Identification of Plasma Lipidome Changes Associated with Low Dose Space-Type Radiation Exposure in a Murine Model
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While in orbit, Astronauts are exposed to a much higher dose of ionizing radiation than when on the ground. It is important to model how shielding designs on spacecraft reduce radiation effective dose pre-flight, and determine whether or not a danger to humans is presented. However, in order to calculate effective dose, dose equivalent calculations are needed. Dose equivalent takes into account an absorbed dose of radiation and the biological effectiveness of ionizing radiation. This is important in preventing long-term, stochastic radiation effects in humans spending time in space. Monte carlo simulations run with the particle transport code FLUKA, give absorbed and equivalent dose data for relevant shielding. The shielding geometry used in the dose calculations is a layered slab design, consisting of aluminum, polyethylene, and water. Water is used to simulate the soft tissues that compose the human body. The results obtained will provide information on how the shielding performs with many thicknesses of each material in the slab. This allows them to be directly applicable to modern spacecraft shielding geometries.
A tissue-equivalent proportional counter (TEPC) sensitive to the lineal energy range of 0.26-300 keV micrometer-1 was flown on STS-40 (39 degrees x 278 km x 296 km) inside the Spacelab. This instrument was previously flown on STS-31 but was modified to provide a finer resolution at lower lineal energies to better map the South Atlantic Anomaly (SAA) protons. The instrument was turned on 6 June 1991, and operated for 7470 min (124.5 h). The flight duration was characterized by a very large number of X-ray solar flares and enhanced magnetic field fluctuations; however, no significant dose from the solar particles was measured at the location of this instrument. The flight data can be separated into trapped and galactic cosmic radiation parts. The dose rate, dose-equivalent rate and quality factor for trapped radiation were 4.21 +/- 0.03 mrad day-1, 7.72 +/- 0.05 mrem day-1, and 1.83 +/- 0.1, respectively. The dose rate, dose-equivalent rate, and quality factor for galactic cosmic radiation were 5.34 +/- 0.03 mrad day-1, 14.63 +/- 0.06 mrem day-1, and 2.74 +/- 0.1, respectively. The overall quality factor for the flight was 2.38. The dose from the GCR is higher than from SAA protons because of the high inclination and low altitude of this flight. The AP8MAX model of the trapped radiation gives a dose rate of 2.43 mrad day-1 and a quality factor of 1.77. The CREME solar maximum model of galactic cosmic radiation gives a dose rate of 2.54 mrad day-1 and a quality factor of 2.91. Thus the AP8MAX model underestimates the dose by a factor of 1.8 whereas the CREME model leads to an underestimation of the dose by a factor of 2. A comparison of the LET spectra using the AP8MAX model and galactic cosmic radiation transport codes shows only a qualitative agreement.
For over 25 years, NASA has supported the development of space radiation transport models for shielding applications. The NASA space radiation transport model now predicts dose and dose equivalent in Earth and Mars orbit to an accuracy of plus or minus 20%. However, because larger errors may occur in particle fluence predictions, there is interest in further assessments and improvements in NASA's space radiation transport model. In this paper, we consider the effects of the isotopic composition of the primary galactic cosmic rays (GCR) and the isotopic dependence of nuclear fragmentation cross-sections on the solution to transport models used for shielding studies. Satellite measurements are used to describe the isotopic composition of the GCR. Using NASA's quantum multiple-scattering theory of nuclear fragmentation (QMSFRG) and high-charge and energy (HZETRN) transport code, we study the effect of the isotopic dependence of the primary GCR composition and secondary nuclei on shielding calculations. The QMSFRG is shown to accurately describe the iso-spin dependence of nuclear fragmentation. The principal finding of this study is that large errors (plus or minus 100%) will occur in the mass-fluence spectra when comparing transport models that use a complete isotope grid (approximately 170 ions) to ones that use a reduced isotope grid, for example the 59 ion-grid used in the HZETRN code in the past, however less significant errors (less than 20%) occur in the elemental-fluence spectra. Because a complete isotope grid is readily handled on small computer workstations and is needed for several applications studying GCR propagation and scattering, it is recommended that they be used for future GCR studies.
The physiological responses to spaceflight elicit wide-ranging consequences and resemble aspects of aging on Earth. Previous studies have shown that oxidative damage via reactive oxygen species (ROS), contributes to aging-related pathologies. Our study uses 1-year old C57BL/6NJ male and female mice (astronaut-relevant age) that underwent exposure to 0.5 gray of gamma radiation together with social isolation and were euthanized 12 weeks after. We used the longevity MCAT mouse model in which human catalase is overexpressed in the mitochondria, for ROS quenching. We aimed to determine whether in older mice quenching ROS, will mitigate the neuro-behavioral consequences of low dose ionizing radiation and/or social isolation and whether the outcomes will differ in males and females. We have performed five mission relevant behavioral tests which focused on performance, memory, physical stance, and stress. We have detected both sex and radiation effects; the older females look physically better are faster and perform better almost in all behavioral tests compared to their male counterparts. On the other hand, they are more sensitive to low dose radiation in many cases, in some cases this effect was indeed mitigated in the MCAT mice, pointing out to the importance of ROS in response to radiation stress and social isolation. We have measured plasma (7- and 90-days post radiation), cytokines, corticosterone and hippocampal cytokine and microglial activation at the end of the experiment. We saw significant changes in the plasma markers due to radiation, sex, and genotype in both short and long post radiation period and detected long term sex and radiation effects in the brain. Our focus is now on applying advanced statistical modeling to corelate the behavioral tests with our recent molecular findings to look for specific biomarkers that could predict behavioral deficits.
A Solar Sail Radiation Environment (SSRE) model has been developed for characterizing the radiation dose and internal charging environments in the solar wind. The SSRE model defines the 0.01 keV to 1 MeV charged particle environment for use in testing the radiation dose vulnerability of candidate solar sail materials and for use in evaluating the internal charging effects in the interplanetary environment. Solar wind and energetic particle instruments aboard the Ulysses spacecraft provide the particle data used to derive the environments for the high inclination 0.5 AU Solar Polar Imager mission and the 1.0 AU L1 solar sail missions. Ulysses is the only spacecraft to sample high latitude solar wind environments far from the ecliptic plane and is therefore uniquely capable of providing the information necessary for defining radiation environments for the Solar Polar Imager spacecraft. Cold plasma moments are used to derive differential flux spectra based on Kappa distribution functions. Energetic particle flux measurements are used to constrain the high energy, non-thermal tails of the distribution functions providing a comprehensive electron, proton, and helium spectra from less than 0.01 keV to a few MeV.
Space radiation poses an increased risk for cardiovascular diseases (CVD) during and after spaceflight, that should be quantified to plan future space missions such as the flight to Mars. The radiation-induced CVD risk is evaluated using a linear no-threshold dose response excess relative risk (ERR) model, so that the risk is function of the radiation dose and of the background (i.e., non-exposed) incidence rate. The background CVD risk can be evaluated using clinical prediction models (CPMs). The first CPMs developed in the 1960’s have identified CVD risk factors such as blood pressure, diabetes, cholesterol, and smoking. In this work, the steps used to integrate the CVD risk provided by a CPM into the NASA Radiation Risk Model are described. Simulation results calculated using available data for relevant mission scenarios are also shown, and the challenges in CVD risk predictions are discussed.
Space radiation poses an increased risk for cardiovascular diseases (CVD) during and after spaceflight, that should be quantified to plan future space missions such as the flight to Mars. The radiation-induced CVD risk is evaluated using a linear no-threshold dose response excess relative risk (ERR) model, so that the risk is function of the radiation dose and of the background (i.e., non-exposed) incidence rate. The background CVD risk can be evaluated using clinical prediction models (CPMs). The first CPMs developed in the 1960’s have identified CVD risk factors such as blood pressure, diabetes, cholesterol, and smoking. In this work, the steps used to integrate the CVD risk provided by a CPM into the NASA Radiation Risk Model are described. Simulation results calculated using available data for relevant mission scenarios are also shown, and the challenges in CVD risk predictions are discussed.
Current models to estimate radiation risk use the Life Span Study (LSS) cohort that received high doses and high dose rates of radiation. Transferring risks from these high dose rates to the low doses and dose rates received by astronauts in space is a source of uncertainty in our risk calculations. The solid cancer models recommended by BEIR VII [1], UNSCEAR [2], and Preston et al [3] is fitted adequately by a linear dose response model, which implies that low doses and dose rates would be estimated the same as high doses and dose rates. However animal and cell experiments imply there should be curvature in the dose response curve for tumor induction. Furthermore animal experiments that directly compare acute to chronic exposures show lower increases in tumor induction than acute exposures. A dose and dose rate effectiveness factor (DDREF) has been estimated and applied to transfer risks from the high doses and dose rates of the LSS cohort to low doses and dose rates such as from missions in space. The BEIR VII committee [1] combined DDREF estimates using the LSS cohort and animal experiments using Bayesian methods for their recommendation for a DDREF value of 1.5 with uncertainty. We reexamined the animal data considered by BEIR VII and included more animal data and human chromosome aberration data to improve the estimate for DDREF. Several experiments chosen by BEIR VII were deemed inappropriate for application to human risk models of solid cancer risk. Animal tumor experiments performed by Ullrich et al [4], Alpen et al [5], and Grahn et al [6] were analyzed to estimate the DDREF. Human chromosome aberration experiments performed on a sample of astronauts within NASA were also available to estimate the DDREF. The LSS cohort results reported by BEIR VII were combined with the new radiobiology results using Bayesian methods.
A computerized anatomical man (CAM) model, representing the most detailed and anatomically correct geometrical model of the human body yet prepared, has been developed for use in analyzing radiation dose distribution in man. This model of a 50-percentile standing USAF man comprises some 1100 unique geometric surfaces and some 2450 solid regions. Internal body geometry such as organs, voids, bones, and bone marrow are explicitly modeled. A computer program called CAMERA has also been developed for performing analyses with the model. Such analyses include tracing rays through the CAM geometry, placing results on magnetic tape in various forms, collapsing areal density data from ray tracing information to areal density distributions, preparing cross section views, etc. Numerous computer drawn cross sections through the CAM model are presented.
Historical solar particle events (SPEs) provide context for some understanding of acute radiation exposure risk to astronauts traveling outside of low Earth orbit. Modeling of potential doses delivered to exploration crewmembers anticipates limited radiation-induced health impacts, including prodromal symptoms of nausea, emesis, and fatigue, but suggests that more severe clinical manifestations are unlikely. Recent large animal-model research in space-analogs closely mimicking SPEs has identified coagulopathic events independent of the hematopoietic sequelae of higher radiation doses, similar in manifestation to disseminated intravascular coagulation (DIC). We explored the challenges of clinical management of radiation-related clinical manifestations, using currently accepted modeling techniques and anticipated physiological sequelae, to identify medical capabilities needed to successfully manage SPE-induced radiation illnesses during exploration spaceflight.
For space radiation protection it is often useful to calculate dose or dose,equivalent in blood forming organs (BFO). It has been customary to use a 5cm equivalent sphere to. simulate the BFO dose. However, many previous studies have concluded that a 5cm sphere gives very different dose values from the exact BFO values. One study [1] . concludes that a 9 cm sphere is a reasonable approximation for BFO'doses in solar particle event environments. In this study we use a deterministic radiation transport [2] to investigate the reason behind these observations and to extend earlier studies. We take different space radiation environments, including seven galactic cosmic ray environments and six large solar particle events, and calculate the dose and dose equivalent in the skin, eyes and BFO using their thickness distribution functions from the CAM (Computerized Anatomical Man) model [3] The organ doses have been evaluated with a water or aluminum shielding of an areal density from 0 to 20 g/sq cm. We then compare with results from the equivalent sphere model and determine in which cases and at what radius parameters the equivalent sphere model is a reasonable approximation. Furthermore, we address why the equivalent sphere model is not a good approximation in some cases. For solar particle events, we find that the radius parameters for the organ dose equivalent increase significantly with the shielding thickness, and the model works marginally for BFO but is unacceptable for the eye or the skin. For galactic cosmic rays environments, the equivalent sphere model with an organ-specific constant radius parameter works well for the BFO dose equivalent, marginally well for the BFO dose and the dose equivalent of the eye or the skin, but is unacceptable for the dose of the eye or the skin. The ranges of the radius parameters are also being investigated, and the BFO radius parameters are found to be significantly, larger than 5 cm in all cases, consistent with the conclusion of an earlier study [I]. The radius parameters for the dose equivalent in GCR environments are approximately between 10 and I I cm for the BFO, 3.7 to 4.8 cm for the eye, and 3.5 to 5.6 cm for the skin; while the radius parameters are between 10 and 13 cm for the BFO dose.
Solar particle events (SPEs) pose the risk of acute radiation sickness (ARS) to astronauts, because organ doses from large SPEs may reach critical levels during extra vehicular activities (EVAs) or lightly shielded spacecraft. NASA has developed an organ dose projection model of Baryon transport code (BRYNTRN) with an output data processing module of SUMDOSE, and a probabilistic model of acute radiation risk (ARR). BRYNTRN code operation requires extensive input preparation, and the risk projection models of organ doses and ARR take the output from BRYNTRN as an input to their calculations. With a graphical user interface (GUI) to handle input and output for BRYNTRN, these response models can be connected easily and correctly to BRYNTRN in a user friendly way. The GUI for the Acute Radiation Risk and BRYNTRN Organ Dose (ARRBOD) projection code provides seamless integration of input and output manipulations required for operations of the ARRBOD modules: BRYNTRN, SUMDOSE, and the ARR probabilistic response model. The ARRBOD GUI is intended for mission planners, radiation shield designers, space operations in the mission operations directorate (MOD), and space biophysics researchers. Assessment of astronauts organ doses and ARS from the exposure to historically large SPEs is in support of mission design and operation planning to avoid ARS and stay within the current NASA short-term dose limits. The ARRBOD GUI will serve as a proof-of-concept for future integration of other risk projection models for human space applications. We present an overview of the ARRBOD GUI product, which is a new self-contained product, for the major components of the overall system, subsystem interconnections, and external interfaces.
Grid2 is a program that utilizes the Galileo Interim Radiation Electron model 2 (GIRE2) Jovian radiation model to compute fluences and doses for Jupiter missions. (Note: The iterations of these two softwares have been GIRE and GIRE2; likewise Grid and Grid2.) While GIRE2 is an important improvement over the original GIRE radiation model, the GIRE2 model can take as long as a day or more to compute these quantities for a complete mission. Grid2 fits the results of the detailed GIRE2 code with a set of grids in local time and position thereby greatly speeding up the execution of the model-minutes as opposed to days. The Grid2 model covers the time period from 1971 to 2050 and distances of 1.03 to 30 Jovian diameters (Rj). It is available as a direct-access database through a FORTRAN interface program. The new database is only slightly larger than the original grid version: 1.5 gigabytes (GB) versus 1.2 GB.
Grid2 is a program that utilizes the Galileo Interim Radiation Electron model 2 (GIRE2) Jovian radiation model to compute fluences and doses for Jupiter missions. (Note: The iterations of these two softwares have been GIRE and GIRE2; likewise Grid and Grid2.) While GIRE2 is an important improvement over the original GIRE radiation model, the GIRE2 model can take as long as a day or more to compute these quantities for a complete mission. Grid2 fits the results of the detailed GIRE2 code with a set of grids in local time and position thereby greatly speeding up the execution of the model--minutes as opposed to days. The Grid2 model covers the time period from 1971 to 2050and distances of 1.03 to 30 Jovian diameters (Rj). It is available as a direct-access database through a FORTRAN interface program. The new database is only slightly larger than the original grid version: 1.5 gigabytes (GB) versus 1.2 GB.
The radiation space environment includes particles such as protons and multiple species of heavy ions, with much of the exposure to these radiations occurring at extremely low average dose-rates. Limitations in databases needed to predict cancer hazards in human beings from such radiations are significant and currently do not provide confidence that such predictions are acceptably precise or accurate. In this article, we outline the need for animal carcinogenesis data based on a more sophisticated understanding of the dose-response relationship for induction of cancer and correlative cellular endpoints by representative space radiations. We stress the need for a model that can interrelate human and animal carcinogenesis data with cellular mechanisms. Using a broad model for dose-response patterns which we term the "subalpha-alpha-omega (SAO) model", we explore examples in the literature for radiation-induced cancer and for radiation-induced cellular events to illustrate the need for data that define the dose-response patterns more precisely over specific dose ranges, with special attention to low dose, low dose-rate exposure. We present data for multiple endpoints in cells, which vary in their radiosensitivity, that also support the proposed model. We have measured induction of complex chromosome aberrations in multiple cell types by two space radiations, Fe-ions and protons, and compared these to photons delivered at high dose-rate or low dose-rate. Our data demonstrate that at least three factors modulate the relative efficacy of Fe-ions compared to photons: (i) intrinsic radiosensitivity of irradiated cells; (ii) dose-rate; and (iii) another unspecified effect perhaps related to reparability of DNA lesions. These factors can produce respectively up to at least 7-, 6- and 3-fold variability. These data demonstrate the need to understand better the role of intrinsic radiosensitivity and dose-rate effects in mammalian cell response to ionizing radiation. Such understanding is critical in extrapolating databases between cellular response, animal carcinogenesis and human carcinogenesis, and we suggest that the SAO model is a useful tool for such extrapolation.
Space weather is an important driver of the exposure of aircrew and passengers to cosmic rays at flight altitudes. The assessment of the corresponding radiation doses can be realized by measurements or model calculations that cover the whole range of the radiation field in terms of geomagnetic shielding, atmospheric shielding, and the effects of space weather. Since the radiation field at aviation altitudes is very complex in terms of particle composition and energy distribution, the accurate experimental determination of doses at aviation altitudes is still a challenging task. Accordingly, the amount of data with comparatively small uncertainties is scarce. The Community Coordinated Modeling Center invited the Federal Aviation Administration, the German Aerospace Center, and the National Aeronautics and Space Administration to make their radiation models for aviation CARI-7A, PANDOCA, and NAIRAS available for interested users via the Community Coordinated Modeling Center web site. A concomitant comparison of model calculations with measuring data provided information on the predicting capabilities and the uncertainties of the current versions of these models under quiet space weather conditions.
The space radiation environment, particularly solar particle events (SPEs), poses the risk of acute radiation sickness (ARS) to humans; and organ doses from SPE exposure may reach critical levels during extra vehicular activities (EVAs) or within lightly shielded spacecraft. NASA has developed an organ dose projection model using the BRYNTRN with SUMDOSE computer codes, and a probabilistic model of Acute Radiation Risk (ARR). The codes BRYNTRN and SUMDOSE, written in FORTRAN, are a Baryon transport code and an output data processing code, respectively. The ARR code is written in C. The risk projection models of organ doses and ARR take the output from BRYNTRN as an input to their calculations. BRYNTRN code operation requires extensive input preparation. With a graphical user interface (GUI) to handle input and output for BRYNTRN, the response models can be connected easily and correctly to BRYNTRN in friendly way. A GUI for the Acute Radiation Risk and BRYNTRN Organ Dose (ARRBOD) projection code provides seamless integration of input and output manipulations, which are required for operations of the ARRBOD modules: BRYNTRN, SUMDOSE, and the ARR probabilistic response model. The ARRBOD GUI is intended for mission planners, radiation shield designers, space operations in the mission operations directorate (MOD), and space biophysics researchers. The ARRBOD GUI will serve as a proof-of-concept example for future integration of other human space applications risk projection models. The current version of the ARRBOD GUI is a new self-contained product and will have follow-on versions, as options are added: 1) human geometries of MAX/FAX in addition to CAM/CAF; 2) shielding distributions for spacecraft, Mars surface and atmosphere; 3) various space environmental and biophysical models; and 4) other response models to be connected to the BRYNTRN. The major components of the overall system, the subsystem interconnections, and external interfaces are described in this report; and the ARRBOD GUI product is explained step by step in order to serve as a tutorial.