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At least 451 records · Page 25

Chromosomal changes in cultured human epithelial cells transformed by low- and high-LET radiation

For a better assessment of radiation risk in space, an understanding of the responses of human cells, especially the epithelial cells, to low- and high-LET radiation is essential. In our laboratory, we have successfully developed techniques to study the neoplastic transformation of two human epithelial cell systems by ionizing radiation. These cell systems are human mammary epithelial cells (H184B5) and human epidermal keratinocytes (HEK). Both cell lines are immortal, anchorage dependent for growth, and nontumorigenic in athymic nude mice. Neoplastic transformation was achieved by irradiating cells successively. Our results showed that radiogenic cell transformation is a multistep process and that a single exposure of ionizing radiation can cause only one step of transformation. It requires, therefore, multihits to make human epithelial cells fully tumorigenic. Using a simple karyotyping method, we did chromosome analysis with cells cloned at various stages of transformation. We found no consistent large terminal deletion of chromosomes in radiation-induced transformants. Some changes of total number of chromosomes, however, were observed in the transformed cells. These transformants provide an unique opportunity for further genetic studies at a molecular level.

NASA Discipline Number 04-10↗

Updates to Composite Analysis Base Case and Null Space Monte Carlo Sensitivity Based on New Unit Dose Factors

This environmental calculation file (ECF) presents the results of the exposure route-specific and total radiological dose assessments for the groundwater exposure pathway as a part of the updated Composite Analysis for Low-Level Waste Disposal in the Hanford Site Central Plateau (FY 2022), based on revised unit dose factors (UDFs) published in CA Special Studies: Updates to the Groundwater Pathway Radiological Dose. The reason for these radiological dose assessments is to estimate the cumulative radiological impacts from all screened sources of ionizing radiation and exposure routes that could potentially contribute to the projected dose to a hypothetical member of the public. Sources of ionizing radiation can include existing or future disposal facilities and other sources including past-practice discharge sites. Additionally, the results of the exposure route-specific and total radiological dose assessments have been revised for the groundwater pathway based on the null space Monte Carlo (NSMC) groundwater concentrations and the most recent updates to the UDFs as a part an uncertainty analysis for the updated Hanford Site CA.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Quantitative image analysis of laminin immunoreactivity in skin basement membrane irradiated with 1 GeV/nucleon iron particles

We previously reported that laminin immunoreactivity in mouse mammary epithelium is altered shortly after whole-body irradiation with 0.8 Gy from 600 MeV/nucleon iron ions but is unaffected after exposure to sparsely ionizing radiation. This observation led us to propose that the effect could be due to protein damage from the high ionization density of the ion tracks. If so, we predicted that it would be evident soon after radiation exposure in basement membranes of other tissues and would depend on ion fluence. To test this hypothesis, we used immunofluorescence, confocal laser scanning microscopy, and image segmentation techniques to quantify changes in the basement membrane of mouse skin epidermis. At 1 h after exposure to 1 GeV/nucleon iron ions with doses from 0.03 to 1.6 Gy, neither the visual appearance nor the mean pixel intensity of laminin in the basement membrane of mouse dorsal skin epidermis was altered compared to sham-irradiated tissue. This result does not support the hypothesis that particle traversal directly affects laminin protein integrity. However, the mean pixel intensity of laminin immunoreactivity was significantly decreased in epidermal basement membrane at 48 and 96 h after exposure to 0.8 Gy 1 GeV/nucleon iron ions. We confirmed this effect with two additional antibodies raised against affinity-purified laminin 1 and the E3 fragment of the long-arm of laminin 1. In contrast, collagen type IV, another component of the basement membrane, was unaffected. Our studies demonstrate quantitatively that densely ionizing radiation elicits changes in skin microenvironments distinct from those induced by sparsely ionizing radiation. Such effects may might contribute to the carcinogenic potential of densely ionizing radiation by altering cellular signaling cascades mediated by cell-extracellular matrix interactions.

Non-NASA Center↗

Thermoluminescent dosimetry for the Apollo 16 microbial response to space environment experiment (M191)

Lithium fluoride thermoluminescent chips were used to provide an integrated dose from the broad spectrum of ionizing radiation to the Microbial Response to Space Environment Experiment (M191). The chips were positioned in the flight hardware to provide data on ionizing radiation within specific volume segments. A uniform radiation dose of 4.8 x 0.001 plus or minus 2 x 0.0001 joule/kg resulted.

Brown, R. D.↗

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↗

Effects of high energy radiation on the mechanical properties of epoxy/graphite fiber reinforced composites

The epoxy resin system formed by tetraglycidyl 4,4'-diamino diphenyl methane (TGDDM) and 4,4'-diamino diphenyl sulfone (DDS) was characterized by dynamic mechanical analysis and differential scanning calorimetry. Dynamic mechanical properties of graphite fiber epoxy composite specimens formulated with two different adhesive systems (NARMCO 5208, NARMCO 5209) were determined. The specimens were exposed to varying dose levels of ionizing radiation (0.5 MeV electrons) with a maximum absorbed dose of 10,000 Mrads. Following irradiation, property measurements were made to assess the influence of radiation on the epoxy and composite specimens. The results established that ionizing radiation has a limited effect on the properties of epoxy and composite specimens.

Fornes, R. E.↗

Cell Radiation Experiment System

The cell radiation experiment system (CRES) is a perfused-cell culture apparatus, within which cells from humans or other animals can (1) be maintained in homeostasis while (2) being exposed to ionizing radiation during controlled intervals and (3) being monitored to determine the effects of radiation and the repair of radiation damage. The CRES can be used, for example, to determine effects of drug, radiation, and combined drug and radiation treatments on both normal and tumor cells. The CRES can also be used to analyze the effects of radiosensitive or radioprotectant drugs on cells subjected to radiation. The knowledge gained by use of the CRES is expected to contribute to the development of better cancer treatments and of better protection for astronauts, medical-equipment operators, and nuclear-power-plant workers, and others exposed frequently to ionizing radiation.

Morrison, Dennis R.↗

Dodecane Radiolysis Yields by Time-Resolved and Steady-State Methods

Liquid organic molecules are present as solvents, complexing ligands, and additives in both used nuclear fuel reprocessing solvent systems and in their subsequent nuclear waste streams. Under these extreme environments, these organic molecules are constantly exposed to ionizing radiation which promotes their radiolysis, forming a variety of short-lived, highly energetic, excited state and radical species.1-4 Here, we demonstrate new experimental results for the steady-state and time-resolved irradiations of dodecane (C12H26), a long chain, liquid, aliphatic hydrocarbon that is the prototypical solvent used for benchtop studies of aqueous-organic solvent extraction systems. When ionizing radiation interacts with neat dodecane, the energy transfer can result in molecular ionization, to give the dodecane radical cation (C12H26+•) and the solvated electron (eS–), and molecular electronic excitation (C12H26*), which rapidly produces transient carbon-centered radical fragments (CxHy•) and hydrogen atoms (H•).1-4 Studies on the initial yields of the ionization and excitation products were performed using time-resolved picosecond electron pulse radiolysis with the use of molecular probes. Using steady-state cobalt-60 gamma irradiations, the suite of products formed by dodecane radiolysis in aerated and deaerated solutions was determined. Then, using iodine as an alkyl radical scavenger, the loss of molecular iodine with dose was quantified, and by correlating with the molecular hydrogen yields of the system, the initial yields of the various carbon-centered radicals were also determined. Finally, the rates of reactions of the C12H26+• and eS– with ligands proposed for use in spent nuclear fuel reprocessing were studied as a function of temperature from 10 – 40 °C.

38 - RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCL↗

Vacuum gage system for radiation environment

Hot-cathode ionization gages used to measure high-vacuum pressures are subject to error when ionizing radiation is present. Because this radiation creates additional ions, a second ion gage is mounted near the pressure-measuring gage to detect and measure the radiation induced error.

Summers, R. L.↗

Solid state neutron dosimeter for space applications

Personnel engaged in space flight are exposed to significant flux of high energy neutrons arising from both primary and secondary sources of ionizing radiation. Presently, there exist no compact neutron sensor capable of being integrated in a flight instrument to provide real time measurement of this radiation flux. A proposal was made to construct such an instrument using special PIN silicon diode which has the property of being insensitive to the other forms of ionizing radiation. Studies were performed to determine the design and construction of a better reading system to allow the PIN diode to be read with high precision. The physics of the device was studied, especially with respect to those factors which affect the sensitivity and reproducibility of the neutron response. This information was then used to develop methods to achieve high sensitivity at low neutron doses. The feasibility was shown of enhancing the PIN diode sensitivity to make possible the measurement of the low doses of neutrons encountered in space flights. The new PIN diode will make possible the development of a very compact, accurate, personal neutron dosimeter.

Entine, Gerald↗

Altered Immune Differentials Between Male and Female Mice Independent of Ionizing Irradiation

As upcoming exploratory missions to the Lunar surface and Mars during the Artemis Program will send both female and male crewmembers, studies identifying sex-specific effects are necessary. It is well-documented that the immune system engages different responses between females and males following exposures to infectious challenge, tumors surveillance, and autoimmune development. Yet, the immune effects of spaceflight-like exposures between the sexes are limited. Therefore, this study sought to address the effects of spaceflight-like conditions on immune differentials in female and male mice. We hypothesized that the spaceflight factor, ionizing radiation, will have sex-specific effects on immune differentials. To test this, singly-housed, 12-month old female and male wildtype (Wt) mice were exposed to acute ionizing gamma irradiation (50 cGy), followed by retro-orbital blood collections at 7-days post-irradiation. Leukocytes were analyzed by flow cytometry characterizing, granulocytes, monocytes, lymphocytes (cytotoxic/helper T cells and B cells), neutrophils, eosinophils, and NK/NKT cells. Briefly, minimal sex-specific effects were observed across the cell types listed at this time point, including changes in granulocyte and lymphocyte populations. The results revealed females displayed elevated granulocytes and reduced lymphocytes compared to their male counterparts, independent of irradiation exposure. These results suggest female mice may be more capable to produce innate inflammatory mediators but may be adaptively immune compromised. In brief, this study provides insight into the sex-specific immune risks following ionizing radiation that may be experienced during spaceflight, which is relevant for future countermeasure development.

spaceflight stressors↗

Altered Immune Differentials Between Male and Female Mice Independent of Ionizing Irradiation

As upcoming exploratory missions to the Lunar surface and Mars during the Artemis Program will send both female and male crewmembers, studies identifying sex-specific effects are necessary. It is well-documented that the immune system engages different responses between females and males following exposures to infectious challenge, tumors surveillance, and autoimmune development. Yet, the immune effects of spaceflight-like exposures between the sexes are limited. Therefore, this study sought to address the effects of spaceflight-like conditions on immune differentials in female and male mice. We hypothesized that the spaceflight factor, ionizing radiation, will have sex-specific effects on immune differentials. To test this, singly-housed, 12-month old female and male wildtype (Wt) mice were exposed to acute ionizing gamma irradiation (50 cGy), followed by retro-orbital blood collections at 7-days post-irradiation. Leukocytes were analyzed by flow cytometry characterizing, granulocytes, monocytes, lymphocytes (cytotoxic/helper T cells and B cells), neutrophils, eosinophils, and NK/NKT cells. Briefly, minimal sex-specific effects were observed across the cell types listed at this time point, including changes in granulocyte and lymphocyte populations. The results revealed females displayed elevated granulocytes and reduced lymphocytes compared to their male counterparts, independent of irradiation exposure. These results suggest female mice may be more capable to produce innate inflammatory mediators but may be adaptively immune compromised. In brief, this study provides insight into the sex-specific immune risks following ionizing radiation that may be experienced during spaceflight, which is relevant for future countermeasure development.

spaceflight stressors↗

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↗

Radiation-induced dry reforming: A negative emission process

The reaction between the most abundant greenhouse gases (GHG) to produce hydrogen might represent the most powerful and effective decarbonizing opportunity, if a low-carbon energy source is used to drive it. This is the case of methane (CH 4 ) dry reforming (MDR) where its reaction with carbon dioxide (CO 2 ) produces synthesis gas (syngas, a mixture of carbon monoxide and hydrogen). Here this study explores the feasibility of using ionizing radiation to induce the MDR reaction, at low temperatures and/or less energy demanding conditions. Additionally, the ionizing radiation is proposed to be supplied by nuclear power plants (NPPs), which are low-carbon reliable energy generation sources. Thus, the radiolysis of CO 2 , CH 4 and their mixtures, under ?-irradiation was evaluated in the absence and presence of nickel catalysts. The radiation-induced MDR reaction and radiation-induced catalytic promotion were proven to take place at temperatures close to ambient though at low conversion, with yields below 1%. Since irradiation and heat can be provided by a nuclear power plant, this radiation-induced reaction establishes a connection between nuclear energy to renewable resources and enables a pathway for a decarbonized cleaner chemical industry, for producing green chemicals.

08 HYDROGEN↗

Reevaluation of Radiation-Protection Standards for Workers and the Public Based on Current Scientific Evidence

President Trump’s recent executive orders to “Usher in a Nuclear Renaissance,” coupled with the global pledge to triple nuclear energy capacity by 2050, underscore nuclear energy’s importance to national security and economic prosperity. This renewed interest has prompted efforts to spur nuclear-energy deployment, including assessing factors impeding it. One issue that has previously been identified as adding to the cost of nuclear energy is excessively conservative requirements, including those related to radiation protection. This technical review, therefore, examines current radiation-protection standards that were established decades ago when more limited data were available and nuclear-energy expansion was not a national priority. The review focuses on scientific evidence regarding the health effects of ionizing radiation at annual doses of 10,000 mrem or less. The review evaluates epidemiological studies, radiobiological research, and positions of relevant professional organizations to assess whether such doses result in discernable or observable increases in negative health outcomes. The review also surveys the literature related to economic and practical implications of current radiation-protection standards and practices. Based on this assessment, we propose maintaining an annual occupational whole-body dose limit of 5,000 mrem/yr and eliminating all “as low as reasonably achievable” requirements and limits below this threshold. This change could potentially reduce radiation-protection costs by millions of dollars annually for each reactor, as well as decrease the overall costs and correct misconceptions about the risks associated with all nuclear technologies. The evidence further supports future consideration of a 10,000 mrem/yr limit that would maintain appropriate safety margins while further reducing protection costs. Similarly, given the data and that the average annual radiation dose per person in the U.S. is 620 mrem, we believe the public dose limits of 100 mrem/yr are unnecessarily restrictive; increasing to 500 mrem/yr would maintain substantial safety margins—a factor of 10 below the occupational limit—while reducing regulatory burdens and associated bureaucracy. While we acknowledge ongoing scientific debate and encourage continued research on the health effects of ionizing radiation, our review indicates current frameworks are overly conservative. These overly stringent limits not only impose unnecessary economic burdens without corresponding health benefits but also divert safety focus and resources from more important considerations. Although this study was motivated by nuclear-power considerations, reforms to radiation-protection requirements have significant positive implications for other areas, such as nuclear medical applications, environmental remediation, nuclear-waste management and disposal, and industrial applications of nuclear technologies.

61 RADIATION PROTECTION AND DOSIMETRY↗

The Formation of Organic Compounds of Astrobiological Interest by the Irradiation Processing of Astrophysical Ices

Many environments in space contain very low temperature mixed molecular ices that are exposed to ionizing radiation in the form of cosmic rays and high-energy photons. While traditional chemistry would not be expected to occur at the temperatures typical of these ices (T < 50 K), ionizing radiation can break bonds in the original molecules in the ices to form highly reactive ions and radicals. These ions and radicals are subsequently free to react despite the low temperatures of the original ices. Laboratory experiments, many of them carried out at the Astrochemistry Laboratory at NASA-Ames, show that the irradiation of ices made of even simple molecules like H2O, CO, CO2, CH4, NH3, etc. can result in the robust formation of large numbers of far more complex organic compounds. Many of these new products are of direct interest to astrobiology. For example, the irradiation of mixed molecular ices has been shown to produce amino acids, amphiphiles, quinones, sugars, heterocyclic compounds, and nucleobases, all molecular building blocks used by terrestrial life. Insofar as the presence of these materials plays a role in the origin of life on planets, this has profound implications for the potential abundance of life in the universe since these experiments simulate universal conditions that are expected to be found wherever new stars and planets form.

Astrobiology↗

Heavy-ion radiobiology: new approaches to delineate mechanisms underlying enhanced biological effectiveness

Shortly after the discovery of polonium and radium by Marie Curie and her husband and colleague, Pierre Curie, it was learned that exposure to these alpha-particle emitters produced deleterious biological effects. The mechanisms underlying the increased biological effectiveness of densely ionizing radiations, including alpha particles, neutrons and highly energetic heavy charged particles, remain an active area of investigation. In this paper, we review recent advances in several areas of the radiobiology of these densely ionizing radiations, also known as heavy ions. Advances are described in the areas of DNA damage and repair, chromosome aberrations, mutagenesis, neoplastic transformation in vitro, genomic instability, normal tissue radiobiology and carcinogenesis in vivo. We focus on technical innovations, including novel applications of pulsed-field gel electrophoresis, fluorescence in situ hybridization (FISH), linkage analysis, and studies of gene expression and protein expression. We also highlight the use of new cellular and animal systems, including those with defined DNA repair deficiencies, as well as epithelial cell model systems to assess neoplastic transformation both in vitro and in vivo. The studies reviewed herein have had a substantial impact on our understanding of the genotoxic effects of heavy ions as well as their distinct effects on tissue homeostasis. The use of these radiations in cancer therapy is also discussed. The use of both heavy-ion and proton therapy is on the upswing in several centers around the world, due to their unique energy deposition characteristics that enhance the therapeutic effect and help reduce damage to normal tissue.

Review, Academic↗