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At least 19 records

Changes in Liver Metabolic Gene Expression from Radiation Exposure

Radiation exposure is one of the unique physiological challenges of human spaceflight that is not encountered on earth. While radiation exposure is known to impart physiological stresses and alter normal function, it is unclear how it specifically affects drug metabolism. A major concern is that the actions of medications used in spaceflight may deviate from the expectations formed from terrestrial use. This concern was investigated at the molecular level by analyzing how gamma radiation exposure affected gene expression in the livers of mice. Three different doses of radiation were administered and after various intervals of recovery time, gene expression was measured with RT-qPCR screening arrays for drug metabolism and DNA repair. After examining the results of 192 genes total from each of 72 mice, 65 genes were found to be significantly affected by at least one of the doses of radiation. In general, the genes affected are involved in the metabolism of drugs with lipid or steroid hormone-like structures, as well as the maintenance of redox homeostasis and repair of DNA damage.

Peters, C. P.↗

A comparison of quality factors and weighting factors for characterizing astronaut radiation exposures

Radiation exposures are typically characterized by two quantities. The first is the absorbed dose, or the energy deposited per unit mass for specific types of radiation passing through specified materials. The same amount of energy deposited in material by two different types of radiation, however, can result in two different levels of risk. Because of this, for the purpose of radiation protection operations, absorbed dose is modified by a second factor intended to normalize the risk associated with a given exposure. We present here an inter-comparison of methods for this modification. First is the radiation quality factor (Q), as defined by ICRP publication 60. This quantity is related functionally to the unrestricted linear energy transfer (LET) of a given radiation, and is multiplied by the absorbed dose to derive the dose equivalent (H). The second method for modifying absorbed dose is the radiation weighting factor, also given in ICRP-60, or as modified in NCRP report 115. To implement the weighting factor, the absorbed dose resulting from incidence of a particular radiation is multiplied by a factor assigned to that type of radiation, giving the equivalent dose. We compare calculations done based on identical fields of radiation representative of that encountered by the MIR space station, applying each of these two methods. c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

NASA Center JSC↗

2013 Space Radiation Standing Review Panel Status Review for: The Risk of Acute and Late Central Nervous System Effects from Radiation Exposure, The Risk of Acute Radiation Syndromes Due to Solar Particle Events (SPEs), The Risk Of Degenerative Tissue Or Other Health Effects From Radiation Exposure, and The Risk of Radiation Carcinogenesis

The Space Radiation Standing Review Panel (from here on referred to as the SRP) was impressed with the strong research program presented by the scientists and staff associated with NASA's Space Radiation Program Element and National Space Biomedical Research Institute (NSBRI). The presentations given on-site and the reports of ongoing research that were provided in advance indicated the potential Risk of Acute and Late Central Nervous System Effects from Radiation Exposure (CNS) and were extensively discussed by the SRP. This new data leads the SRP to recommend that a higher priority should be placed on research designed to identify and understand these risks at the mechanistic level. To support this effort the SRP feels that a shift of emphasis from Acute Radiation Syndromes (ARS) and carcinogenesis to CNS-related endpoints is justified at this point. However, these research efforts need to focus on mechanisms, should follow pace with advances in the field of CNS in general and should consider the specific comments and suggestions made by the SRP as outlined below. The SRP further recommends that the Space Radiation Program Element continue with its efforts to fill the vacant positions (Element Scientist, CNS Risk Discipline Lead) as soon as possible. The SRP also strongly recommends that NASA should continue the NASA Space Radiation Summer School. In addition to these broad recommendations, there are specific comments/recommendations noted for each risk, described in detail below.

Source record↗

Data integration reveals key homeostatic mechanisms following low dose radiation exposure

The goal of this study was to define pathways regulated by low dose radiation to understand how biological systems respond to subtle perturbations in their environment and prioritize pathways for human health assessment. Using an in vitro 3-D human full thickness skin model, we have examined the temporal response of dermal and epidermal layers to 10 cGy X-ray using transcriptomic, proteomic, phosphoproteomic and metabolomic platforms. Bioinformatics analysis of each dataset independently revealed potential signaling mechanisms affected by low dose radiation, and integrating data shed additional insight into the mechanisms regulating low dose responses in human tissue. We examined direct interactions among datasets (top down approach) and defined several hubs as significant regulators, including transcription factors (YY1, MYC and CREB1), kinases (CDK2, PLK1) and a protease (MMP2). These data indicate a shift in response across time — with an increase in DNA repair, tissue remodeling and repression of cell proliferation acutely (24–72 h). Pathway-based integration (bottom up approach) identified common molecular and pathway responses to low dose radiation, including oxidative stress, nitric oxide signaling and transcriptional regulation through the SP1 factor that would not have been identified by the individual data sets. Significant regulation of key downstream metabolites of nitrative stress was measured within these pathways. Among the features identified in our study, the regulation of MMP2 and SP1 was experimentally validated. Our results demonstrate the advantage of data integration to broadly define the pathways and networks that represent the mechanisms by which complex biological systems respond to perturbation. - Highlights: • Low dose ionizing radiation altered homeostasis in 3D skin tissue model. • Global gene/protein/metabolite data integrated using complementary statistical approaches • Time and location-specific change in matrix regulation, ROS/RNS and DNA repair pathways detected • Low dose exposure alters metabolites involved in nitric oxide biosynthesis and wound healing. • Computationally predicted regulators of primary mechanisms were experimentally validated.

60 APPLIED LIFE SCIENCES↗

ATM–dependent phosphorylation of CHD7 regulates morphogenesis-coupled DSB stress response in fetal radiation exposure

Following radiation exposure, unrepaired DNA double-strand breaks (DSBs) persist to some extent in a subset of cells as residual damage; they can exert adverse effects, including late-onset diseases. In search of the factor(s) that characterize(s) cells bearing such damage, we discovered ataxia-telangiectasia mutated (ATM)-dependent phosphorylation of the transcription factor chromodomain helicase DNA binding protein 7 (CHD7). CHD7 controls the morphogenesis of cell populations derived from neural crest cells during vertebrate early development. Indeed, malformations in various fetal bodies are attributable to CHD7 haploinsufficiency. Following radiation exposure, CHD7 becomes phosphorylated, ceases promoter/enhancer binding to target genes, and relocates to the DSB-repair protein complex, where it remains until the damage is repaired. Thus, ATM-dependent CHD7 phosphorylation appears to act as a functional switch. As such stress responses contribute to improved cell survival and canonical nonhomologous end joining, we conclude that CHD7 is involved in both morphogenetic and DSB-response functions. Thus, we propose that higher vertebrates have evolved intrinsic mechanisms underlying the morphogenesis-coupled DSB stress response. In fetal exposure, if the function of CHD7 becomes primarily shifted toward DNA repair, morphogenic activity is reduced, resulting in malformations.

59 BASIC BIOLOGICAL SCIENCES↗

Evidence Report: Risk of Cardiovascular Disease and Other Degenerative Tissue Effects from Radiation Exposure

Occupational radiation exposure from the space environment may result in non-cancer or non-CNS degenerative tissue diseases, such as cardiovascular disease, cataracts, and respiratory or digestive diseases. However, the magnitude of influence and mechanisms of action of radiation leading to these diseases are not well characterized. Radiation and synergistic effects of radiation cause DNA damage, persistent oxidative stress, chronic inflammation, and accelerated tissue aging and degeneration, which may lead to acute or chronic disease of susceptible organ tissues. In particular, cardiovascular pathologies such as atherosclerosis are of major concern following gamma-ray exposure. This provides evidence for possible degenerative tissue effects following exposures to ionizing radiation in the form of the GCR or SPEs expected during long-duration spaceflight. However, the existence of low dose thresholds and dose-rate and radiation quality effects, as well as mechanisms and major risk pathways, are not well-characterized. Degenerative disease risks are difficult to assess because multiple factors, including radiation, are believed to play a role in the etiology of the diseases. As additional evidence is pointing to lower, space-relevant thresholds for these degenerative effects, particularly for cardiovascular disease, additional research with cell and animal studies is required to quantify the magnitude of this risk, understand mechanisms, and determine if additional protection strategies are required.The NASA PEL (Permissive Exposure Limit)s for cataract and cardiovascular risks are based on existing human epidemiology data. Although animal and clinical astronaut data show a significant increase in cataracts following exposure and a reassessment of atomic bomb (A-bomb) data suggests an increase in cardiovascular disease from radiation exposure, additional research is required to fully understand and quantify these adverse outcomes at lower doses (less than 0.5 gray (SI unit for ionizing radiation dosage, i.e. one joule of radiation energy per one kilogram of matter)) to facilitate risk prediction. This risk has considerable uncertainty associated with it, and no acceptable model for projecting degenerative tissue risk is currently available. In particular, risk factors such as obesity, alcohol, and tobacco use can act as confounding factors that contribute to the large uncertainties. The PELs could be violated under certain scenarios, including following a large SPE (solar proton event) or long-term GCR (galactic cosmic ray) exposure. Specifically, for a Mars mission, the accumulated dose is sufficiently high that epidemiology data and preliminary risk estimates suggest a significant risk for cardiovascular disease. Ongoing research in this area is intended to provide the evidence base for accurate risk quantification to determine criticality for extended duration missions. Data specific to the space radiation environment must be compiled to quantify the magnitude of this risk to decrease the uncertainty in current PELs and to determine if additional protection strategies are required. New research results could lead to estimates of cumulative radiation risk from CNS and degenerative tissue diseases that, when combined with the cancer risk, may have major negative impacts on mission design, costs, schedule, and crew selection. The current report amends an earlier report (Human Research Program Requirements Document, HRP-47052, Rev. C, dated Jan 2009) in order to provide an update of evidence since 2009.

Patel, Zarana↗

Radiation Exposure in Biliary Procedures Performed to Manage Anastomotic Strictures in Pediatric Liver Transplant Recipients: Comparison Between Radiation Exposure Levels Using an Image Intensifier and a Flat-Panel Detector-Based System

Purpose: The aim of this study was to estimate radiation exposure in pediatric liver transplants recipients who underwent biliary interventional procedures and to compare radiation exposure levels between biliary interventional procedures performed using an image intensifier-based angiographic system (IIDS) and a flat panel detector-based interventional system (FPDS). Materials and Methods: We enrolled 34 consecutive pediatric liver transplant recipients with biliary strictures between January 2008 and March 2013 with a total of 170 image-guided procedures. The dose-area product (DAP) and fluoroscopy time was recorded for each procedure. The mean age was 61 months (range 4-192), and mean weight was 17 kg (range 4-41). The procedures were classified into three categories: percutaneous transhepatic cholangiography and biliary catheter placement (n = 40); cholangiography and balloon dilatation (n = 55); and cholangiography and biliary catheter change or removal (n = 75). Ninety-two procedures were performed using an IIDS. Seventy-eight procedures performed after July 2010 were performed using an FPDS. The difference in DAP between the two angiographic systems was compared using Wilcoxon rank-sum test and a multiple linear regression model. Results: Mean DAP in the three categories was significantly greater in the group of procedures performed using the IIDS compared with those performed using the FPDS. Statistical analysis showed a p value = 0.001 for the PTBD group, p = 0.0002 for the cholangiogram and balloon dilatation group, and p = 0.00001 for the group with cholangiogram and biliary catheter change or removal. Conclusion: In our selected cohort of patients, the use of an FPDS decreases radiation exposure.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

PLANNING TOOLS FOR ESTIMATING RADIATION EXPOSURE AT THE NATIONAL IGNITION FACILITY

A set of computational tools was developed to help estimate and minimize potential radiation exposure to workers from material activation in the National Ignition Facility (NIF). AAMI (Automated ALARA-MCNP Interface) provides an efficient, automated mechanism to perform the series of calculations required to create dose rate maps for the entire facility with minimal manual user input. NEET (NIF Exposure Estimation Tool) is a web application that combines the information computed by AAMI with a given shot schedule to compute and display the dose rate maps as a function of time. AAMI and NEET are currently used as work planning tools to determine stay-out times for workers following a given shot or set of shots, and to help in estimating integrated doses associated with performing various maintenance activities inside the target bay. Dose rate maps of the target bay were generated following a low-yield 10{sup 16} D-T shot and will be presented in this paper.

42 ENGINEERING↗

Status of cardiovascular PET radiation exposure and strategies for reduction: An Information Statement from the Cardiovascular PET Task Force

Cardiovascular positron emission tomography (PET) imaging provides high-quality visual and quantitative myocardial perfusion and function images. In addition, cardiovascular PET can assess myocardial viability, myocardial inflammatory disorders such as cardiac sarcoid, and infections of implanted devices including pacemakers, ventricular assist devices, and prosthetic heart valves. As with all nuclear cardiology procedures, the benefits need to be considered in relation to the risks of exposure to radiation. When performed properly, these assessments can be obtained while simultaneously minimizing radiation exposure. The purpose of this information statement is to present current concepts to minimize patient and staff radiation exposure while ensuring high image quality.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Behavioral consequences of radiation exposure to simulated space radiation in the C57BL/6 mouse: open field, rotorod, and acoustic startle

Two experiments were carried out to investigate the consequences of exposure to proton radiation, such as might occur for astronauts during space flight. C57BL/6 mice were exposed, either with or without 15-g/cm2 aluminum shielding, to 0-, 3-, or 4-Gy proton irradiation mimicking features of a solar particle event. Irradiation produced transient direct deficits in open-field exploratory behavior and acoustic startle habituation. Rotorod performance at 18 rpm was impaired by exposure to proton radiation and was impaired at 26 rpm, but only for mice irradiated with shielding and at the 4-Gy dose. Long-term (>2 weeks) indirect deficits in open-field activity appeared as a result of impaired experiential encoding immediately following exposure. A 2-week recovery prior to testing decreased most of the direct effects of exposure, with only rotorod performance at 26 rpm being impaired. These results suggest that the performance deficits may have been mediated by radiation damage to hippocampal, cerebellar, and possibly, forebrain dopaminergic function.

Non-NASA Center↗

Optical Properties of Thermal Control Coatings After Weathering, Simulated Ascent Heating, and Simulated Space Radiation Exposure

Spacecraft radiators reject heat to their surroundings and coatings play an important role in this heat rejection. The coatings provide the combined optical properties of low solar absorptance and high infrared emittance. The coatings are applied to the radiator panel in a number of ways, including conventional spraying, plasma spraying, or as an applique. Not designed for a terrestrial weathering environment, the durability of spacecraft paints, coatings, and appliques upon exposure to weathering and subsequent exposure to ascent heating, solar wind, and ultraviolet radiation was studied. In addition to traditional aluminum panels, new isocyanate ester composite panels were exposed for a total of 90 days at the Atmospheric Exposure Site of Kennedy Space Center's (KSC) Beach Corrosion Facility for the purpose of identifying their durability to weathering. Selected panel coupons were subsequently exposed to simulated ascent heating, solar wind, and vacuum ultraviolet (UV) radiation to identify the effect of a simulated space environment on as-weathered surfaces. Optical properties and adhesion testing were used to document the durability of the paints, coatings, and appliques.

Jaworske, Donald A.↗

Elastomeric Seal Performance after Terrestrial Ultraviolet Radiation Exposure

Ultraviolet radiation was evaluated to determine its negative effects on the performance of elastomeric gas pressure seals. The leak rates of the silicone elastomer S0383-70 O-ring test articles were used to quantify the degradation of the seals after exposure to vacuum-ultraviolet and/or middle-to-near-ultraviolet wavelength radiation. Three groups of seals were exposed in terrestrial facilities to 115-165 nm wavelength radiation, 230-500 nm wavelength radiation, or both spectrums, for an orbital spaceflight equivalent of 125 hours. The leak rates of the silicone elastomer S0383-70 seals were quantified and compared to samples that received no radiation. Each lot contained six samples and statistical t-tests were used to determine the separate and combined influences of exposure to the two wavelength ranges. A comparison of the mean leak rates of samples exposed to 115-165 nm wavelength radiation to the control specimens showed no difference, suggesting that spectrum was not damaging. The 230-500 nm wavelength appeared to be damaging, as the mean leak rates of the specimens exposed to that range of wavelengths, and those exposed to the combined 115-165 nm and 230-500 nm spectrums, were significantly different from the leak rates of the control specimens. Most importantly, the test articles exposed to both wavelength spectrums exhibited mean leak rates two orders of magnitude larger than any other exposed specimens, which suggested that both wavelength spectrums are important when simulating the orbital environment.

leakage↗

Risk assessment and management of radiofrequency radiation exposure

Radiofrequency radiation (RFR) industry managers, occupational physicians, security department, and other practitioners must be advised on the basic of biophysics and the health effects of RF electromagnetic fields so as to guide the management of exposure. Information on biophysics of RFR and biological/heath effects is derived from standard texts, literature and clinical experiences. Emergency treatment and ongoing care is outlined, with clinical approach integrating the circumstances of exposure and the patient's symptoms. Experimental risk assessment model in RFR chronic exposure is proposed. Planning for assessment and monitoring exposure, ongoing care, safety measures and work protection are outlining the proper management.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗

Real Time Radiation Exposure And Health Risks

Radiation from solar particle events (SPEs) poses a serious threat to future manned missions outside of low Earth orbit (LEO). Accurate characterization of the radiation environment in the inner heliosphere and timely monitoring the health risks to crew are essential steps to ensure the safety of future Mars missions. In this project we plan to develop an approach that can use the particle data from multiple satellites and perform near real-time simulations of radiation exposure and health risks for various exposure scenarios. Time-course profiles of dose rates will be calculated with HZETRN and PDOSE from the energy spectrum and compositions of the particles archived from satellites, and will be validated from recent radiation exposure measurements in space. Real-time estimation of radiation risks will be investigated using ARRBOD. This cross discipline integrated approach can improve risk mitigation by providing critical information for risk assessment and medical guidance to crew during SPEs.

Hu, Shaowen↗

Comparison of radiation exposure and associated radiation-induced cancer risks from mammography and molecular imaging of the breast

Purpose: Recent studies have raised concerns about exposure to low-dose ionizing radiation from medical imaging procedures. Little has been published regarding the relative exposure and risks associated with breast imaging techniques such as breast specific gamma imaging (BSGI), molecular breast imaging (MBI), or positron emission mammography (PEM). The purpose of this article was to estimate and compare the risks of radiation-induced cancer from mammography and techniques such as PEM, BSGI, and MBI in a screening environment. Methods: The authors used a common scheme for all estimates of cancer incidence and mortality based on the excess absolute risk model from the BEIR VII report. The lifetime attributable risk model was used to estimate the lifetime risk of radiation-induced breast cancer incidence and mortality. All estimates of cancer incidence and mortality were based on a population of 100 000 females followed from birth to age 80 and adjusted for the fraction that survives to various ages between 0 and 80. Assuming annual screening from ages 40 to 80 and from ages 50 to 80, the cumulative cancer incidence and mortality attributed to digital mammography, screen-film mammography, MBI, BSGI, and PEM was calculated. The corresponding cancer incidence and mortality from natural background radiation was calculated as a useful reference. Assuming a 15%-32% reduction in mortality from screening, the benefit/risk ratio for the different imaging modalities was evaluated. Results: Using conventional doses of 925 MBq Tc-99m sestamibi for MBI and BSGI and 370 MBq F-18 FDG for PEM, the cumulative cancer incidence and mortality were found to be 15-30 times higher than digital mammography. The benefit/risk ratio for annual digital mammography was >50:1 for both the 40-80 and 50-80 screening groups, but dropped to 3:1 for the 40-49 age group. If the primary use of MBI, BSGI, and PEM is in women with dense breast tissue, then the administered doses need to be in the range 75-150 MBq for Tc-99m sestamibi and 35 MBq-70 MBq for F-18 FDG in order to obtain benefit/risk ratios comparable to those of mammography in these age groups. These dose ranges should be achievable with enhancements to current technology while maintaining a reasonable examination time. Conclusions: The results of the dose estimates in this study clearly indicate that if molecular imaging techniques are to be of value in screening for breast cancer, then the administered doses need to be substantially reduced to better match the effective doses of mammography.

61 RADIATION PROTECTION AND DOSIMETRY↗