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NASA NTRS2015

Evidence Report: Risk of Cardiovascular Disease and Other Degenerative Tissue Effects from Radiation Exposure

Occupational radiation exposure from the space environment may result in non-cancer or non-CNS degenerative tissue diseases, such as cardiovascular disease, cataracts, and respiratory or digestive diseases. However, the magnitude of influence and mechanisms of action of radiation leading to these diseases are not well characterized. Radiation and synergistic effects of radiation cause DNA damage, persistent oxidative stress, chronic inflammation, and accelerated tissue aging and degeneration, which may lead to acute or chronic disease of susceptible organ tissues. In particular, cardiovascular pathologies such as atherosclerosis are of major concern following gamma-ray exposure. This provides evidence for possible degenerative tissue effects following exposures to ionizing radiation in the form of the GCR or SPEs expected during long-duration spaceflight. However, the existence of low dose thresholds and dose-rate and radiation quality effects, as well as mechanisms and major risk pathways, are not well-characterized. Degenerative disease risks are difficult to assess because multiple factors, including radiation, are believed to play a role in the etiology of the diseases. As additional evidence is pointing to lower, space-relevant thresholds for these degenerative effects, particularly for cardiovascular disease, additional research with cell and animal studies is required to quantify the magnitude of this risk, understand mechanisms, and determine if additional protection strategies are required.The NASA PEL (Permissive Exposure Limit)s for cataract and cardiovascular risks are based on existing human epidemiology data. Although animal and clinical astronaut data show a significant increase in cataracts following exposure and a reassessment of atomic bomb (A-bomb) data suggests an increase in cardiovascular disease from radiation exposure, additional research is required to fully understand and quantify these adverse outcomes at lower doses (less than 0.5 gray (SI unit for ionizing radiation dosage, i.e. one joule of radiation energy per one kilogram of matter)) to facilitate risk prediction. This risk has considerable uncertainty associated with it, and no acceptable model for projecting degenerative tissue risk is currently available. In particular, risk factors such as obesity, alcohol, and tobacco use can act as confounding factors that contribute to the large uncertainties. The PELs could be violated under certain scenarios, including following a large SPE (solar proton event) or long-term GCR (galactic cosmic ray) exposure. Specifically, for a Mars mission, the accumulated dose is sufficiently high that epidemiology data and preliminary risk estimates suggest a significant risk for cardiovascular disease. Ongoing research in this area is intended to provide the evidence base for accurate risk quantification to determine criticality for extended duration missions. Data specific to the space radiation environment must be compiled to quantify the magnitude of this risk to decrease the uncertainty in current PELs and to determine if additional protection strategies are required. New research results could lead to estimates of cumulative radiation risk from CNS and degenerative tissue diseases that, when combined with the cancer risk, may have major negative impacts on mission design, costs, schedule, and crew selection. The current report amends an earlier report (Human Research Program Requirements Document, HRP-47052, Rev. C, dated Jan 2009) in order to provide an update of evidence since 2009.

Patel, Zarana↗

NASA NTRS1991

The NASA Radiation Health Program

The Space Radiation Health Program (SRHP) is defined in terms of motivation and methodology with specific reference given to the impacts of HZE particles and solar energetic particles. The biological hazards are mentioned that can be associated with the two particle types and ionizing radiation in general. The lack of data on the impact of such radiation and effective shielding countermeasures is identified as the primary motivation for worst-case assumptions. However, the resulting shielding designs can potentially overestimate the thickness by a factor of 10 and add unnecessarily to vehicle take-off mass. A space-based validation system is proposed to complement ground-based investigations of the effects of ionizing radiation in interplanetary space. The Lifesat satellite is proposed as a part of the SRHP effort to determine the requirements for protection and future shielding specifications.

Schimmerling, Walter↗

NASA NTRS1992

Engineering design constraints of the lunar surface environment

Living and working on the lunar surface will be difficult. Design of habitats, machines, tools, and operational scenarios in order to allow maximum flexibility in human activity will require paying attention to certain constraints imposed by conditions at the surface and the characteristics of lunar material. Primary design drivers for habitat, crew health and safety, and crew equipment are: ionizing radiation, the meteoroid flux, and the thermal environment. Secondary constraints for engineering derive from: the physical and chemical properties of lunar surface materials, rock distributions and regolith thicknesses, topography, electromagnetic properties, and seismicity. Protection from ionizing radiation is essential for crew health and safety. The total dose acquired by a crew member will be the sum of the dose acquired during EVA time (when shielding will be least) plus the dose acquired during time spent in the habitat (when shielding will be maximum). Minimizing the dose acquired in the habitat extends the time allowable for EVA's before a dose limit is reached. Habitat shielding is enabling, and higher precision in predicting secondary fluxes produced in shielding material would be desirable. Means for minimizing dose during a solar flare event while on extended EVA will be essential. Early warning of the onset of flare activity (at least a half-hour is feasible) will dictate the time available to take mitigating steps. Warning capability affects design of rovers (or rover tools) and site layout. Uncertainty in solar flare timing is a design constraint that points to the need for quickly accessible or constructible safe havens.

Morrison, D. A.↗

NASA NTRS2001

Radiation Transmission Properties of In-Situ Materials

The development of a permanent human presence in space is a key element of NASA's strategic plan for the Human Exploration and Development of Space (HEDS). The habitation of the International Space Station (ISS) is one near-term HEDS objective; the exploration and settlement of the moon and Mars are long-term goals of that plan. Achieving these goals requires maintaining the health and safety of personnel involved in such space operations at a high level, while at the same time reducing the cost of those operations to a reasonable level. Among the limiting factors to prolonged human space operations are the health risks from exposure to the space ionizing radiation environment. In order to keep the risk of radiation induced cancer at acceptable levels, it is necessary to provide adequate shielding from the ionizing radiation environment. The research presented here is theoretical and ground-based experimental study of the neutron production from interactions of GCR-like particles in various shielding components. An emphasis is placed here on research that will aid in the development of in-situ resource utilization. The primary goal of the program is to develop an accurate neutron-production model that is relevant to the NASA HEDS program of designing technologies that will be used in the development of effective shielding countermeasures. A secondary goal of the program is the development of an experimental data base of neutron production cross sections and thick-target yields which will aid model development.

Heilbronn, L.↗

NASA NTRS1999

Overview of Photonic Materials for Application in Space Environments

Future space systems will he based on components evolving from the development and refinement of new and existing photonic materials. Optically based sensors, inertial guidance, tracking systems, communications, diagnostics, imaging and high speed optical processing are but a few of the applications expected to widely utilize photonic materials. The response of these materials to space environment effects (SEE) such as spacecraft charging, orbital debris, atomic oxygen, ultraviolet irradiation, temperature and ionizing radiation will be paramount to ensuring successful space applications. The intent of this paper is to, address the latter two environments via a succinct comparison of the known sensitivities of selected photonic materials to the temperature and ionizing radiation conditions found in space and enhanced space environments Delineation of the known temperature and radiation induced responses in LiNbO3, AlGaN, AlGsAs,TeO2, Si:Ge, and several organic polymers are presented. Photonic materials are realizing rapid transition into applications for many proposed space components and systems including: optical interconnects, optical gyros, waveguide and spatial light modulators, light emitting diodes, lasers, optical fibers and fiber optic amplifiers. Changes to material parameters such as electrooptic coefficients, absorption coefficients, polarization, conductivity, coupling coefficients, diffraction efficiencies, and other pertinent material properties examined for thermo-optic and radiation induced effect. Conclusions and recommendations provide the reader with an understanding of the limitations or attributes of material choices for specific applications.

Taylor, E. W.↗

NASA NTRS2017

Identification of Novel Desiccation-Tolerant S. cerevisiae Strains for Deep Space Biosensors

NASA's BioSentinel mission, a secondary payload that will fly on the Space Launch System's first Exploration Mission (EM-1), utilizes the budding yeast S. cerevisiae to study the biological response to the deep space radiation environment. Yeast samples are desiccated prior to launch to suspend growth and metabolism while the spacecraft travels to its target heliocentric orbit beyond Low Earth Orbit. Each sample is then rehydrated at the desired time points to reactivate the cells. A major risk in this mission is the loss of cell viability that occurs in the recovery period following the desiccation and rehydration process. Cell survival is essential for the detection of the biological response to features in the deep space environment, including ionizing radiation. The aim of this study is to mitigate viable cell loss in future biosensors by identifying mutations and genes that confer tolerance to desiccation stress in rad51, a radiation-sensitive yeast strain. We initiated a screen for desiccation-tolerance after rehydrating cells that were desiccated for three years, and selected various clones exhibiting robust growth. To verify retention of radiation sensitivity in the isolated clones - a crucial feature for a successful biosensor - we exposed them to ionizing radiation. Finally, to elucidate the genetic and molecular bases for observed desiccation-tolerance, we will perform whole-genome sequencing of those rad51 clones that exhibit both robust growth and radiation sensitivity following desiccation. The identification and characterization of desiccation-tolerant strains will allow us to engineer a biological model that will be resilient in face of the challenges of the deep space environment, and will thus ensure the experimental success of future biosensor missions.

S. cerevisiae↗

NASA NTRS2017

Candidate Nutritional Countermeasure to Mitigate Adverse Effects of Spaceflight

Problem statement: During spaceflight, astronauts are subjected to microgravity as well as radiation, both of which have adverse effects on bones, soft tissues and organs, possibly by shared mechanisms. For this reason there is a need to identify broad-spectrum countermeasures to protect multiple tissues from both insults.6.The spaceflight environment poses multiple challenges to homeostasis, including microgravity and ionizing radiation. Together, these factors contribute to cellular stress, and effects include increased generation of reactive oxygen species (ROS), oxidative and DNA damage, cell cycle arrest and cell senescence. We have shown that a purified diet supplemented with dried plum (DP, 25) conferred full protection of cancellous structure from the rapid bone loss caused by exposure to ionizing radiation (Schreurs et al. 2016). Based on these promising results for a new countermeasure to prevent space radiation induced-tissue damage, we will conduct additional studies to advance the potential countermeasure to a higher CRL level. We will test the DP diet for its ability to prevent bone loss caused by simulated microgravity as well as exposure to radiation. This will be achieved by exposing mice to each factor (simulated microgravity and radiation) alone and in combination. We hypothesize that spaceflight conditions lead to oxidative damage and bone loss, and that DP, a dietary additive rich in antioxidant and polyphenolic compounds, is an effective countermeasure for multiple tissues, including bone. To test this hypothesis we will accomplish the following aims: Aim 1 Determine if the antioxidant rich diet DP prevents simulated microgravity-induced bone loss. Aim 2 Determine if DP prevents simulated spaceflight-induced bone loss (microgravity and radiation combined). Aim 3 Determine if DP is effective as a countermeasure for adverse effects of simulated microgravity and radiation on non-skeletal tissues (brain, eye).

Schreurs, Ann-Sofie↗

NASA NTRS2019

GeneLab: A Systems Biology Platform for Omics Analysis

NASA GeneLab is an open-access repository for omics datasets generated by biological experiments conducted in space or experiments relevant to spaceflight (e.g. simulated cosmic radiation, simulated microgravity, bed rest studies). The GeneLab Data Systems (GLDS) version 4.0 will be available on October 1st 2019, and will provide the latest in terms of professional state-of-the-art bioinformatics platform for the space biology and radiation community to upload their data into an omics data commons, to process their data with vetted standard workflows and to compare to existing analyses. Started in 2015 as a repository designed to archive omics data from space experiments, GeneLab has expanded its scope to all ionizing radiation omics experiments conducted on the ground and has put considerable effort in providing carefully characterized radiation metadata on all dataset. GeneLab is also providing processed data derived from the raw data covering a large spectrum of omics (genome, epigenome, transcriptome, epitranscriptome, proteome, metabolome) to help users explore important questions: 1) Which genes or proteins are expressed differently in space for various living organisms? 2) What specific DNA mutations or epigenetic changes happen in space or after exposure to ionizing radiation? and 3) How does genetics affect these responses? Processed data available on GeneLab are derived by standard data analysis workflows vetted by hundreds of scientists who volunteered to join one of the four GeneLab Analysis Working Groups (Animal AWG, Plant AWG, Microbe AWG, Multi-Omics AWG). In this presentation, we will discuss how to bridge the gap between irradiation studies performed on earth and biological experiments conducted in space since the early 1990's. We will discuss how radiation dosimetry was estimated for datasets derived from samples collected during the Space Shuttle era or on the International Space Station. Finally, we will address future strategies regarding dose monitoring in future missions into space, inter-agency efforts to unify data under one umbrella, and knowledge dissemination across the radiation research community and the space biology community.

open-science↗

NASA NTRS1990

Direct simulation Monte Carlo with ionization and radiation

Improvements in the modeling of radiation in low density shock waves with Direct Simulation Monte Carlo (DSMC) are the subject of this study. The physical processes which determine the amount of radiation in a shock wave were investigated and the way in which they were modeled with DSMC was evaluated. Three physical processes were identified for which an improvement in the modeling technique could result in improved radiation predictions. New physical modeling schemes are introduced in this report for the three processes. First a method for determining the electric field and its effect on the flow is introduced. Second, a two step reaction process for electron impact ionization reactions is evaluated. Finally, a new scheme to determine the relaxation collision numbers for excitation of electronic states is proposed. Each new scheme attempts to move the DSMC method toward more accurate physics or more reliance on experimental data. The new schemes are all compared to the current modeling techniques and the differences in the results are evaluated. In all cases the results agree with the available data as well as, or better than the results from earlier schemes.

Carlson, Ann B.↗

NASA NTRSDate not supplied

Planetary Protection at Marshall Space Flight Center

Introduction: NASA Marshall Space Flight Center (MSFC) is historically known for its role in propulsion. While this is still the mainstay of MSFC’s expertise, many unique capabilities exist at MSFC which pertain to Planetary Protection (PP), including 1) identifying PP threats, and 2) developing novel methods to neutralize those threats. Furthermore, because these capabilities exist among diverse groups at MSFC, this work promotes collaboration both within and outside MSFC to expand and develop PP studies related to a full spectrum of NASA research, design, manufacture, and test interests. This abstract describes the PP research ongoing at MSFC and describes how it contributes to NASA’s overall PP objectives. Microbial Identification in Cleanrooms: One of the greatest threats to successful implementation of PP requirements is recontamination post bioburden reduction. One method to prevent recontamination is to keep the spacecraft in clean environments (i.e. cleanrooms) as much as possible during assembly and integration. However, cleanrooms are not without their own sources of contamination, which is why NASA is interested in monitoring the cleanliness of cleanrooms and characterizing the microbial species present. Such information allows a greater understanding of the resistance of these microbes to cleaning methods, as well as the risk of their contaminating the targeted planetary body of a given mission. MSFC has multiple cleanrooms of various ISO cleanliness levels onsite. We sampled the air and surfaces of three of these rooms, isolated microbes, and then sequenced the 16S rRNA gene or ITS region of the 18S rRNA gene for bacterial and fungal isolates, respectively. This has resulted in a microbial library which currently includes nearly 100 isolates. Microbial Enumeration of Spacecraft Materials: Currently, there are only a couple bioburden reduction methods approved by NASA, and often the harshness of these methods presents additional concerns or risks related to material properties. The goal of this research is to assess the microbial content of solid rocket motor (SRM) materials potentially used for lander missions. This work aims to more accurately define the risk of planetary contamination by providing empirical data associated with commonly used SRM raw materials. In this study, we pulverized nonmetallic SRM materials using a cryogenic grinder, then analyzed the resulting substrate for microbial colony forming units (CFU). We found that many SRM nonmetallic materials do not harbor detectable bioburden, though a range existed depending on the material. The results from this work provide quantitative data to potentially reduce concerns of contamination, while also providing a foundation for follow up studies into additional sterilization methods and molecular identification of contaminating microbes. Space Environmental Effects on Microbial Survival: One potential area of microbial reduction is the space environment. Understanding the survivability of hardy microbes in space-like conditions is a crucial first step in answering how space may reduce bioburden and if it can be relied upon for adherence to PP requirements. This work studied the effects of ultraviolet (UV) and ionizing radiation on survival of Bacillus atrophaeus spores. Microbes were dried on relevant polymeric materials then exposed to space environmental stressors. Coupons were submerged in water, diluted, and plated to determine survival compared with controls. We found that both UV and ionizing radiation were capable of reducing viability by nearly 99%, but there were still survivors, some with changed morphology indicating resistance mechanisms within certain cells. Manufacturing credit: Finally, given the above-mentioned limitations of the NASA-approved bioburden reduction methods, there is interest in understanding if manufacturing processes may provide enough bioburden reduction without additional PP-specific bakeouts. For instance, some material additives may be antimicrobial. Given this, we investigated the effects of several commonly used rubber additives on the growth of B. atrophaeus spores. We found that some of the materials inhibited growth of the spores, possibly supporting the use of these additives on missions with PP constraints. Future work into manufacturing credit for bioburden reduction includes inoculation of green insulation with B. atrophaeus spores, followed by a typical cure. Thermal profiles will be verified for appropriate temperature and durations to meet PP requirements, and cured samples will be analyzed using a cryogenic grinder to determine survivability of spores.

Chelsi D. Cassilly↗

NASA NTRS2013

Time-Dependent Photoionization of Gaseous Nebulae: The Pure Hydrogen Case

We study the problem of time-dependent photoionization of low density gaseous nebulae subjected to sudden changes in the intensity of ionizing radiation. To this end, we write a computer code that solves the full timedependent energy balance, ionization balance, and radiation transfer equations in a self-consistent fashion for a simplified pure hydrogen case. It is shown that changes in the ionizing radiation yield ionizationthermal fronts that propagate through the cloud, but the propagation times and response times to such fronts vary widely and nonlinearly from the illuminated face of the cloud to the ionization front (IF). IFthermal fronts are often supersonic, and in slabs initially in pressure equilibrium such fronts yield large pressure imbalances that are likely to produce important dynamical effects in the cloud. Further, we studied the case of periodic variations in the ionizing flux. It is found that the physical conditions of the plasma have complex behaviors that differ from any steady-state solution. Moreover, even the time average of ionization and temperature is different from any steady-state case. This time average is characterized by overionization and a broader IF with respect to the steady-state solution for a mean value of the radiation flux. Around the time average of physical conditions there is a large dispersion in instantaneous conditions, particularly across the IF, which increases with the period of radiation flux variations. Moreover, the variations in physical conditions are asynchronous along the slab due to the combination of nonlinear propagation times for thermal frontsIFs and equilibration times.

Seyfert↗

NASA NTRS1998

Rejoining and misrejoining of radiation-induced chromatin breaks. IV. Charged particles

We have recently reported the kinetics of chromosome rejoining and exchange formation in human lymphocytes exposed to gamma rays using the techniques of fluorescence in situ hybridization (FISH) and premature chromosome condensation (PCC). In this paper, we have extended previous measurements to cells exposed to charged particles. Our goal was to determine differences in chromatin break rejoining and misrejoining after exposure to low- and high-linear energy transfer (LET) radiation. Cells were irradiated with hydrogen, neon, carbon or iron ions in the LET range 0.3-140 keV/microm and were incubated at 37 degrees C for various times after exposure. Little difference was observed in the yield of early prematurely condensed chromosome breaks for the different ions. The kinetics of break rejoining was exponential for all ions and had similar time constants, but the residual level of unrejoined breaks after prolonged incubation was higher for high-LET radiation. The kinetics of exchange formation was also similar for the different ions, but the yield of chromosome interchanges measured soon after exposure was higher for high-LET particles, suggesting that a higher fraction of DNA breaks are misrejoined quickly. On the other hand, the rate of formation of complete exchanges was slightly lower for densely ionizing radiation. The ratios between the yields of different types of aberrations observed at 10 h postirradiation in prematurely condensed chromosome preparations were dependent on LET. We found significant differences between the yields of aberrations measured in interphase (after repair) and metaphase for densely ionizing radiation. This difference might be caused by prolonged mitotic delay and/or interphase death. Overall, the results point out significant differences between low- and high-LET radiation for the formation of chromosome aberrations.

NASA Center JSC↗

NASA NTRS2002

Radiation Effect on Human Tissue

Predicting the occurrence of human cancer following exposure of an epidemiologic population to any agent causing genetic damage is a difficult task. To an approximation, this is because the uncertainty of uniform exposure to the damaging agent, and the uncertainty of uniform processing of that damage within a complex set of biological variables, degrade the confidence of predicting the delayed expression of cancer as a relatively rare event within clinically normal individuals. This situation begs the need for alternate controlled experimental models that are predictive for the development of human cancer following exposures to agents causing genetic damage. Such models historically have not been of substantial proven value. It is more recently encouraging, however, that developments in molecular and cell biology have led to an expanded knowledge of human carcinogenesis, and of molecular markers associated with that process. It is therefore appropriate to consider new laboratory models developed to accomodate that expanded knowledge in order to assess the cancer risks associated with exposures to genotoxic agents. When ionizing radiation of space is the genotoxic agent, then a series of additional considerations for human cancer risk assessment must also be applied. These include the dose of radiation absorbed by tissue at different locations in the body, the quality of the absorbed radiation, the rate at which absorbed dose accumulates in tissue, the way in which absorbed dose is measured and calculated, and the alterations in incident radiation caused by shielding materials. It is clear that human cancer risk assessment for damage caused by ionizing radiation is a multidisciplinary responsibility, and that within this responsibility no single discipline can hold disproportionate sway if a risk assessment model of radiation-induced human cancer is to be developed that has proven value. Biomolecular and cellular markers from the work reported here are considered for use in assessing human cancer risk related to exposure to space radiation. This potential use must be integrated within the specified multidisciplinary context in order to create a new tool of molecular epidemiology that can hopefully then realistically assess this cancer risk.

Richmond, Robert C.↗

NASA NTRS1994

Chemically anomalous, pre-accretionally irradiated grains in interplanetary dust -- interstellar grains?

Ultrafine-grained matrix is a unique and fundamental building block of chondritic porous (CP) interplanetary dust particles. Most IDPs so far determined to be of cometary origin belong to the CP class. The matrix in CP IDPs is not homogeneous but rather a loose mixture of discrete single crystals (e.g., olivine, pyroxene, Fe sulfides) and polyphase grains. The petrographic diversity observed among the polyphase grains suggest that they were formed under variable physiochemical conditions. One particular class of polyphase grains are a dominant component in cometary IDPs. Although their occurrence is well documented, the terminology used to describe them is confused. They have been called many names. Here they are simply called GEMS (Glass with Embedded Metal and Sulfides). The bulk compositions of GEMS are within a factor of 3 chondritic (solar) for all major elements except C. Quantitative thin-film X-ray (EDS) analyses have shown that GEMS are systematically depleted in Mg and Si, enriched in S, Fe, and Ni, and stoichiometrically enriched in O. Electron energy-loss spectroscopy (EELS) suggests that the excess O is present as hydroxyl (-OH) groups. These same chemical 'anomalies' were observed in solar-wind-irradiated amorphous rims on the surfaces of IDPs, suggesting that the compositions of GEMS reflect prior exposure to ionizing radiation. In order to test this hypothesis, a sample of Allende (CV3) matrix was exposed to proton flux. Radiation-damaged amorphous rims on olivine and pyroxene crystals in the Allende sample were found to be depleted in Mg and Ca, enriched in S, Fe, and Ni, and stoichiometrically enriched in O. Thus, the compositions of GEMS are indeed consistent with exposure to ionizing radiation. This study suggests that chemical as well as isotopic anomalies may be used to identify presolar interstellar grains in primitive meteoritic materials.

Bradley, J. P.↗

NASA NTRS2004

Immunofluorescent Detection of DNA Double Strand Breaks induced by High-LET Radiation

Within cell nuclei, traversing charged heavy ion particles lead to the accumulation of proteins related to DNA lesions and repair along the ion trajectories. Irradiation using a standard geometric setup with the beam path perpendicular to the cell monolayer generates discrete foci of several proteins known to localize at sites of DNA double strand breaks (DSBs). One such molecule is the histone protein H2AX (gamma-H2AX), which gets rapidly phosphorylated in response to ionizing radiation. Here we present data obtained with a modified irradiation geometry characterized by a beam path parallel to a monolayer of human fibroblast cells. This new irradiation geometry leads to the formation of gamma-H2AX aggregates in the shape of streaks stretching over several micrometers in the x/y plane, thus enabling the analysis of the fluorescence distributions along the particle trajectories. Qualitative analysis of these distributions presented insights into the DNA repair kinetics along the primary track structure and visualization of possible chromatin movement. We also present evidence of colocalization of gamma-H2AX with several other proteins in responses to ionizing radiation exposure. Analysis of gamma-H2AX has the potential to provide useful information on human cell responses to high LET radiation after exposure to space-like radiation.

Cucinotta, Francis A.↗

NASA NTRSDate not supplied

BLOOD-BASED MULTI-SCALE MODEL FOR CANCER RISK FROM GCR IN GENETICALLY DIVERSE POPULATIONS

OBJECTIVES AND METHODS This project addresses the challenge of understanding and predicting individual radiation sensitivity by integrating genetics, demographics and biomarker characteristics across species (mice and humans). We hypothesize that ex vivo DNA repair response to GCR components is a central determinant of cancer risk from space radiation and can serve as a biomarker of radiation risk in combination with genetics. Automated image quantification of 53BP1+ radiation-induced foci (RIF) during the first 4-48 h post-irradiation was performed as a function of dose and LET in non-immortalized primary skin fibroblasts derived from 76 mice across 15 strains (5 inbred reference strains and 10 collaborative-cross strains) exposed to X rays (0.1, 1 and 4 Gy), 350 MeV/n 40Ar and 600 MeV/n 56Fe (1.1 and 3 particles/100μm2), as well as in peripheral blood mononuclear cells (PBMCs) from 768 healthy donors (matched ethnicity, 50/50 male/female, 18-70 years old) exposed to gamma rays (0.1 and 1 Gy), 350 MeV/n 28Si, 350 MeV/n 40Ar and 600 MeV/n 56Fe (1.1 and 3 particles/100μm2). QUANTIFICATION OF 53BP1+ FOCI IN VITRO AND ASSOCIATIONS TO IN VIVO RADIATION SUSCEPTIBILITY IN 15 MOUSE STRAINS We reported in vitro repair kinetic and repairable fractions of RIF for the 15 mouse strains and introduced a mathematical model for RIF as a function of time, dose and LET. We noted that the metabolic activity of cells modulates the RIF response, and we introduced the open access tool terRIFic (Tool for Enhanced Results of RIF In Cells, https://radbiolab.shinyapps.io/terrific/) to correct for such bias using confluence level. Notably, at 4h post-irradiation, RIF/Gy decreased with dose or LET: as the dose or LET increases, so does the proximity of DNA double-strand-breaks (DSB) and our data suggest that proximal DSBs are brought together inside isolated RIF for repair. The RIF/Gy trend was inverted at 24h, suggesting RIF with high DSB content are more difficult to repair. We showed that in vitro metrics correlate with in vivo measurements in the same 15 mouse strains, such as survival levels of immune cells or spontaneous cancer incidence, suggesting a relationship between the efficiency of DSB repair and cancer risk or radiation toxicity. In addition to the efficiency of repair and persistent RIF, the amount of spontaneous foci before irradiation was also found to be strain dependent. Finally, we performed genome-wide association study in the same 15 mouse strains using all RIF phenotypes measured in vitro, identifying genes of interest and validating RIF as an ideal biomarker for individual radiation sensitivity. BASELINE 53BP1+ FOCI PREDICTS INDIVIDUAL HUMAN RESPONSE TO GCR COMPONENTS Based on the analysis of radiation responses of 576 donor PBMCs (using quantification of 53BP1+ foci, oxidative stress and cell death), we observed a wide variability of subject- and LET-dependent radiation responses, with radiation-induced DNA repair foci increasing with LET, though oxidative stress being notably reduced by high-LET irradiation, potentially due to a switch between hydrogen peroxide and oxygen radical-based mechanisms. We identified a relationship between few spontaneous DNA foci at baseline and increased DNA repair after irradiation, accompanied by an alteration in immunoregulatory cytokine secretion, which might be adapted as biomarkers to predict ionizing radiation sensitivity. Among demographic variables, only latent cytomegalovirus infection and age were predictive of high baseline foci formation. Finally, we have performed low-throughput whole genome sequencing of all samples and are currently in the process of identifying the genes and pathways associated with low and high-LET ionizing radiation sensitivity in humans.

53BP1↗

NASA NTRSDate not supplied

The Environmental Data Application for Analysis of Space Telemetry Data

Sensors on the International Space Station (ISS) and multiple spacecraft elsewhere in Earth orbit and in deep space continuously monitor and collect environmental data, transmitting this information back to Earth. These data include ionizing radiation and, on the ISS and spacecrafts, CO2, relative humidity levels, and temperature, and are of great importance to space biology research. Looking ahead to future long duration crewed missions beyond low Earth orbit, the ability to study how factors including CO2 levels, light cycle, temperature modulate the response to ionizing radiation and microgravity is essential. To date, access to these data has been fragmented across space agencies, spacecraft, and databases. To address this issue, NASA’s Open Science Data Repository (OSDR) has developed a user interface for interrogation of telemetry data: the Environmental Data Application (EDA). The EDA provides the capability to visualize telemetry and radiation data collected on the International Space Station and corresponding ground platforms during the Rodent Research missions. Telemetry data includes temperature, relative humidity, and CO2 levels. Radiation data includes galactic cosmic rays, the contribution of the South Atlantic Anomaly, total radiation dose rate, and accumulated radiation dose. The application allows users to view single missions, compare multiple missions, and view and download summary or full data tables. In summary, the EDA provides GUIs for data visualization and exploration, as well as means for data export, making these data FAIR (Findable, Accessible, Interoperable, and Reusable), complementing the biological data contained in OSDR, and providing the space science community with a valuable resource for scientific analyses.

telemetry↗

NASA NTRS1989

Microlesions - Theory and reality

Efforts to assess radiation risk in space have been complicated by the considerable unknowns regarding the biological effects of the heavy ion component (HZE particles) of the cosmic rays. The attention has focused primarily on the assignation of a quality factor (Q) which would take into account the greater effectiveness of heavy ions vis-a-vis other forms of ionizing radiation. If, however, as the so-called 'microlesion theory' allows, the passage of HZE particles through living tissue produces unique biological damage, the traditional use of Q becomes meaningless. Therefore, it is critical to determine if microlesions, in fact, do exist. While the concept does not necessarily require detectable morphological damage, 'tunnel-lesions' or holes in ocular tissues have been cited as evidence of microlesions. These data, however, are open to reinterpretation. Ongoing light, scanning and transmission electron microscopic studies of the corneas, lenses and retinas of rat eyes exposed to 450 MeV/amu Fe-56 ions thus far have not revealed tunnel-lesion damage. The morphological effects of the heavy ions have been found to be qualitatively similar to the changes following other kinds of ionizing radiation.

Worgul, Basil V.↗