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All sourcesNASA NTRSDOE OSTI
NASA NTRSDate not supplied

Deep Space Radiation Affects Neurovascular Functions in Human Organ-on-a-Chip Models

A major health risk for human deep space exploration is central nervous system (CNS) damage by galactic cosmic ray radiation. Simulated galactic cosmic rays or their components, especially the high- linear energy transfer (LET) particles such as 56 Fe ions, cause CNS damage, neuroinflammation and cognitive dysfunction in rodent models, but their effects on human CNS remain to be investigated. CNS damage from any insult, including ionizing radiation, is partially mediated by the blood-brain barrier (BBB), which regulates the interactions between CNS and the rest of the body. The main cellular regulators of BBB permeability are astrocytes, which also modulate neuronal health and neuroinflammation. However, there have been few studies on BBB and astrocyte functions in regulating CNS responses, especially in human tissue/organ analogs. Therefore, we utilized a high-throughput human 3D organ-on-a-chip system, seeded with induced pluripotent stem cell-derived endothelial cells, astrocytes and neurons, to study human neurovascular responses to simulated deep space radiation. We investigated BBB permeability, oxidative stress, cellular and tissue damage, and secreted factors over the time period of 24 hours-1 week after irradiation with 0.25-0.5 Gy 5-ion simplified simulated galactic cosmic rays and 0.3-0.8 Gy high-LET 600MeV/n 56 Fe particles, and compared the outcomes to low-LET irradiation with 0.1-1 Gy doses of X-rays and gamma rays. Both high and low-LET radiation increased neurovascular permeability, caused oxidative stress, damaged endothelial cells and tight junctions, and altered expression of inflammatory cytokines. Ionizing radiation- induced neurovascular permeability and oxidative stress peaked at 3 days after irradiation and were further exacerbated by the presence of astrocytes. Furthermore, in response to particle irradiation, astrocytes stimulated interleukin-1 signaling by inhibiting the expression of interleukin-1 receptor antagonist. Thus, we also evaluated interleukin-1 receptor antagonist as a potential countermeasure against particle radiation. Ultimately, our results may help develop countermeasures to mitigate human CNS damage in deep space exploration.

Sonali D Verma↗
NASA NTRS2012

Calculation of the Frequency Distribution of the Energy Deposition in DNA Volumes by Heavy Ions

Radiation quality effects are largely determined by energy deposition in small volumes of characteristic sizes less than 10 nm representative of short-segments of DNA, the DNA nucleosome, or molecules initiating oxidative stress in the nucleus, mitochondria, or extra-cellular matrix. On this scale, qualitatively distinct types of molecular damage are possible for high linear energy transfer (LET) radiation such as heavy ions compared to low LET radiation. Unique types of DNA lesions or oxidative damages are the likely outcome of the energy deposition. The frequency distribution for energy imparted to 1-20 nm targets per unit dose or particle fluence is a useful descriptor and can be evaluated as a function of impact parameter from an ions track. In this work, the simulation of 1-Gy irradiation of a cubic volume of 5 micron by: 1) 450 (1)H(+) ions, 300 MeV; 2) 10 (12)C(6+) ions, 290 MeV/amu and 3) (56)Fe(26+) ions, 1000 MeV/amu was done with the Monte-Carlo simulation code RITRACKS. Cylindrical targets are generated in the irradiated volume, with random orientation. The frequency distribution curves of the energy deposited in the targets is obtained. For small targets (i.e. <25 nm size), the probability of an ion to hit a target is very small; therefore a large number of tracks and targets as well as a large number of histories are necessary to obtain statistically significant results. This simulation is very time-consuming and is difficult to perform by using the original version of RITRACKS. Consequently, the code RITRACKS was adapted to use multiple CPU on a workstation or on a computer cluster. To validate the simulation results, similar calculations were performed using targets with fixed position and orientation, for which experimental data are available [5]. Since the probability of single- and double-strand breaks in DNA as function of energy deposited is well know, the results that were obtained can be used to estimate the yield of DSB, and can be extended to include other targeted or non-target effects.

Plante, Ianik↗
NASA NTRS2016

Metabolomic and Genomic Markers of Atherosclerosis as Related to Oxidative Stress, Inflammation, and Vascular Function in Twin Astronauts

Background: Future human space travel will consist primarily of long-duration missions onboard the International Space Station (ISS) or exploration-class missions to Mars, its moons, or nearby asteroids. Astronauts participating in long-duration missions may be at an increased risk of oxidative stress and inflammatory damage due to radiation, psychological stress, altered physical activity, nutritional insufficiency, and hyperoxia during extravehicular activity. By studying one identical twin during his 1-year ISS mission and one ground-based twin, this work extends a current NASA-funded investigation to determine whether these spaceflight factors contribute to an accelerated progression of atherosclerosis. This study of twins affords a unique opportunity to examine the spaceflight-related atherosclerosis risk independent of the confounding factors associated with different genotypes. Purpose: The purpose of this investigation is to determine whether biomarkers of oxidative and inflammatory stress are elevated during and after long-duration spaceflight and determine if a relation exists between levels of these biomarkers and structural and functional indices of atherosclerotic risk measured in the carotid and brachial arteries. These physiological and biochemical data will be extended by using an exploratory approach to investigate the relationship between intermediate phenotypes and risk factors for atherosclerosis and the metabolomic signature from plasma and urine samples. Since metabolites are often the indirect products of gene expression, we will simultaneously assess gene expression and DNA methylation in leukocytes. Hypothesis: We predict that the space-flown twin will experience elevated biomarkers of oxidative stress and inflammatory damage, altered arterial structure and function, accelerated telomere shortening, dysregulation of genes associated with oxidative stress and inflammation, and a metabolic profile shift that is associated with elevated atherosclerosis risk factors. Conversely, these will not be observed in the ground-based twin. Methods: We will measure blood and urine biomarkers of oxidative stress and inflammation as well as arterial structure and function (carotid intima-medial thickness and brachial artery flow-mediated dilation) in one twin astronaut before, during, and after long-duration spaceflight and in his twin serving as a ground-based control. Furthermore, we will measure metabolomics (targeted and untargeted approaches) and genomic markers (DNA methylation, mRNA gene expression, telomere length) to elucidate the molecular mechanisms involved. A panel of biomarkers of oxidative and inflammatory stress will be measured in venous blood samples and 24-hour (in-flight) and 48-hour (pre- and post-flight) urine pools twice before flight, early (flight days 15 and 60) and late (2 weeks before landing) during the mission, and early in the post-flight recovery phase (approximately 3-5 days after landing). Arterial structure, assessed from measures of intima-media thickness, will be measured at the same times. Arterial function will be assessed using brachial flow-mediated dilation, a well-validated measure used to assess endothelium-dependent vasodilation and a sensitive predictor of atherosclerotic risk, only before and after spaceflight. Discussion: Pre- and in-flight data collection is in progress for the space-flown twin, and similar data have been obtained from the ground-based twin. Blood and urine samples will be batch processed when received from ISS after the conclusion of the 1-year mission. Results from these individual subjects will be compared to the larger complement of subjects participating in the companion study currently ongoing in ISS astronauts.

Lee, Stuart M. C.↗
NASA NTRS2017

Metabolomic and Genomic Markers of Atherosclerosis as Related to Oxidative Stress, Inflammation, and Vascular Function in Twin Astronauts

BACKGROUND: Future human space travel will consist primarily of long-duration missions onboard the International Space Station (ISS) or exploration-class missions to Mars, its moons, or nearby asteroids. Astronauts participating in long-duration missions may be at an increased risk of oxidative stress and inflammatory damage due to radiation, psychological stress, altered physical activity, nutritional insufficiency, and hyperoxia during extravehicular activity. By studying one identical twin during his 1-year ISS mission and his ground-based twin, this work extends a current NASA-funded investigation to determine whether these spaceflight factors contribute to an accelerated progression of atherosclerosis. This study of twins affords a unique opportunity to examine spaceflight-related atherosclerosis risk that is independent of the confounding factors associated with different genotypes. PURPOSE: The purpose of this investigation was to determine whether biomarkers of oxidative and inflammatory stress are elevated during and after long-duration spaceflight and determine if a relation exists between levels of these biomarkers and structural and functional indices of atherosclerotic risk measured in the carotid and brachial arteries. These physiological and biochemical data will be extended by using an exploratory approach to investigate the relationship between intermediate phenotypes and risk factors for atherosclerosis and the metabolomic signature from plasma and urine samples. Since metabolites are often the indirect products of gene expression, we simultaneously assessed gene expression and DNA methylation in leukocytes. HYPOTHESIS: We predict that, compared to the ground-based twin, the space-flown twin will experience elevated biomarkers of oxidative stress and inflammatory damage, altered arterial structure and function, accelerated telomere shortening, dysregulation of genes associated with oxidative stress and inflammation, and a metabolic profile shift that is associated with elevated atherosclerosis risk factors. METHODS: In the space-flown twin, a panel of biomarkers of oxidative and inflammatory stress were measured in venous blood samples and in 24-h (in-flight) and 48-h (pre- and post-flight) urine pools collected twice before flight, six times during the mission (~FD15, 75, 180, 240, 300, 335), and early in the post-flight recovery phase (3-5 days after landing). We also measured metabolomic (targeted and untargeted approaches) and genomic markers (DNA methylation, mRNA gene expression, telomere length) in these samples. Arterial structure, assessed from measures of intima-media thickness, also were measured using standard clinical ultrasound at the same time points. Arterial function was assessed using brachial flow-mediated dilation, a well-validated measure used to assess endothelium-dependent vasodilation and a sensitive predictor of atherosclerotic risk, only before and after spaceflight. All of the same measures were obtained in the ground-based twin, but less frequently. DISCUSSION: All data collection has been completed for both the space-flown twin and the ground-based twin. Vascular structure and function measures have been analyzed, blood and urine samples have been batch-processed. Results from these individuals will be compared to each other, to data from other Twin Study investigations, and to the larger complement of subjects participating in the companion study currently ongoing in ISS astronauts.

Lee, Stuart M. C.↗
NASA NTRSDate not supplied

Foreign Object Damage in Yb 2 Si 2 O 7 Environmental Barrier Coatings

Environmental Barrier Coatings (EBCs) have been developed as an enabling technology for silicon carbide based ceramic matrix composites in gas turbine engines. Two of the key failure mechanisms identified in EBC systems are foreign object damage (FOD) and the oxidative growth of a SiO 2 thermally grown oxide (TGO) layer that can lead to premature coating spallation. Previously the effects of FOD on NASA’s second generation Ytterbium Disilicate EBC were studied and recently it was shown that the addition of oxide modifiers resulted in improved oxidation resistance in the EBC. This work will compare FOD of the baseline Ytterbium Disilicate EBC to the that of the modified EBC. FOD was performed at room temperature using a 1.59 mm hardened steel ball with projectile velocities of 50-300 m/s. Additionally, the effects of oxidation via cyclic steam exposure prior to impact were investigated.

environmental barrier coatings (EBCs)↗
NASA NTRS1996

Measuring High Temperatures In Ceramic-Fiber Blankets

Thermocouple assemblies devised specifically for measuring temperatures at fixed locations within insulating blankets made of such ceramic fibers as alumina, silicon carbide, and/or aluminoborosilicate. Thermocouples measure temperatures from 100 to 3,200 degrees F in oxidizing atmospheres. Wires enclosed in alumina sheath for protection against hot oxidation and mechanical damage.

Kourtides, Demetrius A.↗
NASA NTRS2006

Space Shuttle Body Flap Actuator Bearing Testing for NASA Return to Flight

The Space Shuttle body flap (BF) is located beneath the main engine nozzles and is required for proper aerodynamic control during orbital descent. The body flap is controlled by four actuators connected by a common shaft and driven by the hydraulic power drive unit. Inspection of the actuators during refurbishment revealed three shaft bearings with unexpected damage. One was coated with black oxide on the balls and race wear surfaces, a second contained a relatively deep wear scar, and the third with scratches and an aluminum particle in the wear track. A shaft bearing life test program was initiated to measure the wear life and explain the 5.08-micrometer wear scar. A tribological analysis was conducted to demonstrate that the black oxide coated wear surfaces did not damage the bearing, interfere with the lubrication, or cause severe bearing wear. Pre-damaged (equivalent of 30 missions), commercial equivalent bearings and previously flown shaft bearings were tested at axial loads, speeds, and temperatures seen during flight operations. These bearing were successfully life tested at 60 C for 24 hours or 90 flights. With a safety factor of 4X, the bearings were qualified for 22 flights when only a maximum of 12 flights are expected. Additional testing at 23 C was performed to determine the lubricant life and to further understand the mechanism that caused the blackened balls. Test results indicating bearing life was shortened at a lower temperature surprised the investigators. Start\Stop bearing testing that closely simulates mission profile was conducted at 23 C. Results of this testing showed lubricant life of 12 flights including a safety factor of four. Additional testing with bearings that have the equivalent of 30 missions of damage is being tested at 23 C. These tests are being performed over the Shuttle load profile to demonstrate the residual bearing life in the actuators exceeds 12 missions. Testing showed that the end of the shaft bearing life was characterized by bearing temperature rise, preload drop, and the onset of a severe wear bearing failure mechanism. The severe wear failure mechanism is characterized by rough wear scars, extensive bearing wear and steel transfer between the balls and the races.

Jet, Timothy R.↗
NASA NTRS2008

Interphase for ceramic matrix composites reinforced by non-oxide ceramic fibers

A ceramic matrix composite material is disclosed having non-oxide ceramic fibers, which are formed in a complex fiber architecture by conventional textile processes; a thin mechanically weak interphase material, which is coated on the fibers; and a non-oxide or oxide ceramic matrix, which is formed within the interstices of the interphase-coated fiber architecture. During composite fabrication or post treatment, the interphase is allowed to debond from the matrix while still adhering to the fibers, thereby providing enhanced oxidative durability and damage tolerance to the fibers and the composite material.

DiCarlo, James A.↗
NASA NTRS2010

DF-1, A Nontoxic Carbon Fullerene Based Antioxidant, is Effective as a Biomedical Countermeasure Against Radiation

A long-term goal of radiation research is the mitigation of inherent risks of radiation exposure. Thus the study and development of safe agents, whether biomedical or dietary, that act as effective radioprotectors is an important step in accomplishing this long-term goal. Some of the most effective agents to date have been aminothiols and their derivatives. Unfortunately, most of these agents have side effects such as nausea, vomiting, hypotension, weakness, and fatigability. For example, nausea and emesis occur in most patients treated with WR-2721 (Amifostine), requiring the use of effective antiemetics, with hypotension being the dose-limiting side effect in patients treated. Clearly, the need for a radioprotector that is both effective and safe still exists. Development of biocompatible nano-materials for radioprotection is a promising emerging technology that could be exploited to address the need to minimize biological effects when exposure is unavoidable. Testing free radical scavenging nanoparticles for potential use in radioprotection is exciting and highly relevant. Initial investigations presented here demonstrate the ability of a particular functionalized carbon fullerene nanoparticle, (DF-1), to act as an effective radioprotector. DF-1 was first identified as the most promising candidate in a screen of several functionalized carbon fullerenes based on lack of toxicity and antioxidant therapeutic potential against oxidative injuries (i.e. organ reperfusion and ionizing radiation). Subsequently, DF-1 has been shown to reduce chromosome aberration yield and cell death, as well as overall ROS levels in human lymphocytes and fibroblasts after exposure to gamma radiation and energetic protons while demonstrating no associated toxicity. The dose-reducing factor of DF-1 at LD50 is nearly 2.0 for gamma radiation. In addition, DF-1 treatment also significantly prevented cell cycle arrest after exposure. Finally, DF-1 markedly attenuated COX2 upregulation in cell culture after irradiation thus preventing an inflammatory response to irradiation. Taken together, these results suggest that DF-1 provides potent protection against several deleterious cellular consequences of irradiation in mammalian systems including oxidative stress, DNA damage, inflammation and cell death.

Theriot, Corey A.↗
NASA NTRS2019

Cross Kingdom Analysis of Data Within the GeneLab Repository Identifies a Potential Conserved Response of Life to the Stress Associated with Spaceflight

It is important to determine the health risks and potential survival for astronauts associated with long-term space missions. This entails not only understanding the impact the space environment will have on humans, but also how it will affect other organisms needed for humans to survive in space such as plants. In addition, it has been reported in the literature that hundreds of genes seem to be conserved and/or transferred between different organisms from bacteria, archaea, fungi, microorganisms, and plants to animals. Since space travel involves humans in a closed environment over a long period of time, we hypothesize that potential conserved biological factors will occur between the different organisms in that environment possibly due to transfer of genes. Determining the conserved factors that are commonly being regulated in space can shed insight into possible universal master regulators and also determine the symbiotic relationship between the organisms in space. Utilizing NASA's GeneLab Data Repository (a rapidly expanding, curated clustering of spaceflight-related ‘omics-level datasets for all organisms), we were able to uncover a novel pathway and factors that were commonly shared between humans, mice, plants, C. Elegans, and drosophilas. Through ChIP-Seq enrichment analysis techniques utilizing various GeneLab datasets from each species that were flown in space, we found the following factors to be conserved across all species: oxidative stress, DNA damage (through GABPA/NRFs and NFY), SIX5, GTF2B and glutamine synthetase. Such commonalities would likely reflect the effects of factors such as microgravity and the increased radiation exposure inherent in spaceflight on basic physical processes shared by all biological systems at the cellular level. Differences between organismal responses revealed by GeneLab's data should also help understand the unique reactions to life in space that arise from the very different lifestyles of microbes, animals and plants.

Barker, Richard↗
NASA NTRS1974

Technique for recovery of voice data from heat damaged magnetic tape

A method for conditioning, and thus enabling retrieval of intelligence from, magnetic tapes after damage from heat has caused the tape to wrinkle and curl severely thereby reducing tape width to less than one-half its original size. The damaged tape is superposed on a first piece of splicing tape with the oxide side of the magnetic tape in contact with the adhesive side of the splicing tape and then carefully smoothed by a special tool. A second piece of splicing tape is placed on the backing side of the magnetic tape then the resulting tape stack is trimmed to the original width of the magnetic tape. After the first piece of splicing tape is carefully removed from the oxide side of the damaged magnetic tape, the resulting magnetic tape is then ready to be placed into a recorder for playback.

Melugin, J. F.↗
NASA NTRS2017

Role of Mitochondrial Oxidative Stress in Spaceflight-Induced Tissue Degeneration

Microgravity and ionizing radiation in the spaceflight environment poses multiple challenges to homeostasis and may contribute to cellular stress. Effects may include increased generation of reactive oxygen species (ROS), DNA damage and repair error, cell cycle arrest, cell senescence or death. Our central hypothesis is that prolonged exposure to the spaceflight environment leads to the excess production of ROS and oxidative damage, culminating in accelerated tissue degeneration. The main goal of this project is to determine the importance of cellular redox defense for physiological adaptations and tissue degeneration in the space environment.

transgenic mic↗
NASA NTRS2001

Fiber-type susceptibility to eccentric contraction-induced damage of hindlimb-unloaded rat AL muscles

Slow oxidative (SO) fibers of the adductor longus (AL) were predominantly damaged during voluntary reloading of hindlimb unloaded (HU) rats and appeared explainable by preferential SO fiber recruitment. The present study assessed damage after eliminating the variable of voluntary recruitment by tetanically activating all fibers in situ through the motor nerve while applying eccentric (lengthening) or isometric contractions. Muscles were aldehyde fixed and resin embedded, and semithin sections were cut. Sarcomere lesions were quantified in toluidine blue-stained sections. Fibers were typed in serial sections immunostained with antifast myosin and antitotal myosin (which highlights slow fibers). Both isometric and eccentric paradigms caused fatigue. Lesions occurred only in eccentrically contracted control and HU muscles. Fatigue did not cause lesions. HU increased damage because lesioned- fiber percentages within fiber types and lesion sizes were greater than control. Fast oxidative glycolytic (FOG) fibers were predominantly damaged. In no case did damaged SO fibers predominate. Thus, when FOG, SO, and hybrid fibers are actively lengthened in chronically unloaded muscle, FOG fibers are intrinsically more susceptible to damage than SO fibers. Damaged hybrid-fiber proportions ranged between these extremes.

Non-NASA Center↗
NASA NTRS1985

Analysis of cavitation damage on the Space Shuttle main engine high pressure oxidizer turbopump

The performance of the Space Shuttle Main Engines (SSME) has met or exceeded specifications. However, the durability for selected components has not met the desired lifetime criteria. Thus, the High-Pressure Oxidizer Turbopump (HPOTP) has experienced cavitation erosion problems in a number of locations in the pump. An investigation was conducted, taking into account an analysis of the cavitation damage, the development of a flow model for the pump, and the recommendation of design changes which would increase the life expectancy of the unit. The present paper is concerned with the cavitation damage analysis. A model is presented which relates the heavy damage on the housing and over the inducer blades to unsteady blade surface cavitation. This cavitation occurs on the inducer blades in the wakes downstream of the pump inlet housing vanes.

Stinebring, D. R.↗
NASA NTRS2005

Titania Deposition on PMR-15

The formation, degree of crystallinity and adherence of dense titania (TiO2) thin film coatings on a high-temperature polyimide resin (PMR-15) can be influenced by the chemical composition of the polymer surface. Furthermore, solution deposition conditions can be adjusted to provide additional control over the morphology and crystallinity of the titania films. Recipes for solution-based titania deposition that used a slowly-hydrolyzing titanium fluoride salt in the presence of boric acid as a fluoride scavenger allowed growth of films up to 750 nm thick in 22 h. By adjusting solution pH and temperature, either amorphous titania or oriented crystalline anatase films could be formed. Surface sulfonate groups enhance the adhesion of solution-deposited oxide thin film coatings. While most sulfonation procedures severely damaged the PMR-15 surface, the use of chlorosulfonic acid followed by hydrolysis of the installed chlorosulfonyl groups provided effective surface sulfonation without significant surface damage. In some cases, the oxide deposition solution caused partial hydrolysis of the polymer surface, which itself was sufficient to allow adhesion of the titania film through chelation of titanium ions by exposed benzoic acid groups on the polymer surface.

Meador, Mary B.↗
NASA NTRS2006

Advanced Coating Removal Techniques

An important step in the repair and protection against corrosion damage is the safe removal of the oxidation and protective coatings without further damaging the integrity of the substrate. Two such methods that are proving to be safe and effective in this task are liquid nitrogen and laser removal operations. Laser technology used for the removal of protective coatings is currently being researched and implemented in various areas of the aerospace industry. Delivering thousands of focused energy pulses, the laser ablates the coating surface by heating and dissolving the material applied to the substrate. The metal substrate will reflect the laser and redirect the energy to any remaining protective coating, thus preventing any collateral damage the substrate may suffer throughout the process. Liquid nitrogen jets are comparable to blasting with an ultra high-pressure water jet but without the residual liquid that requires collection and removal .As the liquid nitrogen reaches the surface it is transformed into gaseous nitrogen and reenters the atmosphere without any contamination to surrounding hardware. These innovative technologies simplify corrosion repair by eliminating hazardous chemicals and repetitive manual labor from the coating removal process. One very significant advantage is the reduction of particulate contamination exposure to personnel. With the removal of coatings adjacent to sensitive flight hardware, a benefit of each technique for the space program is that no contamination such as beads, water, or sanding residue is left behind when the job is finished. One primary concern is the safe removal of coatings from thin aluminum honeycomb face sheet. NASA recently conducted thermal testing on liquid nitrogen systems and found that no damage occurred on 1/6", aluminum substrates. Wright Patterson Air Force Base in conjunction with Boeing and NASA is currently testing the laser remOval technique for process qualification. Other applications of liquid nitrogen operations include cutting of both soft and hard materials. While the laser will not cut materials, it can be used to roughen surfaces and to remove other materials from the substrate including oil, grease, and mold. The space program can benefit from several of these applications with the need for precise removal of coatings and other organic compounds in areas adjacent to sensitive space flight hardware. Significant advantages are evident when comparing liquid nitrogen and laser removal operations over current techniques of media blasting and sanding.

Seibert, Jon↗
NASA NTRS1972

Fretting wear in titanium, Monel-400, and cobalt 25-percent-molybdenum using scanning electron microscopy

Damage scar volume measurements taken from like metal fretting pairs combined with scanning electron microscopy observations showed that three sequentially operating mechanisms result in the fretting of titanium, Monel-400, and cobalt - 25-percent molybdenum. Initially, adhesion and plastic deformation of the surface played an important role. This was followed after a few hundred cycles by a fatigue mechanism which produced spall-like pits in the damage scar. Finally, a combination of oxidation and abrasion by debris particles became most significant. Damage scar measurements made on several elemental metals after 600,000 fretting cycles suggested that the ratio of oxide hardness to metal hardness was a measure of the susceptibility of a metal to progressive damage by fretting.

Bill, R. C.↗
NASA NTRS2009

Study of the Genes and Mechanism Involved in the Radioadaptive Response

The radioadaptive response is a phenomenon where exposure to a prior low dose of radiation reduces the level of damage induced by a subsequent high radiation dose. The molecular mechanism behind this is still not well understood. Learning more about the radioadaptive response is critical for long duration spaceflight since astronauts are exposed to low levels of cosmic radiation. The micronucleus assay was used to measure the level of damage caused by radiation. Although cells which were not washed with phosphate buffered saline (PBS) after a low priming dose of 5cGy did not show adaptation to the challenge dose, washing the cells with PBS and giving the cells fresh media after the low dose did allow radioadaptation to occur. This is consistent with the results of a previous publication by another research group. In the present study, genes involved in DNA damage signaling and the oxidative stress response were studied using RT PCR techniques in order to look at changes in expression level after the low dose with or without washing. Our preliminary results indicate that upregulation of oxidative stress response genes ANGPTL7, NCF2, TTN, and SRXN1 may be involved in the radioadaptive response. The low dose of radiation alone was found to activate the oxidative stress response genes GPR156 and MTL5, whereas, washing the cells alone caused relatively robust upregulation of the oxidative stress response genes DUSP1 and PTGS2. Washing after the priming dose showed some changes in the expression level of several DNA damage signaling genes. In addition, we studied whether washing the cells after the priming dose has an effect on the level of nitric oxide in both the media and cells, since nitric oxide levels are known to increase in the media of the cells after a high dose of radiation only if the cells were already exposed to a low priming dose. Based on this preliminary study, we propose that washing the cells after priming exposure actually eliminates some factor secreted by the cells that inhibits radioadaptation leading to the upregulation of some genes which initiates the response.

Dasgupta, Pushan R.↗