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Optically stimulated luminescence and thermoluminescence efficiencies for high-energy heavy charged particle irradiation in Al2O3:C.

The thermally and optically stimulated luminescence (TL and OSL) response to high energy heavy-charged particles (HCPs) was investigated for two types of Al2O3:C luminescence dosimeters. The OSL signal was measured in both continuous-wave (CW) and pulsed mode. The efficiencies of the HCPs at producing TL or OSL, relative to gamma radiation, were obtained using four different HCPs beams (150 MeV/u 4He, 400 MeV/u 12C, 490 MeV/u 28Si, and 500 MeV/u 56Fe). The efficiencies were determined as a function of the HCP linear energy transfer (LET). It was observed that the efficiency depends on the type of detector, measurement technique, and the choice of signal. Additionally, it is shown that the shape of the CW-OSL decay curve from Al2O3:C depends on the type of radiation, and, in principle, this can be used to extract information concerning the LET of an unknown radiation field. The response of the dosimeters to low-LET radiation was also investigated for doses in the range from about 1-1000 Gy. These data were used to explain the different efficiency values obtained for the different materials and techniques, as well as the LET dependence of the CW-OSL decay curve shape.

Aluminum Oxide↗

The activation of a specific DNA binding protein by neutron irradiation.

PURPOSE: To determine whether the quality of ionizing radiation is critical for activation of a radiation-specific DNA binding protein. METHODS AND MATERIALS: We have previously shown that after exposing Epstein Barr virus-transformed lymphoblastoid cells to ionizing radiation, a specific DNA binding factor appears in the nucleus apparently as a result of translocation from the cytoplasm. This protein binds to a number of different genomic sequences and a consensus motif has been identified. Because the protein was not activated by UV light, it was of interest whether high linear energy transfer (LET) radiation was capable of activation. RESULTS: We describe here the activation of a specific DNA binding protein by high LET neutron radiation. The protein binds a region adjacent to and overlapping with the distal repeat within a 179 base-pair fragment of the well-characterized Simian Virus (SV40) bidirectional promoter/enhancer element. The appearance of the DNA binding activity was dose dependent and reached a maximum level by 90 min postirradiation. A reduction in DNA binding activity was evident at later times after irradiation. CONCLUSIONS: The specific nature of this response and the rapidity of activation may indicate a pivotal role for this protein in repair or in some other aspect of the cellular response to radiation damage.

Base Sequence↗

Radiation environment on the Mir orbital station during solar minimum.

The Mir station has been in a 51.65 degrees inclination orbit since March 1986. In March 1995, the first US astronaut flew on the Mir-18 mission and returned on the Space Shuttle in July 1995. Since then three additional US astronauts have stayed on orbit for up to 6 months. Since the return of the first US astronaut, both the Spektr and Priroda modules have docked with Mir station, altering the mass shielding distribution. Radiation measurements, including the direct comparison of US and Russian absorbed dose rates in the Base Block of the Mir station, were made during the Mir-18 and -19 missions. There is a significant variation of dose rates across the core module; the six locations sampled showed a variation of a factor of nearly two. A tissue equivalent proportional counter (TEPC) measured a total absorbed dose rate of 300 microGy/day, roughly equally divided between the rate due to trapped protons from the South Atlantic Anomaly (SAA) and galactic cosmic radiation (GCR). This dose rate is about a factor of two lower than the rate measured by the thinly shielded (0.5 g cm-2 of Al) operational ion chamber (R-16), and about 3/2 of the rate of the more heavily shielded (3.5 g cm-2 of Al) ion chamber. This is due to the differences in the mass shielding properties at the location of these detectors. A comparison of integral linear energy transfer (LET) spectra measured by TEPC and plastic nuclear track detectors (PNTDs) deployed side by side are in remarkable agreement in the LET region of 15-1000 keV/micrometer, where the PNTDs are fully efficient. The average quality factor, using the ICRP-26 definition, was 2.6, which is higher than normally used. There is excellent agreement between the measured GCR dose rate and model calculations, but this is not true for trapped protons. The measured Mir-18 crew skin dose equivalent rate was 1133 microSv/day. Using the skin dose rate and anatomical models, we have estimated the blood-forming organ (BFO) dose rate and the maximum stay time in orbit for International Space Station crew members.

Atlantic Ocean↗

Interpretation of mutation induction by accelerated heavy ions in bacteria.

In this report, a quantitative interpretation of mutation induction cross sections by heavy charged particles in bacterial cells is presented. The approach is based on the calculation of the fraction of energy deposited by indirect hits in the sensitive structure. In these events the particle does not pass through the sensitive volume, but this region is hit by delta rays. Four track structure models, developed by Katz (in Quantitative Mathematical Models in Radiation Biology, pp. 57-83, Springer-Verlag, 1988). Chatterjee et al. (Radiat. Res. 54, 479-494, 1973), Kiefer and Straaten (Phys. Med. Biol. 31, 1201-1209, 1982) and Kudryashov et al. (Proceedings of the First Soviet Congress on Microdosimetry, Atomizdat, Moscow, 1973), respectively, were used for the calculations. With the latter two models, very good agreement of the calculations with experimental results on mutagenesis in bacteria was obtained. Depending on the linear energy transfer (LET infinity) of the particles, two different modes of mutagenic action of heavy ions are distinguished: "delta-ray mutagenesis," which is related to those radiation qualities that preferentially kill the cells in direct hits (LET infinity > or = 100 keV/microns), and "track core mutagenesis," which arises from direct hits and is observed for lighter ions or ions with high energy (LET infinity < or = 100 keV/microns).

Bacillus subtilis↗

Intra-arm and interarm chromosome intrachanges: tools for probing the geometry and dynamics of chromatin.

Many chromosome-type, exchange-type chromosomal aberrations produced by radiation are intrachanges, i.e. involve only one chromosome. It is assumed such intrachanges are formed by illegitimate reunion of two double-strand breaks (DSBs) on the chromosome. The yield of intra-arm intrachanges (acentric rings or paracentric inversions) relative to that of interarm intrachanges (centric rings or pericentric inversions) is larger than would occur if production and illegitimate reunion of DSBs were spatially random. The excess of intra-arm intrachanges is presumably due to proximity effects for illegitimate reunions, i.e. enhancement of the intrachange probability when two DSBs are formed close to one another. Radiation track structure may also play a role. Using a polymer description for "large-scale" chromatin geometry (>2 Mb), and using two alternate (rapid or slow motion) models for the way that DSBs move after they are produced, theoretical estimates are given for size distributions of intrachanges at low or high linear energy transfer (LET). The ratio of intra-arm to interarm intrachanges is derived from the size distribution and compared with data from the literature on centric rings, inversions, interstitial deletions and excess acentric fragments. Proximity effects enhance yields of intra-arm relative to interarm intrachanges at least severalfold and perhaps as much as 10-fold compared to expectations based on spatial randomness. We argue that further measurements of intra-arm and interarm intrachanges would be informative about large-scale chromatin structure and chromosome motion. Because inversions are more frequent than estimates of randomness would indicate, and are transmissible to daughter cells, their size distribution could also help characterize past exposure to high-LET radiation.

Chromatin↗

Alpha-particle-induced chromosomal instability in human bone marrow cells.

alpha-particles, which are ionising radiation of high linear-energy-transfer emitted, for example, from radon or plutonium, pass through tissue as highly structured tracks. Single target cells in the path of the tracks might be damaged by even low-dose alpha-irradiation. We found non-clonal cytogenetic aberrations, characterised by a high frequency of chromatid aberrations with chromosome aberrations, in clonal descendants of haemopoietic stem cells after exposure to alpha-particles of bone marrow cells from two of four haematologically normal individuals (up to 25% abnormal metaphases). The data are consistent with a transmissible genetic instability induced in a stem cell resulting in a diversity of aberrations in its clonal progeny many cell divisions later.

Alpha Particles↗

DNA damage induced by the direct effect of He ion particles.

We present here evidence showing that the yields of DNA lesions induced by He(2+) ions strongly depend on Linear energy transfer (LET). In this study, hydrated plasmid DNA was irradiated with He(2+) ions with LET values of 19, 63 and 95 keVmicrom(-1). The yields of prompt single-strand breaks (SSBs) are very similar at the varying LET values, whereas the yields of prompt double-strand breaks (DSBs) increase with increasing LET. Further, base lesions were revealed as additional strand breaks by post-irradiation treatment of the DNA with endonuclease III (Nth) and formamidopyrimidine-DNA glycosylase (Fpg). The reduction in the yield of these enzymatically induced SSBs and DSBs becomes significant as the LET increases. These results suggest that the clustering of DNA lesions becomes more probable in regions of high LET.

Base Pair Mismatch↗

Summary of current radiation dosimetry results on manned spacecraft.

Measurements of radiation exposures aboard manned space flights of various altitudes, orbital inclinations and durations were performed by means of passive radiation detectors, thermoluminescent detectors (TLD's), and in some cases by active electronic counters. The TLD's and electronic counters covered the lower portion of the LET (linear energy transfer) spectra, while the nuclear track detectors measured high-LET produced by HZE particles. In Spacelab (SL-1), TLD's recorded a range of 102 to 190-millirad, yielding an average low-LET dose rate of 11.2 mrad per day inside the module, about twice the dose rate measured on previous space shuttle flights. Because of a higher inclination of the SL-1 orbit (57 degrees versus 28.5 degrees for previous shuttle flights), substantial fluxes of highly ionizing HZE particles were also observed, yielding an overall average mission dose-equivalent of about 135 millirem, about three times higher than measured an previous shuttle missions. A dose rate more than an order of magnitude higher than for any other space shuttle light was obtained for mission STS-41C, reflecting the highest orbital altitude to date of 519 km.

Cosmic Radiation↗

Apoptosis induced by high- and low-LET radiations.

Cell death after irradiation occurs by apoptosis in certain cell populations in tissues. The phenomenon also occurs after high linear energy transfer (LET) irradiation, and the relative biological effectiveness (RBE) is 3 to 4 (with respect to low-LET radiation and apoptosis in intestinal crypts) for neutrons with energies of 14 MeV and up to 600 MeV. It is thought that p53 plays a role in the phenomenon, as radiation-induced apoptosis is not observed in p53-null animals.

Animals↗

Heavy ion induced membrane damage: hemolysis of erythrocytes and changes in erythrocyte membrane fluidity.

Human erythrocytes were irradiated with heavy ions of energies between 4 and 18 MeV/u having linear energy transfer (LET) values between 92 and 14,000 keV/microns. Hemolysis has been studied as a macroscopic parameter for membrane damage and changes of the fluidity as a more microscopic parameter. The membrane fluidity changed in a characteristic dose-dependent manner as detected by electron spin resonance employing 12-doxylstearic acid methyl ester spin label (SL 12). Lysis cross sections and RBE values were determined from dose effect curves. The results demonstrate a high hemolytic efficiency of heavy ions compared to X rays. With increasing LET values the measured relative biological efficiency (RBE) values increase continuously. In the complete LET range the cross sections formed one common curve as function of LET and no saturation effects are observed. This is in direct contrast to other biological endpoints such as cell inactivation or DNA damage.

DNA Damage↗

Tumor therapy with targeted atomic nanogenerators.

A single, high linear energy transfer alpha particle can kill a target cell. We have developed methods to target molecular-sized generators of alpha-emitting isotope cascades to the inside of cancer cells using actinium-225 coupled to internalizing monoclonal antibodies. In vitro, these constructs specifically killed leukemia, lymphoma, breast, ovarian, neuroblastoma, and prostate cancer cells at becquerel (picocurie) levels. Injection of single doses of the constructs at kilobecquerel (nanocurie) levels into mice bearing solid prostate carcinoma or disseminated human lymphoma induced tumor regression and prolonged survival, without toxicity, in a substantial fraction of animals. Nanogenerators targeting a wide variety of cancers may be possible.

Actinium↗

Lethality of single-track events: comparison between calculations and experimental data.

Recent results on cell killing by microbeams were analysed using three parameters (k, L, L1), where k is the mean number of lethal particles per cell nucleus, L [keV/microm] is the track-average LET (linear energy transfer) in cells, and L1 [keV/microm] is a critical value for inducing lethal damage by a single track. Analysis showed that calculations are consistent with two data sets. The existence of a quadratic dependence on LET of cellular effects is confirmed in the high-LET region between 30 and 500 keV/microm. L1 approximately 150 keV/microm was found to give the best fit and the sensitive area of the cell nucleus was determined as approximately 50 microm2 for Chinese hamster V79 cells. In microbeam experiments with several MeV alpha-particles, the relationship between k and L for V79 cells can be expressed as L = approximately 150(k)-1/2. For a given survival level, the difference in the required dose (or L) between the microbeam and broad-beam experiments is also analytically described.

Alpha Particles↗

Genome-wide gene expression changes in normal human fibroblasts in response to low-LET gamma-radiation and high-LET-like 125IUdR exposures.

Functional genomics studies were carried out to characterize the transcriptional response of normal human fibroblasts to ionizing radiation (IR) of different types. To this end, lung fibroblast IMR-90 cultures were exposed either to external beam gamma-radiation or to internal irradiation from decay of (125)I-labeled deoxyuridine ((125)IUdR) incorporated into the cellular DNA. A relatively small dose of 1 Gy of gamma-radiation was delivered to cell cultures either at a high dose-rate (HDR, 1 Gy, 1 min) or at a low dose-rate (LDR, 1 Gy, 22 h). More than 41,000 transcripts were assayed by oligo DNA microarray featuring all known and predicted genes in human genome. Gene expression profiles following gamma-radiation and decays of high-linear energy transfer (LET)-like (125)I share the majority of genes in common, indicating the involvement of similar pathways in signal transduction after IR exposures of different modalities. Gene Ontology (GO) analysis revealed that the oxidative phosphorylation, metabolism of nt, protein kinase cascade and cell cycle are among the up-regulated biological processes mostly affected by gamma-radiation in IMR-90 cells. The translational elongation, negative regulation of cell growth, antigen processing and protein targeting are down-regulated following IR exposures. About one-third of genes differentially expressed following either HDR or LDR gamma-radiation exposures in the same absorbed dose were different, indicating the involvement of distinct transcriptional programs in cellular response to irradiation delivered with the different dose rates.

Cell Line↗

RBE of fast neutrons for apoptosis in mouse thymocytes.

We compared apoptosis in mouse thymocytes following exposure to low doses of high linear energy transfer (LET), 62.5-MeV (p-->Be+) fast neutrons and low LET, 4-MeV photons by flow cytometric analysis of hypodiploid cells. The incidence of apoptotic cell death rose steeply at very low radiation doses reaching a plateau of 3 Gy. Both the time course and the radiation dose-response curves were similar for high and low LET radiation modalities. The relative biological effectiveness (RBE) of 1.0 for apoptosis in the mouse thymocyte system contrasts with the much higher value typically seen in many classical systems of clonogenic cell survival and tissue response. This difference suggests that while radiation-induced apoptosis may contribute significantly to loss of susceptible cells at doses of < or = 2 Gy, it appears to have a questionable role in determining the relative intrinsic radiosensitivity of mammalian cells to high and low LET irradiation at clinically relevant levels of cell kill.

Animals↗

Relative biological effectiveness of accelerated heavy ions for induction of morphological transformation in Syrian hamster embryo cells.

Syrian hamster embryo cells were used to study the morphological transformation induced by accelerated heavy ions with different linear energy transfer (LET) ranging from 13 to 400 keV/micron. Exponentially growing cells were irradiated with 12C or 28Si ion beams generated by the Heavy Ion Medical Accelerator in Chiba (HIMAC), then inoculated to culture dishes. Morphologically altered colonies were scored as transformants. Over the LET range examined, the frequency of transformation induced by the heavy ions increased sharply at very low doses no greater than 5 cGy. The relative biological effectiveness (RBE) of the heavy ions relative to X-rays first increased with LET, reached a maximum value of about 7 at 100 keV/micron, then decreased with the further increase of LET. Our findings confirmed that high LET heavy ions are much more effective than X-rays for the induction of in vitro cell transformation.

Animals↗

The biological effects of space radiation during long stays in space.

Many space experiments are scheduled for the International Space Station (ISS). Completion of the ISS will soon become a reality. Astronauts will be exposed to low-level background components from space radiation including heavy ions and other high-linear energy transfer (LET) radiation. For long-term stay in space, we have to protect human health from space radiation. At the same time, we should recognize the maximum permissible doses of space radiation. In recent years, physical monitoring of space radiation has detected about 1 mSv per day. This value is almost 150 times higher than that on the surface of the Earth. However, the direct effects of space radiation on human health are currently unknown. Therefore, it is important to measure biological dosimetry to calculate relative biological effectiveness (RBE) for human health during long-term flight. The RBE is possibly modified by microgravity. In order to understand the exact RBE and any interaction with microgravity, the ISS centrifugation system will be a critical tool, and it is hoped that this system will be in operation as soon as possible.

Aerospace Medicine↗

Effects of target fragmentation on evaluation of LET spectra from space radiation in low-earth orbit (LEO) environment: impact on SEU predictions.

Recent improvements in the radiation transport code HZETRN/BRYNTRN and galactic cosmic ray environmental model have provided an opportunity to investigate the effects of target fragmentation on estimates of single event upset (SEU) rates for spacecraft memory devices. Since target fragments are mostly of very low energy, an SEU prediction model has been derived in terms of particle energy rather than linear energy transfer (LET) to account for nonlinear relationship between range and energy. Predictions are made for SEU rates observed on two Shuttle flights, each at low and high inclination orbit. Corrections due to track structure effects are made for both high energy ions with track structure larger than device sensitive volume and for low energy ions with dense track where charge recombination is important. Results indicate contributions from target fragments are relatively important at large shield depths (or any thick structure material) and at low inclination orbit. Consequently, a more consistent set of predictions for upset rates observed in these two flights is reached when compared to an earlier analysis with CREME model. It is also observed that the errors produced by assuming linear relationship in range and energy in the earlier analysis have fortuitously canceled out the errors for not considering target fragmentation and track structure effects.

Aluminum↗

Radiation dosimetry and biophysical models of space radiation effects.

Estimating the biological risks from space radiation remains a difficult problem because of the many radiation types including protons, heavy ions, and secondary neutrons, and the absence of epidemiology data for these radiation types. Developing useful biophysical parameters or models that relate energy deposition by space particles to the probabilities of biological outcomes is a complex problem. Physical measurements of space radiation include the absorbed dose, dose equivalent, and linear energy transfer (LET) spectra. In contrast to conventional dosimetric methods, models of radiation track structure provide descriptions of energy deposition events in biomolecules, cells, or tissues, which can be used to develop biophysical models of radiation risks. In this paper, we address the biophysical description of heavy particle tracks in the context of the interpretation of both space radiation dosimetry and radiobiology data, which may provide insights into new approaches to these problems.

Astronauts↗