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At least 73 records · Page 4

Estimation of spatially restricted LET using track structure models

The spatial distribution of energy deposition is an important determinant in the formation of biologically significant lesions. It has been widely realized that Linear Energy Transfer (LET) being an average quantity is not sufficient to describe the situation at a submicroscopic scale. To remedy this to some extent 'energy-cut-off' values are sometimes used but since they are related to secondary electron energy and only indirectly to their range they are also not adequate although they may be easily calculated. 'Range-restricted LET' appears to be better but its determination is usually quite involved. Xapsos (1992) suggested a semi-empirical approximation based on a modified Bethe-formula which contains a number of assumption which are difficult to verify. A simpler and easier way is to use existing beam-models which describe energy deposition around an ion's path. They all agree that the energy density (i. e., energy deposited per unit mass) decreases with the inverse square of the distance from the track center. This simple dependence can be used to determine the fraction of total LET which is deposited in a cylinder of a given radius. As an example our own beam model. Energy density depends on distance x (measured in m) from the track center according to the presented formula.

Kiefer, J.↗

Miniature High-Let Radiation Spectrometer for Space and Avionics Applications

This paper reports on the design and characterization of a small, low power, and low weight instrument, a High-LET Radiation Spectrometer (HiLRS), that measures energy deposited by heavy ions in microelectronic devices. The HILRS operates on pulse-height analysis principles and is designed for space and avionics applications. The detector component in the instrument is based on large scale arrays of p-n junctions. In this system, the pulse amplitude from a particle hit is directly proportional to the particle LET. A prototype flight unit has been fabricated and calibrated using several heavy ions with varying LETs and protons with several energies. The unit has been delivered to the Ballistic Missile Defense Organization (BMDO) c/o the Air Force Research Laboratory in Albuquerque, NM, for integration into the military Space Technology Research Vehicle (STRV), a US-UK cooperative mission. Another version of HILRS is being prepared for delivery in April to the Hubble Space Telescope (HST) project, to fly on the HST Orbital Systems Test (HOST) Platform on a shuttle mission.

Stassinopoulos, E. G.↗

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 (TLDs), plastic nuclear track detectors (PNTDs), 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.

NASA Discipline Radiation Health↗

Comparisons of LET distributions measured in low-earth orbit using tissue-equivalent proportional counters and the position-sensitive silicon-detector telescope (RRMD-III)

Determinations of the LET distribution, phi(L), of charged particles within a spacecraft in low-Earth orbit have been made. One method used a cylindrical tissue-equivalent proportional counter (TEPC), with the assumption that for each measured event, lineal energy, y, is equal to LET and thus phi(L) = phi(y). The other was based on the direct measurement of LETs for individual particles using a charged-particle telescope consisting of position-sensitive silicon detectors called RRMD-III. There were differences of up to a factor of 10 between estimates of phi(L) using the two methods on the same mission. This caused estimates of quality factor to vary by a factor of two between the two methods.

Flight Experiment↗

High- and low-LET induced chromosome damage in human lymphocytes: a time-course of aberrations in metaphase and interphase

PURPOSE: To investigate how cell-cycle delays in human peripheral lymphocytes affect the expression of complex chromosome damage in metaphase following high- and low-LET radiation exposure. MATERIALS AND METHODS: Whole blood was irradiated in vitro with a low and a high dose of 1 GeV u(-1) iron particles, 400MeV u(-1) neon particles or y-rays. Lymphocytes were cultured and metaphase cells were collected at different time points after 48-84h in culture. Interphase chromosomes were prematurely condensed using calyculin-A, either 48 or 72 h after exposure to iron particles or gamma-rays. Cells in first division were analysed using a combination of FISH whole-chromosome painting and DAPI/ Hoechst 33258 harlequin staining. RESULTS: There was a delay in expression of chromosome damage in metaphase that was LET- and dose-dependant. This delay was mostly related to the late emergence of complex-type damage into metaphase. Yields of damage in PCC collected 48 h after irradiation with iron particles were similar to values obtained from cells undergoing mitosis after prolonged incubation. CONCLUSION: The yield of high-LET radiation-induced complex chromosome damage could be underestimated when analysing metaphase cells collected at one time point after irradiation. Chemically induced PCC is a more accurate technique since problems with complicated cell-cycle delays are avoided.

Non-NASA Center↗

Distributions of Low- and High-LET Radiation-Induced Breaks in Chromosomes are Associated with Inter- and Intrachromosome Exchanges

To study the breakpoint along the length of the chromosome induced by low- and high-LET radiations, we exposed human epithelial cells in vitro to Cs-137 rays at both low and high dose rates, secondary neutrons at a low dose rate, and 600 MeV/u Fe ions at a high dose rate. The location of the breaks was identified using the multicolor banding in situ hybridization (mBAND) that paints Chromosome 3 in 23 different colored bands. The breakpoint distributions were found to be similar between rays of low and high dose rates and between the two high-LET radiation types. Detailed analysis of the chromosome break ends involved in inter- and intrachromosome exchanges revealed that only the break ends participating in interchromosome exchanges contributed to the hot spots found for low-LET. For break ends participating in intrachromosome exchanges, the distributions for all four radiation scenarios were similar with clusters of breaks found in three regions. Analysis of the locations of the two break ends in Chromosome 3 that joined to form an intrachromosome exchange demonstrated that two breaks with a greater genomic separation may be more likely to rejoin than two closer breaks, indicating that chromatin folding can play an important role in the rejoining of chromosome breaks. Our study demonstrated that the gene-rich regions do not necessarily contain more breaks. The breakpoint distribution depends more on the likelihood that a break will join with another break in the same chromosome or in a different chromosome.

Hada, Megumi↗

Distribution of Chromosome Breakpoints in Human Epithelial Cells Exposed to Low- and High-LET Radiation

Low-and high-LET radiations produced distinct breakpoint distributions. The difference of the breakpoint distributions between low-and high-LET only appeared in break ends involved in interchromosome exchanges. The breakpoint distributions for break ends participating in intrachromosome exchanges were similar. Gene-rich regions do not necessarily have more chromosome breaks. High-LET appeared to produce long live (data not shown) or longer live breaks that can migrate a longer distance before rejoining with other breaks. Domains occupied by different segments of the chromosomes may be responsible for the breakpoint distribution. The dose responses for interchromosomal exchanges were linear in all four exposures. However, the dose response for intrachromosomal exchanges were none linear. Increasing dose of high dose rate exposure (Fe-ions or -rays) increase the fraction of cells with intrachromosome aberrations, whereas increasing dose of low dose rate exposure (neutrons or -rays) does not affect the fraction of cells with intrachromosome aberrations.

Hada, Megumi↗

High LET Radiation Can Enhance TGF(Beta) Induced EMT and Cross-Talk with ATM Pathways

The TGF(Beta) pathway has been shown to regulate or directly interact with the ATM pathway in the response to radiation in mammary epithelial cells. We investigated possible interactions between the TGF(Beta) and ATM pathways following simulated space radiation using hTERT immortalized human esophageal epithelial cells (EPC-hTERT), mink lung epithelial cells (Mv1lu), and several human fibroblast cell lines. TGF(Beta) is a key modulator of the Epithelial-Mesenchymal Transition (EMT), important in cancer progression and metastasis. The implication of EMT by radiation also has several lines of developing evidence, however is poorly understood. The identification of TGF(Beta) induced EMT can be shown in changes to morphology, related gene over expression or down regulation, which can be detected by RT-PCR, and immunostaining and western blotting. In this study, we have observed morphologic and molecular alternations consistent with EMT after Mv1lu cells were treated with TGF(Beta) High LET radiation enhanced TGF(Beta) mediated EMT with a dose as low as 0.1Gy. In order to consider the TGF(Beta) interaction with ATM we used a potent ATM inhibitor Ku55933 and investigated gene expression changes and Smad signaling kinetics. Ku559933 was observed to reverse TGF(Beta) induced EMT, while this was not observed in dual treated cells (radiation+TGF(Beta)). In EPC-hTERT cells, TGF(Beta) alone was not able to induce EMT after 3 days of application. A combined treatment with high LET, however, significantly caused the alteration of EMT markers. To study the function of p53 in the process of EMT, we knocked down P53 through RNA interference. Morphology changes associated with EMT were observed in epithelial cells with silenced p53. Our study indicates: high LET radiation can enhance TGF(Beta) induced EMT; while ATM is triggering the process of TGF(Beta)-induced EMT, p53 might be an essential repressor for EMT phenotypes.

Wang, Minli↗

The Biological Effectiveness of Accelerated Particles for the Induction of Chromosome Damage: Track Structure Effects and Cytogenetic Signatures of High-LET Exposure

Track structure models predict that at a fixed value of LET, particles with lower charge number, Z will have a higher biological effectiveness compared to particles with a higher Z. In this report we investigated how track structure effects induction of chromosomal aberration in human cells. Human lymphocytes were irradiated in vitro with various energies of accelerated iron, silicon, neon, or titanium ions and chromosome damage was assessed in using three color FISH chromosome painting in chemically induced PCC samples collected a first cell division post irradiation. The LET values for these ions ranged from 30 to 195 keV/micrometers. Of the particles studied, Neon ions have the highest biological effectiveness for induction of total chromosome damage, which is consistent with track structure model predictions. For complex-type exchanges 64 MeV/ u Neon and 450 MeV/u Iron were equally effective and induced the most complex damage. In addition we present data on chromosomes exchanges induced by six different energies of protons (5 MeV/u to 2.5 GeV/u). The linear dose response term was similar for all energies of protons suggesting that the effect of the higher LET at low proton energies is balanced by the production of nuclear secondaries from the high energy protons. All energies of protons have a much higher percentage of complex-type chromosome exchanges than gamma rays, signifying a cytogenetic signature for proton exposures.

George, K.↗

Let Dependent Low Dose and Synergistic Inhibition of Human Angiogenesis by Charged Particles: Validation of Micrornas That Drive Inhibition

The microvasculature permeates all tissues at the microscopic level making the whole body a target for Space Radiation. Depending on the trajectory a single heavy ion particle would traverse many micro-vessels as it passes through the body causing a widespread response. Studies on the effects of charged particles on the development of human 3D micro-vessel models show that angiogenesis is inhibited by all ions detectible at a dose of 1.25c Gy. However, there are two distinct mechanisms of inhibition depending on the linear energy transfer (LET). We show here that the inhibition of angiogenesis is demarcated into two groups. The blockage of the early motile stage of micro-vessel development occurs after exposure to light ions (LET 3 KeV/n or lower) whereas the prevention of the later stages of development when the microvessels widen into tubes occurs after exposure to heavy ions (LET 8 KeV/n or higher). Strikingly, the combined effect of each ion has a synergistic effect detectible as low as 0.6 cGy. The low fluence of these doses indicates a bystander effect where the response is transmitted to other cells by the secretion of molecules by targeted cells. Prime candidates are microRNAs (miRNAs) and we have previously identified three angiogenesis-associated miRNA regulators from serum, cardiac tissue, and micro-vessels exposed to a simplified Galactic Cosmic Radiation (GCR) simulation – a mixture of heavy and light ions found in Space. Synthetic molecules (Antagomirs) designed to inhibit the predicted miRNAs were successfully used to reverse the inhibition of angiogenesis by Space Radiation. With the simple application of the antagomirs as a countermeasure we have for the first time shown an amelioration of the complex response(s) of angiogenesis to Space Radiation. This opens a new avenue of possible mitigation strategies based on the regulation and understanding of master regulators. These results not only have impact with Space Radiation research, but also provide clues of possible therapeutics for terrestrial diseases in the clinical setting.

Yen-Ruh Wuu↗

Neoplastic cell transformation by high-LET radiation - Molecular mechanisms

Quantitative data were collected on dose-response curves of cultured mouse-embryo cells (C3H10T1/2) irradiated with heavy ions of various charges and energies. Results suggests that two breaks formed on DNA within 80 A may cause cell transformation and that two DNA breaks formed within 20 A may be lethal. From results of experiments with restriction enzymes which produce DNA damages at specific sites, it was found that DNA double strand breaks are important primary lesions for radiogenic cell transformation and that blunt-ended double-strand breaks can form lethal as well as transformational damages due to misrepair or incomplete repair in the cell. The RBE-LET relationship for high-LET radiation is similar to that for HGPRT locus mutation, chromosomal deletion, and cell transformation, indicating that common lesions may be involved in these radiation effects.

Yang, Tracy Chui-Hsu↗

Radiation effects in Caenorhabditis elegans - Mutagenesis by high and low LET ionizing radiation

The nematode C. elegans was used to measure the effectiveness of high-energy ionized particles in the induction of three types of genetic lesions. Recessive lethal mutations in a 40-map unit autosomal region, sterility, and X-chromosome nondisjunction or damage were investigated. Induction rates were measured as a function of linear energy transfer, LET(infinity), for nine ions of atomic nunmber 1-57 accelerated at the BEVALAC accelerator. Linear kinetics were observed for all three types of lesions within the dose/fluence ranges tested and were found to vary strongly as a function of particle LET(infinity). Relative biological effectiveness (RBE) values of up to 4.2 were measured, and action cross sections were calculated and compared to mutagenic responses in other systems.

Nelson, Gregory A.↗

Measurements of LET spectra and comparison to models

Measurements of LET spectra for near-earth orbits with various inclinations and altitudes are presented. A comparison with calculated LET spectra shows that the contribution from direct ionizing galactic cosmic rays is well described by the models. An additional contribution to the spectra originates from stopping protons and from nuclear interactions of particles with material. In the case of an interaction, a large amount of energy is deposited in a small volume by target recoils or target fragments. These events will be called short range (SR) events. For a low-inclination orbit radiation belt protons are the main source of these events while galactic protons become more important when increasing the inclination to near-polar orbits. It is shown that the contribution of SR events for orbits with low altitude (324 km) and 57-deg inclination is comparable to that for an orbit with 28-deg inclination at a high altitude (510 km).

Wiegel, B.↗

LET spectra of fragmented 600-MeV/A iron beam on aluminum and polyethylene: A preliminary analysis

An iron beam experiment recently conducted at the Lawrence Berkeley Laboratory Bevalac by Benton et al. provides an opportunity for verifying the new Green's function computer code (GRNTRN) and assessing the related nuclear database. The iron beam with 600 MeV/A at extraction traversed a series of beam transport elements, lead foil, and several triggering devices before impacting the target. Of these, only the 2.24 g/sq cm lead foil and target are considered in the transport analysis with an assumed (inferred from calibration) beam energy of 557 MeV/A. A thin layer of CR-39 plastic nuclear track detector (PNTD) was placed in front of the target to monitor the incident flux and a stack of four PNTD's placed behind to measure the linear energy transfer (LET) distribution of the transported beam. Test data are analyzed for three separate targets: 2 g/sq cm aluminum, 5-cm polyethylene, and 8-cm polyethylene. The two-layer GRNTRN results were mapped into the detector response function for comparison with the measured LET spectra. Reasonable agreement is obtained. Future research and analysis can be improved by using a more accurate isotope set or including other important media which significantly alter the beam. The assumption that the fragmentation cross sections are too small for aluminum is inconclusive because the production of fragments by 2 g/sq cm aluminum can be more significantly affected by the fragment contribution originating from the media in front of the target than that currently considered in the analysis.

Shinn, Judy L.↗

LET spectra of trapped anomalous cosmic rays in low-Earth orbit

Observations aboard Cosmos satelites discovered trapped anomalous cosmic rays (ACRs), tracked the variation in their intensity in 1986-1988, and measured their fluence, spectrum, and composition at solar minimum in the previous solar cycle. The MAST instrument aboard the SAMPEX satellite has observed trapped anomalous cosmic rays in the present solar cycle, confirmed the general features of the Cosmos data, and provided the first detailed observations of trapped ACRs. In this paper we apply theoretical modeling of trapped ACRs, which is shown to provide a reasonably good description of both the Cosmos and SAMPEX data, to calculate the integral linear-energy-transfer (LET) spectra due to trapped ACRs in typical low-Earth orbits. We compare these calculations with the LET spectra produced by galactic cosmic rays (GCRs) and non-trapped ACRs in order to assess the relative radiation hazard posed by trapped ACRs.

Tylka, A. J.↗

Energetic particles and coronal mass ejections in the high latitude heliosphere: Ulysses-LET observations

The COSPIN Low Energy Telescope (LET) onboard the Ulysses spacecraft measures protons, alphas and heavier ions at energies of approximately 1 to 50 MeV/n. Ulysses measurements offer favorable opportunities to study the effects of solar activity in the out-of-ecliptic regions of the heliosphere. Using LET data, we have investigated the properties of transient energetic ions at high heliographic latitudes when Ulysses was permanently immersed in high speed solar wind and magnetically connected to the Sun on open magnetic field lines. Recurrent increases in the fluxes of energetic ions at high heliographic latitudes at frequencies related to the solar rotation period were found to occur in association with co-rotating interaction regions (CIRs). Here we investigate fluxes of energetic particles that showed no relationship to ClRs. From the investigation of plasma and magnetic held data it is found that all of the transient high latitude particle events were associated with the passage of a coronal mass ejection (CME) over Ulysses. Enhancements in particle fluxes several days prior to the arrival of a CME, but with a significant time delay with respect to the estimated CME-onset at the Sun, were most probably associated with interplanetary shocks driven by fast CMEs. These particle events exhibit unusually high rho/alpha-ratios and are not observed for CMEs not driving a shock. However, not all CMEs that passed Ulysses were associated with a particle event. We find evidence that at high solar latitudes, solar flare particles cannot reach Ulysses on open magnetic field lines, but can reach the spacecraft if particles are injected into magnetic flux-ropes (CMEs) at the Sun. These findings are supported by soft X-ray observations from the Japanese Yohkoh-satellite.

Bothmer, V.↗

A Low LET Radiation Spectrometer for Measuring Particle Doses in Space and Aircraft

This paper presents experimental data that demonstrates the feasibility of fabricating a miniature nuclear particle dosimeter for monitoring doses in aircraft and satellites. The basic instrument is a Low Linear-Energy-Transfer (LET) Radiation Spectrometer (LoLRS) that is designed to measure the energy deposited by particles with low LET values. The heart of the instrument is a Silicon-Lithium Drifted Diode (SLDD). Test results show that the LoLRS can be used to monitor the radiation threat to personnel in flights of space- and aircraft and also to generate a comprehensive data base from aviation and satellite measurements that can contribute to the formulation of more accurate environmental radiation models for dose predictions with reduced uncertainty factors.

Stassinopoulos, E. G.↗

Ascorbate, added after irradiation, reduces the mutant yield and alters the spectrum of CD59- mutations in A(L) cells irradiated with high LET carbon ions

It has been reported that X-ray induced HPRT- mutation in cultured human cells is prevented by ascorbate added after irradiation. Mutation extinction is attributed to neutralization by ascorbate, of radiation-induced long-lived radicals (LLR) with half-lives of several hours. We here show that post-irradiation treatment with ascorbate (5 mM added 30 min after radiation) reduces, but does not eliminate, the induction of CD59- mutants in human-hamster hybrid A(L) cells exposed to high-LET carbon ions (LET of 100 KeV/microm). RibCys, [2(R,S)-D-ribo-1',2',3',4'-Tetrahydroxybutyl]-thiazolidene-4(R)-ca riboxylic acid] (4 mM) gave a similar but lesser effect. The lethality of the carbon ions was not altered by these chemicals. Preliminary data are presented that ascorbate also alters the spectrum of CD59- mutations induced by the carbon beam, mainly by reducing the incidence of small mutations and mutants displaying transmissible genomic instability (TGI), while large mutations are unaffected. Our results suggest that LLR are important in initiating TGI.

NASA Discipline Radiation Health↗