Anomalous phosphenes in ocular protontherapy

We have undertaken a clinical ground study of proton-induced light flashes (phosphenes). Patients treated at the Institut Curie – Centre de Protonthérapie in Orsay, France, received radiation therapy to cure ocular and skull-base cancers. Sixty percent of the patients treated for choroidal melanomas using 73 MeV protons report anomalous phosphenes. Delivering a radiation dose on the retina only is not sufficient to trigger the light flash. The present study may be the first indication of phosphenes triggered by protons of few tens of MeV.     

Use of primary cell cultures to measure the late effects in the skins of rhesus monkeys irradiated with protons.

Previous pilot investigations of the uses of primary cell cultures to study late damage in stem cells of the skin of the New Zealand white (NZW) rabbit and the rhesus monkey, have been extended to individual monkeys exposed to 55 MeV protons. Protons of this energy have a larger range in tissue of (approximately 2.6 cm) than the 32 MeV protons (approximately 0.9 cm) to which the animals in our earlier studies had been exposed. Although the primary emphases in the current studies were improvement and simplification in the techniques and logistics of transportation of biopsies to a central analytical facility, comparison of the quantitative measurements obtained thus far for survival of stem cells in the skins from animals irradiated 21 years ago reveals that the effects of both proton energies are similar.     

A model of radiation conditions during spacecraft flights in the interplanetary space and in the Earth's magnetosphere.

Based on the available measurement data, simulations of radiation conditions during spacecraft flights in the interplanetary space and in the Earth's and Jupiter's radiation belts has been carried out. The > or = 10 MeV and > or = 30 MeV solar flare proton fluence forecast has been proposed for Cycle 22. Radiation conditions due to both magnetospheric electrons and protons and to solar flare protons, magnetic rigidity cutoff being taken into account, have been evaluated on spacecraft trajectories in the Earth's and Jupiter's magnetospheres.     

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.     

地磁长期变化引起的低高度卫星轨道辐射带粒子环境的变化

利用IGRF2000模式计算了几个典型轨道辐射带粒子环境并与IGRF1970模式计算的结果进行了比较。计算结果表明，在辐射带的低部，对应某些倾角的能量大于0．1MeV质子的轨道积分通量变化达到2个量级，而通量大10MeV的辐射带质子的轨道积分通量变化达到1个量级；轨道积分通量的最大值变化为1个量级。能量大于0．04MeV辐射带电子的轨道积分通量变化在某些倾角达到3个量级，但轨道积分最大值的变化低于1个量级。1000km以上高度辐射带粒子环境的变化很小。     

Late skin damage in rabbits and monkeys after exposure to particulate radiations.

Skin biopsies were taken from the central regions of the ears of New Zealand white rabbits following localized exposure of one ear of each rabbit to 530 MeV/amu Ar or 365 MeV/amu Ne ions. The unirradiated ears served as controls. Biopsies were taken also from the chests and inner thighs of rhesus monkeys after whole-body exposure to 32 MeV protons and from unirradiated control animals. The linear energy transfers (LET infinity's) for the radiations were 90 +/- 5, 35 +/- 3, and approximately 1.2 keV/micrometer, respectively. In the rabbit studies, explants were removed with a 2 mm diameter dermal punch at post-irradiation times up to five years after exposure. Similar volumes of monkey tissue were taken from skin samples excised surgically 16-18 years following proton irradiation. Fibroblast cultures were initiated from the explants and were propagated in vitro until terminal senescence (cessation of cell division) occurred. Cultures from irradiated tissue exhibited decreases in doubling potential that were dependent on radiation dose and LET infinity and seemed to reflect damage to stem cell populations. The implications of these results for astronauts exposed to heavy ions and/or protons in space include possible manifestations of residual effects in the skin many years after exposure (e.g. unsatisfactory responses to trauma or surgery).     

Fluence-based relative biological effectiveness for charged particle carcinogenesis in mouse Harderian gland.

Neoplasia in the rodent Harderian gland has been used to determine the carcinogenic potential of irradiation by HZE particles. Ions from protons to lanthanum at energies up to 670 MeV/a have been used to irradiate mice, and prevalence of Harderian gland tumors has been measured 16 months after irradiation. The RBE for tumor induction has been expressed as the RBEmax, which is the ratio of the initial slopes of the dose vs prevalence curve. The RBEmax has been found to be approximately 30 for ions with LET values in excess of 100 keV/micrometer. Analysis on the basis of fluence as a substitute for dose has shown that on a per particle basis all of the ions with LET values in excess of 100 keV/micrometer have equal effectiveness. An analysis of the probabilities of ion traversals of the nucleus has shown that for these high stopping powers that a single hit is effective in producing neoplastic transformation.     

Relative biological effectiveness and microdosimetry of a mixed energy field of protons up to 200 MeV.

We have studied radiation effects utilizing the new 250 MeV Synchrotron at Loma Linda University Medical Center. In this paper we present the data collected for the survival of Chinese hamster lung (V79) cells, that were irradiated with a beam of mixed energy protons up to 200 MeV. The RBE for protons, when compared to 60Co gamma rays, ranged from a low of 1.2 at the high energy portion of the field to 1.3+ at the low energy portion of the field. These results are consistent with the measured lineal energy (microdosimetric) spectra.     

MONITORING OF ENERGETIC PARTICLE ENVIRONMENT INSIDE THE CHINA-BRAZIL EARTH RESOURCE SATELLITE

On 14 October 1999, the Chinese-Brazil earth resource satellite (CBERS-1) was launched in China. On board of the satellite there was an instrument designed at Peking University to detect the energetic particle radiation inside the satellite so the radiation fluxes of energetic particles in the cabin can be monitored continuously. Inside a satellite cabin, radiation environment consists of ether penetrated energetic particles or secondary radiation from satellite materials due to the interactions with primary cosmic rays.Purpose of the detectors are twofold, to monitor the particle radiation in the cabin and also to study the space radiation environment The data can be used to study the radiation environment and their effects on the electronics inside the satelhte cabin. On the other hand, the data are useful in study of geo-space energetic particle events such as solar proton events, particle precipitation and variations of the radiation belt since there should be some correlation between the radiation situation inside and outside the satellite.The instrument consists of two semi-conductor detectors for protons and electrons respectively. Each detector has two channels of energy ranges. They are 0.5-2MeV and ≥2MeV for electrons and 5-30MeV and 30-60MeV for protons. Counting rate for all channels are up to 104/(cm2@s)and power consumption is about 2.5 W. There are also the additional functions of CMOS TID (total integrated dose) effect and direct SEU monitoring. The data of CBMC was first sent back on Oct. 17 1999 and it's almost three years from then on. The detector has been working normally and the quality of data is good.The preliminary results of data analysis of CBMC not only reveal the effects of polar particle precipitation and radiation belt on radiation environment inside a satellite, but also show some important features of the geo-space energetic particle radiation.As one of the most important parameters of space weather, the energetic charged particles have great influences on space activities and ground tech nology. CBMC is perhaps the first long-term on-board special equipment to monitor the energetic particle radiation environment inside the satellite and the data it accnmulated are very useful in both satellite designing and space research.     

High energy charged particle experiment – A payload proposal to KuaFu-B mission

High Energy Charged Particle Experiment (HECPE) is to measure the fluxes of MeV electrons and tens of MeV protons. The two satellites of KuaFu-B are in the same polar orbit with apogee 7.0R_E, perigee 1.8R_E. They can sweep large L values and pass through the inner and outer radiation belts. The high energy electrons and protons in the radiation belts are principal sources for failures of satellites and spacecrafts in the Earth orbits. The enhancements of the high energy electrons and protons, so-called energetic particle events, are important phenomena of the Space Weather. The energy ranges monitored by HECPE are 0.3–0.5 MeV, 0.5–1.0 MeV, 1.0–2.0 MeV, and E > 2.0 MeV for electrons, 5–10 MeV, 10–20 MeV, 20–40 MeV, and 40–80 MeV for protons.     

Sources of inner radiation zone energetic helium ions: Cross-field transport versus in-situ nuclear reactions

Radial transport theory for inner radiation zone MeV He ions has been extended by combining radial diffusive transport, losses due to Coulomb friction and charge exchange reaction with local generation of ³He and ⁴He ions due to nuclear reactions taking place on the inner edge of the inner radiation zone. From interactions between high energy trapped protons and upper atmospheric constituents we have included a nuclear reaction yield helium flux source that was numerically derived from a nuclear reaction model originally developed at the Institute of Nuclear Researches of Moscow, Russia and implemented in the computer system at the University of Campinas, Brazil. Magnetospheric transport computations have been made covering the L-shell range L=1.0 to 1.6 and the resulting MeV He ion flux distributions show a strong influence of the local nuclear source mechanism on the inner zone energetic He ion content.     

Radiation effects in space.

The radiation protection guidelines of the National Aeronautics and Space Administration (NASA) are under review by Scientific Committee 75 of the National Council Protection and Measurements. The re-evaluation of the current guidelines is necessary, first, because of the increase in information about radiation risks since 1970 when the original recommendations were made and second, the population at risk has changed. For example, women have joined the ranks of the astronauts. Two types of radiation, protons and heavy ions, are of particular concern in space. Unfortunately, there is less information about the effects on tissues and cancer by these radiations than by other radiations. The choice of Quality Factors (Q) for obtaining dose equivalents for these radiations, is an important aspect of the risk estimate for space travel. There are not sufficient data for the induction of late effects by either protons or by heavy ions. The current information suggests a RBE for the relative protons of about 1, whereas, a RBE of 20 for tumor induction by heavy ions, such as iron-56, appears appropriate. The recommendations for the dose equivalent career limits for skin and the lens of the eye have been reduced but the 30-day and annual limits have been raised.     

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.     

The influence of radiation quality on the formation of DNA breaks.

We have aimed to present a comprehensive review of our understanding to date of the formation of DNA strand breaks induced by high LET radiation. We have discussed data obtained from DNA in solution as well as from the formation and "repair" of strand breaks in cell DNA. There is good agreement, qualitatively, between these two systems. Results were evaluated for two parameters: (1) effectivity per particle, the cross section (sigma) in micrometers 2/particle; and (2) the strand break induction frequency as number of breaks per Gy per unit DNA (bp or dalton). A series of biological effects curves (one for each Z-number) is obtained in effectivity versus LET plots. The relationships between induction frequencies of single-strand breaks, or double-strand breaks, or the residual "irrepairable" breaks and LET-values have been evaluated and discussed for a wide spectrum of heavy ions, both for DNA in solution and for DNA in the cell. For radiation induced total breaks in cell DNA, the RBE is less than one, while the RBE for the induction of DSBs can be greater than one in the 100-200 keV/micrometers range. The level of irrepairable strand breaks is highest in this same LET range and may reach 25 percent of the initial break yield. The data presented cover results obtained for helium to uranium particles, covering a particle incident energy range of about 2 to 900 MeV/u with a corresponding LET range of near 16 to 16000 keV/micrometers.     

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

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

Maps of hydrogen isotopes at low altitudes in the inner zone from sampex observations

The PET instrument aboard the SAMPEX satellite has provided us with long-term intra-calibrated observations of geomagnetically trapped protons and deuterons in the inner zone, suitable for use in constraining the low-altitude portions of radiation belt models being developed as successors to AP-8. These observations have been summarized elsewhere (Looper et al., 1996). Here we report a detection of geomagnetically-trapped tritium at energies from 14 to 35 MeV/nuc below L = 1.2, at about 1/8 the flux of deuterium previously reported at that location and at similar energy per nucleon. We also demonstrate the utility of the SAMPEX/PET observations for measuring the east-west anisotropy in the trapped particle flux at low altitudes, which is due to displacement of particle gyrocenters from the position of observation in a region of strong flux gradients. This anisotropy is implicitly ignored in omnidirectional radiation-flux models, but it can be important to mission planners considering how to distribute shielding over the surface of oriented spacecraft in low Earth orbit.     

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.     

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.     

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.      

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.