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Atmospheric Ionizing Radiation and the High Speed Civil Transport

Atmospheric ionizing radiation is produced by extraterrestrial radiations incident on the Earth's atmosphere. These extraterrestrial radiations are of two sources: ever present galactic cosmic rays with origin outside the solar system and transient solar particle events that are at times very intense events associated with solar activity lasting several hours to a few days. Although the galactic radiation penetrating through the atmosphere to the ground is low in intensity, the intensity is more than two orders of magnitude greater at commercial aircraft altitudes. The radiation levels at the higher altitudes of the High Speed Civil Transport (HSCT) are an additional factor of two higher. Ionizing radiation produces chemically active radicals in biological tissues that alter the cell function or result in cell death. Protection standards against low levels of ionizing radiation are based on limitation of excess cancer mortality or limitation of developmental injury resulting in permanent damage to the offspring during pregnancy. The crews of commercial air transport operations are considered as radiation workers by the EPA, the FAA, and the International Commission on Radiological Protection (ICRP). The annual exposures of aircrews depend on the latitudes and altitudes of operation and flight time. Flight hours have significantly increased since deregulation of the airline industry in the 1980's. The FAA estimates annual subsonic aircrew exposures to range from 0.2 to 9.1 mSv compared to 0.5 mSv exposure of the average nuclear power plant worker in the nuclear industry. The commercial aircrews of the HSCT may receive exposures above recently recommended allowable limits for even radiation workers if flying their allowable number of flight hours. An adequate protection philosophy for background exposures in HSCT commercial airtraffic cannot be developed at this time due to current uncertainty in environmental levels. In addition, if a large solar particle event occurs during flight at HSCT altitudes then passengers and crew may greatly exceed allowable limits unless means are available to reduce exposures.

Maiden, D. L.↗

Using DNA Damage to Investigate the Individual Variability of Human Sensitivity to Ionizing Radiation

High-LET ionizing radiation is a major occupational health hazard for astronauts, but risk assessment remains elusive due to limited epidemiological data. Identifying genetic factors modulating the individual radiation response may be the most effective strategy to provide individualized risk management for long-duration high-radiation missions. We have started tackling the challenge of predicting individual risks by identifying human genetic loci associated with various radiation sensitivity phenotypes in primary blood mononuclear cells from a relatively large healthy human cohort. To date, we have performed the isolation of PBMCs from 768 subjects of the same ethnicity, and irradiated PBMCs from 576 subjects with 1 and 3 particles/100µm2 of 600 MeV/n 56Fe, 350 MeV/n 40Ar and 350 MeV/n 28Si ions. The phenotypes of interest were: number of radiation-induced foci (or RIFs), CellROX oxidative stress responses and cell death, at 4h and 24h following irradiation. We have observed a significant inter-individual variability at 0 Gy between the 576 studied subjects, with a mean fold difference between the 10% lowest and highest responders of 5.6 of RIFs/cell, 7.9 in mean CellRox intensity, and 9.3 in percentage of dead cells. In order to better assess genetic factors influencing DNA repair, we used a metric previously introduced by our group to sort out radiation sensitivity phenotypes in mice: i.e. the ratio of the first to the second slope of RIFs/cell (between 0 and 1, and between 1 and 3 particle/100µm2). Preliminary data on 192 individuals showed a distribution of low-dose responders (ratio > 1) to high-dose responders (ratio < 1) at 4h of 12%, 55% and 52% respectively for Fe, Ar and Si. The average value for the first and the second slopes was very similar for the two lowest LET (0.10 [-0.26;0.58] and 0.09 [-0.45;0.41] for Ar, 0.07 [-0.27;0.38] and 0.08 [-0.19;0.42] for Si), indicating a linear dose response across both fluence. Fe showed clear saturation for the highest dose with a slope of -0.09 [-0.86;1.51] against 0.68 [-2.21;2.20] for the low dose range, which probably reflects that many PBMCs are beyond repair at the high dose. Note that other significances were found for additional factors such as BMI and age whereas none were found for sex. GWAS will be performed on all phenotypes upon completion of measurements.

Pariset, E.↗

Using DNA Damage to Investigate the Individual Variability of Human Sensitivity to Ionizing Radiation

High-LET ionizing radiation is a major occupational health hazard for astronauts, but risk assessment remains elusive due to limited epidemiological data. Identifying genetic factors modulating the individual radiation response may be the most effective strategy to provide individualized risk management for long-duration high-radiation missions. We have started tackling the challenge of predicting individual risks by identifying human genetic loci associated with various radiation sensitivity phenotypes in primary blood mononuclear cells from a relatively large healthy human cohort. To date, we have performed the isolation of PBMCs from 768 subjects of the same ethnicity, and irradiated PBMCs from 576 subjects with 1 and 3 particles/100µm2 of 600 MeV/n 56Fe, 350 MeV/n 40Ar and 350 MeV/n 28Si ions. The phenotypes of interest were: number of radiation-induced foci (or RIFs), CellROX oxidative stress responses and cell death, at 4h and 24h following irradiation. We have observed a significant inter-individual variability at 0 Gy between the 576 studied subjects, with a mean fold difference between the 10% lowest and highest responders of 5.6 of RIFs/cell, 7.9 in mean CellRox intensity, and 9.3 in percentage of dead cells. In order to better assess genetic factors influencing DNA repair, we used a metric previously introduced by our group to sort out radiation sensitivity phenotypes in mice: i.e. the ratio of the first to the second slope of RIFs/cell (between 0 and 1, and between 1 and 3 particle/100µm2). Preliminary data on 192 individuals showed a distribution of ?low-dose responders? (ratio > 1) to ?high-dose responders? (ratio < 1) at 4h of 12%, 55% and 52% respectively for Fe, Ar and Si. The average value for the first and the second slopes was very similar for the two lowest LET (0.10 [-0.26;0.58] and 0.09 [-0.45;0.41] for Ar, 0.07 [-0.27;0.38] and 0.08 [-0.19;0.42] for Si), indicating a linear dose response across both fluence. Fe showed clear saturation for the highest dose with a slope of -0.09 [-0.86;1.51] against 0.68 [-2.21;2.20] for the low dose range, which probably reflects that many PBMCs are beyond repair at the high dose. Note that other significances were found for additional factors ? such as BMI and age ? whereas none were found for sex. GWAS will be performed on all phenotypes upon completion of measurements.

Pariset, E.↗

Developing High-Throughput Organ-On-A-Chip Models to Investigate the Effects of Ionizing Radiation on the Central Nervous System

One of the main health risks in human space exploration is central nervous system (CNS) damage by ionizing radiation. Irradiation with simulated GCRs or their components, or high doses of low-LET radiation such as gamma rays, in animal models has been shown to cause neuronal damage together with glial cell activation and neuroinflammation and has been associated with prolonged cognitive and behavioral dysfunction. The extent of CNS damage in response to any insult, including ionizing radiation, is partially regulated by the blood-brain barrier (BBB), which enables immune cells to enter the CNS. The main cellular regulators of BBB permeability are astrocytes, which also modulate neuronal death, immune responses and oxidative stress, and thus could serve as a robust CNS-specific target for countermeasure development. However, studies on BBB permeability and astrocyte functions in regulating CNS responses to ionizing radiation have been limited, especially in human tissue/organ analogs. Therefore, we have established a high throughput 3D organ-on-a-chip system to study human CNS functions in response to ionizing radiation, with the eventual goal of adapting it to spaceflight missions. We utilized commercially available OrganoPlate system (Mimetas, Inc.) seeded with primary or induced pluripotent stem cell-derived human cells for developing 3D neuronal-astrocytic and BBB models. We investigated both immediate and delayed CNS dose responses to 0.5-1 Gy X-rays by measuring BBB permeability and morphology, and astrocyte activation. We have also quantified secreted markers of oxidative stress and cell viability. In the future, we are planning to monitor dendritic, axonal and synaptic changes in neurons, evaluate the combined exposures to simulated microgravity and ionizing radiation, and compare the responses to low and high-LET ionizing radiation. We anticipate these studies could indicate novel cellular and mechanistic targets for countermeasure developments to improve CNS functions in astronauts.

Malkani, Sherina↗

Biodosimetry of ionizing radiation by selective painting of prematurely condensed chromosomes in human lymphocytes

Painting of interphase chromosomes can be useful for biodosimetric purposes in particular cases such as radiation therapy, accidental exposure to very high radiation doses and exposure to densely ionizing radiation, for example during space missions. Biodosimetry of charged-particle radiation is analyzed in the present paper. Target cells were human peripheral blood lymphocytes irradiated in vitro with gamma rays, protons and iron ions. After exposure, lymphocytes were incubated for different times to allow repair of radiation-induced damage and then fused to mitotic hamster cells to promote premature condensation in the interphase chromosomes. Chromosome spreads were then hybridized with whole-chromosome DNA probes labeled with fluorescent stains. Dose-response curves for the induction of chromatin fragments shortly after exposure, as well as the kinetics of rejoining and misrejoining, were not markedly dependent on linear energy transfer. However, after exposure to heavy ions, more aberrations were scored in the interphase cells after incubation for repair than in metaphase samples harvested at the first postirradiation mitosis. On the other hand, no significant differences were observed in the two samples after exposure to sparsely ionizing radiation. These results suggest that interphase chromosome painting can be a useful tool for biodosimetry of particle radiation.

NASA Center JSC↗

Ionizing Radiation from Ex Vivo Sterilization Diminishes Collagen Integrity and Vertebral Body Mechanics

Clinical exposure to ionizing radiation could put cancer radiotherapy or bone allograft patients at an increased risk of fracture. In these applications, ionizing radiation levels can range from accumulative 50 Gy for radiotherapy cancer treatment, to acute 35,000 Gy for allograft sterilization. Ionizing radiation has been shown to decrease bon equality through reduced strength and post-yield properties and degrade collagen integrity through either increased crosslinks (advanced glycation end products, AGEs)or fragmentation. It is unclear which collagen structural change accounts for reduced strength. The dose-dependent effect of ionizing radiation on mechanical and biochemical properties of whole bones are not well understood, particularly for ex vivo doses ranging from 50 to 35,000 Gy.

Radiation↗

Ionizing Radiation from Ex Vivo Sterilization Diminishes Fatigue but Not Static Murine Vertebral Body Mechanics

For a variety of medical and scientific reasons, human bones can be exposed to ionizing radiation. At relatively high doses (30,000±5,000 Gy), ex vivo ionizing radiation is commonly used to sterilize bone allografts. However, ionizing radiation in these applications has been shown to increase risk of fracture clinically and decrease bone quality. Previously, we observed a significant decrease in compressive static strength and fatigue life of ex vivo whole bones exposed to x-ray radiation at 17,000 Gy and above; no changes in compressive mechanical properties were observed for radiation doses of 1,000 Gy and below. The gap in doses between no mechanical change (1,000 Gy) and significant mechanical degradation (17,000 Gy) is large, and it is unclear at what dose mechanical integrity begins to diminish in whole bones, and if its effects differ in response to static versus cyclic mechanical loading. This is a major clinical concern, as trabecular and cortical bone allografts are commonly used in structural, load-bearing applications. To gain insight into the effect of ionizing radiation from 1,000-17,000 Gy, we conducted an ex vivo radiation study on the static and fatigue mechanical properties of the vertebral whole bone. Our objectives were to: (1) quantify the effect of exposure to ex vivo ionizing radiation on the mechanical integrity (compressive static and fatigue) of whole bones; and (2) evaluate, if there are observed differences in mechanics, if they differ in magnitude for static versus cyclic properties. The results of this study will give insight into the need for changes in protocols for bone allograft radiation sterilization procedures.

bone mechanics↗

The Effect of a SEP Event on Astronauts Doing a Spacewalk As Computed By the Nowcast of Aerospace Ionizing Radiation System (NAIRAS)

The Nowcast of Aerospace Ionizing Radiation System (NAIRAS) is a sophisticated physics-based model that has been providing real-time global predictions of cosmic radiation exposure, pertinent to both galactic and solar sources, to air travelers for a decade. The utility of NAIRAS, however, extends beyond the atmospheric ionizing radiation environment. The recently developed NAIRAS 3.0 version demonstrates an expansion of its domain to the space radiation environment. This extension incorporates an additional trapped inner belt proton source, coupled with altitude-dependent and rigidity-dependent geomagnetic shielding for galactic cosmic rays (GCR) and solar energetic particle (SEP) protons. The latest version of NAIRAS operates in two modes: real-time global predictions of the atmospheric radiation environment and a user-specified run-on-request service for global dosimetric calculations or predictions of dosimetric and particle flux quantities along user-uploaded flight path. It is available to the public at the Community Coordinated Modeling Center (CCMC). In this work, we present the computations of the dose in the ISS vicinity during the SEP event of August 8, 2023; which happened a day before a scheduled spacewalk. We demonstrate that astronauts would not have suffered a dose equivalent in excess of 1 mSv if the event happened a day later. As such, NAIRAS 3.0 holds significant potential for human safety and technological advancement in aerospace travel and exploration.

Guillaume Gronoff↗

Moss Tolerance of Deep Space-Like Ionizing Radiation, Singular or Combined With Spaceflight Microgravity-Preparation for the BRIC-27 Experiment to the ISS

Understanding how terrestrial life perceives and tolerates deep space environments is essential to advancing human space exploration missions and searching for life beyond our solar system. Throughout evolution moss adapted to living in extreme environments from the edge of habitability. Moss inhabits areas with high UVB/UVC photon levels such as polar regions subject to ozone holes, high elevation mountain environments, and sites with elevated ionizing particle levels such as those found at nuclear plant accident sites, atomic bomb test sites or radioactive element-rich regions. We investigate if moss tolerance of ionizing radiation encounter terrestrially extends to resistance to deep space ionizing radiation. We exposed moss to high energy ion beams simulating Galactic Cosmic Ray (GCRSim) and Solar Particle Event (SPESim) (NSRL, BNL) that permeate deep space, and moss was unharmed. We also exposed moss to high doses of gamma rays as released in astrophysical events, and moss survived absorption of extremely high doses. Next, we ask if moss tolerance of deep space-like ionizing radiation observed terrestrially differs from that in other deep space environments. In the upcoming BRIC-27 spaceflight experiment we will sequentially expose Antarctic moss C.purpureus to GCRSim and SPESim followed by exposure to spaceflight microgravity and compare gene expression profiles in deep space-like ionizing radiation, singular or combined with spaceflight microgravity. Additionally, we will compare gene expression profiles in spaceflight microgravity, singular or combined with deep space-like ionizing radiation. Hence, BRIC-27 will advance our understanding of the combined effects of both deep space ionizing radiation and microgravity, which may have different and more profound effects on plant physiology and performance than each condition separately.

Agata Klaudia Zupanska↗

Ionizing radiation induces heritable disruption of epithelial cell interactions

Ionizing radiation (IR) is a known human breast carcinogen. Although the mutagenic capacity of IR is widely acknowledged as the basis for its action as a carcinogen, we and others have shown that IR can also induce growth factors and extracellular matrix remodeling. As a consequence, we have proposed that an additional factor contributing to IR carcinogenesis is the potential disruption of critical constraints that are imposed by normal cell interactions. To test this hypothesis, we asked whether IR affected the ability of nonmalignant human mammary epithelial cells (HMEC) to undergo tissue-specific morphogenesis in culture by using confocal microscopy and imaging bioinformatics. We found that irradiated single HMEC gave rise to colonies exhibiting decreased localization of E-cadherin, beta-catenin, and connexin-43, proteins necessary for the establishment of polarity and communication. Severely compromised acinar organization was manifested by the majority of irradiated HMEC progeny as quantified by image analysis. Disrupted cell-cell communication, aberrant cell-extracellular matrix interactions, and loss of tissue-specific architecture observed in the daughters of irradiated HMEC are characteristic of neoplastic progression. These data point to a heritable, nonmutational mechanism whereby IR compromises cell polarity and multicellular organization.

Non-NASA Center↗

Space Weather Nowcasting of Atmospheric Ionizing Radiation for Aviation Safety

There is a growing concern for the health and safety of commercial aircrew and passengers due to their exposure to ionizing radiation with high linear energy transfer (LET), particularly at high latitudes. The International Commission of Radiobiological Protection (ICRP), the EPA, and the FAA consider the crews of commercial aircraft as radiation workers. During solar energetic particle (SEP) events, radiation exposure can exceed annual limits, and the number of serious health effects is expected to be quite high if precautions are not taken. There is a need for a capability to monitor the real-time, global background radiations levels, from galactic cosmic rays (GCR), at commercial airline altitudes and to provide analytical input for airline operations decisions for altering flight paths and altitudes for the mitigation and reduction of radiation exposure levels during a SEP event. The Nowcast of Atmospheric Ionizing Radiation for Aviation Safety (NAIRAS) model is new initiative to provide a global, real-time radiation dosimetry package for archiving and assessing the biologically harmful radiation exposure levels at commercial airline altitudes. The NAIRAS model brings to bear the best available suite of Sun-Earth observations and models for simulating the atmospheric ionizing radiation environment. Observations are utilized from ground (neutron monitors), from the atmosphere (the METO analysis), and from space (NASA/ACE and NOAA/GOES). Atmospheric observations provide the overhead shielding information and the ground- and space-based observations provide boundary conditions on the GCR and SEP energy flux distributions for transport and dosimetry simulations. Dose rates are calculated using the parametric AIR (Atmospheric Ionizing Radiation) model and the physics-based HZETRN (High Charge and Energy Transport) code. Empirical models of the near-Earth radiation environment (GCR/SEP energy flux distributions and geomagnetic cut-off rigidity) are benchmarked against the physics-based CMIT (Coupled Magnetosphere- Ionosphere-Thermosphere) and SEP-trajectory models.

Mertens, Christopher J.↗

Clustered DNA damages induced in isolated DNA and in human cells by low doses of ionizing radiation

Clustered DNA damages-two or more closely spaced damages (strand breaks, abasic sites, or oxidized bases) on opposing strands-are suspects as critical lesions producing lethal and mutagenic effects of ionizing radiation. However, as a result of the lack of methods for measuring damage clusters induced by ionizing radiation in genomic DNA, neither the frequencies of their production by physiological doses of radiation, nor their repairability, nor their biological effects are known. On the basis of methods that we developed for quantitating damages in large DNAs, we have devised and validated a way of measuring ionizing radiation-induced clustered lesions in genomic DNA, including DNA from human cells. DNA is treated with an endonuclease that induces a single-strand cleavage at an oxidized base or abasic site. If there are two closely spaced damages on opposing strands, such cleavage will reduce the size of the DNA on a nondenaturing gel. We show that ionizing radiation does induce clustered DNA damages containing abasic sites, oxidized purines, or oxidized pyrimidines. Further, the frequency of each of these cluster classes is comparable to that of frank double-strand breaks; among all complex damages induced by ionizing radiation, double-strand breaks are only about 20%, with other clustered damage constituting some 80%. We also show that even low doses (0.1-1 Gy) of high linear energy transfer ionizing radiation induce clustered damages in human cells.

NASA Discipline Radiation Health↗