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All sourcesNASA NTRSDOE OSTI
NASA NTRS2011

A Hypothesis on Biological Protection from Space Radiation Through the Use of New Therapeutic Gases

Radiation exposure to astronauts could be a significant obstacle for long duration manned space exploration because of current uncertainties regarding the extent of biological effects. Furthermore, concepts for protective shielding also pose a technically challenging issue due to the nature of cosmic radiation and current mass and power constraints with modern exploration technology. The concern regarding exposure to cosmic radiation is the biological damage it induces. As damage is associated with increased oxidative stress, it is important and would be enabling to mitigate and/or prevent oxidative stress prior to the development of clinical symptoms and disease. This paper hypothesizes a "systems biology" approach in which a combination of chemical and biological mitigation techniques are used conjunctively. It proposes using new, therapeutic, medical gases as both chemical radioprotectors for radical scavenging and biological signaling molecules for management of the body s response to exposure. From reviewing radiochemistry of water, biological effects of CO, H2, NO, and H2S gas, and mechanisms of radiation biology, it is concluded that this approach may have great therapeutic potential for radiation exposure. Furthermore, it also appears to have similar potential for curtailing the pathogenesis of other diseases in which oxidative stress has been implicated including, cardiovascular disease, cancer, chronic inflammatory disease, hypertension, ischemia/reperfusion injury, acute respiratory distress syndrome, parkinson s and alzheimer s disease, cataracts, and aging

Schoenfeld, Michael P.↗
NASA NTRS2012

A Hypothesis on Biological Protection from Space Radiation Through the Use of New Therapeutic Gases as Medical Counter Measures

Radiation exposure to astronauts could be a significant obstacle for long duration manned space exploration because of current uncertainties regarding the extent of biological effects. Furthermore, concepts for protective shielding also pose a technically challenging issue due to the nature of cosmic radiation and current mass and power constraints with modern exploration technology. The concern regarding exposure to cosmic radiation is the biological damage it induces. As damage is associated with increased oxidative stress, it is important and would be enabling to mitigate and/or prevent oxidative stress prior to the development of clinical symptoms and disease. This paper hypothesizes a "systems biology" approach in which a combination of chemical and biological mitigation techniques are used conjunctively. It proposes using new, therapeutic, medical gases as both chemical radioprotectors for radical scavenging and biological signaling molecules for management of the body s response to exposure. From reviewing radiochemistry of water, biological effects of CO, H2, NO, and H2S gas, and mechanisms of radiation biology, it is concluded that this approach may have great therapeutic potential for radiation exposure. Furthermore, it also appears to have similar potential for curtailing the pathogenesis of other diseases in which oxidative stress has been implicated including cardiovascular disease, cancer, chronic inflammatory disease, hypertension, ischemia/reperfusion injury, acute respiratory distress syndrome, Parkinson s and Alzheimer s disease, cataracts, and aging.

Schoenfeld, Michael P.↗
NASA NTRS2011

A Hypothesis on Biological Protection from Space Radiation Through the Use of New Therapeutic Gases

Radiation exposure to astronauts could be a significant obstacle for long duration manned space exploration because of current uncertainties regarding the extent of biological effects. Furthermore, concepts for protective shielding also pose a technically challenging issue due to the nature of cosmic radiation and current mass and power constraints with modern exploration technology. The concern regarding exposure to cosmic radiation is the biological damage it induces. As damage is associated with increased oxidative stress, it is important and would be enabling to mitigate and/or prevent oxidative stress prior to the development of clinical symptoms and disease. This paper hypothesizes a "systems biology" approach in which a combination of chemical and biological mitigation techniques are used conjunctively. It proposes using new, therapeutic, medical gases as both chemical radioprotectors for radical scavenging and biological signaling molecules for management of the body s response to exposure. From reviewing radiochemistry of water, biological effects of CO, H2, NO, and H2S gas, and mechanisms of radiation biology, it is concluded that this approach may have great therapeutic potential for radiation exposure. Furthermore, it also appears to have similar potential for curtailing the pathogenesis of other diseases in which oxidative stress has been implicated including cardiovascular disease, cancer, chronic inflammatory disease, hypertension, ischemia/reperfusion injury, acute respiratory distress syndrome, Parkinson s and Alzheimer s disease, cataracts, and aging.

Schoenfeld, Michael P.↗
NASA NTRS2001

Improved Spacecraft Materials for Radiation Protection

Methods by which radiation shielding is optimized need to be developed and materials of improved shielding characteristics identified and validated. The galactic cosmic rays (GCR) are very penetrating and the energy absorbed by the astronaut behind the shield is nearly independent of shield composition and even the shield thickness. However, the mix of particles in the transmitted beam changes rapidly with shield material composition and thickness. This results in part from the breakup of the high-energy heavy ions of the GCR which make contributions to biological effects out of proportion to their deposited energy. So the mixture of particles in the radiation field changes with shielding and the control of risk contributions from dominant particle types is critical to reducing the hazard to the astronaut. The risk of biological injury for a given particle type depends on the type of biological effect and is specific to cell or tissue type. Thus, one is faced with choosing materials which may protect a given tissue against a given effect but leave unchanged or even increase the risk of other effects in the same tissue or increase the risks to other adjacent tissues of a different type in the same individual. The optimization of shield composition will then be tied to a specific tissue and risk to that tissue. Such peculiarities arise from the complicated mixture of particles, the nature of their biological response, and the details of their interaction with material constituents. Aside from the understanding of the biological response to specific components, one also needs an accurate understanding of the radiation emerging from the shield material. This latter subject has been a principal element of this project. In the past ten years our understanding of space radiation interactions with materials has changed radically, with a large impact on shield design. For example, the NCRP estimated that only 2 g/sq cm. of aluminum would be required to meet the annual 500 mSv limit for the exposure of the blood forming organs (this limit is strictly for LEO but can be used as a guideline for the Mars mission analysis). The current estimates require aluminum shield thicknesses above 50 g/sq cm., which is impractical. In such a heavily shielded vehicle, the neutrons produced throughout the vehicle also contribute significantly to the exposure and this demands greater care in describing the angular dependence of secondary particle production processes. As such the continued testing of databases and transport procedures in laboratory and spaceflight experiments has continued. This has been the focus of much of the last year's activity and has resulted in improved neutron prediction capability. These new methods have also improved our understanding of the surface environment of Mars. The Mars 2003 NRA HEDS related surface science requirements were driven by the need to validate predictions on the upward flux of neutrons produced in the Martian regolith and bedrock made by the codes developed under this project. The codes used in the surface environment definition are also being used to look at in situ resources for the development of construction material for Martian surface facilities. For example, synthesis of polyimides and polyethylene as binders of regolith for developing basic structural elements has been studied and targets built for accelerator beam testing of radiation shielding properties. Preliminary mechanical tests have also been promising. Improved spacecraft materials have been identified (using the criteria reported by this project at the last conference) as potentially important for future shielding materials. These are liquid hydrogen, hydrogenated nanofibers, liquid methane, LiH, Polyethylene, Polysulfone, and Polyetherimide (in order of decreasing shield performance). Some of the materials are multifunctional and are required for other onboard systems. We are currently preparing software for trade studies with these materials relative to the Mars Reference Mission as required in the project's final year.

Wilson, John W.↗
NASA NTRS2010

Monte-Carlo Simulation of Heavy Ion Track Structure Calculation of Local Dose and 3D Time Evolution of Radiolytic Species

Heavy ions have gained considerable importance in radiotherapy due to their advantageous dose distribution profile and high Relative Biological Effectiveness (RBE). Heavy ions are difficult to produce on Earth, but they are present in space and it is impossible at this moment to completely shield astronauts from them. The risk of these radiations is poorly understood, which is a concern for a 3-years Mars mission. The effects of radiation are mainly due to DNA damage such as DNA double-strand breaks (DSBs), although non-targeted effects are also very important. DNA can be damaged by the direct interaction of radiation and by reactions with chemical species produced by the radiolysis of water. The energy deposition is of crucial importance to understand biological effects of radiation. Therefore, much effort has been done recently to improve models of radiation tracks.

Plante, Ianik↗
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 NTRS1995

Space and radiation protection: scientific requirements for space research

Ionizing radiation poses a significant risk to humans living and working in space. The major sources of radiation are solar disturbances and galactic cosmic rays. The components of this radiation are energetic charged particles, protons, as well as fully ionized nuclei of all elements. The biological effects of these particles cannot be extrapolated in a straightforward manner from available data on x-rays and gamma-rays. A radiation protection program that meets the needs of spacefaring nations must have a solid scientific basis, capable not only of predicting biological effects, but also of making reliable estimates of the uncertainty in these predictions. A strategy leading to such predictions is proposed, and scientific requirements arising from this strategy are discussed.

NASA Discipline Radiation Health↗
NASA NTRS2005

Inter- and Intra-Chromosomal Aberrations in Human Cells Exposed in vitro to Space-like Radiations

Energetic heavy ions pose a great health risk to astronauts in extended ISS and future exploration missions. High-LET heavy ions are particularly effective in causing various biological effects, including cell inactivation, genetic mutations and cancer induction. Most of these biological endpoints are closely related to chromosomal damage, which can be utilized as a biomarker for radiation insults. Previously, we had studied chromosome aberrations in human lymphocytes and fibroblasts induced by both low- and high-LET radiation using FISH and multicolor fluorescence in situ hybridization (mFISH) techniques. In this study, we exposed human cells in vitro to gamma rays and energetic particles of varying types and energies and dose rates, and analyzed chromosomal damages using the multicolor banding in situ hybridization (mBAND) procedure. Confluent human epithelial cells and lymphocytes were exposed to energetic heavy ions at NASA Space Radiation Laboratory (NSRL) at the Brookhaven National Laboratory (Upton, NY) or Cs-137 gamma radiation source at the Baylor College (Houston, TX). After colcemid and Calyculin A treatment, cells were fixed and painted with XCyte3 mBAND kit (MetaSystems) and chromosome aberrations were analyzed with mBAND analysis system (MetaSystems). With this technique, individually painted chromosomal bands on one chromosome allowed the identification of interchromosomal aberrations (translocation to unpainted chromosomes) and intrachromosomal aberrations (inversions and deletions within a single painted chromosome). The possible relationship between the frequency of inter- and intra-chromosomal exchanges and the track structure of radiation is discussed. The work was supported by the NASA Space Radiation Health Program.

Hada, Megumi↗
NASA NTRS2006

Inter- and Intra-Chromosomal Aberrations in Human Cells Exposed in vitro to High and Low LET Radiations

Energetic heavy ions pose a health risk to astronauts in extended ISS and future Mars missions. High-LET heavy ions are particularly effective in causing various biological effects including cell inactivation, genetic mutations and cancer induction. Most of these biological endpoints are closely related to chromosomal damage, which can be utilized as a biomarker for radiation insults. Previously, we had studied chromosome aberrations in human lymphocytes and fibroblasts induced by both low- and high-LET radiation using FISH and multicolor fluorescence in situ hybridization (mFISH) techniques. In this study, we exposed human epithelial cells in vitro to gamma rays and energetic particles of varying types and energies and dose rates, and analyzed chromosomal damages using the multicolor banding in situ hybridization (mBAND) procedure. Confluent human epithelial cells (CH184B5F5/M10) were exposed to energetic heavy ions at NASA Space Radiation Laboratory (NSRL) at the Brookhaven National Laboratory, high energy neutron at the Los Alamos Nuclear Science Center (LANSCE) or Cs-137-gamma radiation source at the University of Texas, MD Anderson Cancer Center. After colcemid and Calyculin A treatment, cells were fixed and painted with XCyte3 mBAND kit (MetaSystems) and chromosome aberrations were analyzed with mBAND analysis system (MetaSystems). With this technique, individually painted chromosomal bands on one chromosome allowed the identification of interchromosomal aberrations (translocation to unpainted chromosomes) and intrachromosomal aberrations (inversions and deletions within a single painted chromosome). The results of the mBAND study showed a higher ratio of inversion involved with interchromosomal exchange in heavy ions compared to -ray irradiation. Analysis of chromosome aberrations using mBAND has the potential to provide useful information on human cell response to space-like radiation.

Hada, M.↗
NASA NTRS2007

Biomarker for Space Radiation Risk: Painting Analysis of Chromosome Aberrations Induced by Energetic Heavy Ions in Human Cells

Energetic heavy ions pose a great health risk to astronauts in extended ISS and future Lunar and Mars missions. High-LET heavy ions are particularly effective in causing various biological effects, including cell inactivation, genetic mutations, cataracts and cancer induction. Most of these biological endpoints are closely related to chromosomal damage, which can be utilized as a biomarker for radiation insults. Over the years, we have studied chromosomal damage in human fibroblast, epithelia and lymphocyte cells exposed in vitro to energetic charged particles generated at several accelerator facilities in the world. We have also studied chromosome aberrations in astronaut s peripheral blood lymphocytes before and after space flight. Various fluorescence in situ hybridization painting techniques have been used to identify from only the telomere region of the chromosome to every chromosome in a human cell. We will summarize the results of the investigations, and discuss the unique radiation signatures and biomarkers for space radiation exposure.

Hada, Megumi↗
NASA NTRS2008

M-BAND Analysis of Chromosome Aberration Induced by Fe-Ions in Human Epithelial Cells Cultured in 3-Dimensional Matrices

Energetic heavy ions pose a great health risk to astronauts in extended ISS and future lunar and Mars missions. High-LET heavy ions are particularly effective in causing various biological effects, including cell inactivation, genetic mutations, cataracts and cancer induction. Most of these biological endpoints are closely related to chromosomal damage, which can be utilized as a biomarker for radiation insults. Previously, we had studied low- and high-LET radiation-induced chromosome aberrations in human epithelial cells cultured in 2-dimension (2D) using the multicolor banding fluorescence in situ hybridization (mBAND) technique. However, it has been realized that the biological response to radiation insult in a 2D cellular environment in vitro can differ significantly from the response in 3-dimension (3D) or at the actual tissue level. In this study, we cultured human epithelial cells in 3D to provide a more suitable model for human tissue. Human mammary epithelia cells (CH184B5F5/M10) were grown in Matrigel to form 3D structures, and exposed to Fe-ions at NASA Space Radiation Laboratory (NSRL) at the Brookhaven National Laboratory or 137Cs-gamma radiation source at the University of Texas MD Anderson Cancer Center. After exposure, cells were allowed to repair for 16hr before dissociation and subcultued at low density in 2D. G2 and metaphase chromosomes in the first cell cycle were collected using a chemical-induced premature chromosome condensation (PCC) technique, and chromosome aberrations were analyzed using mBAND technique. With this technique, individually painted chromosomal bands on one chromosome allowed the identification of interchromosomal aberrations (translocation to unpainted chromosomes) and intrachromosomal aberrations (inversions and deletions within a single painted chromosome). Our data indicate a significant difference of the chromosome aberration yield between 2D and 3D cell cultures for gamma exposures, but not for Fe ion exposures. Therefore, the RBE for chromosome aberrations obtained in a 2D model may not represent accurately the RBE for tissues.

Hada, M.↗
NASA NTRSDate not supplied

AMMPER: a user-friendly agent-based model that recapitulates simple metabolic responses of yeast to deep-space radiation

For humans venturing to deep space, radiation exposure poses a major health risk. Fundamental research into the biological effects of space radiation are essential for enabling exploration, and the first experimental organisms we send to deep space will be microbial. Yet there are many ways in which microorganisms are likely to experience the effects of high-energy particle radiation (such as Galactic Cosmic Rays) differently from multicellular animals, partly due to the simple fact that microbes are small and unicellular-- less likely to get hit in the first place, and less likely to communicate damage between cells. Computational modeling can aid in designing experiments and predicting the biological effects of radiation, but thus far particle radiation models have not focused on microbes. Here we present the latest developments in AMMPER, the Agent-based Model for Microbial Populations Exposed to Radiation. Originally written in 2021, AMMPER is a Python-based model that incorporates radiation track data from NASA's RITRACKS software and simulates the growth, damage, and death of yeast cells in 3D. It is now freely available as an open-source package on NASA's GitHub repository. Recent improvements include the ability to simulate the dynamics of alamarBlue, a color-changing redox dye commonly used to track metabolic activity in microbial spaceflight experiments. We demonstrate that a simple blue-pink-clear transition model is able to recapitulate key features observed in empirical data from ground studies. AMMPER also includes a new graphical user interface and introductory tutorial to facilitate ease of use by a wider audience. AMMPER can help us to understand how spatially heterogeneous particle radiation damage at the single-cell level can translate to growth differences at the population level, ultimately allowing us to better interpret experiments using microbes as model organisms and how well their results apply to humans.

yeast↗
NASA NTRS2018

Track Structure and the Quality Factor for Space Radiation Cancer Risk

A major risk from exposure to space radiation is the induction of cancer and it is from estimates of this risk that the maximum career flight times of NASA space crew members are restricted by a permissible exposure limit. For the purpose of demonstrating compliance with the career limit, NASA has developed a cancer risk projection model for exposure-induced fatal cancer, in which the formulation and numerical values of the quality factor (QFNASA) are substantially different from those of the quality factor (Q) or radiation weighting factor (wR) routinely applied for radiation protection on earth. The quality factor is used to account for the increased effectiveness of radiations of high linear energy transfer (LET), compared to the effectiveness of low-LET γ-rays derived from epidemiological studies of the atomic-bomb survivors. The need for a special approach for space radiation is dictated by the special characteristics of the charged particles from solar radiation and especially the charged particles of high energy and charge (HZE) in galactic cosmic rays (GCR). This article considers aspects of radiation track structure in relation to the relative biological effectiveness (RBE) of HZE particles and the quality factor used for space radiation. The NASA quality factor (QFNASA) is composed of two terms, which can be interpreted as broadly representing the low- and the high-ionization-density components of the HZE particle tracks. These are discussed in turn as they relate to available experimental evidence on the biological effectiveness of such components. Also briefly described are subsequent published proposals for a reformulation of the quality factor to relate more directly to the acute γ-ray exposures from the atomic bombs and for further refinement of the parameter values (and their uncertainties) that determine the shape of the quality factor function. Other recent developments are also mentioned.

Mullenax, Carol A.↗
NASA NTRS2020

Predicting Cell Death and Mutation Frequency for a Wide Spectrum of LET by Assuming DNA Break Clustering Inside Repair Domains

Cosmic radiation, which is composed of high charged and energy (HZE) particles, is responsible for cell death and mutation, which may be involved in cancer induction. Mutations are consequences of mis-repaired DNA breaks – especially double-strand breaks (DSBs) – that induce inter- and intra-chromosomal rearrangements (translocations, deletions, inversion). In this study, a computer simulation model is used to investigate the clustering of DSBs in repair domains, previously evidenced by our group in human breast cells [1]. This model is calibrated with experimental data measuring persistent 53BP1 radiation-induced foci (RIF) and is used to explain the high relative biological effectiveness (RBE) of HZE for both cell death and DNA mutation frequencies. We first validate our DSB cluster model using a new track structure model deployed on a simple geometrical configuration for repair domains in the nucleus; then we extend the scope from cell death to mutation induction. This work suggests that mechanism based on DSB repair process can explain several biological effects induced by HZE particles on different type of living cells

Plante, Ianik↗
NASA NTRSDate not supplied

Predicting cell death and mutation frequency for a wide spectrum of LET and across cell lines from DNA break clustering inside repair domains

Cosmic radiation, which is composed of high charged and energy (HZE) particles, is responsible for cell death and mutation, which may be involved in cancer induction. Mutations are consequences of mis-repaired DNA breaks – especially double-strand breaks (DSBs) – that induce inter- and intra-chromosomal rearrangements (translocations, deletions, inversion). In this study, a computer simulation model is used to investigate the clustering of DSBs in repair domains, previously evidenced by our group in human breast cells. This model is calibrated with experimental data measuring persistent 53BP1 radiation-induced foci (RIF) and is used to explain the high relative biological effectiveness (RBE) of HZE for both cell death and DNA mutation frequencies. We first validate our DSB cluster model using a new track structure model deployed on a simple geometrical configuration for repair domains in the nucleus; then we extend the scope from cell death to mutation induction. This work suggests that mechanism based on DSB repair process can explain several biological effects induced by HZE particles on different type of living cells.

Ianik Plante↗
NASA NTRS1992

Microbeam studies of the sensitivity of structures within living cells

Determining the biological effects of low doses of radiation with high linear energy transfer (LET) is complicated by the stochastic nature of charged-particle interactions. Populations of cells exposed to very low radiation doses contain a few cells which have been hit by a charged particle, while the majority of the cells receive no radiation damage. At somewhat higher doses, a few cells receive two or more events. Because the effects of damage produced by separate events can interact in the cell, we have had to make assumptions about the nature of these interactions in order to interpret the results of the experiments. Many of those assumptions can be tested if we can be sure of the number of charged-particle events which occur in individual cells, and correlate this number with the biological effect. We have developed a special irradiation facility at Pacific Northwest Laboratory (PNL) to control the actual number of charged particle tracks that pass through cell nuclei. The beam from a 2 MeV tandem accelerator is collimated to approximately 5 microns. Cells, grown in special dishes with 1.5 microns thick plastic bottoms, are positioned so that the desired portion of the cell aligns with the collimator. A shutter in the beam line is opened and closed after the desired number of particle tracks has been counted. This approach can be used to investigate the effects of the interaction between irradiated and unirradiated cells in an organized system, as well as to study the effects of spatial and temporal distribution of radiation damage within single cells.(ABSTRACT TRUNCATED AT 250 WORDS).

Non-NASA Center↗