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At least 433 records · Page 24

Modeled microgravity-induced protein kinase C isoform expression in human lymphocytes

In long-term space travel, the crew is exposed to microgravity and radiation that invoke potential hazards to the immune system. T cell activation is a critical step in the immune response. Receptor-mediated signaling is inhibited in both microgravity and modeled microgravity (MMG) as reflected by diminished DNA synthesis in peripheral blood lymphocytes and their locomotion through gelled type I collagen. Direct activation of protein kinase C (PKC) bypassing cell surface events using the phorbol ester PMA rescues MMG-inhibited lymphocyte activation and locomotion, whereas the calcium ionophore ionomycin had no rescue effect. Thus calcium-independent PKC isoforms may be affected in MMG-induced locomotion inhibition and rescue. Both calcium-dependent isoforms and calcium-independent PKC isoforms were investigated to assess their expression in lymphocytes in 1 g and MMG culture. Human lymphocytes were cultured and harvested at 24, 48, 72, and 96 h, and serial samples were assessed for locomotion by using type I collagen and expression of PKC isoforms. Expression of PKC-alpha, -delta, and -epsilon was assessed by RT-PCR, flow cytometry, and immunoblotting. Results indicated that PKC isoforms delta and epsilon were downregulated by >50% at the transcriptional and translational levels in MMG-cultured lymphocytes compared with 1-g controls. Events upstream of PKC, such as phosphorylation of phospholipase Cgamma in MMG, revealed accumulation of inactive enzyme. Depressed calcium-independent PKC isoforms may be a consequence of an upstream lesion in the signal transduction pathway. The differential response among calcium-dependent and calcium-independent isoforms may actually result from MMG intrusion events earlier than PKC, but after ligand-receptor interaction.

Lymphocytes/enzymology↗

International collaboration on Russian spacecraft and the case for free flyer biosatellites

Animal research has been critical to the initiation and progress of space exploration. Animals were the original explorers of "space" two centuries ago and have played a crucial role by demonstrating that the space environment, with precautions, is compatible with human survival. Studies of mammals have yielded much of our knowledge of space physiology. As spaceflights to other planets are anticipated, animal research will continue to be essential to further reveal space physiology and to enable the longer missions. Much of the physiology data collected from space was obtained from the Cosmos (Bion) spaceflights, a series of Russian (Soviet)-International collaborative flights, over a 22 year period, which employed unmanned, free flyer biosatellites. Begun as a Soviet-only program, after the second flight the Russians invited American and other foreign scientists to participate. This program filled the 10 year hiatus between the last US biosatellite and the first animal experiments on the shuttles. Of the 11 flights in the Cosmos program nine of them were international; the flights continued over the years regardless of political differences between the Soviet Union and the Western world. The science evolved from sharing tissues to joint international planning and development, and from rat postmortem tissue analysis to in vivo measurements of a host of monkey physiological parameters during flight. Many types of biological specimens were carried on the modified Vostok spacecraft, but only the mammalian studies are discussed herein. The types of studies done encompass the full range of physiology and have begun to answer "critical" questions of space physiology posed by various ad hoc committees. The studies have not only yielded a prodigious and significant body of data, they have also introduced some new perspectives in physiology. A number of the physiological insights gained are relevant to physiology on Earth. The Cosmos flights also added significantly to flight-related technology, some of which also has application on our planet. In summary, the Cosmos biosatellite flights were extremely productive and of low cost. The Bion vehicles are versatile in that they can be placed into a variety of orbits and altitudes, and can carry radiation sources or other hazardous material which cannot be carried on manned vehicles. With recent advances in sensor, robotic, and data processing technology, future free flyers will be even more productive, and will largely preclude the need to fly animal experiments on manned vehicles. Currently, mammalian researchers do not have access to space for an unknown time, seriously impeding the advancement and understanding of space physiology during long duration missions. Initiation of a new, international program of free flyer biosatellites is critical to our further understanding of space physiology, and essential to continued human exploration of space.

short duration↗

Working Group Reports and Presentations: Cis-lunar

Space agencies are committed to the "safe, sustained, affordable human and robotic exploration of the Moon, Mars, and beyond." However, we recommend that they explicitly define our ultimate goal and motivation in order to portray a sense of purpose to the public. Our goal is sustainable human settlement of the Moon and Mars and our motivation is to preserve the human race. All secondary exploration and science objectives flow from this main goal and are still imperative to our success. As an economic guiding principle, governments should be limited to those areas where only government can perform the activity and should recognize and coordinate with the larger private and military sectors. Also, space agencies must continue to fund the interdisciplinary science necessary to characterize environmental hazards associated with dust, radiation, surface charging, topology, and meteorites in order to make our first attempts at extraterrestrial living viable.

Laubscher, Bryan↗

The Living With a Star Geospace Program

NASA's Living With a Star program addresses research problems with societal impact. As specified by its mission definition team, the Geospace component of the program addresses two regions which pose the greatest hazards: the Earth's radiation belts and the mid-latitude ionosphere. Two Radiation Belt Storm Probe spacecraft with identical energetic particle, plasma wave, and magnetic field instrumentation will make the observations needed to distinguish spatial from temporal effects and identify the mechanisms governing particle energization, transport, and loss. Two Ionosphere- Thermosphere Storm Probes on inclined low-altitude and midlatitude orbits will make the observations needed to distinguish between special and temporal effects, characterize the response to varying solar EUV radiation and geomagnetic storms, and identify the mechanisms generating mid-latitude ionospheric irregularities. An imager on a mission of opportunity will provide the observations needed to place these in situ measurements in context.

Sibeck, D. G.↗

Modeled Microgravity-Induced Protein Kinase C Isoform Expression in Human Lymphocytes

In long-term space travel, the crew is exposed to microgravity and radiation that invoke potential hazards to the immune system. T cell activation is a critical step in the immune response. Receptor-mediated signaling is inhibited both in microgravity and modeled microgravity (MMG) as reflected in diminished DNA synthess in peripheral blood lymphocytes and their locomotion through gelled type 1 collagen. Direct activation of Protein Kinase C (PKC) bypassing cell surface events using the phorbol ester PMA rescues MMG-inhibited lymphocyte activation and locomotion, whereas calcium ionophore ionomycin had no rescue effect. Thus calcium-independent PKC isoforms may be affected in MMG-induced locomotion inhibition and rescue. Both calcium-dependent isoforms and calcium-independent PKC isoforms were investigated to assess their expression in lymphocytes in 19 and MMG-culture. Human lymphocytes were cultured and harvested at 24, 48, 72 and 96 hours and serial samples assessed for locomotion using type I collagen and expression of PKC isoforms. Expression of PKC-alpha, -delta and -epsilon was assessed by RT-PCR, flow cytometry and immunoblotting. Results indicated that PKC isoforms delta and epsilon were down-regulated by more than 50% at the transcriptional and translational levels in MMG-cultured lymphocytes compared with 19 controls. Events upstream of PKC such as phosphorylation of Phospholipase C(gamma) (PLC-gamma) in MMG, revealed accumulation of inactive enzyme. Depressed Ca++ -independent PKC isoforms may be a consequence of an upstream lesion in the signal transduction pathway. The differential response among calcium-dependent and calcium-independent isoforms may actually result from MMG intrusion events earlier than, but after ligand-receptor interaction. Keywords: Signal transduction, locomotion, immunity

Sundaresan, A.↗

Electromagnetic Simulations of Ground-Penetrating Radar Propagation near Lunar Pits and Lava Tubes

Placing an Orion capsule at the Earth-Moon L2 point (EML2) would potentially enable telerobotic operation of a rover on the lunar surface. The Human Exploration Virtual Institute (HEVI) is proposing that rover operations be carried out near one of the recently discovered lunar pits, which may provide radiation shielding for long duration human stays as well as a cross-disciplinary, science-rich target for nearer-term telerobotic exploration. Ground penetrating radar (GPR) instrumentation included onboard a rover has the potential to reveal many details of underground geologic structures near a pit, as well as characteristics of the pit itself. In the present work we employ the full-wave electromagnetic code MEEP to simulate such GPR reflections from a lunar pit and other subsurface features including lava tubes. These simulations will feed forward to mission concepts requiring knowledge of where to hide from harmful radiation and other environmental hazards such as plama charging and extreme diurnal temperatures.

Lava Tubes↗

NASA Omics Archive Project

The space environment consists of a complex set of hazards including altered gravity, radiation, psychological/physiological stress, isolation, and confinement leading to complex biological responses. Advances in biotechnology capabilities offer considerable potential to provide novel insight into those responses as well as innovative diagnostic, treatment, and countermeasure solutions for astronauts as NASA begins to travel beyond low Earth orbit. Omics data (genomics, transcriptomics, proteomics, etc.) is one example that can provide NASA with critical knowledge of how a crewmember’s genetics, environment, and lifestyle can be used to develop individualized approaches for disease prevention, advance diagnostics, and improve treatment strategies. NASA ventured into the field of omics on human subjects with the successful completion of the NASA Twins Study which was the first step in mapping the multi-omic profile of astronauts to understand and mitigate the health consequences of spaceflight. The Human Research Program aims to build upon the success of the Twins Study with the NASA Omics Archive flight study, establishing a longitudinal biospecimen archive and efficiently generating a comprehensive high-quality multi-omic dataset from astronauts for the purpose of studying molecular, metabolic, and microbial changes associated with longduration spaceflight missions. The goal is to facilitate scientific and medical research community efforts to characterize and mitigate spaceflight health and performance risks. In this presentation, we will review details regarding the biospecimen and data archive to be generated by the NASA Omics Archive flight study. Data generated as part of this project will be archived in the NASA Life Sciences Portal (NLSP) and be made available for future hypothesis-driven research efforts or occupational surveillance through Institutional Review Board-approved data sharing and retrospective data requests submitted to the Life Sciences Data Archive (LSDA) team. We will also present results of a ground study performed to evaluate in-house procedures, new sample collection hardware, and vendor capabilities. The data repository generated and the samples to be archived by this study will enable future research efforts to assess an astronauts’ unique molecular and genetic profile with respect to individual spaceflight responses. Results of which will be instrumental in enabling precision health capabilities to better assess and mitigate spaceflight risks, detect disease states earlier, and actively monitor countermeasure treatments, ultimately improving clinical outcomes during future exploration class missions.

C. A. Theriot↗

Evaluation of H-Canyon Ventilation Exhaust Tunnel Inspection at the Savannah River Site - 20052

The Department of Energy (DOE) H-Canyon Facility at the Savannah River Site (SRS) is operated by Savannah River Nuclear Solutions (SRNS). The Facility Structural Integrity Program [1] provides a process to inspect, evaluate, and document the conditions of passive safety related structural systems and components, their degradation mechanisms and their impact on the safety envelope. The Structural Integrity Program performs periodic visual inspections to confirm the systems and components can perform their safety function and recommend corrective actions before the function is compromised. The H-Canyon Exhaust Tunnel is part of the H-Canyon Ventilation System and is periodically inspected under the Structural Integrity Program. The Tunnel performs a Safety Class passive design feature function that is available 100% of the time. The underground reinforced concrete Tunnel directs Canyon process air from the Canyon to the Sand Filter System. The radiological and chemical airborne activity coupled with the physical configuration of the tunnel precludes a manned entry into the tunnel to perform the inspection. Unlike active systems that can be subjected to physical testing to confirm capability, qualification calculations, including modeling, is performed to assess passive design feature capabilities relative to operational, accident and natural phenomena hazards events. Input for these calculations come from knowledge of field conditions, design drawings and conservative assumptions. The knowledge of field conditions comes from concrete and soil testing activities as well as inspection data. The use of cameras on crawlers to obtain inspection data and how that data is used in qualification calculations is the focus of this discussion. Remote Tunnel inspections have been performed using cameras on a stick, referred to as pole cameras, prior to Calendar Year 2003 (CY2003). Since CY2003, six camera equipped crawlers have been used. Crawlers have evolved and improved by incorporating lessons learned from the previous inspections. The latest 2019 crawler successfully traveled the entire length of the tunnel between the Canyon and Sand Filter System and captured images that were previously unseen, thus providing key visual data for the Structural Integrity Program report [2]. The inspection data serves as 1) input to qualification calculations, 2) validates current conditions remain bounded by qualification calculations, and 3) documents a record of change over time. This data is vital for the effective evaluation of the tunnel structure and aids with predicting the life cycle service life safety envelope to protect the public, environment, and facility worker. The goal of the 2019 deployment was to use a more robust vehicle to ensure travel over obstacles, perform the inspection with higher resolution cameras, and have the ability to elevate the cameras to view surfaces previously obscured by abandon-in-place ducts in the tunnel. The inspection information will serve to strengthen the input basis for qualification calculations, versus using excessive conservative calculation assumptions. This 2019 inspection was compared with previous crawler visual evidence to identify change over time to project remaining service life and confirm field conditions remain bounded by qualification calculations. The results of the 2019 Exhaust Tunnel inspection continue to improve and provide a firm basis to make sound engineering judgements regarding tunnel capability and approaches in projecting remaining service life with an aging system and component. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Maintaining Human Health for Humans-Mars

The Human Health Research Program states that Radiation is the most challenging hazard to human spaceflight beyond LEO. The International Space Station provides an analog for evaluating techniques for dealing with Altered Gravity, the Radiation Environment of the ISS is only about 45% of the deep space values where radiation due to Galactic Cosmic Rays (GCR) dominate the spectrum. The Moon and cis-lunar space are being considered as a Mars Analog training ground for preparing crews for human mission to Mars. Spending more than 200 days in deep space is considered unsafe based on our current proxy for lifetime radiation dose. The paper outlines a way forward for spending days training near the Moon and for completing roundtrip missions to Mars while remaining below the current proxy. In the first case, a GCR overcoat shields crews from radiation during cis-lunar activities before making fast transits without in-space GCR overcoats to and from Mars. This case requires continued maturation of low TRL propulsion and power technologies currently around 4 to 5 while depending on repeatable reductions in launch costs by a factor of 6 expected of current reusable rockets. The second case requires no new technology development except for the expectation that the next near-term generation of reusable rockets will reduce launch costs by a factor of around 14. Five trajectories and GCR overcoat sizes for all mission legs are presented herein to illustrate the opportunities to maintain human health for Humans-Mars missions.

Robert W Moses↗

Individual Variability and Predictive Biomarkers of Human Sensitivity to Ionizing Radiation

High-linear energy transfer (LET) ionizing radiation is a major health hazard for astronauts who will be exposed to galactic cosmic rays during upcoming lunar and Mars missions. Predicting and mitigating personalized health risks from space radiation exposure requires understanding the factors underlying individual radiation sensitivity, which currently remain unknown. We started to address this challenge by identifying the genomic and demographic associations with sensitivity to low and high-LET ionizing radiation in the largest human sample cohort to date and by evaluating baseline DNA damage as a potential predictor of radiation responses. We have collected and irradiated peripheral blood mononuclear cells (PBMCs) from 768 healthy donors of matched ethnicity, 50/50 male/female, 18-70 years old. We have analyzed the responses of 576 donor PBMCs to irradiation with simulated galactic cosmic ray components: 350MeV/n 28Si, 350MeV/n 40Ar and 600MeV/n 56Fe, at 1.1 and 3 particles/100μm2 fluences, as well as 0.1Gy and 1Gy doses of gamma rays, at 4 and 24 hours post irradiation. We quantified post-irradiation DNA repair based on radiation-induced 53BP1+ foci formation, together with oxidative stress and cell death using a flow cytometry-based assay. We also assessed baseline levels of DNA repair in PBMCs at the time of sample collection prior to irradiation experiments. 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 also identified a relationship between few DNA repair 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, baseline foci levels were positively associated with age and latent cytomegalovirus infection. Finally, we have performed low-throughput whole genome sequencing of all samples and are currently in process of identifying the genes and pathways associated with low and high-LET ionizing radiation sensitivity in humans.

Space radiation, human spaceflight, DNA damage↗

Genomic and Phenotypic Associations to Predict Human Sensitivity to SpaceRadiation

High-linear energy transfer (LET) ionizing radiation is a major health hazard for astronauts who will be exposed to galactic cosmic rays during upcoming lunar and Mars missions. Predicting and mitigating this risk requires understanding the factors underlying individual radiation sensitivity. We started to address this challenge by identifying the genomic and phenotypic associations with sensitivity to low and high-LET ionizing radiation ex vivo in over 750 healthy human donors. We exposed primary human blood mononuclear cells to simulated galactic cosmic ray components: 350MeV/n 28Si, 350MeV/n 40Ar and 600MeV/n 56Fe particles, at 1.1 and 3 particles/100 sq.m fluences, as well as 0.1 Gy and 1 Gy doses of gamma rays, and analyzed the outcomes at 4 and 24 hours post-irradiation. We quantified DNA damage and repair responses based on 53BP1+ radiation-induced foci formation, together with oxidative stress and changes in secreted factors including immune cytokines and exosomes. We also analyzed phenotypic associations with spontaneous DNA repair foci at baseline prior to irradiation. We identified an increase in spontaneous DNA repair associated with age and latent viral infection, and observed that human spontaneous DNA repair foci at baseline can serve as a negative predictor of DNA repair and immunoregulatory cytokine production after irradiation. Furthermore, we observed a wide variability of subject- and LET-dependent radiation responses, with radiation-induced DNA repair foci increasing by dose and LET, and high-LET particle radiation resulting in more residual DNA damage compared to low-LET particles and gamma rays. We have developed multiple metrics to quantify human radio sensitivity across the spectrum of conditions. Here we present their dependence on radiation quality and phenotypic variables, including an age-dependent decrease in DNA repair after irradiation, and genomic associations with radio sensitivity based on low-coverage whole genome sequencing. We anticipate that our work will pave the way for understanding the spectrum of human radio sensitivity and identifying targets for countermeasure development to reduce DNA and cellular damage and radiation carcinogenesis during deep space exploration.

GWAS radiation human↗

Genomic and Phenotypic Predictors of Human Ex Vivo Sensitivity to Simulated Deep Space Radiation

High-linear energy transfer (LET) ionizing radiation is a major health hazard for astronauts who will be exposed to galactic cosmic rays during upcoming lunar and Mars missions. Predicting and mitigating this risk requires understanding the factors underlying individual radiation sensitivity. We started to address this challenge by identifying the genomic and phenotypic associations with sensitivity to low and high-LET ionizing radiation ex vivo in over 750 healthy human donors. We exposed primary human blood mononuclear cells to simulated galactic cosmic ray components: 350 MeV/n 28Si, 350 MeV/n 40Ar and 600 MeV/n 56Fe particles, at 1.1 and 3 particles/100 sq.m fluences, as well as 0.1 Gy and 1 Gy doses of gamma rays, and analyzed the outcomes at 4 and 24 hours post-irradiation. We quantified DNA damage and repair responses based on 53BP1+ radiation-induced foci formation, together with oxidative stress and changes in secreted factors including immune cytokines and exosomes. We also analyzed phenotypic associations with spontaneous DNA repair foci at baseline prior to irradiation. We identified an increase in spontaneous DNA repair associated with age and latent viral infection, and observed that human spontaneous DNA repair foci at baseline can serve as a negative predictor of DNA repair and immunoregulatory cytokine production after irradiation. Furthermore, we observed a wide variability of subject- and LET-dependent radiation responses, with radiation-induced DNA repair foci increasing by dose and LET, and high-LET particle radiation resulting in more residual DNA damage compared to low-LET particles and gamma rays. We have developed multiple metrics to quantify human radiosensitivity across the spectrum of conditions. Here we present their dependence on radiation quality and phenotypic variables, including an age-dependent decrease in DNA repair after irradiation, and genomic associations with radiosensitivity based on low-coverage whole genome sequencing. We anticipate that our work will pave the way for understanding the spectrum of human radiosensitivity and identifying targets for countermeasure development to reduce DNA and cellular damage and radiation carcinogenesis during deep space exploration.

GWAS↗

Genomic and phenotypic predictors of human ex vivo sensitivity to simulated deep space radiation

High-linear energy transfer (LET) ionizing radiation is a major health hazard for astronauts who will be exposed to galactic cosmic rays during upcoming lunar and Mars missions. Predicting and mitigating this risk requires understanding the factors underlying individual radiation sensitivity. We started to address this challenge by identifying the genomic and phenotypic associations with sensitivity to low and high-LET ionizing radiation ex vivo in over 750 healthy human donors. We exposed primary human blood mononuclear cells to simulated galactic cosmic ray components: 350MeV/n (28)Si, 350MeV/n (40)Ar and 600MeV/n (56)Fe particles, at 1.1 and 3 particles/100µm^(2) fluences, as well as 0.1 Gy and 1 Gy doses of gamma rays, and analyzed the outcomes at 4 and 24 hours post-irradiation. We quantified DNA damage and repair responses based on 53BP1^(+) radiation-induced foci formation, together with oxidative stress and changes in secreted factors including immune cytokines and exosomes. We also analyzed phenotypic associations with spontaneous DNA repair foci at baseline prior to irradiation. We identified an increase in spontaneous DNA repair associated with age and latent viral infection, and observed that human spontaneous DNA repair foci at baseline can serve as a negative predictor of DNA repair and immunoregulatory cytokine production after irradiation. Furthermore, we observed a wide variability of subject- and LET-dependent radiation responses, with radiation-induced DNA repair foci increasing by dose and LET, and high-LET particle radiation resulting in more residual DNA damage compared to low-LET particles and gamma rays. We have developed multiple metrics to quantify human radiosensitivity across the spectrum of conditions. Here we present their dependence on radiation quality and phenotypic variables, including an age-dependent decrease in DNA repair after irradiation, and genomic associations with radiosensitivity based on low-coverage whole genome sequencing. We anticipate that our work will pave the way for understanding the spectrum of human radiosensitivity and identifying targets for countermeasure development to reduce DNA and cellular damage and radiation carcinogenesis during deep space exploration.

GWAS↗

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.↗

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.↗

Predicting cancer rates in astronauts from animal carcinogenesis studies and cellular markers

The radiation space environment includes particles such as protons and multiple species of heavy ions, with much of the exposure to these radiations occurring at extremely low average dose-rates. Limitations in databases needed to predict cancer hazards in human beings from such radiations are significant and currently do not provide confidence that such predictions are acceptably precise or accurate. In this article, we outline the need for animal carcinogenesis data based on a more sophisticated understanding of the dose-response relationship for induction of cancer and correlative cellular endpoints by representative space radiations. We stress the need for a model that can interrelate human and animal carcinogenesis data with cellular mechanisms. Using a broad model for dose-response patterns which we term the "subalpha-alpha-omega (SAO) model", we explore examples in the literature for radiation-induced cancer and for radiation-induced cellular events to illustrate the need for data that define the dose-response patterns more precisely over specific dose ranges, with special attention to low dose, low dose-rate exposure. We present data for multiple endpoints in cells, which vary in their radiosensitivity, that also support the proposed model. We have measured induction of complex chromosome aberrations in multiple cell types by two space radiations, Fe-ions and protons, and compared these to photons delivered at high dose-rate or low dose-rate. Our data demonstrate that at least three factors modulate the relative efficacy of Fe-ions compared to photons: (i) intrinsic radiosensitivity of irradiated cells; (ii) dose-rate; and (iii) another unspecified effect perhaps related to reparability of DNA lesions. These factors can produce respectively up to at least 7-, 6- and 3-fold variability. These data demonstrate the need to understand better the role of intrinsic radiosensitivity and dose-rate effects in mammalian cell response to ionizing radiation. Such understanding is critical in extrapolating databases between cellular response, animal carcinogenesis and human carcinogenesis, and we suggest that the SAO model is a useful tool for such extrapolation.

Non-NASA Center↗

Space vehicle propulsion systems - Environmental space hazards

An evaluation of hazards which exist in geo-lunar space and have the potential to negatively affect a long-term mission-oriented spacecraft systems is presented based on published data. The hazards are categorized as pervasive (radiation), incident specific (meteoroids and thermal shock), and chemically corrosive (monatomic oxygen). It appears that the number one priority should be the development of new materials; and the secondary concern should be the development of fabrication techniques for the exterior hull, so that incident specific hazards can be minimized in an active fashion. The pervasive hazard can be dealt with by exploring on-board circuit technology with ancillary monitoring systems. Effects of thermal shock on the exterior nozzle, directional gimbals, and internal combustion chamber geometry seem to need more investigation.

Bahr, G. K.↗

Correlated measurements of UHF radar signatures, RF radiation, and electric field changes from lightning

During Storm Hazards - 82, simultaneous measurements were made of radar echoes, fast and slow field changes and RF radiation from lightning near the Wallops Flight Facility. RF radiation and radar echoes were also obtained during periods when the NASA F106 research aircraft was struck by lightning. These data are presently being used to better understand the electrical processes which occur during strikes to the aircraft. Preliminary conclusions based on data obtained in 1982 verify that the events recorded aboard the aircraft occurred during lightning but also indicate that they occur with surprising frequency very early in the flash.

Levine, D. M.↗