Results for “radiation carcinogenesis” — Page 4

NASA NTRS2016

Risky Business: The Science and Art of Radiation Risk Communication in the High Risk Context of Space Travel

Successfully communicating the complex risks associated with radiation exposure is a difficult undertaking; communicating those risks within the high-risk context of space travel is uniquely challenging. Since the potential risks of space radiation exposure are not expected to be realized until much later in life, it is hard to draw comparisons between other spaceflight risks such as hypoxia and microgravity-induced bone loss. Additionally, unlike other spaceflight risks, there is currently no established mechanism to mitigate the risks of incurred radiation exposure such as carcinogenesis. Despite these challenges, it is the duty of the Space Radiation Analysis Group (SRAG) at NASA's Johnson Space Center to provide astronauts with the appropriate information to effectively convey the risks associated with exposure to the space radiation environment. To this end, astronauts and their flight surgeons are provided with an annual radiation risk report documenting the astronaut's individual radiation exposures from space travel, medical, and internal radiological procedures throughout the astronaut's career. In an effort to improve this communication and education tool, this paper critically reviews the current report style and explores alternative report styles to define best methods to appropriately communicate risk to astronauts, flight surgeons, and management.

Elgart, Shona Robin↗

NASA NTRS1999

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↗

NASA NTRSDate not supplied

RadLab: Graphical and Programming Interfaces for Interrogation of Space Telemetry Data

Sensors on multiple spacecraft in and beyond low Earth orbit continuously monitor and collect space radiation data and transmit it back to Earth. These data are of vast importance to space biology research, as ionizing radiation affects living organisms—astronauts and non-human experiment subjects alike—placing them at higher risk of carcinogenesis, degenerative diseases, and radiation sickness. Therefore, knowledge of the biological effects of space radiation is essential for planning future crewed missions beyond low Earth orbit. The RadLab project, initiated by GeneLab and ALSDA (the Open Science Data Repository; OSDR) and sponsored by the NASA Human Research Program, is a new effort aimed at connecting dosimetry data from radiation detectors located on the International Space Station (ISS), as well as other spacecraft. To date, access to these data has been fragmented across space agencies and databases; to address this issue, we have developed an application programming interface (API) and an associated graphical user interface (GUI) designed to provide a single point of access to the data. As of now, OSDR has focused on the detectors located on the ISS, with the long-term goal to establish a self-sustained portal receiving continuous updates through APIs connecting to multiple radiation databases of varying scope, as well as individual investigator contributions. The RadLab API implements a request syntax enabling users to query data by craft, sensor type, timespan, etc, allowing for arbitrary combinations of original source data, thus providing programmatic access for use in computational pipelines, while the GUI facilitates data visualization and exploration, making these data FAIR (Findable, Accessible, Interoperable, and Reusable), complementing the biological data contained in OSDR, and providing the space science community with a valuable resource for scientific analyses.

radiation↗

DOE OSTI2021

Quantitative modeling of carcinogenesis induced by single beams or mixtures of space radiations using targeted and non-targeted effects

Abstract Ionizing radiations encountered by astronauts on deep space missions produce biological damage by two main mechanisms: (1) Targeted effects (TE) due to direct traversals of cells by ionizing tracks. (2) Non-targeted effects (NTE) caused by release of signals from directly hit cells. The combination of these mechanisms generates non-linear dose response shapes, which need to be modeled quantitatively to predict health risks from space exploration. Here we used a TE + NTE model to analyze data on APC (1638N/+) mouse tumorigenesis induced by space-relevant doses of protons, 4 He, 12 C, 16 O, 28 Si or 56 Fe ions, or γ rays. A customized weighted Negative Binomial distribution was used to describe the radiation type- and dose-dependent data variability. This approach allowed detailed quantification of dose–response shapes, NTE- and TE-related model parameters, and radiation quality metrics (relative biological effectiveness, RBE, and radiation effects ratio, RER, relative to γ rays) for each radiation type. Based on the modeled responses for each radiation type, we predicted the tumor yield for a Mars-mission-relevant mixture of these radiations, using the recently-developed incremental effect additivity (IEA) synergy theory. The proposed modeling approach can enhance current knowledge about quantification of space radiation quality effects, dose response shapes, and ultimately the health risks for astronauts.

60 APPLIED LIFE SCIENCES↗

NASA NTRSDate not supplied

Modeling Space-Radiation Induced Chromosome Aberrations

Exposure to ionizing radiation is identified as one of the main hazards of space flight. Galactic cosmic rays (GCRs) are composed of energetic protons (87%), helium nuclei (12%) and high-charge and energy (HZE) ions. At the cellular scale, HZE ions have a pattern of energy deposition that depends on the ion linear energy transfer (LET), with high LET ions favoring the formation of complex DNA damages that induce chromosome aberrations (CAs). Understanding how physical (e.g., ion type and energy) and biological (e.g., cell type) parameters impact CA formation is required to assess space radiation risks such as carcinogenesis. The Monte Carlo tool RITCARD/RITRACKS [1,2] developed by NASA allows simulation of the transport of HZE ions and subsequent energy deposition at the cellular scale and models the creation of DNA double strand breaks (DSBs), DNA repair and formation of CAs. We used this radiation transport code to further understand how radiation quality and cell size affects CA formation.

Floriane Poignant↗

NASA NTRS2015

Addressing Human System Risks to Future Space Exploration

NASA is contemplating future human exploration missions to destinations beyond low Earth orbit, including the Moon, deep-space asteroids, and Mars. While we have learned much about protecting crew health and performance during orbital space flight over the past half-century, the challenges of these future missions far exceed those within our current experience base. To ensure success in these missions, we have developed a Human System Risk Board (HSRB) to identify, quantify, and develop mitigation plans for the extraordinary risks associated with each potential mission scenario. The HSRB comprises research, technology, and operations experts in medicine, physiology, psychology, human factors, radiation, toxicology, microbiology, pharmacology, and food sciences. Methods: Owing to the wide range of potential mission characteristics, we first identified the hazards to human health and performance common to all exploration missions: altered gravity, isolation/confinement, increased radiation, distance from Earth, and hostile/closed environment. Each hazard leads to a set of risks to crew health and/or performance. For example the radiation hazard leads to risks of acute radiation syndrome, central nervous system dysfunction, soft tissue degeneration, and carcinogenesis. Some of these risks (e.g., acute radiation syndrome) could affect crew health or performance during the mission, while others (e.g., carcinogenesis) would more likely affect the crewmember well after the mission ends. We next defined a set of design reference missions (DRM) that would span the range of exploration missions currently under consideration. In addition to standard (6-month) and long-duration (1-year) missions in low Earth orbit (LEO), these DRM include deep space sortie missions of 1 month duration, lunar orbital and landing missions of 1 year duration, deep space journey and asteroid landing missions of 1 year duration, and Mars orbital and landing missions of 3 years duration. We then assessed the likelihood and consequences of each risk against each DRM, using three levels of likelihood (Low: less than or equal to 0.1%; Medium: 0.1%–1.0%; High: greater than or equal to 1.0%) and four levels of consequence ranging from Very Low (temporary or insignificant) to High (death, loss of mission, or significant reduction to length or quality of life). Quantitative evidence from clinical, operational, and research sources were used whenever available. Qualitative evidence was used when quantitative evidence was unavailable. Expert opinion was used whenever insufficient evidence was available. Results: A set of 30 risks emerged that will require further mitigation efforts before being accepted by the Agency. The likelihood by consequence risk assessment process provided a means of prioritizing among the risks identified. For each of the high priority risks, a plan was developed to perform research, technology, or standards development thought necessary to provide suitable reduction of likelihood or consequence to allow agency acceptance. Conclusion: The HSRB process has successfully identified a complete set of risks to human space travelers on planned exploration missions based on the best evidence available today. Risk mitigation plans have been established for the highest priority risks. Each risk will be reassessed annually to track the progress of our risk mitigation efforts.

Paloski, W. H.↗

NASA NTRS2005

Managing Space Radiation Risks On Lunar and Mars Missions: Risk Assessment and Mitigation

Radiation-induced health risks are a primary concern for human exploration outside the Earth's magnetosphere, and require improved approaches to risk estimation and tools for mitigation including shielding and biological countermeasures. Solar proton events are the major concern for short-term lunar missions (<60 d), and for long-term missions (>60 d) such as Mars exploration, the exposures to the high energy and charge (HZE) ions that make-up the galactic cosmic rays are the major concern. Health risks from radiation exposure are chronic risks including carcinogenesis and degenerative tissue risks, central nervous system effects, and acute risk such as radiation sickness or early lethality. The current estimate is that a more than four-fold uncertainty exists in the projection of lifetime mortality risk from cosmic rays, which severely limits analysis of possible benefits of shielding or biological countermeasure designs. Uncertainties in risk projections are largely due to insufficient knowledge of HZE ion radiobiology, which has led NASA to develop a unique probabilistic approach to radiation protection. We review NASA's approach to radiation risk assessment including its impact on astronaut dose limits and application of the ALARA (As Low as Reasonably Achievable) principle. The recently opened NASA Space Radiation Laboratory (NSRL) provides the capability to simulate the cosmic rays in controlled ground-based experiments with biological and shielding models. We discuss how research at NSRL will lead to reductions in the uncertainties in risk projection models. In developing mission designs, the reduction of health risks and mission constraints including costs are competing concerns that need to be addressed through optimization procedures. Mitigating the risks from space radiation is a multi-factorial problem involving individual factors (age, gender, genetic makeup, and exposure history), operational factors (planetary destination, mission length, and period in the solar cycle), and shielding characteristics (materials, mass, and topology). We review optimization metrics for radiation protection including scenarios that integrate biophysics models of radiation risks, operational variables, and shielding design tools needed to assess exploration mission designs. We discuss the application of a crosscutting metric, based on probabilistic risk assessment, to lunar and Mars mission trade studies including the assessment of multi-factorial problems and the potential benefits of new radiation health research strategies or mitigation technologies.

Cucinotta, F. A.↗

NASA NTRS2005

Managing Space Radiation Risks on Lunar and Mars Missions: Risk Assessment and Mitigation

Radiation-induced health risks are a primary concern for human exploration outside the Earth's magnetosphere, and require improved approaches to risk estimation and tools for mitigation including shielding and biological countermeasures. Solar proton events are the major concern for short-term lunar missions (<60 d), and for long-term missions (>60 d) such as Mars exploration, the exposures to the high energy and charge (HZE) ions that make-up the galactic cosmic rays are the major concern. Health risks from radiation exposure are chronic risks including carcinogenesis and degenerative tissue risks, central nervous system effects, and acute risk such as radiation sickness or early lethality. The current estimate is that a more than four-fold uncertainty exists in the projection of lifetime mortality risk from cosmic rays, which severely limits analysis of possible benefits of shielding or biological countermeasure designs. Uncertainties in risk projections are largely due to insufficient knowledge of HZE ion radiobiology, which has led NASA to develop a unique probabilistic approach to radiation protection. We review NASA's approach to radiation risk assessment including its impact on astronaut dose limits and application of the ALARA (As Low as Reasonably Achievable) principle. The recently opened NASA Space Radiation Laboratory (NSRL) provides the capability to simulate the cosmic rays in controlled ground-based experiments with biological and shielding models. We discuss how research at NSRL will lead to reductions in the uncertainties in risk projection models. In developing mission designs, the reduction of health risks and mission constraints including costs are competing concerns that need to be addressed through optimization procedures. Mitigating the risks from space radiation is a multi-factorial problem involving individual factors (age, gender, genetic makeup, and exposure history), operational factors (planetary destination, mission length, and period in the solar cycle), and shielding characteristics (materials, mass, and topology). We review optimization metrics for radiation protection including scenarios that integrate biophysics models of radiation risks, operational variables, and shielding design tools needed to assess exploration mission designs. We discuss the application of a crosscutting metric, based on probabilistic risk assessment, to lunar and Mars mission trade studies including the assessment of multi-factorial problems and the potential benefits of new radiation health research strategies or mitigation technologies.

Cucinotta, F. A.↗

NASA NTRS2006

Managing Space Radiation Risks on Lunar and Mars Missions: Risk Assessment and Mitigation

Radiation-induced health risks are a primary concern for human exploration outside the Earth's magnetosphere, and require improved approaches to risk estimation and tools for mitigation including shielding and biological countermeasures. Solar proton events are the major concern for short-term lunar missions (<60 d), and for long-term missions (>60 d) such as Mars exploration, the exposures to the high energy and charge (HZE) ions that make-up the galactic cosmic rays are the major concern. Health risks from radiation exposure are chronic risks including carcinogenesis and degenerative tissue risks, central nervous system effects, and acute risk such as radiation sickness or early lethality. The current estimate is that a more than four-fold uncertainty exists in the projection of lifetime mortality risk from cosmic rays, which severely limits analysis of possible benefits of shielding or biological countermeasure designs. Uncertainties in risk projections are largely due to insufficient knowledge of HZE ion radiobiology, which has led NASA to develop a unique probabilistic approach to radiation protection. We review NASA's approach to radiation risk assessment including its impact on astronaut dose limits and application of the ALARA (As Low as Reasonably Achievable) principle. The recently opened NASA Space Radiation Laboratory (NSRL) provides the capability to simulate the cosmic rays in controlled ground-based experiments with biological and shielding models. We discuss how research at NSRL will lead to reductions in the uncertainties in risk projection models. In developing mission designs, the reduction of health risks and mission constraints including costs are competing concerns that need to be addressed through optimization procedures. Mitigating the risks from space radiation is a multi-factorial problem involving individual factors (age, gender, genetic makeup, and exposure history), operational factors (planetary destination, mission length, and period in the solar cycle), and shielding characteristics (materials, mass, and topology). We review optimization metrics for radiation protection including scenarios that integrate biophysics models of radiation risks, operational variables, and shielding design tools needed to assess exploration mission designs. We discuss the application of a crosscutting metric, based on probabilistic risk assessment, to lunar and Mars mission trade studies including the assessment of multi-factorial problems and the potential benefits of new radiation health research strategies or mitigation technologies.

Cucinotta, F. A.↗

NASA NTRS2024

Conclusions of a Mini Technical Interchange Meeting on New Cross Risk Integration Projects Managed by the NASA Space Radiation Element

To enable deep space exploration and sustained human presence in space, the NASA Human Research Program’s (HRP) Space Radiation Element (SRE) funds research to characterize and mitigate adverse health outcomes from exposure to space radiation that include risks of carcinogenesis, cardiovascular disease, and central nervous system decrements. Recently, the SRE was tasked with supporting multiple HRP Elements with innovative and enabling projects to inform risk characterization, facilitate mitigation activities, and support crew health and performance. These projects, such as precision health initiative, NASA Omics Archive (NOA) and human sample repositories, are agnostic to any HRP Element, hence the name, Cross-Risk Integration Projects (CRIP). CRIP serves 3 broad purposes: - Services: Generate samples and data and manage the receipt, inventory, archive, and ultimate redistribution of biospecimens created in HRP-funded spaceflight and analog research activities—includes NASA Omics Archive project and various human and animal sample repositories. - Method Development: Identify and evaluate new-to-NASA research or analysis methods or techniques that could fundamentally improve existing or planned research efforts—includes the Translational Radiation Research and Countermeasures Project. - Enabling Capabilities: Demonstrate real-world application by adapting, adopting, and/or developing capabilities to benefit crew health and performance and improve risk mitigation—includes Precision Health Initiative (Pharmacogenomics) and advanced biological systems and engineered tissue microsystems initiative (tissue chips, organ-on-a-chip). To identify new technologies, future work, and solicitations, the SRE organizes themed sessions at annual HRP Investigators’ Workshops (IWS). These technical interchange meetings (TIMs) provide a venue for the scientific community to present ongoing work and engage in open discussion of results, limitations of current approaches, and incorporation of novel experimental strategies, model systems, and other innovative techniques. Here, a summary of the studies presented at the SRE-sponsored mini-TIM at the HRP IWS along with the goals and objectives of the CRIP projects is communicated. The 90-min TIM had 6 speakers who presented impressive novel ideas and work, some of which are funded under CRIP by the Space Radiation Element.

Janapriya Saha↗

NASA NTRS2000

Induction of a bystander mutagenic effect of alpha particles in mammalian cells

Ever since the discovery of X-rays was made by Rontgen more than a hundred years ago, it has always been accepted that the deleterious effects of ionizing radiation such as mutation and carcinogenesis are attributable mainly to direct damage to DNA. Although evidence based on microdosimetric estimation in support of a bystander effect appears to be consistent, direct proof of such extranuclear/extracellular effects are limited. Using a precision charged particle microbeam, we show here that irradiation of 20% of randomly selected A(L) cells with 20 alpha particles each results in a mutant fraction that is 3-fold higher than expected, assuming no bystander modulation effect. Furthermore, analysis by multiplex PCR shows that the types of mutants induced are significantly different from those of spontaneous origin. Pretreatment of cells with the radical scavenger DMSO had no effect on the mutagenic incidence. In contrast, cells pretreated with a 40 microM dose of lindane, which inhibits cell-cell communication, significantly decreased the mutant yield. The doses of DMSO and lindane used in these experiments are nontoxic and nonmutagenic. We further examined the mutagenic yield when 5-10% of randomly selected cells were irradiated with 20 alpha particles each. Results showed, likewise, a higher mutant yield than expected assuming no bystander effects. Our studies provide clear evidence that irradiated cells can induce a bystander mutagenic response in neighboring cells not directly traversed by alpha particles and that cell-cell communication process play a critical role in mediating the bystander phenomenon.

Non-NASA Center↗

NASA NTRSDate not supplied

Conclusions of a Mini Technical Interchange Meeting on Mechanisms and Pathways Common Between Adverse Health Outcomes from Exposures to Space Radiation

To enable deep space exploration and sustained human presence in space, the NASA Human Research Program’s (HRP) Space Radiation Element (SRE) funds research to characterize and mitigate adverse health outcomes from exposure to space radiation that include risks of carcinogenesis, cardiovascular disease (CVD) and central nervous system (CNS) decrements. Over the past decade, a growing body of compelling experimental evidence suggests shared mechanisms and pathophysiological processes for CVD, neurodegenerative effects, and cancer development and progression, which are traditionally managed as separate disease processes. Additionally, epidemiological studies have identified cross-sectional and longitudinal associations between some specific types of cancer and CVD, and accumulating evidence indicates that the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease may overlap with CVD and cancer pathogenesis. Identifying the mechanisms and pathways common to these important health decrements will not only accelerate development of effective countermeasures and improve management of spaceflight-induced risk, it will also help to develop new treatment strategies for patients on Earth. To identify common pathways and mechanisms of disease induction and progression from current SR-funded studies and to inform future work and solicitations, the SRE organizes themed sessions at annual HRP Investigators’ Workshops (IWS). These technical interchange meetings (TIMs) provide a venue for the scientific community to present ongoing work and engage in open discussion on results, limitations of current approaches, and incorporation of novel experimental strategies, model systems, and other innovative techniques. Here a summary and lessons learned from the SRE-sponsored mini-TIM titled “mechanisms and pathways common between adverse health outcomes” held at HRP IWS 2023 will be communicated. The 90-min TIM had 30-min dedicated to discussing and developing potential collaboration and tissue sharing opportunities among investigators. The SRE facilitated the discussion using a set of pressing questions and gaps in knowledge that need to be addressed by the scientific community. This poster presents the outcomes of the session along with proposed future workshops and other SRE initiatives.

Janapriya Saha↗

NASA NTRSDate not supplied

Conclusions of a Mini Technical Interchange Meeting on Mechanisms and Pathways Common Between Adverse Health Outcomes from Exposures to Space Radiation

To enable deep space exploration and sustained human presence in space, the NASA Human Research Program’s (HRP) Space Radiation Element (SRE) funds research to characterize and mitigate adverse health outcomes from exposure to space radiation that include risks of carcinogenesis, cardiovascular disease (CVD) and central nervous system (CNS) decrements. Over the past decade, a growing body of compelling experimental evidence suggests shared mechanisms and pathophysiological processes for CVD, neurodegenerative effects, and cancer development and progression, which are traditionally managed as separate disease processes. Additionally, epidemiological studies have identified cross-sectional and longitudinal associations between some specific types of cancer and CVD, and accumulating evidence indicates that the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease may overlap with CVD and cancer pathogenesis. Identifying the mechanisms and pathways common to these important health decrements will not only accelerate development of effective countermeasures and improve management of spaceflight-induced risk, it will also help to develop new treatment strategies for patients on Earth. To identify common pathways and mechanisms of disease induction and progression from current SR-funded studies and to inform future work and solicitations, the SRE organizes themed sessions at annual HRP Investigators’ Workshops (IWS). These technical interchange meetings (TIMs) provide a venue for the scientific community to present ongoing work and engage in open discussion on results, limitations of current approaches, and incorporation of novel experimental strategies, model systems, and other innovative techniques. Here a summary and lessons learned from the SRE-sponsored mini-TIM titled “mechanisms and pathways common between adverse health outcomes” held at HRP IWS 2023 will be communicated. The 90-min TIM had 30-min dedicated to discussing and developing potential collaboration and tissue sharing opportunities among investigators. The SRE facilitated the discussion using a set of pressing questions and gaps in knowledge that need to be addressed by the scientific community. This poster presents the outcomes of the session along with proposed future workshops and other SRE initiatives.

Janapriya Saha↗

NASA NTRS2000

The 'Pro-Drug' RibCys Decreases The Mutagenicity of High LET Radiation in Cultured Mammalian Cells

We have initiated studies aimed at reducing the mutational effects of high LET radiation such as Fe-56 ions and C-12 ions with certain drugs. The mutagenicity of high LET (143 keV/micrometer) Fe-56 or C-12 ions (LET = 100 keV/micrometer) was quantified at the CD59 locus of human-hamster hybrid AL cells. RibCys [2,S)-D-ribo-(1',2',3',4'- Tetrahydroxybutyl)-thiazolidine-4(R)-ca riboxylic acid], formed by condensation of L-cysteine with D-ribose, is designed so that the sulfhydryl amino acid L-cysteine is released intracellularly via nonenzymatic ring opening and hydrolysis leading to increased levels of glutathione (GSH). RibCys (4 or 10 mM), present during irradiation and a few hours post-irradiation, significantly decreased the yield of CD59(-) mutants induced by radiation. RibCys did not affect the clonogenic survival of irradiated cells, nor was it mutagenic itself. These results, together with the minimal side effects reported in mice and pigs, indicate that RibCys may be useful, perhaps even when used prophylactically, in reducing the load of mutations created by high LET radiation in astronauts or other exposed individuals. RibCys is an attractive drug that may reduce the risk of carcinogenesis in people exposed to high LET radiation.

Lenarczyk, M.↗

NASA NTRS2001

Genomic instability, bystander effect, cytoplasmic irradiation and other phenomena that may achieve fame without fortune

The possible risk of induced malignancies in astronauts, as a consequence of the radiation environment in space, is a factor of concern for long term missions. Cancer risk estimates for high doses of low LET radiation are available from the epidemiological studies of the A-bomb survivors. Cancer risks at lower doses cannot be detected in epidemiological studies and must be inferred by extrapolation from the high dose risks. The standard setting bodies, such as the ICRP recommend a linear, no-threshold extrapolation of risks from high to low doses, but this is controversial. A study of mechanisms of carcinogenesis may shed some light on the validity of a linear extrapolation. The multi-step nature of carcinogenesis suggests that the role of radiation may be to induce a mutation leading to a mutator phenotype. High energy Fe ions, such as those encountered in space are highly effective in inducing genomic instability. Experiments involving the single particle microbeam have demonstrated a "bystander effect", ie a biological effect in cells not themselves hit, but in close proximity to those that are, as well as the induction of mutations in cells where only the cytoplasm, and not the nucleus, have been traversed by a charged particle. These recent experiments cast doubt on the validity of a simple linear extrapolation, but the data are so far fragmentary and conflicting. More studies are necessary. While mechanistic studies cannot replace epidemiology as a source of quantitative risk estimates, they may shed some light on the shape of the dose response relationship and therefore on the limitations of a linear extrapolation to low doses.

NASA Discipline Radiation Health↗

NASA NTRS2020

An Adverse Outcome Pathway for Potential Space Radiation Induced Neurological Diseases

Astronauts have begun to spend increasingly longer periods in space, putting themselves in foreign environments in order to explore the unknown. Space radiation is one of the largest health risks faced by astronauts on their missions. The space radiation environment has the ability to cause high levels of irreversible damage. Multiple sources of charged particle radiation exist in the space environment that may increase risk of carcinogenesis, degeneration of bodily tissue (e.g. gastrointestinal, cardiovascular, or pulmonary), acute radiation syndromes, and acute and late central nervous system (CNS) disorders. In order to help inform an understanding of the risk of degenerative CNS disease due to radiation exposure, an initial step is presented here to develop an adverse outcome pathway from radiation exposure focused on Alzheimer’s disease.

Mi, Kaitlyn↗

NASA NTRS1998

The potential influence of radiation-induced microenvironments in neoplastic progression

Ionizing radiation is a complete carcinogen, able both to initiate and promote neoplastic progression and is a known carcinogen of human and murine mammary gland. Tissue response to radiation is a composite of genetic damage, cell death and induction of new gene expression patterns. Although DNA damage is believed to initiate carcinogenesis, the contribution of these other aspects of radiation response are beginning to be explored. Our studies demonstrate that radiation elicits rapid and persistent global alterations in the mammary gland microenvironment. We postulate that radiation-induced microenvironments may affect epithelial cells neoplastic transformation by altering their number or susceptibility. Alternatively, radiation induced microenvironments may exert a selective force on initiated cells and/or be conducive to progression. A key impetus for these studies is the possibility that blocking these events could be a strategy to interrupt neoplastic progression.

Review, Academic↗

NASA NTRS2007

Interpreting Chromosome Aberration Spectra

Ionizing radiation can damage cells by breaking both strands of DNA in multiple locations, essentially cutting chromosomes into pieces. The cell has enzymatic mechanisms to repair such breaks; however, these mechanisms are imperfect and, in an exchange process, may produce a large-scale rearrangement of the genome, called a chromosome aberration. Chromosome aberrations are important in killing cells, during carcinogenesis, in characterizing repair/misrepair pathways, in retrospective radiation biodosimetry, and in a number of other ways. DNA staining techniques such as mFISH ( multicolor fluorescent in situ hybridization) provide a means for analyzing aberration spectra by examining observed final patterns. Unfortunately, an mFISH observed final pattern often does not uniquely determine the underlying exchange process. Further, resolution limitations in the painting protocol sometimes lead to apparently incomplete final patterns. We here describe an algorithm for systematically finding exchange processes consistent with any observed final pattern. This algorithm uses aberration multigraphs, a mathematical formalism that links the various aspects of aberration formation. By applying a measure to the space of consistent multigraphs, we will show how to generate model-specific distributions of aberration processes from mFISH experimental data. The approach is implemented by software freely available over the internet. As a sample application, we apply these algorithms to an aberration data set, obtaining a distribution of exchange cycle sizes, which serves to measure aberration complexity. Estimating complexity, in turn, helps indicate how damaging the aberrations are and may facilitate identification of radiation type in retrospective biodosimetry.

Levy, Dan↗