Protection by WR-2721 and WR-151327 against late effects of gamma rays and neutrons.

Two thiophosphoroate compounds WR-2721 and WR-151327 were assessed for their ability to modify the deleterious effects (life shortening and carcinogenesis) of fission-spectrum neutrons (kerma-weighted mean energy of 0.85 MeV) or gamma rays on B6CF1 hybrid mice. Male and female mice, 200 of each sex per experimental group, were irradiated individually at 110 days of age. Radioprotectors (400 mg/kg of WR-2721 or 580 mg/kg of WR-151327) were administered intraperitoneally 30 min prior to irradiation. Neutron doses were 10 cGy or 40 cGy and gamma ray doses were 206 cGy or 417 cGy. Animals were housed five to a cage; cage locations in the holding rooms were randomized by computer. Animals were checked daily and all deceased animals were necropsied. WR-2721 afforded protection against both neutron- and gamma-ray-induced carcinogenesis and subsequent life shortening. Cumulative survival curves for unirradiated mice of either sex were unaffectecd by protectors. WR-2721 protected irradiated groups against life shortening by approximately 10 cGy of neutrons or 100 cGy of gamma rays. WR-151327 was as effective as WR-2721 against neutron irradiation.     

Chromosome aberrations in human lymphocytes induced by 250 MeV protons: effects of dose, dose rate and shielding.

Although the space radiation environment consists predominantly of energetic protons, astronauts inside a spacecraft are chronically exposed to both primary particles as well as secondary particles that are generated when the primary particles penetrate the spacecraft shielding. Secondary neutrons and secondary charged particles can have an LET value that is greater than the primary protons and, therefore, produce a higher relative biological effectiveness (RBE). Using the accelerator facility at Loma Linda University, we exposed human lymphocytes in vitro to 250 MeV protons with doses ranging from 0 to 60 cGy at three different dose rates: a low dose rate of 7.5 cGy/h, an intermediate dose rate of 30 cGy/h and a high dose rate of 70 cGy/min. The effect of 15 g/cm2 aluminum shielding on the induction of chromosome aberrations was investigated for each dose rate. After exposure, lymphocytes were incubated in growth medium containing phytohemagglutinin (PHA) and chromosome spreads were collected using a chemical-induced premature chromosome condensation (PCC) technique. Aberrations were analyzed using the fluorescence in situ hybridization (FISH) technique with three different colored chromosome-painting probes. The frequency of reciprocal and complex-type chromosome exchanges were compared in shielded and unshielded samples.     

The influence of dose, dose-rate and particle fragmentation on cataract induction by energetic iron ions.

Because activities in space necessarily involve chronic exposure to a heterogeneous charged particle radiation field it is important to assess the influence of dose-rate and the possible modulating role of heavy particle fragmentation on biological systems. Using the well-studied cataract model, mice were exposed to plateau 600 MeV/amu 56Fe ions either as acute or fractionated exposures at total doses of 5 - 504 cGy. Additional groups of mice received 20, 360 and 504 cGy behind 50 mm of polyethylene, which simulates body shielding. The reference radiation consisted of 60Co gamma radiation. The animals were examined by slit lamp biomicroscopy over their three year life spans. In accordance with our previous observations with heavy particles, the cataractogenic potential of the 600 MeV/amu 56Fe ions was greater than for low-LET radiation and increased with decreasing dose relative to gamma-rays. Fractionation of a given dose of 56Fe ions did not reduce the cataractogenicity of the radiation compared to the acute regimen. Fragmentation of the beam in the polyethylene did not alter the cataractotoxicity of the ions, either when administered singly or in fractions.     

G2-chromosome aberrations induced by high-LET radiations.

We report measurement of initial G2-chromatid breaks in normal human fibroblasts exposed to various types of high-LET particles. Exponentially growing AG 1522 cells were exposed to gamma rays or heavy ions. Chromosomes were prematurely condensed by calyculin A. Chromatid-type breaks and isochromatid-type breaks were scored separately. The dose response curves for the induction of total chromatid breaks (chromatid-type + isochromatid-type) and chromatid-type breaks were linear for each type of radiation. However, dose response curves for the induction of isochromatid-type breaks were linear for high-LET radiations and linear-quadratic for gamma rays. Relative biological effectiveness (RBE), calculated from total breaks, showed a LET dependent tendency with a peak at 55 keV/micrometer silicon (2.7) or 80 keV/micrometer carbon (2.7) and then decreased with LET (1.5 at 440 keV/micrometer). RBE for chromatid-type break peaked at 55 keV/micrometer (2.4) then decreased rapidly with LET. The RBE of 440 keV/micrometer iron particles was 0.7. The RBE calculated from induction of isochromatid-type breaks was much higher for high-LET radiations. It is concluded that the increased production of isochromatid-type breaks, induced by the densely ionizing track structure, is a signature of high-LET radiation exposure.     

Relationships between neutron fluxes and rain flows

Registration of secondary cosmic ray neutrons is a convenient tool for investigation of primary cosmic ray variations and meteorological effects as well. At present a large network of neutron monitors exists, providing the studies of cosmic ray variations related to the interplanetary conditions and geomagnetic activity. At the same time cosmic ray variations may be caused by some atmospheric processes. In this connection, using the data from standard and lead-free neutron monitors, and gamma and muon detectors, we studied relations between rain flows and neutron, gamma and ionization component behavior. To explain observable results the calculations of neutron and gamma absorption and albedo neutron spectra have been performed on the basis of universal software package FLUKA-2006. In this study we used hourly data on the neutron flux, corrected for barometric pressure and data from local meteorological stations. It was shown that secondary neutron radiation, recorded by lead-free NM, and gamma radiation as well are strongly effected by meteorological factors. The neutron component behavior depends on the moisture content in the soil, and above its surface.     

Can late effects of neutron irradiation in man be estimated from early responses?1

Slowly-developing tissue changes after neutron irradiation should be more easily predicted from acutely-developing injury than is the case with X rays. The difference between tissue responses to neutrons and X rays is that cell survival in both rapidly and slowly responding tissues is a direct logarithmic function of neutron dose, at least up to about 3 Gy, whereas the X-ray dose-survival relationship differs between the two types of tissue: the target cells for late injury are more susceptible to killing from accumulation of sub-lethal X-ray injury and hence the survival curve diverges from its initial essentially linear region more rapidly than does that for the target cells for acute injury.     

空间中子辐射及其测量技术

空间辐射环境包含大量高能带电粒子,其与航天器的结构材料相互作用会产生次级中子辐射,由于这些中子的平均品质因子是带电粒子的约4~5倍,因而对生物组织的剂量当量相对贡献更大。由于中子与物质的作用机制更为复杂,测量难度大,使得准确测量空间中子注量及其剂量当量贡献成为空间辐射剂量学中最具挑战性的工作之一。主要介绍了空间中子辐射的产生机制以及国外相关测量方法及其相关校准技术的研究状况。     

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.     

Hematopoietic responses under protracted exposures to low daily dose gamma irradiation.

In attempting to evaluate the possible health consequences of chronic ionizing radiation exposure during extended space travel (e.g., Mars Mission), ground-based experimental studies of the clinical and pathological responses of canines under low daily doses of 60Co gamma irradiation (0.3-26.3 cGy d-1) have been examined. Specific reference was given to responses of the blood forming system. Results suggest that the daily dose rate of 7.5 cGy d-1 represents a threshold below which the hematopoietic system can retain either partial or full trilineal cell-producing capacity (erythropoiesis, myelopoiesis, and megakaryopoiesis) for extended periods of exposure (>1 yr). Trilineal capacity was fully retained for several years of exposure at the lowest dose-rate tested (0.3 cGy d-1) but was completely lost within several hundred days at the highest dose-rate (26.3 cGy d-1). Retention of hematopoietic capacity under chronic exposure has been demonstrated to be mediated by hematopoietic progenitors with acquired radioresistance and repair functions, altered cytogenetics, and cell-cycle characteristics. Radiological, biological, and temporal parameters responsible for these vital acquisitions by hematopoietic progenitors have been partially characterized. These parameters, along with threshold responses, are described and discussed in relation to potential health risks of the space traveler under chronic stress of low-dose irradiation.     

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.     

Effects of exposure to different types of radiation on behaviors mediated by peripheral or central systems.

The effects of exposure to ionizing radiation on behavior may result from effects on peripheral or on central systems. For behavioral endpoints that are mediated by peripheral systems (e.g., radiation-induced conditioned taste aversion or vomiting), the behavioral effects of exposure to heavy particles (56Fe, 600 MeV/n) are qualitatively similar to the effects of exposure to gamma radiation (60Co) and to fission spectrum neutrons. For these endpoints, the only differences between the different types of radiation are in terms of relative behavioral effectiveness. For behavioral endpoints that are mediated by central systems (e.g., amphetamine-induced taste aversion learning), the effects of exposure to 56Fe particles are not seen following exposure to lower LET gamma rays or fission spectrum neutrons. These results indicate that the effects of exposure to heavy particles on behavioral endpoints cannot necessarily be extrapolated from studies using gamma rays, but require the use of heavy particles.     

Recent results form measurements of the energy spectrum of cosmic-ray induced neutrons aboard an ER-2 airplane and on the ground.

Crews of future high-altitude commercial aircraft may be significantly exposed to atmospheric cosmic radiation from galactic cosmic rays (GCR). To help determine such exposures, the Atmospheric Ionizing Radiation Project, an international collaboration of 15 laboratories, made simultaneous radiation measurements with 14 instruments on a NASA ER-2 high-altitude aircraft. The primary instrument was a sensitive extended-energy multisphere neutron spectrometer, which was also used to make measurements on the ground. Its detector responses were calculated for neutrons and charged hadrons at energies up to 100 GeV using the radiation transport code MCNPX. We have now recalculated the detector responses including the effects of the airplane structure. We are also using new FLUKA calculations of GCR-induced hadron spectra in the atmosphere to correct for spectrometer counts produced by charged hadrons. Neutron spectra are unfolded from the corrected measured count rates using the MAXED code. Results for the measured cosmic-ray neutron spectrum (thermal to >10 GeV), total neutron fluence rate, and neutron dose equivalent and effective dose rates, and their dependence on altitude and geomagnetic cutoff generally agree well with results from recent calculations of GCR-induced neutron spectra.     

Early and late mammalian responses to heavy charged particles.

This overview summarizes murine results on acute lethality responses, inactivation of marrow CFU-S and intestinal microcolonies, testes weight loss, life span shortening, and posterior lens opacification in mice irradiated with heavy charged particles. RBE-LET relationships for these mammalian responses are compared with results from in vitro studies. The trend is that the maximum RBE for in vivo responses tends to be lower and occurs at a lower LET than for inactivation of V79 and T-1 cells in culture. Based on inactivation cross sections, the response of CFU-S in vivo conforms to expectations from earlier studies with prokaryotic systems and mammalian cells in culture. Effects of heavy ions are compared with fission spectrum neutrons, and the results are consistent with the interpretation that RBEs are lower than for fission neutrons at about the same LET, probably due to differences in track structure. Issues discussed focus on challenges associated with assessments of early and late effects of charged particles based on dose, RBE and LET, and with the concordance or discordance of results obtained with in vivo and in vitro model systems. Models for radiation damage/repair and misrepair should consider effects observed with in vivo as well as in vitro model systems.     

Late radiation responses in man: current evaluation from results from Hiroshima and Nagasaki.

Among the late effects of exposure to the atomic bombings of Hiroshima and Nagasaki, none looms larger than radiation related malignancies. Indeed, the late effects of A-bomb radiation on mortality appear to be limited to an increase in malignant tumors. At present, it can be shown that cancers of the breast, colon, esophagus, lungs, stomach, thyroid, and urinary tract as well as leukemia and multiple myeloma increase in frequency with an increase in exposure. No significant relationship to radiation can as yet be established for malignant lymphoma, nor cancers of the rectum, pancreas or uterus. Radiation induced malignancies other than leukemia seem to develop proportionally to the natural cancer rate for the attained age. For specific age-at-death intervals, both relative and absolute risks tend to be higher for those of younger age at the time of bombing. Other late effects include radiation-related lenticular opacities, disturbances of growth among those survivors still growing at the time of exposure, and mental retardation and small head sizes among the in utero exposed. Chromosomal abnormalities too are more frequently encountered in the peripheral leukocytes of survivors, and this increase is functionally related to their exposure. Some uncertainty continues to surround both the quantity and quality of the radiation released by these two nuclear devices, particularly the Hiroshima bomb. A recent reassessment suggests that the gamma radiation estimates which have been used in the past may be too low at some distances and the neutron radiation estimates too high at all distances; moreover, the energies of the neutrons released now appear "softer" than previously conjectured. These uncertainties are not sufficiently large, however, to compromise the reality of the increased frequency of malignancy, but make estimates of the dose response, particularly in terms of gamma and neutron exposures, tentative.     

Overview on experience to date on human exposure to space radiations.

The human exposure in space depends on the three factors: the flight trajectory, its date and duration and the cyclogram of the cosmonaut's activities. In the near-Earth orbits the daily dose varies within the limits of (1.5-5.0) 10(-4) Gy day-1 and greatly increases if the altitude increases. The mean daily quality factor is 1.6-2.0. Strong solar proton events in the orbits with the inclination of < 52 degrees result in the dose rate increase up to 2-3 cGy day-1. On the surface of the orbital spacecrafts the daily dose reaches 2 Gy. The neutron dose depends on the shielding mass distribution varying within the limits of 6%-30% of the charged particles dose. In deep space the dose is mainly formed by the galactic and solar cosmic rays(GCR,SCR). Behind the shielding of 2-3 g cm-2 Al the GCR dose varies in the range of (20-30) 10(-5) Gy day-1. The SCR dose can reach hundreds of cSv.     

Comparisons of several transport models in their predictions in typical space radiation environments

We have used several transport codes to calculate dose and dose equivalent values as well as the particle spectra behind a slab or inside a spherical shell shielding in typical space radiation environments. Two deterministic codes, HZETRN and UPROP, and two Monte Carlo codes, FLUKA and Geant4, are included. A soft solar particle event, a hard solar particle event, and a solar minimum galactic cosmic rays environment are considered; and the shielding material is either aluminum or polyethylene. We find that the dose values and particle spectra from HZETRN are in general rather consistent with Geant4 except for neutrons. The dose equivalent values from HZETRN and Geant4 are not far from each other, but the HZETRN values behind shielding are often lower than the Geant4 values. Results from FLUKA and Geant4 are mostly consistent for considered cases. However, results from the legacy code UPROP are often quite different from the other transport codes, partly due to its non-consideration of neutrons. Comparisons for the spherical shell geometry exhibit the same qualitative features as for the slab geometry. In addition, results from both deterministic and Monte Carlo transport codes show that the dose equivalent inside the spherical shell decreases from the center to the inner surface and this decrease is large for solar particle events; consistent with an earlier study based on deterministic radiation transport results. This study demonstrates both the consistency and inconsistency among these transport models in their typical space radiation predictions; further studies will be required to pinpoint the exact physics modules in these models that cause the differences and thus may be improved.     

以载荷为中心的暗物质探测卫星机电热一体化设计

暗物质粒子探测卫星是中国第一颗空间高能探测卫星,用于实现5GeV~10TeV大动态范围高能宇宙线（电子、正电子、伽马射线等）能谱测量.卫星有效载荷包括BGO量能器、硅阵列探测器、塑闪阵列探测器和中子探测器,是目前中国发射的载荷比最大的卫星.本文介绍了卫星相关技术方案,包括技术指标、轨道方案、工作模式及系统组成等,突出了其以载荷为中心的机电热一体化设计特点.      

Mutational effects of space flight on Zea mays seeds.

The growth and development of more than 500 Zea mays seeds flown on LDEF were studied. Somatic mutations, including white-yellow stripes on leaves, dwarfing, change of leaf sheath color or seedling color were observed in plants developed from these seeds. When the frequency of white-yellow formation was used as the endpoint and compared with data from ground based studies, the dose to which maize seeds might be exposed during the flight was estimated to be equivalent to 635 cGy of gamma rays. Seeds from one particular holder gave a high mutation frequency and a wide mutation spectrum. White-yellow stripes on leaves were also found in some of the inbred progenies from plants displayed somatic mutation. Electron microscopy studies showed that the damage of chloroplast development in the white-yellow stripe on leaves was similar between seeds flown on LDEF and that irradiated by accelerated heavy ions on ground.     

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

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