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All sourcesNASA NTRSDOE OSTI
NASA NTRSDate not supplied

Lunar BioSensor: An Autonomous Instrument to Study the Effects of the Lunar Environment on Biological Organisms

One of the major challenges to long-duration space travel and habitation in deep space is an in-depth understanding of the biological effects of space radiation, often convoluted by the impact of reduced gravity. Nonetheless, due to the near impossibility of simulating prolonged exposure to these combined effects in terrestrial facilities, actual missions are needed to characterize the radiobiological hazards of this environment. NASA Ames has been the leader in developing autonomous bio nanosatellites to address strategic knowledge gaps about the effects of space travel on biological organisms, including GeneSat, PharmaSat, EcAMSat, and BioSentinel. BioSentinel will be the first interplanetary bio nanosatellite or CubeSat to study the biological response to space radiation outside Low Earth Orbit (LEO). BioSentinel is an autonomous platform able to support biology and to investigate the effects of space radiation on a model organism in interplanetary deep space. It will fly onboard NASA’s Artemis-1, from which it will be deployed on a lunar fly-by trajectory and into a heliocentric orbit. The BioSentinel nanosatellite, a 6U deep space CubeSat (1U = 10-cm cube), will measure the DNA damage and response to ambient space radiation in a model biological organism, the budding yeast S. cerevisiae, which will be compared to information provided by an onboard physical radiation sensor and to data obtained in LEO (on the ISS) and on Earth. Even though the primary objective of the mission is to develop an autonomous spacecraft capable of conducting biological experiments in deep space, the 4U BioSensor science payload contained within the 6U free-flyer is an adaptable instrument platform that can perform biological measurements with different microorganisms and in multiple space environments, including the ISS, lunar gateway, and on the surface of the Moon. The proposed 4U instrument will leverage the payload design of the 6U free-flyer, utilizing the lunar lander or vehicle for power and data relay. Thus, nanosatellites like BioSentinel (and Lunar BioSensor) can be used to study the effects of both reduced gravity and space radiation and can house different bio organisms to answer specific science questions. In addition to their flexibility, nanosatellites also provide a low-cost alternative to more complex and larger missions, and require minimal crew support, if any.

space biosensors↗
NASA NTRS2017

Building Better Biosensors for Exploration into Deep-Space, Using Humanized Yeast

1.BioSentinel is 1 of 13 secondary payloads hitching a ride beyond Low Earth Orbit on Exploration Mission 1 (EM-1), set to launch from NASAs Space Launch System in 2019. EM-1 is our first opportunity to investigate the effects of the deep space environment on a eukaryotic biological system, the budding yeast S. cerevisiae. Though separated by a billion years of evolution we share hundreds of genes important for basic cell function, including responses to DNA damage. Thus, yeast is an ideal biosensor for detecting typesextent of damage induced by deep-space radiation.We will fly desiccated cells, then rehydrate to wake them up when the automated payload is ready to initiate the experiment. Rehydration solution contains SC (Synthetic Complete) media and alamarBlue, an indicator for changes in growth and metabolism. Telemetry of LED readings will then allow us to detect how cells respond throughout the mission. The desiccation-rehydration process can be extremely damaging to cells, and can severely diminish our ability to accurately measure and model cellular responses to deep-space radiation. The aim of this study is to develop a better biosensor: yeast strains that are more resistant to desiccation stress. We will over-express known cellular protectants, including hydrophilin Sip18, the protein disaggregase Hsp104, and thioredoxin Trx2, a responder to oxidative stress, then measure cell viability after desiccation to determine which factors improve stress tolerance. Over-expression of SIP18 in wine yeast starter cultures was previously reported to increase viability following desiccation stress by up to 70. Thus, we expect similar improvements in our space-yeast strains. By designing better yeast biosensors we can better prepare for and mitigate the potential dangers of deep-space radiation for future missions.This work is funded by NASAs AES program.

biosensor↗
NASA NTRS2005

NBS1 knockdown by small interfering RNA increases ionizing radiation mutagenesis and telomere association in human cells

Hypomorphic mutations which lead to decreased function of the NBS1 gene are responsible for Nijmegen breakage syndrome, a rare autosomal recessive hereditary disorder that imparts an increased predisposition to development of malignancy. The NBS1 protein is a component of the MRE11/RAD50/NBS1 complex that plays a critical role in cellular responses to DNA damage and the maintenance of chromosomal integrity. Using small interfering RNA transfection, we have knocked down NBS1 protein levels and analyzed relevant phenotypes in two closely related human lymphoblastoid cell lines with different p53 status, namely wild-type TK6 and mutated WTK1. Both TK6 and WTK1 cells showed an increased level of ionizing radiation-induced mutation at the TK and HPRT loci, impaired phosphorylation of H2AX (gamma-H2AX), and impaired activation of the cell cycle checkpoint regulating kinase, Chk2. In TK6 cells, ionizing radiation-induced accumulation of p53/p21 and apoptosis were reduced. There was a differential response to ionizing radiation-induced cell killing between TK6 and WTK1 cells after NBS1 knockdown; TK6 cells were more resistant to killing, whereas WTK1 cells were more sensitive. NBS1 deficiency also resulted in a significant increase in telomere association that was independent of radiation exposure and p53 status. Our results provide the first experimental evidence that NBS1 deficiency in human cells leads to hypermutability and telomere associations, phenotypes that may contribute to the cancer predisposition seen among patients with this disease.

Non-NASA Center↗
NASA NTRS2014

MicroRNA Expression Profiles in Cultured Human Fibroblasts in Space

Microgravity, or an altered gravity environment from the static 1g, has been shown to influence global gene expression patterns and protein levels in living organisms. However, it is unclear how these changes in gene and protein expressions are related to each other or are related to other factors regulating such changes. A different class of RNA, the small non-coding microRNA (miRNA), can have a broad effect on gene expression networks by mainly inhibiting the translation process. Previously, we investigated changes in the expression of miRNA and related genes under simulated microgravity conditions on the ground using the NASA invented bioreactor. In comparison to static 1 g, simulated microgravity altered a number of miRNAs in human lymphoblastoid cells. Pathway analysis with the altered miRNAs and RNA expressions revealed differential involvement of cell communication and catalytic activity, as well as immune response signaling and NGF activation of NF-kB pathways under simulated microgravity condition. The network analysis also identified several projected networks with c- Rel, ETS1 and Ubiquitin C as key factors. In a flight experiment on the International Space Station (ISS), we will investigate the effects of actual spaceflight on miRNA expressions in nondividing human fibroblast cells in mostly G1 phase of the cell cycle. A fibroblast is a type of cell that synthesizes the extracellular matrix and collagen, the structural framework for tissues, and plays a critical role in wound healing and other functions. In addition to miRNA expressions, we will investigate the effects of spaceflight on the cellular response to DNA damages from bleomycin treatment.

Wu, Honglu↗
NASA NTRS2020

BioSentinel ISS Control Experiment Investigation Summary Form

The main science objective of BioSentinel is to develop biosensors to study the effects of the space radiation environment on biological organisms. Given its similarities to human cells, we decided to use the budding yeast Saccharomyces cerevisiae. Yeast cells share homology to human cells, particularly in the response to DNA damage caused by ionizing radiation. Most importantly, yeast cells can be desiccated and survive in that form for long periods of time. Thus, budding yeast is the ideal model organism for long-term experiments in preparation for future manned missions to deep space. In addition to the ISS mission, our biosensors will fly in a nanosatellite designed for deep space, which is manifested to fly as a secondary payload onboard NASA’s Artemis-1 rocket.

BioSentinel↗
NASA NTRSDate not supplied

Development of Genetic Countermeasures for Enhancing Cellular Stress Tolerance on a Lunar Surface Mission

The Lunar Explorer Instrument for space biology Applications (LEIA) LEIA investigates the response to partial gravity and ionizing radiation of: Different DNA damage and stress response pathways and Bioproduction of antioxidants LEIA utilizes: Various strains of the yeast Saccharomyces cerevisiae, which will be desiccated in fluidic cards and rehydrated on the lunar surface LEIA develops: Genetic countermeasures to improve tolerance to the desiccation process and the constraints associated with long duration missions beyond low Earth orbit (LEO)

Neha Lingam↗
NASA NTRSDate not supplied

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↗
NASA NTRSDate not supplied

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↗
NASA NTRSDate not supplied

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↗
NASA NTRS2017

Modeling Space Radiation with Radiomimetic Agent Bleomycin

Space radiation consists of proton and helium from solar particle events (SPE) and high energy heavy ions from galactic cosmic ray (GCR). This mixture of radiation with particles at different energy levels has different effects on biological systems. Currently, majority studies of radiation effects on human were based on single-source radiation due to the limitation of available method to model effects of space radiation on living organisms. While NASA Space Radiation Laboratory is working on advanced switches to make it possible to have a mixed field radiation with particles of different energies, the radiation source will be limited. Development of an easily available experimental model for studying effects of mixed field radiation could greatly speed up our progress in our understanding the molecular mechanisms of damage and responses from exposure to space radiation, and facilitate the discovery of protection and countermeasures against space radiation, which is critical for the mission to Mars. Bleomycin, a radiomimetic agent, has been widely used to study radiation induced DNA damage and cellular responses. Previously, bleomycin was often compared to low low Linear Energy Transfer (LET) gamma radiation without defined characteristics. Our recent work demonstrated that bleomycin could induce complex clustered DNA damage in human fibroblasts that is similar to DNA damage induced by high LET radiation. These type of DNA damage is difficult to repair and can be visualized by gamma-H2Ax staining weeks after the initial insult. The survival ratio between early and late plating of human fibroblasts after bleomycin treatment is between low LET and high LET radiation. Our results suggest that bleomycin induces DNA damage and other cellular stresses resembling those resulted from mixed field radiation with both low and high LET particles. We hypothesize that bleomycin could be used to mimic space radiation in biological systems. Potential advantages and limitations of using bleomycin to treat biological specimen as an easily available model to study effects of space radiation on biological systems and to develop countermeasures for space radiation associated risks will be discussed.

Lu, Tao↗
NASA NTRSDate not supplied

Differential Gene Expression in A Cross-Feeding Two-Species Model Microbial Community Under Simulated Microgravity and Deep-Space Radiation

A long-term goal of space biology is to understand interspecies microbial interactions in space. Presently, little is known about the combined effect of microgravity and ionizing radiation on bacterial community response when species are interdependent through exchange of metabolites in fluid medium (cross-feeding). Microgravity is expected to slow interspecies mass transfer and growth in cross-feeding communities in the low-shear, diffusion-limited environment, while ionizing radiation may influence stress response to direct (DNA damage) and indirect damage (ROS). Using a well-understood, two-species (Escherichia coli and Salmonella enterica) microbial community engineered to be a model for studying cross-feeding, we simulated galactic cosmic rays (GCRsim) and microgravity to test the hypothesis: exposure to ionizing radiation causes cell damage or stress, altering transcriptomic community responses in metabolically interdependent cells, which is exacerbated by microgravity. We expect to see differential gene expression between cross-feeding and non-cross-feeding communities. We measured GCRsim effects on growth and gene expression in well-mixed versus simulated-microgravity conditions and in cross-feeding and non-cross-feeding medium. Microbial cultures were inoculated into liquid medium in rotating wall vessels (RWV) with different rotation rates: 5 RPM (simulated microgravity) and 50 RPM (well-mixed). The E. coli-S. enterica consortium, under simulated microgravity, were exposed to 500 mGy of Simplified 5-ion Galactic Cosmic Ray Simulation for 2 hours at Brookhaven National Lab. We harvested samples 40 minutes after irradiation for extraction and sequencing (NASA GeneLab). Here we present the differential gene expression analysis results, which reveal altered transcriptomic community responses, even where growth rate differences are not observed. Gene expression of these actively metabolizing microbial communities in GCRsim may illuminate molecular mechanisms of microbial interactions in space. Understanding how microbial community gene expression, metabolism, and other cellular processes are influenced by spaceflight stressors can inform the use of microbes in human life support for low Earth orbit missions and beyond.

microgravity↗
NASA NTRSDate not supplied

Improving Data Analyses for a Biological Mission to Deep Interplanetary Space

Onboard the Artemis 1 rocket, NASA plans to launch the first deep space bioscience mission past low Earth orbit (LEO) since 1972, BioSentinel, a 6-Unit (6U) biological CubeSat. BioSentinel’s goals are to assess the effect of deep space ionizing radiation (IR) on DNA and cell damage response, using Saccharomyces cerevisiae, or budding yeast, as a model organism. BioSentinel accomplishes this by measuring Optical Density (OD) in addition to metabolic activity using the redox dye alamarBlue, both of which will be read through light emitting diode (LED) lights of differing wavelengths. With the largest and most sophisticated energy-providing solar panels utilized on a biological CubeSat to date, BioSentinel will be equipped with an IR dosimeter to identify what doses of radiation the yeast is exposed to at any point in time, in addition to a transponder to send such data back to NASA Ames’ Multi Mission Operations Center (MMOC). Biology computational programs and data processing scripts are necessary to analyze this complex data once it is received, including automated subroutines to analyze duplication rate, alamarBlue reduction, and time periods when paired against numerous other variables. Overall, we have implemented several VisualBasic biocomputational programs to analyze such data in an organized and efficient manner so that conclusions can be made rapidly. Furthermore, we showcase why efficient analysis of particular parameters is important to better understand the risks that deep space IR poses to astronauts, especially when considering the upcoming Artemis missions.

Bijan Harandi↗
NASA NTRS2015

BioSentinel: Developing a Space Radiation Biosensor

BioSentinel is an autonomous fully self-contained science mission that will conduct the first study of the biological response to space radiation outside low Earth orbit (LEO) in over 40 years. The 4-unit (4U) BioSentinel biosensor system, is housed within a 6-Unit (6U) spacecraft, and uses yeast cells in multiple independent microfluidic cards to detect and measure DNA damage that occurs in response to ambient space radiation. Cell growth and metabolic activity will be measured using a 3-color LED detection system and a metabolic indicator dye with a dedicated thermal control system per fluidic card.

Radiation biosensor↗
NASA NTRS2007

Chromosome Model reveals Dynamic Redistribution of DNA Damage into Nuclear Sub-domains

Several proteins involved in the response to DNA double strand breaks (DSB) form microscopically visible nuclear domains, or foci, after exposure to ionizing radiation. Radiation-induced foci (RIF) are believed to be located where DNA damage is induced. To test this assumption, we analyzed the spatial distribution of 53BP1, phosphorylated ATM and gammaH2AX RIF in cells irradiated with high linear energy transfer (LET) radiation. Since energy is randomly deposited along high-LET particle paths, RIF along these paths should also be randomly distributed. The probability to induce DSB can be derived from DNA fragment data measured experimentally by pulsed-field gel electrophoresis. We used this probability in Monte Carlo simulations to predict DSB locations in synthetic nuclei geometrically described by a complete set of human chromosomes, taking into account microscope optics from real experiments. As expected, simulations produced DNA-weighted random (Poisson) distributions. In contrast, the distributions of RIF obtained as early as 5 min after exposure to high LET (1 GeV/amu Fe) were non-random. This deviation from the expected DNA-weighted random pattern can be further characterized by relative DNA image measurements. This novel imaging approach shows that RIF were located preferentially at the interface between high and low DNA density regions, and were more frequent in regions with lower density DNA than predicted. This deviation from random behavior was more pronounced within the first 5 min following irradiation for phosphorylated ATM RIF, while gammaH2AX and 53BP1 RIF showed very pronounced deviation up to 30 min after exposure. These data suggest the existence of repair centers in mammalian epithelial cells. These centers would be nuclear sub-domains where DNA lesions would be collected for more efficient repair.

Costes, Sylvain V.↗
NASA NTRS2002

Computational Model of the Modulation of Gene Expression Following DNA Damage

High linear energy transfer (LET) radiation, such as heavy ions or neutrons, has an increased biological effectiveness compared to X rays for gene mutation, genomic instability, and carcinogenesis. In the traditional paradigm, mutations or chromosomal aberrations are causative of late effects. However, in recent years experimental evidence has demonstrated the important role of the description of the modification of gene expression by radiation in understanding the mechanisms of radiation action. In this report, approaches are discussed to the mathematical description of mRNA and protein expression kinetics following DNA damage. Several hypotheses for models of radiation modulation of protein expression are discussed including possible non-linear processes that evolve from the linear dose responses that follow the initial DNA damage produced by radiation.

NASA Center JSC↗
NASA NTRS2002

Relative biological effectiveness of light ions in human tumoural cell lines: role of protein p53

Protons and alpha particles of high linear energy transfer (LET) have shown an increased relative biological effectiveness (RBE) with respect to X/gamma rays for several cellular and molecular endpoints in different in vitro cell systems. To contribute to understanding the biochemical mechanisms involved in the increased effectiveness of high LET radiation, an extensive study has been designed. The present work reports the preliminary result of this study on two human tumoural cell lines, DLD1 and HCT116, (with different p53 status), which indicate that for these cell lines, p53 does not appear to take a part in the response to radiation induced DNA damage, suggesting an alternative p53-independent pathway and a cell biochemical mechanism dependent on the cell type.

NASA Center JSC↗
NASA NTRS2016

Effects of Hindlimb Unloading and Ionizing Radiation on Murine Gene Expression in Skin and Bone

Long duration spaceflight causes a negative calcium balance and reduces bone density in astronauts. The underlying mechanisms of spaceflight-induced bone loss and the possible influences of both microgravity and radiation are not fully understood although emerging evidence suggests that these two factors may interact to result in increased bone loss. Previously, gene expression analysis of hair follicles from astronauts, as well as skin from space-flown mice, revealed changes in the expression of genes related to DNA damage and oxidative stress responses. These results resemble the responses of bone to spaceflight-like radiation and simulated weightlessness by hindlimb unloading (HU). Hence in this study, we initiated studies to determine whether skin can be used to predict the responses of bone to simulated microgravity and radiation. We examined oxidative stress and growth arrest pathways in mouse skin and long bones by measuring gene expression levels via quantitative polymerase chain reaction (qPCR). To investigate the effects of irradiation andor HU on gene expression, we used skin and femora (cortical shaft) from the following treatment groups: control (normally loaded, sham-irradiated) (CT), hindlimb unloading (HU), 56Fe radiation (IR) and both HU+IR. Animals were euthanized 11 days post-IR, and results were analyzed by 1-way ANOVA. In skin samples, Cdkn1a was decreased to the same extent in HU and HU+IR (47 of CT). In addition, HU reduced FoxO3 expression (46 of CT) and IR increased Gadd45g expression 135 compared CT in skin. But in bone, HU increased FoxO3 expression 31 compared the level of CT. These results suggest that radiation and simulated weightlessness regulated simliar oxidative stress and cell cycle arrest genes in both skin and bone, although the time course and direction of changes may differ. This research may lead to the development of a relatively simple diagnostic tool for bone loss with the advantage that hair follicles and skin are relatively easy to acquire from subjects.

Terada, Masahiro↗
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.↗