The effects of proton exposure on neurochemistry and behavior.

Future space missions will involve long-term travel beyond the magnetic field of the Earth, where astronauts will be exposed to radiation hazards such as those that arise from galactic cosmic rays. Galactic cosmic rays are composed of protons, alpha particles, and particles of high energy and charge (HZE particles). Research by our group has shown that exposure to HZE particles, primarily 600 MeV/n and 1 GeV/n 56Fe, can produce significant alterations in brain neurochemistry and behavior. However, given that protons can make up a significant portion of the radiation spectrum, it is important to study their effects on neural functioning and on related performance. Therefore, these studies examined the effects of exposure to proton irradiation on neurochemical and behavioral endpoints, including dopaminergic functioning, amphetamine-induced conditioned taste aversion learning, and spatial learning and memory as measured by the Morris water maze. Male Sprague-Dawley rats received a dose of 0, 1.5, 3.0 or 4.0 Gy of 250 MeV protons at Loma Linda University and were tested in the different behavioral tests at various times following exposure. Results showed that there was no effect of proton irradiation at any dose on any of the endpoints measured. Therefore, there is a contrast between the insignificant effects of high dose proton exposure and the dramatic effectiveness of low dose (<0.1 Gy) exposures to 56Fe particles on both neurochemical and behavioral endpoints.     

Effects of heavy ions on cycling stem cells.

Murine marrow stem cells assayed with the spleen colony assay have been shown to be largely in a noncycling state, Go. In the unirradiated animal where these spleen-colony forming units (CFUs) transit normally between a non-proliferative state and active proliferation, exposure to a sufficient dose of ionizing radiation increases the frequency (probability) of this transition. For low-LET irradiation, marrow stem cells are not induced into cycle until a threshold dose is achieved. This dose appears to be in the range 50 to 100 cGy, inducing proliferation in an all-or-nothing manner. For irradiation with heavy charged-particles, however, the threshold dose is dependent on mass and energy. Irradiation with particles of sufficient mass and energy stimulates active proliferation even at the smallest doses tested, 5 cGy. Further, this response does not appear to result from an all-or-nothing effect. Rather, individual animals with intermediate levels of stem cell cycling have been observed. These data support the notion that locally controlled hemopoiesis can be affected by local deposition of radiation damage.     

Cataractogenesis from high-LET radiation and the Casarett model.

Space radiations, especially heavy ions, constitute significant hazards to astronauts. These hazards will increase as space missions lengthen. Moreover, the dangers to astronauts will be enhanced by the persistence, or even the progression, of biological damage throughout their subsequent life spans. To assist in the assessment of risks to astronauts, we are investigating the long-term effects of heavy ions on specific animal tissues. In one study, the eyes of rabbits of various ages were exposed to a single dose of Bragg plateau 20Ne ions (LET infinity approximately equals 30 keV/micrometer). The development of cataracts has shown a pronounced age-related response during the first year after irradiation, and will be followed for two more years. In other studies, mice were exposed to single or fractionated doses of 12C ions (4-cm spread-out Bragg peak; dose-averaged LET infinity = 70-80 keV/micrometer) or 60Co gamma-photons (LET infinity = 0.3 keV/micrometer). Measurements of the frequency of posterior lens opacification have shown that the tissue sparing observed with dose fractionation of gamma-photons was absent when 12C-ion doses were fractionated. Development of posterior lens cataracts was also followed for long periods (up to 21 months) in mice exposed to single doses of Bragg plateau HZE particles (40Ar, 20Ne and 12C ions: LET infinity approximately equals 100, 30 and 10 keV/micrometer, respectively) or 225 kVp X-rays. Based on average cataract levels at the different observation times, the RBE's (RBE = relative biological effectiveness) for the ions were circa 5, 3 and 1-2, respectively, over the range of doses used (0.05-0.9 Gy). Investigations of cataractogenesis are useful for exploring the model of radiation damage proposed by Casarett and by Rubin and Casarett with a tissue not connected directly to the vasculature.     

Characterization of the near Earth radiation environment by Liulin type spectrometers

Comprehensive study of the dose, flux and deposited energy spectra shape data obtained by Liulin type spectrometers on spacecraft (five different experiments) and aircraft since 2001 is performed with the aim of understanding how well these parameters can characterize the type of predominant particles and their energy in the near Earth radiation environment. Three different methods for characterisation of the incoming radiation from Liulin spectrometers are described. The results revealed that the most informative one is by the shape of the deposited energy spectra. Spectra generated by Galactic Cosmic Rays (GCR) protons and their secondaries are with linear falling shape in the coordinates deposited energy/deposited per channel dose rate. The position of the maximum of the deposited energy spectra inside the South Atlantic Anomaly (SAA) region depends on the incident energy of the incoming protons. Spectra generated by relativistic electrons in the outer radiation belt have a maximum in the first channels. For higher energy depositions these spectra are similar to the GCR spectra. Mixed radiation by protons and electrons and/or bremsstrahlung is characterized by spectra with 2 maxima. All type of spectra has a knee close to 6.2 MeV deposited energy, which correspond to the stopping energy of protons in the detector. Dose to flux ratio known also as specific dose is another high information parameter, which is given by experimentally obtained formulae [Heffner, J. Nuclear radiation and safety in space. M. Atomizdat. 115, 1971 (in Russian)] connecting the dose to flux ratio and the incident energy of the particles.     

Radiation protection issues in galactic cosmic ray risk assessment.

Radiation protection involves the limitation of exposure to below threshold doses for direct (or deterministic) effects and a knowledge of the risk of stochastic effects after low doses. The principal stochastic risk associated with low dose rate galactic cosmic rays is the increased risk of cancer. Estimates of this risk depend on two factors (a) estimates of cancer risk for low-LET radiation and (b) values of the appropriate radiation weighting factors, WR, for the high-LET radiations of galactic cosmic rays. Both factors are subject to considerable uncertainty. The low-LET cancer risk derived from the late effects of the atomic bombs is vulnerable to a number of uncertainties including especially that from projection in time, and from extrapolation from high to low dose rate. Nevertheless, recent low dose studies of workers and others tend to confirm these estimates. WR, relies on biological effects studied mainly in non-human systems. Additional laboratory studies could reduce the uncertainties in WR and thus produce a more confident estimate of the overall risk of galactic cosmic rays.     

Unique biological aspects of radiation hazards--an overview.

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

Investigation of the low-energy component of primary cosmic radiation on the outside of spacecrafts.

We have developed a method to investigate the low-energy radiation environment on the outside of spacecrafts. Thereby, ultra-thin thermoluminescent (TL) detectors on the base of CaF2:Mn-PTFE are arranged in stacks and exposed to the unshielded cosmic radiation. The dose distribution within a stack is determined by successive evaluation of the thin TL sheets. The analysis of LiF thermoluminescent detector glow curves permits conclusions on the dose contribution caused by either low-energy electrons or by protons. The method was applied aboard Russian COSMOS spacecrafts as well as the MIR station. It was shown that along low-earth orbits dose rates up to 10 Gy/day within the first few mg/cm2 are typical, mainly as a result of the electron impact.     

Uncertainties in radiation effect predictions for the natural radiation environments of space.

Future manned missions beyond low earth orbit require accurate predictions of the risk to astronauts and to critical systems from exposure to ionizing radiation. For low-level exposures, the hazards are dominated by rare single-event phenomena where individual cosmic-ray particles or spallation reactions result in potentially catastrophic changes in critical components. Examples might be a biological lesion leading to cancer in an astronaut or a memory upset leading to an undesired rocket firing. The risks of such events appears to depend on the amount of energy deposited within critical sensitive volumes of biological cells and microelectronic components. The critical environmental information needed to estimate the risks posed by the natural space environments, including solar flares, is the number of times more than a threshold amount of energy for an event will be deposited in the critical microvolumes. These predictions are complicated by uncertainties in the natural environments, particularly the composition of flares, and by the effects of shielding. Microdosimetric data for large numbers of orbits are needed to improve the environmental models and to test the transport codes used to predict event rates.     

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.     

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.     

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.     

RBE for non-stochastic effects.

Evidence is reviewed concerning the variation of RBE values of high-LET radiations for non-stochastic effects, generally impairment of tissue integrity and function. The RBE values are dependent on the type of radiation, the type of tissue effect and the dose rate or fractionation schedule. RBE values depend strongly on the effect considered, with high values for late effects in lung, kidney and central nervous system. RBE values generally increase with decreasing dose rate or dose per fraction. Maximum values can be derived by extrapolation on the basis of a radiobiological model. These values are denoted RBEm to distinguish them from RBEM derived for stochastic effects, e.g. carcinogenesis. Values of RBEm are generally in the range of 2 to 10 and are considerably smaller by a factor of 2 to 5 than values of RBEM for various types of stochastic effects. RBE values for effects from actual exposures to mixtures of high-LET and low-LET radiations can be derived by considering the doses received and the tissue at risk. Applications of RBEm values will yield estimates of maximum values of equivalent doses and these should only be applied for planning medical interventions if the contribution from high-LET radiation is small. The selection of Q values for radiation protection is mostly based on RBE--values and the application of Q values in cases where non-stochastic effects are important might therefore result in an overestimate of the risks of exposure.     

Energetic particle environment in near-Earth orbit.

The hazard of exposure to high doses of ionizing radiation is one of the primary concerns of extended manned space missions and a continuous threat for the numerous spacecraft in operation today. In the near-Earth environment the main sources of radiation are solar energetic particles (SEP), galactic cosmic rays (GCR), and geomagnetically trapped particles, predominantly protons and electrons. The intensity of the SEP and GCR source depends primarily on the phase of the solar cycle. Due to the shielding effect of the Earth's magnetic field, the observed intensity of SEP and GCR particles in a near-Earth orbit will also depend on the orbital parameters altitude and inclination. The magnetospheric source strength depends also on these orbital parameters because they determine the frequency and location of radiation belt passes. In this paper an overview of the various sources of radiation in the near-Earth orbit will be given and first results obtained with the Solar, Anomalous, and Magnetospheric Particle Explorer (SAMPEX) will be discussed. SAMPEX was launched on 3 July 1992 into a near polar (inclination 82 degrees) low altitude (510 x 675 km) orbit. The SAMPEX payload contains four separate instruments of high sensitivity covering the energy range 0.5 to several hundred MeV/nucleon for ions and 0.4 to 30 MeV for electrons. This low altitude polar orbit with zenith-oriented instrumentation provides a new opportunity for a systematic study of the near-Earth energetic particle environment.     

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.     

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.     

航天员受银河宇宙线辐射的剂量计算

在近地空间(LEO)和深空探测中,航天员遭受的辐射风险主要来自于银河宇宙线(GCR)照射.银河宇宙线的辐射剂量是航天员辐射风险评价的基础.国际放射防护委员会(ICRP)于2013年提出了新的航天员空间辐射剂量估算方法,以更准确给出空间重离子辐射的剂量.基于此方法,开发了宇宙线粒子在物质中输运的蒙特卡罗程序,并在程序中实现用中国成年男性人体数字模型来仿真航天员.采用该程序计算了粒子(Z=1~92)各向同性照射航天员时器官的通量-器官剂量转换因数,并估算出航天员在近地轨道空间受银河宇宙线辐射的剂量.     

Tissue responses to low protracted doses of high LET radiations or photons: early and late damage relevant to radio-protective countermeasures.

Early and late murine tissue responses to single or fractionated low doses of heavy charged particles, fission-spectrum neutrons or gamma rays are considered. Damage to the hematopoietic system is emphasized, but results on acute lethality, host response to challenge with transplanted leukemia cells and life-shortening are presented. Low dose rates per fraction were used in some neutron experiments. Split-dose lethality studies (LD 50/30) with fission neutrons indicated greater accumulation of injury during a 9 fraction course (over 17 days) than was the case for gamma-radiation. When total doses of 96 or 247 cGy of neutrons or gamma rays were given as a single dose or in 9 fractions, a significant sparing effect on femur CFU-S depression was observed for both radiation qualities during the first 11 days, but there was not an earlier return to normal with dose fractionation. During the 9 fraction sequence, a significant sparing effect of low dose rate on CFU-S depression was observed in both neutron and gamma-irradiated mice. CFU-S content at the end of the fractionation sequence did not correlate with measured LD 50/30. Sustained depression of femur and spleen CFU-S and a significant thrombocytopenia were observed when a total neutron dose of 240 cGy was given in 72 fractions over 24 weeks at low dose rates. The temporal aspects of CFU-S repopulation were different after a single versus fractionated neutron doses. The sustained reduction in the size of the CFU-S population was accompanied by an increase in the fraction in DNA synthesis. The proliferation characteristics and effects of age were different for radial CFU-S population closely associated with bone, compared with the axial population that can be readily aspirated from the femur. In aged irradiated animals, the CFU-S proliferation/redistribution response to typhoid vaccine showed both an age and radiation effect. After high single doses of neutrons or gamma rays, a significant age- and radiation-related deficiency in host defense mechanisms was detected by a shorter mean survival time following challenge with transplantable leukemia cells. Comparison of dose-response curves for life shortening after irradiation with fission-spectrum neutrons or high energy silicon particles indicated high initial slopes for both radiation qualities at low doses, but for higher doses of silicon, the effect per Gy decreased to a value similar to that for gamma rays. The two component life-shortening curve for silicon particles has implications for the potential efficacy of radioprotectants. Recent studies on protection against early and late effects by aminothiols, prostaglandins, and other compounds are discussed.     

FY-3A卫星与NOAA系列卫星高能带电粒子实测结果的比较

FY-3A卫星是运行于830 km高度的太阳同步轨道气象卫星, 其搭载的空间环境监测器可观测3~300 MeV的高能质子和0.15~5.70 MeV的高能电子. FY-3A卫星在轨工作期间, 太阳活动处于由谷年向峰年过渡期, 空间环境非常平静, 探测结果显示3~300 MeV的高能质子分布主要集中在南大西洋辐射带异常区, 0.15~5.70 MeV的高能电子分布区域除南大西洋异常区外, 还分布在南北两极高纬区域. FY-3A与NOAA卫星测量结果反映出带电粒子强度及分布区域随投掷角变化的空间各向异性特征. 本文在充分考虑了带电粒子时间、空间分布差异以及比对探测器之间自身设计差异的前提下, 经过归一化处理后, 首次对两颗卫星同期探测结果进行相关性分析, 验证了两颗卫星相同时空条件下高能带电粒子通量分布的一致性; 说明FY-3A空间环境监测器不仅具备空间带电粒子辐射监测能力, 且探测结果有效可靠, 可用作辐射带环境数据源的组成部分, 为发展新的模型, 深入研究辐射带高能粒子的分布、起源和传输等提供新的观测依据.      

FY-3A卫星与NOOA系列卫星高能带电粒子实测结果的比较

FY-3A卫星是运行于830 km高度的太阳同步轨道气象卫星,其搭载的空间环境监测器可观测3～300 MeV的高能质子和0.15～5.70 MeV的高能电子.FY-3A卫星在轨工作期间,太阳活动处于由谷年向峰年过渡期,空间环境非常平静,探测结果显示3～300 MeV的高能质子分布主要集中在南大西洋辐射带异常区,0.15～5.70 MeV的高能电子分布区域除南大西洋异常区外,还分布在南北两极高纬区域.FY-3A与NOAA卫星测量结果反映出带电粒子强度及分布区域随投掷角变化的空间各向异性特征.本文在充分考虑了带电粒子时间、空间分布差异以及比对探测器之间自身设计差异的前提下,经过归一化处理后,首次对两颗卫星同期探测结果进行相关性分析,验证了两颗卫星相同时空条件下高能带电粒子通量分布的一致性;说明FY-3A空间环境监测器不仅具备空间带电粒子辐射监测能力,且探测结果有效可靠,可用作辐射带环境数据源的组成部分,为发展新的模型,深入研究辐射带高能粒子的分布、起源和传输等提供新的观测依据.