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All sourcesNASA NTRSDOE OSTI
NASA NTRS2007

Space Radiation Organ Doses for Astronauts on Past and Future Missions

We review methods and data used for determining astronaut organ dose equivalents on past space missions including Apollo, Skylab, Space Shuttle, NASA-Mir, and International Space Station (ISS). Expectations for future lunar missions are also described. Physical measurements of space radiation include the absorbed dose, dose equivalent, and linear energy transfer (LET) spectra, or a related quantity, the lineal energy (y) spectra that is measured by a tissue equivalent proportional counter (TEPC). These data are used in conjunction with space radiation transport models to project organ specific doses used in cancer and other risk projection models. Biodosimetry data from Mir, STS, and ISS missions provide an alternative estimate of organ dose equivalents based on chromosome aberrations. The physical environments inside spacecraft are currently well understood with errors in organ dose projections estimated as less than plus or minus 15%, however understanding the biological risks from space radiation remains a difficult problem because of the many radiation types including protons, heavy ions, and secondary neutrons for which there are no human data to estimate risks. The accuracy of projections of organ dose equivalents described here must be supplemented with research on the health risks of space exposure to properly assess crew safety for exploration missions.

Cucinotta, Francis A.↗
DOE OSTI2021

Organs at Risk Considerations for Thoracic Stereotactic Body Radiation Therapy: What Is Safe for Lung Parenchyma?

Stereotactic body radiation therapy (SBRT) has become the standard of care for inoperable early-stage non-small cell lung cancer and is often used for recurrent lung cancer and pulmonary metastases. Radiation-induced lung toxicity (RILT), including radiation pneumonitis and pulmonary fibrosis, is a major concern for which it is important to understand dosimetric and clinical predictors.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2023

Influence of the irradiated pulmonary microenvironment on macrophage and T cell dynamics

The lung is sensitive to radiation, which increases the risk of normal tissue toxicity following radiation therapy. Adverse outcomes include pneumonitis and pulmonary fibrosis, which are thought to result from dysregulated intercellular communication within the pulmonary microenvironment. Macrophage accumulation in the lung following radiation exposure is implicated in these pathogenic outcomes. Here we investigate the role of the microenvironment in macrophage and T cell dynamics. Materials and methods C57Bl/6 mice received 6Gyx5 x-ray irradiation to the right lung. Macrophage and T cell dynamics were investigated in ipsilateral right lungs, contralateral left lungs and compared to those from non-irradiated control subjects at 4-26wk post exposure. Lungs were evaluated by flow cytometry, histology and proteomics. Results In uni-lung irradiated subjects, focal regions of macrophage accumulation were noted in both lungs by 8wk, however fibrotic lesions were observed only in ipsilateral lungs by 26wk. Both infiltrating and alveolar macrophages populations transiently expanded in both lungs, however a transitional CD11b+ alveolar macrophage population persisted only in ipsilateral lungs and expressed lower CD206. Concurrently, arginase-1+ macrophages were noted within areas of macrophage accumulation in ipsilateral but not contralateral lungs at 8 and 26wk post exposure, while CD206+ macrophages were absent from these accumulations. While CD8+ T cells were present in both lungs of irradiated subjects, T regulatory cells were only increased in ipsilateral lungs. Unbiased proteomics analysis of immune cells revealed a substantial number of differentially expressed proteins in ipsilateral lungs when compared to either contralateral or non-irradiated lungs, as well as between contralateral lungs from irradiated subjects and non-irradiated controls. Conclusions Pulmonary macrophage and T cell dynamics are impacted by the microenvironmental conditions that develop in the lung following radiation exposure, both locally and systemically. Our findings demonstrate that while macrophages and T cells infiltrate and expand in both lungs, they diverge phenotypically depending on their environment.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
NASA NTRS2013

Orion GNC Mitigation Efforts for Van Allen Radiation

The Orion Crew Module (CM) is NASA's next generation manned space vehicle, scheduled to return humans to lunar orbit in the coming decade. The Orion avionics and GN&C architectures have progressed through a number of project phases and are nearing completion of a major milestone. The first unmanned test mission, dubbed "Exploration Flight Test One" (EFT-1) is scheduled to launch from NASA Kennedy Space Center late next year and provides the first integrated test of all the vehicle systems, avionics and software. The EFT-1 mission will be an unmanned test flight that includes a high speed re-entry from an elliptical orbit, which will be launched on an expendable launch vehicle (ELV). The ELV will place CM and the ELV upper stage into a low Earth orbit (LEO) for one revolution. After the first LEO, the ELV upper stage will re-ignite and place the combined upper stage/CM into an elliptical orbit whose perigee results in a high energy entry to test CM response in a relatively high velocity, high heating environment. While not producing entry velocities as high as those experienced in returning from a lunar orbit, the trajectory was chosen to provide higher stresses on the thermal protection and guided entry systems, as compared against a lower energy LEO entry. However the required entry geometry with constraints on inclination and landing site result in a trajectory that lingers for many hours in the Van Allen radiation belts. This exposes the vehicle and avionics to much higher levels of high energy proton radiation than a typical LEO or lunar trajectory would encounter. As a result, Van Allen radiation poses a significant risk to the Orion avionics system, and particularly the Flight Control Module (FCM) computers that house the GN&C flight software. The measures taken by the Orion GN&C, Flight Software and Avionics teams to mitigate the risks associated with the Van Allen radiation on EFT-1 are covered in the paper. Background on the Orion avionics subsystem is provided, as well as an overview of the GN&C software architecture. The measures taken to handle radiation induced failure of the one or both of the FCM's are presented, and finally simulation and actual hardware-in-the-loop (HWIL) results are shown confirming the validity of the implementation. The paper presents an overview of the Orion avionics architecture describing the GNC sensors, onboard data network as well as the flight control computers and their planned restart capabilities. GN&C sensors include two Orion Inertial Measurement Units (OIMU's), a Vision Processing Unit (VPU) to process camera images, three barometric altimeters and a single GPS receiver. All of the sensors communicate to one of two Power and Data Units (PDU's). The PDU's multiplex analog and serial data from the sensors and write the data to the Orion Data Network (ODN). The OIMU s write measurement messages directly as onto the ODN, but they are routed through PDU network switches.

King, Ellis T.↗
DOE OSTI2020

Analysis of Exposure during Transportation of Waste to the Nevada National Security Site (NNSS) - 20445

Safety is a priority for the U.S. Department of Energy (DOE) Environmental Management (EM) Nevada Program. This commitment to safety is integrated into requirements and work procedures at DOE sites across the U.S. that generate low-level radioactive waste, mixed low-level radioactive waste, and classified waste that is transported to the Nevada National Security Site (NNSS) for permanent disposal. Generators of this waste are responsible for ensuring it is packaged and transported in a safe and compliant manner. These generators and their contracted commercial carriers must comply with U.S. Department of Transportation (DOT) regulations; the Nevada National Security Site Waste Acceptance Criteria (NNSSWAC); and other applicable federal, state, and local regulations and requirements. This includes packaging and shipping the waste to meet DOT regulatory radiation dose limits to ensure public safety during transportation. NNSS waste generators have a solid safety record for complying with these stringent regulations as demonstrated by the fact that no shipments exceeding DOT dose rate limits were received at the NNSS Area 5 Radioactive Waste Management Complex (RWMC) during FY 2014 through FY 2018. A 2005 study conducted by the Desert Research Institute validated shipments to the NNSS comply with DOT radiation dose limits. In response to recent Nevada stakeholder requests for an updated study, an analysis was conducted to verify and provide evidence that the public continues to be safe from exposure to radioactive waste shipment to the NNSS. Radiation exposure from radioactive waste shipments in transit to the NNSS was evaluated. Three studies were performed: 1. Confirm compliance of waste shipments to the DOT radiation limits using dose rate surveys taken at the generator site and at the disposal site. 2. Estimate the dose to the public from waste shipments using the dosimetry results for disposal site personnel by comparing time of exposure for various individuals/scenarios. 3. Estimate the truck driver dose using the receipt dose rate surveys and time of exposure, and from dosimetry results. Study 1 confirmed compliance with the DOT dose rate limits for a sample of waste shipments (123 of 1,038) received during fiscal year (FY) 2017. Study 2 showed that the average annual radiation equivalent dose for disposal site personnel during FY 2017 was approximately 6.7% [0.415 mSv (41.5 millirem)] of the annual average dose that a person living in the U.S. receives from all sources [6.2 mSv (620 mrem)]. Maximum dose to a member of the public, a person resting/sleeping in an adjacent truck at a rest area to a waste shipment, was 0.0166 mSv (1.66 mrem), which is less than the dose received from a person taking a round trip from the east coast to the west coast of the continental U.S. on an airplane [0.07 mSv (7 mrem) per round trip]. Study 3 showed that the truck driver who made the most shipments of radioactive waste to the NNSS, who drove the most hours (estimated time of exposure 2,520 hours), during FY 2017 had a total dose of 0.15 mSv (15 mrem), which was obtained from their personal dosimeter. The annual dose recorded for disposal site personnel, the dose estimates for the public, and the truck driver dose were all a small percentage of the average radiation dose a person receives from all sources (e.g., background and medical radiation). At these levels, risk should only be described qualitatively. Radiation exposure from radioactive waste shipments to the NNSS were shown to be compliant with the DOT dose rate limits, safe, and very low (i.e., within background levels). (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗
NASA NTRS1993

Genetic effects of HZE and cosmic radiation (L-9)

The purpose of our experiment is to detect mutations in Drosophila possibly induced by space radiation during the SL-J mission, so that we will be able to obtain basic information about 'the genetic (mutational) risk of space radiation' which can be used to estimate human risk of cancer induction by space flight. As an example of somatic mutation, we will analyze morphological changes in hair growing on the surface of the wing of an adult fly. A piece of wing consists of about 30 thousand wing cells and in the wild type Drosophila a long single piece of hair is growing on the surface of each wing cell. When Drosophila is exposed to radiation as its early stage of development, such as embryonic stage or larval (maggot) stage, some mutations will appear in the wing hair of the adult fly with a certain low frequency, depending on the radiation dose. Among the mutations, the most frequent one is a change in the number of hairs per cell, that is, usually three or more hairs are coming out from a single wing cell. In the actual SL-J flight, we will install thousands of Drosophila larvae (maggots) into the Space Shuttle Discovery and expose them to space radiation during the 7-day mission. Immediately after the re-entry to the ground, these larvae are expected to develop (emerge) into adult flies. Then the wings will be fixed by ethylalcohol and permanent samples will be prepared. Finally, we will analyze the wing samples microscopically in order to detect mutations.

Ikenaga, Mituo↗
NASA NTRS2017

Cancer Risk in Astronauts: A Constellation of Uncommon Consequences

Excess cancers resulting from external radiation exposures have been noted since the early 1950s, when a rise in leukemia rates was first reported in young atomic bomb survivors [1]. Further studies in atomic bomb survivors, cancer patients treated with radiotherapy, and nuclear power plant workers have confirmed that radiation exposure increases the risk of not only leukemia, but also a wide array of solid cancers [2,3]. NASA has long been aware of this risk and limits astronauts' risk of exposure-induced death (REID) from cancer by specifying permissible mission durations (PMD) for astronauts on an individual basis. While cancer is present among astronauts, current data does not suggest any excess of known radiation-induced cancers relative to a comparable population of U.S. adults; however, very uncommon cancers have been diagnosed in astronauts including nasopharyngeal cancer, lymphoma of the brain, and acral myxoinflammatory fibroblastic sarcoma. In order to study cancer risk in astronauts, a number of obstacles must be overcome. Firstly, several factors make the astronaut cohort considerably different from the cohorts that have previously been studied for effects resulting from radiation exposure. The high rate of accidents and the much healthier lifestyle of astronauts compared to the U.S. population make finding a suitable comparison population a problematic task. Space radiation differs substantially from terrestrial radiation exposures studied in the past; therefore, analyses of galactic cosmic radiation (GCR) in animal models must be conducted and correctly applied to the human experience. Secondly, a large enough population of exposed astronauts must exist in order to obtain the data necessary to see any potential statistically significant differences between the astronauts and the control population. Thirdly, confounders and effect modifiers, such as smoking, diet, and other space stressors, must be correctly identified and controlled for in those analyses. In order to begin work assessing the astronaut population, the earliest groups of astronauts (selection groups 1-7) provide a unique model. These astronauts were relatively homogenous, white males whose lifestyle characteristics were similar to an average U.S. citizen of the same birth cohort. This work reviews radiation exposure levels, age, and causes of mortality among these early NASA astronauts and discusses the benefits and limitations of assessing such a cohort for radiation-induced cancer risk.

Milder, Caitlin M.↗
NASA NTRS2017

Temporal Dependence of Chromosomal Aberration on Radiation Quality and Cellular Genetic Background

Radiation induced cancer risks are driven by genetic instability. It is not well understood how different radiation sources induce genetic instability in cells with different genetic background. Here we report our studies on genetic instability, particularly chromosome instability using fluorescence in situ hybridization (FISH), in human primary lymphocytes, normal human fibroblasts, and transformed human mammary epithelial cells in a temporal manner after exposure to high energy protons and Fe ions. The chromosome spread was prepared 48 hours, 1 week, 2 week, and 1 month after radiation exposure. Chromosome aberrations were analyzed with whole chromosome specific probes (chr. 3 and chr. 6). After exposure to protons and Fe ions of similar cumulative energy (??), Fe ions induced more chromosomal aberrations at early time point (48 hours) in all three types of cells. Over time (after 1 month), more chromosome aberrations were observed in cells exposed to Fe ions than in the same type of cells exposed to protons. While the mammary epithelial cells have higher intrinsic genetic instability and higher rate of initial chromosome aberrations than the fibroblasts, the fibroblasts retained more chromosomal aberration after long term cell culture (1 month) in comparison to their initial frequency of chromosome aberration. In lymphocytes, the chromosome aberration frequency at 1 month after exposure to Fe ions was close to unexposed background, and the chromosome aberration frequency at 1 month after exposure to proton was much higher. In addition to human cells, mouse bone marrow cells isolated from strains CBA/CaH and C57BL/6 were irradiated with proton or Fe ions and were analyzed for chromosome aberration at different time points. Cells from CBA mice showed similar frequency of chromosome aberration at early and late time points, while cells from C57 mice showed very different chromosome aberration rate at early and late time points. Our results suggest that relative biological effectiveness (RBE) of radiation are different for different radiation sources, for different cell types, and for the same cell type with different genetic background at different times after radiation exposure. Caution must be taken in using RBE value to estimate biological effects from radiation exposure.

Lu, Tao↗
NASA NTRS2005

An Algorithm for the Transport of Anisotropic Neutrons

One major obstacle to human space exploration is the possible limitations imposed by the adverse effect of long-term exposure to the space environment. Even before human spaceflight began, the potentially brief exposure of astronauts to the very intense random solar particle events (SPE) were of great concern. A new challenge appears in deep space exploration from exposure to the low-intensity heavy-ion flux of the galactic cosmic rays (GCR) since the missions are of long duration and the accumulated GCR exposures can be high. Because cancer induction rates increase behind low to rather large thicknesses of aluminum shielding, according to available biological data on mammalian exposures to GCR like ions, the shield requirements for a Mars mission are prohibitively expensive in terms of mission launch costs. Therefore, a critical issue in the Human Exploration and Development of Space enterprise is cost effective mitigation of risk associated with ionizing radiation exposure. In order to estimate astronaut risk to GCR exposure and associated cancer risks and health hazards, it is necessary to do shield material studies. To determine an optimum radiation shield material it is necessary to understand nuclear interaction processes such as fragmentation and secondary particle production which is a function of energy dependent cross sections. This requires knowledge of material transmission characteristics either through laboratory testing or improved theoretical modeling. Here ion beam transport theory is of importance in that testing of materials in the laboratory environment generated by particle accelerators is a necessary step in materials development and evaluation for space use. The approximations used in solving the Boltzmann transport equation for the space setting are often not sufficient for laboratory work and those issues are a major emphasis of the present work.

Tweed, J.↗
NASA NTRS2006

The NASA Space Radiation Research Program

We present a comprehensive overview of the NASA Space Radiation Research Program. This program combines basic research on the mechanisms of radiobiological action relevant for improving knowledge of the risks of cancer, central nervous system and other possible degenerative tissue effects, and acute radiation syndromes from space radiation. The keystones of the NASA Program are five NASA Specialized Center's of Research (NSCOR) investigating space radiation risks. Other research is carried out through peer-reviewed individual investigations and in collaboration with the US Department of Energies Low-Dose Research Program. The Space Radiation Research Program has established the Risk Assessment Project to integrate data from the NSCOR s and other peer-reviewed research into quantitative projection models with the goals of steering research into data and scientific breakthroughs that will reduce the uncertainties in current risk projections and developing the scientific knowledge needed for future individual risk assessment approaches and biological countermeasure assessments or design. The NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory was created by the Program to simulate space radiation on the ground in support of the above research programs. New results from NSRL will be described.

Cucinotta, Francis A.↗
DOE OSTI2024

Verification of RESRAD-BUILD Code Version 4

This report documents the verification of the RESRAD-BUILD code, Version 4.0, which was released on December 22, 2022. Two earlier reports verifying Versions 3.0 and 3.1, respectively, were published in 2001 (Kamboj, et al. 2001) and 2003 (Tetra Tech NUS 2003). Version 4.0 of the RESRAD-BUILD code has many new features and modeling enhancements over the earlier versions, including the previously released Version 3.5. Chapter 2 of this report focuses on verifying the external dose and risk modeling for point, line, area, and volume sources, as well as for floor deposition. Besides verification, the external radiation doses calculated by RESRAD-BUILD were also benchmarked with those calculated by the MCNP code (Briemeister 1993). Section J.3 of the RESRAD-BUILD User’s Manual Vol. 1 (Yu et al. 2022) documents the results of that benchmarking effort. Chapter 3 of this report focuses on verifying the ventilation modeling, from checking the remaining source inventory, releases of radionuclides to the air, air concentrations and deposited floor concentrations over time, to the radiation dose and risk associated with inhalation, ingestion, and air submersion, with and without vacuuming. The verification efforts involve designing spreadsheets to perform calculations the same as or like those performed by the RESRAD-BUILD code and then comparing the spreadsheet results with those produced by the code. When the results agree or the differences are within acceptable range, the accuracy of model implementation in the code is verified. In addition to model implementation, the implementation of key functions and features that facilitate the modeling or the use of the code were also verified during the release testing of the code. Appendix A presents the test cases developed for these verification testing, and Appendix B presents the testing results that verify proper implementation of key functions and features.

54 ENVIRONMENTAL SCIENCES↗
NASA NTRS2010

Probabilistic Assessment of Cancer Risk from Solar Particle Events

For long duration missions outside of the protection of the Earth s magnetic field, space radiation presents significant health risks including cancer mortality. Space radiation consists of solar particle events (SPEs), comprised largely of medium energy protons (less than several hundred MeV); and galactic cosmic ray (GCR), which include high energy protons and heavy ions. While the frequency distribution of SPEs depends strongly upon the phase within the solar activity cycle, the individual SPE occurrences themselves are random in nature. We estimated the probability of SPE occurrence using a non-homogeneous Poisson model to fit the historical database of proton measurements. Distributions of particle fluences of SPEs for a specified mission period were simulated ranging from its 5 th to 95th percentile to assess the cancer risk distribution. Spectral variability of SPEs was also examined, because the detailed energy spectra of protons are important especially at high energy levels for assessing the cancer risk associated with energetic particles for large events. We estimated the overall cumulative probability of GCR environment for a specified mission period using a solar modulation model for the temporal characterization of the GCR environment represented by the deceleration potential (^). Probabilistic assessment of cancer fatal risk was calculated for various periods of lunar and Mars missions. This probabilistic approach to risk assessment from space radiation is in support of mission design and operational planning for future manned space exploration missions. In future work, this probabilistic approach to the space radiation will be combined with a probabilistic approach to the radiobiological factors that contribute to the uncertainties in projecting cancer risks.

Kim, Myung-Hee Y.↗
NASA NTRS2010

Depth Dose Distribution Study within a Phantom Torso after Irradiation with a Simulated Solar Particle Event at NSRL

The adequate knowledge of the radiation environment and the doses incurred during a space mission is essential for estimating an astronaut's health risk. The space radiation environment is complex and variable, and exposures inside the spacecraft and the astronaut's body are compounded by the interactions of the primary particles with the atoms of the structural materials and with the body itself Astronauts' radiation exposures are measured by means of personal dosimetry, but there remains substantial uncertainty associated with the computational extrapolation of skin dose to organ dose, which can lead to over- or underestimation of the health risk. Comparisons of models to data showed that the astronaut's Effective dose (E) can be predicted to within about a +10% accuracy using space radiation transport models for galactic cosmic rays (GCR) and trapped radiation behind shielding. However for solar particle event (SPE) with steep energy spectra and for extra-vehicular activities on the surface of the moon where only tissue shielding is present, transport models predict that there are large differences in model assumptions in projecting organ doses. Therefore experimental verification of SPE induced organ doses may be crucial for the design of lunar missions. In the research experiment "Depth dose distribution study within a phantom torso" at the NASA Space Radiation Laboratory (NSRL) at BNL, Brookhaven, USA the large 1972 SPE spectrum was simulated using seven different proton energies from 50 up to 450 MeV. A phantom torso constructed of natural bones and realistic distributions of human tissue equivalent materials, which is comparable to the torso of the MATROSHKA phantom currently on the ISS, was equipped with a comprehensive set of thermoluminescence detectors and human cells. The detectors are applied to assess the depth dose distribution and radiation transport codes (e.g. GEANT4) are used to assess the radiation field and interactions of the radiation field with the phantom torso. Lymphocyte cells are strategically embedded at selected locations at the skin and internal organs and are processed after irradiation to assess the effects of shielding on the yield of chromosome damage. The initial focus of the present experiment is to correlate biological results with physical dosimetry measurements in the phantom torso. Further on, the results of the passive dosimetry within the anthropomorphic phantoms represent the best tool to generate reliable data to benchmark computational radiation transport models in a radiation field of interest. The presentation will give first results of the physical dose distribution, the comparison with GEANT4 computer simulations based on a Voxel model of the phantom, and a comparison with the data from the chromosome aberration study.

Berger, Thomas↗
NASA NTRS2004

Requirements for Simulating Space Radiation With Particle Accelerators

Interplanetary space radiation consists of fully ionized nuclei of atomic elements with high energy for which only the few lowest energy ions can be stopped in shielding materials. The health risk from exposure to these ions and their secondary radiations generated in the materials of spacecraft and planetary surface enclosures is a major limiting factor in the management of space radiation risk. Accurate risk prediction depends on a knowledge of basic radiobiological mechanisms and how they are modified in the living tissues of a whole organism. To a large extent, this knowledge is not currently available. It is best developed at ground-based laboratories, using particle accelerator beams to simulate the components of space radiation. Different particles, in different energy regions, are required to study different biological effects, including beams of argon and iron nuclei in the energy range 600 to several thousand MeV/nucleon and carbon beams in the energy range of approximately 100 MeV/nucleon to approximately 1000 MeV/nucleon. Three facilities, one each in the United States, in Germany and in Japan, currently have the partial capability to satisfy these constraints. A facility has been proposed using the Brookhaven National Laboratory Booster Synchrotron in the United States; in conjunction with other on-site accelerators, it will be able to provide the full range of heavy ion beams and energies required. International cooperation in the use of these facilities is essential to the development of a safe international space program.

Schimmerling, W.↗
NASA NTRS2011

Radio-Adaptive Responses of Mouse Myocardiocytes

One of the most significant occupational hazards to an astronaut is the frequent exposure to radiation. Commonly associated with increased risk for cancer related morbidity and mortality, radiation is also known to increase the risk for cardiovascular related disorders including: pericarditis, hypertension, and heart failure. It is believed that these radiation-induced disorders are a result of abnormal tissue remodeling. It is unknown whether radiation exposure promotes remodeling through fibrotic changes alone or in combination with programmed cell death. Furthermore, it is not known whether it is possible to mitigate the hazardous effects of radiation exposure. As such, we assessed the expression and mechanisms of radiation-induced tissue remodeling and potential radio-adaptive responses of p53-mediated apoptosis and fibrosis pathways along with markers for oxidative stress and inflammation in mice myocardium. 7 week old, male, C57Bl/6 mice were exposed to 6Gy (H) or 5cGy followed 24hr later with 6Gy (LH) Cs-137 gamma radiation. Mice were sacrificed and their hearts extirpated 4, 24, or 72hr after final irradiation. Real Time - Polymerase Chain Reaction was used to evaluate target genes. Pro-apoptotic genes Bad and Bax, pro-cell survival genes Bcl2 and Bcl2l2, fibrosis gene Vegfa, and oxidative stress genes Sod2 and GPx4 showed a reduced fold regulation change (Bad,-6.18; Bax,-6.94; Bcl2,-5.09; Bcl2l2,-4.03; Vegfa, -11.84; Sod2,-5.97; GPx4*,-28.72; * = Bonferroni adjusted p-value . 0.003) 4hr after H, but not after 4hr LH when compared to control. Other p53-mediated apoptosis genes Casp3, Casp9, Trp53, and Myc exhibited down-regulation but did not achieve a notable level of significance 4hr after H. 24hr after H, genetic down-regulation was no longer present compared to 24hr control. These data suggest a general reduction in genetic expression 4hrs after a high dose of gamma radiation. However, pre-exposure to 5cGy gamma radiation appears to facilitate a radio-adaptive response that mitigates the reduction in genetic expression associated with single high-dose gamma radiation exposure. This radio-adaptive response may serve as a potential countermeasure to radiation-induced myocardial remodeling and preserve the cardiovascular health of astronauts; thus, reducing the risks of human space exploration.

Seawright, John W.↗
NASA NTRS2011

Induction of a Radio-Adaptive Response by Low-dose Gamma Irradiation in Mouse Cardiomyocytes

One of the most significant occupational hazards to an astronaut is the frequent exposure to radiation. Commonly associated with increased risk for cancer related morbidity and mortality, radiation is also known to increase the risk for cardiovascular related disorders including: pericarditis, hypertension, and heart failure. It is believed that these radiation-induced disorders are a result of abnormal tissue remodeling. It is unknown whether radiation exposure promotes remodeling through fibrotic changes alone or in combination with programmed cell death. Furthermore, it is not known whether it is possible to mitigate the hazardous effects of radiation exposure. As such, we assessed the expression and mechanisms of radiation-induced tissue remodeling and potential radio-adaptive responses of p53-mediated apoptosis and fibrosis pathways along with markers for oxidative stress and inflammation in mice myocardium. 7 week old, male, C57Bl/6 mice were exposed to 6Gy (H) or 5cGy followed 24hr later with 6Gy (LH) 137Cs gamma radiation. Mice were sacrificed and their hearts extirpated 4, 24, or 72hr after final irradiation. Real Time - Polymerase Chain Reaction was used to evaluate target genes. Apoptotic genes Bad and Bax, pro-cell survival genes Bcl2 and Bcl2l2, fibrosis gene Vegfa, and oxidative stress genes Sod2 and GPx4 showed a reduced fold regulation change (Bad,-6.18; Bax,-6.94; Bcl2,-5.09; Bcl2l2,-4.03; Vegfa, -11.84; Sod2,-5.97; GPx4*,-28.72; * = Bonferroni adjusted p-value < or = 0.003) 4hr after H, but not after 4hr LH compared to control. Other p53-mediated apoptosis genes Casp3, Casp9, Trp53, and Myc exhibited down-regulation but did not achieve a notable level of significance 4hr after H. 24hr after H, genetic down-regulation was no longer present compared to 24hr control. These data suggest a general reduction in genetic expression 4hrs after a high dose of gamma radiation. However, pre-exposure to 5cGy gamma radiation appears to facilitate a radio-adaptive response that mitigates the reduction in genetic expression associated with single high-dose gamma radiation exposure. This radio-adaptive response may serve as a potential countermeasure to radiation-induced myocardial remodeling and preserve the cardiovascular health of astronauts; thus, reducing the risks of human space exploration.

Westby, Christian M.↗
NASA NTRSDate not supplied

Track Structure Components: Characterizing Energy Deposition from Direct and Peripheral Hits in Spherical Cells

Energy deposition by ionizing radiation in micrometric targets (microdosimetry), representative of cells, is very important to understand the effect of radiation and the cellular and biological response. Microdosimetry is used to estimate quality factors for risk assessment in radiation protection and quantify Relative Biological Effectiveness (RBE) for treatment planning of hadron radiation therapy. Radiation physics has shown that ionizing radiation deposit their energy in a complex manner, the track structure. Consequently, energy deposited in a target is a function of factors like the ion type, its energy and the irradiated volume.

Ianik Plante↗