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.     

Medical survey of European astronauts during Mir missions

This paper reviews the medical operations performed on six European astronauts during seven space missions on board the space station Mir. These missions took place between November 1988 and August 1999, and their duration ranged from 14 days to 189 days. Steps of pre-flight medical selection and flight certification are presented. Countermeasures program used during the flight, as well as rehabilitation program following short and long-duration missions are described. Also reviewed are medical problems encountered during the flight, post-flight physiological changes such as orthostatic intolerance, exercise capacity, blood composition, muscle atrophy, bone density, and radiation exposure.     

Perspective on space radiation for space flights in 2020–2040

The Sun undergoes several well known periodicities in activity, such as the Schwabe 11 year cycle, the Gleissberg 80–90 year cycle, the Suess 200–210 year cycle and the Halstatt 2200–2300 year cycle. In addition, there is evidence that the 20th century levels of solar activity are unusually high. The years 2020–2040 are expected to coincide with increased activity in human space flight beyond low Earth orbit. The solar cycles and the present level of solar activity are reviewed and their activities during the years 2020–2040 are discussed with a perspective on space radiation and the future program of space flight. It is prudent to prepare for continuing levels of high solar activity as well as for the low levels of the current deep minimum, which has corresponded to high galactic cosmic ray flux.