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At least 55 records · Page 3

Chromosome aberrations induced by high-LET radiations

Measurements of chromosome aberrations in peripheral blood lymphocytes are currently the most sensitive and reliable indicator of radiation exposure that can be used for biological dosimetry. This technique has been implemented recently to study radiation exposures incurred by astronauts during space flight, where a significant proportion of the dose is delivered by high-LET particle exposure. Traditional methods for the assessing of cytogenetic damage in mitotic cells collected at one time point after exposure may not be suitable for measuring high-LET radiation effects due to the drastic cell cycle perturbations and interphase cell death induced by this type of exposure. In this manuscript we review the recent advances in methodology used to study high-LET induced cytogenetic effects and evaluate the use of chemically-induced Premature Chromosome Condensation (PCC) as an alternative to metaphase analysis. Published data on the cytogenetic effects of in vitro exposures of high-LET radiation is reviewed, along with biodosimetry results from astronauts after short or long space missions.

ISS Project↗

G2 Chromatid Damage and Repair Kinetics in Normal Human Fibroblast Cells Exposed to Low-or High-LET Radiation

Radiation-induced chromosome damage can be measured in interphase using the Premature Chromosome Condensation (PCC) technique. With the introduction of a new PCC technique using the potent phosphatase inhibitor calyculin-A, chromosomes can be condensed within five minutes, and it is now possible to examine the early damage induced by radiation. Using this method, it has been shown that high-LET radiation induces a higher frequency of chromatid breaks and a much higher frequency of isochromatid breaks than low-LET radiation. The kinetics of chromatid break rejoining consists of two exponential components representing a rapid and a slow time constant, which appears to be similar for low- and high- LET radiations. However, after high-LET radiation exposures, the rejoining process for isochromatid breaks influences the repair kinetics of chromatid-type breaks, and this plays an important role in the assessment of chromatid break rejoining in the G2 phase of the cell cycle.

Kawata, T.↗

M-Band Analysis of Chromosome Aberrations in Human Epithelial Cells Induced By Low- and High-Let Radiations

Energetic primary and secondary particles pose a health risk to astronauts in extended ISS and future Lunar and Mars missions. High-LET radiation is much more effective than low-LET radiation in the induction of various biological effects, including cell inactivation, genetic mutations, cataracts and cancer. Most of these biological endpoints are closely correlated to chromosomal damage, which can be utilized as a biomarker for radiation insult. In this study, human epithelial cells were exposed in vitro to gamma rays, 1 GeV/nucleon Fe ions and secondary neutrons whose spectrum is similar to that measured inside the Space Station. Chromosomes were condensed using a premature chromosome condensation technique and chromosome aberrations were analyzed with the multi-color banding (mBAND) technique. With this technique, individually painted chromosomal bands on one chromosome allowed the identification of both interchromosomal (translocation to unpainted chromosomes) and intrachromosomal aberrations (inversions and deletions within a single painted chromosome). Results of the study confirmed the observation of higher incidence of inversions for high-LET irradiation. However, detailed analysis of the inversion type revealed that all of the three radiation types in the study induced a low incidence of simple inversions. Half of the inversions observed in the low-LET irradiated samples were accompanied by other types of intrachromosome aberrations, but few inversions were accompanied by interchromosome aberrations. In contrast, Fe ions induced a significant fraction of inversions that involved complex rearrangements of both the inter- and intrachromosome exchanges.

Hada, M.↗

MSFC Lunar Environments Test System (LETS) System Development

A review of the NASA MSFC Lunar Environment Test System (LETS) System Development is presented. The contents include: 1) MSFC LETS Chamber Status; 2) LETS Simulant Containment Box Development; 3) Tests Conducted in LETS To date: Simulant Dust Migration; 4) Summary; and 5) Forward Work.

Craven, Paul↗

A Monte Carlo Model for LET Spectra of 200 MeV Protons Used for Microelectronic Testing

The direct ionization Linear Energy Transfer (LET) for 200 MeV protons in silicon is much smaller than that for higher charged particles since LET increases as the square of the ion charge. However, occasionally the proton interacts with the silicon nuclei and produces a shower of fragments and a recoiling nucleus. When this happens, the LET produced is much greater than the direct ionization LET. Testing the single event effect susceptibility of components using energetic (200 MeV) protons is often the only viable option for system level testing commercial-off-the-shelf (COTS) avionics that have not been designed for space environments. However, the question of how a system tested with protons will perform in a heavy ion environment arises. Here the concern is not only with prediction of on-orbit upset rate, but also about possibility of on-orbit failures that were not observed during proton testing.

O'Neill, Patrick M.↗

Genotoxic Effects of Low- and High-LET Radiation on Human Epithelial Cells Grown in 2-D Versus 3-D Culture

Risk estimation for radiation-induced cancer relies heavily on human epidemiology data obtained from terrestrial irradiation incidents from sources such as medical and occupational exposures as well as from the atomic bomb survivors. No such data exists for exposures to the types and doses of high-LET radiation that will be encountered during space travel; therefore, risk assessment for space radiation requires the use of data derived from cell culture and animal models. The use of experimental models that most accurately replicate the response of human tissues is critical for precision in risk projections. This work compares the genotoxic effects of radiation on normal human epithelial cells grown in standard 2-D monolayer culture compared to 3-D organotypic co-culture conditions. These 3-D organotypic models mimic the morphological features, differentiation markers, and growth characteristics of fully-differentiated normal human tissue and are reproducible using defined components. Cultures were irradiated with 2 Gy low-LET gamma rays or varying doses of high-LET particle radiation and genotoxic damage was measured using a modified cytokinesis block micronucleus assay. Our results revealed a 2-fold increase in residual damage in 2 Gy gamma irradiated cells grown under organotypic culture conditions compared to monolayer culture. Irradiation with high-LET particle radiation gave similar results, while background levels of damage were comparable under both scenarios. These observations may be related to the phenomenon of "multicellular resistance" where cancer cells grown as 3-D spheroids or in vivo exhibit an increased resistance to killing by chemotherapeutic agents compared to the same cells grown in 2-D culture. A variety of factors are likely involved in mediating this process, including increased cell-cell communication, microenvironment influences, and changes in cell cycle kinetics that may promote survival of damaged cells in 3-D culture that would otherwise die or be rendered reproductively inactive in 2-D culture.

Patel, Z. S.↗

Electromagnetic Dissociation Cross Sections for High LET Fragments

Nuclear interaction cross sections are used in space radiation transport codes to calculate the probability of fragment emission in high energy nucleus-nucleus collisions. Strong interactions usually dominate in these collisions, but electromagnetic (EM) interactions can also sometimes be important. Strong interactions typically occur when the projectile nucleus hits a target nucleus, with a small impact parameter. For impact parameters larger than the sum of the nuclear radii, EM reactions dominate and the process is called electromagnetic dissociation (EMD) if one of the nuclei undergo fragmentation. Previous models of EMD have been used to calculate single proton (p) production, single neutron (n) production or light ion production, where a light ion is defined as an isotope of hydrogen (H) or helium (He), such as a deuteron (2H), a triton (3H), a helion (3He) or an alpha particle (4He). A new model is described which can also account for multiple nucleon production, such as 2p, 2n, 1p1n, 2p1n, 2p2n, etc. in addition to light ion production. Such processes are important to include for the following reasons. Consider, for example, the EMD reaction 56Fe + Al --> 52Cr + X + Al, for a 56Fe projectile impacting Al, which produces the high linear energy transfer (LET) fragment 52Cr. In this reaction, the most probable particles representing X are either 2p2n or 4He. Therefore, production of the high LET fragment 52Cr, must include the multiple nucleon production of 2p2n in addition to the light ion production of 4He. Previous models, such as the NUCFRG3 model, could only account for the 4He production process in this reaction and could not account for 2p2n. The new EMD model presented in this work accounts for both the light ion and multiple nucleon processes, and is therefore able to correctly account for the production of high LET products such as 52Cr. The model will be described and calculations will be presented that show the importance of light ion and multiple nucleon production. The work will also show that EMD reactions contribute most to those fragments with the highest LET.

Norbury, John↗

Dealing with Ion LET Uncertainties: An Application of Generalized Linear Models

Although most SEE rate estimation methods presume a fit to SEE cross section vs. LET, fitting SEE data is challenging because the data are not compatible with the assumptions of many common fitting techniques (e.g. linear regression. The difficulty of fitting such data is compounded when the LET of the ion responsible for an SEE is uncertain. We modify a Generalized Linear Model SEE data fitting methodology to accommodate uncertain LET and apply the method to the problem of backside heavy-ion SEE testing to demonstrate the utility of the method, explore the dependence of systematic errors that arise from improper treatment of LET uncertainty and develop guidelines for minimizing such systematic errors when proper treatment is not possible. Additional applications are suggested and assessed for suitability of treatment by the model.

Single-event effects↗

Heavy-Ion-Induced Lung Tumors: Dose- & LET-Dependence

There is a limited published literature reporting dose-dependent data for in vivo tumorigenesis prevalence in different organs of various rodent models after exposure to low, single doses of charged particle beams. The goal of this study is to reduce uncertainties in estimating particle-radiation-induced risk of lung tumorigenesis for manned travel into deep space by improving our understanding of the high-LET-dependent dose-response from exposure to individual ion beams after low particle doses (0.03 - 0.80 Gy). Female CB6F1 mice were irradiated with low single doses of either oxygen, silicon, titanium, or iron ions at various energies to cover a range of dose-averaged LET values from 0.2 - 193 keV/µm, using 137Cs γ-rays as the reference radiation. Sham-treated controls were included in each individual experiment totally 398 animals across the 5 studies reported. Based on power calculations, between 40 - 156 mice were included in each of the treatment groups. Tumor prevalence at 16 months after radiation exposure was determined and compared to the age-matched, sham-treated animals. Results indicate that lung tumor prevalence is non-linear as a function of dose with suggestions of threshold doses depending on the LET of the beams. Histopathological evaluations of the tumors showed that the majority of tumors were benign bronchioloalveolar adenomas with occasional carcinomas or lymphosarcomas which may have resulted from metastases from other sites.

60 APPLIED LIFE SCIENCES↗

DNA Damage Response to Low and High-LET in a Large Cohort of Mice and Humans and Latest Advancement in NASA Space Omics

This presentation will first focus on a thorough evaluation of the DNA damage response to both low and high-LET in a cohort of 76 mice primary skin fibroblast derived from 15 different strains or in human blood mononuclear cells derived from 550 healthy donors. In both the human and mice work, we have hypothesized that DNA repair capacity can be used as a marker to evaluate and differentiate individual radiation sensitivity. More specifically, this work is based on the concept that the combined time-dose dependence of radiation-induced foci (RIF) of p53-binding protein 1 (53BP1) following low-LET exposure contains sufficient information to infer sensitivity to any other LET. This work is one of the most extensive studies on the kinetics and possible genetic underpinnings of radiation-induced DNA damage and repair. Results on humans are still preliminary as we are still in the process of collecting and isolating primary blood mononuclear cells from 500 to 800 healthy subjects of European descent, 18-75 years of age, 50/50 male/female distribution. We have analyzed 53BP1+ RIF formation as well as oxidative stress and cell death in primary cells from 192 subjects in response to the same HZE particles as used in mice: 600 MeV/n Fe, 350 MeV/n Ar and 350 MeV/n Si, 1.1 and 3 particles/100m2, 4 and 24 hours after irradiation. The second part of the talk will focus on describing GeneLab: The NASA Systems Biology Platform for Space Omics Repository, Analysis and Visualization. NASA GeneLab is an open-access repository for omics datasets generated by biological experiments conducted in space or experiments relevant to spaceflight (e.g. simulated cosmic radiation, simulated microgravity, bed rest studies). Started as a repository designed to archive precious omics from space experiments, GeneLab has expanded its scope to maximize the intelligibility of the raw data (e.g. RNAseq, microarray, WGBS, metagenome), particularly for users with limited bioinformatics knowledge. As such GeneLab is now providing processed data derived from the raw data covering a large spectrum of omics (genome, epigenome, transcriptome, epitranscriptome, proteome, metabolome), to help users explore important questions: Which genes or proteins are expressed differently in space for various living organisms? What are the consequences arising from these changes? What specifics DNA mutations or epigenetic changes happen in space? What species or genetic features lead to better adaption to such a unique environment? In this presentation, we will report on the current and future objectives for GeneLab, and review recent published studies relating molecular changes observed in various animal models and tissue with microgravity, radiation, circadian rhythm, hydration and carbon dioxide conditions.

DNA repair kinetics↗

Low and High LET Degradation Studies of Metal-Loaded Organic Phase Ligands in the ALSEP Process

Organic solutions comprising the Actinide Lanthanide Separation Process (ALSEP) solvent consisting of 0.5 M 2-ethylhexyl phosphonic acid mono-2-ethylhexyl ester (HEH[EHP]) and 0.05 M N,N,N’,N’-tetra(2-ethylhexyl)diglycolamide (T2EHDGA) in n-dodecane were subjected to low LET and high LET irradiation before and after equilibration with an aqueous phase of 3 M HNO 3 . Degradation dose constants revealed greater ligand degradation due to gamma irradiation than alpha irradiation for both ligands. Furthermore, equilibration with nitric acid did not have a significant impact on ligand degradation for either irradiation source. Identified degradation products were similar for both gamma and alpha irradiation and occurred mostly through the rupture of the N–C carbonyl and C–O ether bonds for T2EHDGA and the C–Oether bond in HEH[EHP]. Acid contact appears to alter the degradation pathway by favoring the formation of higher molecular weight recombination products. Furthermore, mixed T2EHDGA-HEH[EHP]-NO 3 complexes were formed with Nd(III) after extraction from 3 M HNO 3 , and low LET gamma irradiation of the Nd(III) loaded organic solution produced similar degradation products as the organic solution absent of Nd(III). Interestingly, and likely due to the greater radiolytic susceptibility of T2EHDGA than HEH[EHP], a HEH[EHP]-Nd(III) complex appears to form as the T2EHDGA degrades with increasing absorbed dose.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Dose protraction studies with low- and high-LET radiations on neoplastic cell transformation in vitro

The effects of the low- and high-LET radiation (by X-rays, Co-60, and heavy ions) on the transformation of neoplastic cells were studied using cultured C3H10T1/2 mouse embryo cells. The transformed colonies in the confluent cell monolayers were recognized as focuses composed of highly polar fibroblastic multilayered criss-cross arrays of densely stained cells. For the low-LET radiation, there was a decrease in cell killing and cell transformation frequency when cells were irradiated with fractionated doses and at a low dose rate, indicating that cultured mammalian cells can repair both subtransformation and potential transformation lesions. No sparing effect, however, was found for the high-LET radiation. An enhancement of cell transformation was observed for low-dose/rate argon (400 MeV/u; 120 keV/micron) and iron particles (600 MeV/u; 200 keV/micron). The molecular mechanism for this enhancement effect is not known.

Yang, Tracy Chui-Hsu↗

Charged particle LET-spectra measurements aboard LDEF

The linear energy transfer (LET) spectra of charged particles was measured in the 5 to 250 keV/micron (water) interval with CR-39 and in the 250 to 1000 keV/micron (water) interval with polycarbonate plastic nuclear track detectors (PNTDs) under different shielding depths in the P0006 experiment. The optimal processing conditions were determined for both PNTDs in relation to the relatively high track densities due to the long term exposure in space. The total track density was measured over the selected samples, and tracks in coincidence on the facing surfaces of two detector sheets were selected for measuring at the same position on each sheet. The Short Range (SR) and Galactic Cosmic Ray (GCR) components were measured separately. The integral dose and dose rate spectra of charged particles are also given. The high LET portion of the LET spectra was measured with high statistical accuracy. This is a unique result of this experiment due to the low flux of this type of particle under typical shielding conditions.

Csige, I.↗

Charged particle LET-spectra measurements aboard LDEF

The linear energy transfer (LET) spectra of charged particles was measured in the 5 to 250 keV/micron (water) interval with CR-39 and in the 500 to 1500 keV/micron (water) interval with polycarbonate plastic nuclear track detectors (PNTDs) under different shielding depths in the P0006 experiment. The optimal processing conditions were determined for both PNTDs in relation to the relatively high track densities due to the long term exposure in space. The total track density was measured over the selected samples, and tracks in coincidence on the facing surfaces of two detector sheets were selected for measuring at the same position on each sheet. The short range (SR) and Galactic Cosmic Ray (GCR) components were measured separately with CR-39 PNTDs and the integral dose and dose rate spectra of charged particles were also determined. The high LET portion of the LET spectra was measured with polycarbonate PNTDs with high statistical accuracy. This is a unique result of this exposure due to the low flux of these types of particles for typical spaceflight durations. The directional dependence of the charged particles at the position of the P0006 experiment was also studied by four small side stacks which surrounded the main stack and by analyzing the dip angle and polar angle distributions of the measured SR and GCR particle tracks in the main stack.

Csige, I.↗

LET analyses of biological damage during solar particle events

The effects of nuclear reactions on integral low-linear-energy-transfer (LET) protons spectra are studied, behind typical levels of spacecraft and body shielding, for the historically largest flares using the high-energy transport code BRYNTRN in conjunction with several biological damage models. The cellular track model of Katz provides an accurate description of cellular damage from heavy ion exposure. The track model is applied with BRYNTRN to provide a LET decomposition of survival and transformation rates for solar proton events. In addition, a fluence-based risk coefficient formalism is used to estimate Harderian gland-tumor induction in rodents and cataractogenesis in rabbits from solar flares, and a LET analysis is used to assess the relative contribution from target fragments on these biological endpoints.

Cucinotta, Francis A.↗

Predictions of LET spectra measured on LDEF

The linear energy transfer (LET) spectra measured by plastic (CR-39) detectors in Exp. P0006 on LDEF are much higher at high LET than expected from methods commonly used to predict LET spectra produced by the space ionizing radiation environment. This discrepancy is being investigated by examining modeling approximations used in the predictions, and some interim results are presented.

Armstrong, T. W.↗

High LET, passive space radiation dosimetry and spectrometry

The development of high linear energy transfer (LET), passive radiation dosimetry and spectrometry is needed for the purpose of accurate determination of equivalent doses and assessment of health risks to astronauts on long duration missions. Progress in the following research areas is summerized: intercomparisons of cosmic ray equivalent dose and LET spectra measurements between STS missions and between astronauts; increases LET spectra measurement accuracy with ATAS; space radiation measurements for intercomparisons of passive (PNTD, TLD, TRND, Emulsion) and active (TEPC, RME-111) dosimeters; interaction of cosmic ray particles with nuclei in matter; radiation measurements after long duration space exposures; ground based dosimeter calibrations; neutron detector calibrations; radiation measurements on Soviet/Russian spacecraft; space radiation measurements under thin shielding; and space radiation.

Benton, E. V.↗

Linear Energy Transfer (LET) spectra of cosmic radiation in low Earth orbit

Integral linear energy transfer (LET) spectra of cosmic radiation (CR) particles were measured on five Cosmos series spacecraft in low Earth orbit (LEO). Particular emphasis is placed on results of the Cosmos 1887 biosatellite which carried a set of joint U.S.S.R.-U.S.A. radiation experiments involving passive detectors that included thermoluminescent detectors (TLD's), plastic nuclear track detectors (PNTD's), fission foils, nuclear photo-emulsions, etc. which were located both inside and outside the spacecraft. Measured LET spectra are compared with those theoretically calculated. Results show that there is some dependence of LET spectra on orbital parameters. The results are used to estimate the CR quality factor (QF) for the COSMOS 1887 mission.

Parnell, T. A.↗