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PubMed2002

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.

Aerospace Medicine↗
PubMed2005

Neoplastic transformation in vitro induced by low doses of 232 MeV protons.

The aim was to define the dose--response curve for high-energy proton-induced neoplastic transformation in vitro. The HeLa x skin fibroblast human hybrid cell assay was used to determine the frequency of neoplastic transformation following doses of 232 MeV protons (mean linear energy transfer, LET=0.44 keV microm(-1)) in the range 5-600 mGy. Proton irradiations were carried out at the Loma Linda University Proton Treatment Facility, CA, USA. The data indicate no evidence for induction of transformation below a dose of 100 mGy. At doses of 5 and 50 mGy, there is evidence for a possible suppression of transformation frequencies below that for spontaneous transformation. The shape of the dose--response curve for high-energy proton-induced transformation of the human hybrid cell line CGL1 does not follow a linear no-threshold model and shows evidence for a threshold as well as for possible suppression of transformation at doses <100 mGy, similar to that seen for other low-LET radiations.

Cell Transformation, Neoplastic↗
PubMed2000

Model for radial dependence of frequency distributions for energy imparted in nanometer volumes from HZE particles.

This paper develops a deterministic model of frequency distributions for energy imparted (total energy deposition) in small volumes similar to DNA molecules from high-energy ions of interest for space radiation protection and cancer therapy. Frequency distributions for energy imparted are useful for considering radiation quality and for modeling biological damage produced by ionizing radiation. For high-energy ions, secondary electron (delta-ray) tracks originating from a primary ion track make dominant contributions to energy deposition events in small volumes. Our method uses the distribution of electrons produced about an ion's path and incorporates results from Monte Carlo simulation of electron tracks to predict frequency distributions for ions, including their dependence on radial distance. The contribution from primary ion events is treated using an impact parameter formalism of spatially restricted linear energy transfer (LET) and energy-transfer straggling. We validate our model by comparing it directly to results from Monte Carlo simulations for proton and alpha-particle tracks. We show for the first time frequency distributions of energy imparted in DNA structures by several high-energy ions such as cosmic-ray iron ions. Our comparison with results from Monte Carlo simulations at low energies indicates the accuracy of the method.

Alpha Particles↗
PubMed1999

Determination of the absorbed dose and the average LET of space radiation in dependence on shielding conditions.

The HTR method, developed for determination of absorbed dose and average LET of mixed radiation fields in space, was applied during several space missions on space station MIR, space shuttles and satellites. The method utilises the changes of peak height ratios in the glow curves in dependence on the linear energy transfer LET. Due to the small size of the dosemeters the evaluation of the variation of absorbed dose and average LET in dependence on the position of the dosemeters inside the space station is possible. The dose and LET distribution was determined during the experiment ADLET where dosemeters were exposed in two positions with different shielding conditions and during two following experiments (MIR-95, MIR-96) using six positions inside the space station. The results were compared with the shielding conditions of the positions. Calculations of the absorbed dose were carried out for comparison. Results have shown that the average LET increases with increasing absorbing thickness while the absorbed dose decreases.

Cosmic Radiation↗
PubMedDate not supplied

Issues in deep space radiation protection.

The exposures in deep space are largely from the Galactic Cosmic Rays (GCR) for which there is as yet little biological experience. Mounting evidence indicates that conventional linear energy transfer (LET) defined protection quantities (quality factors) may not be appropriate for GCR ions. The available biological data indicates that aluminum alloy structures may generate inherently unhealthy internal spacecraft environments in the thickness range for space applications. Methods for optimization of spacecraft shielding and the associated role of materials selection are discussed. One material which may prove to be an important radiation protection material is hydrogenated carbon nanofibers.

Aluminum↗
PubMed1999

Contribution of cosmic ray heavy ions to the radiation hazard in manned space flights.

Primary cosmic radiation arriving near the Earth may be classified into two general categories: the gamma component and the hadronic component. The hadronic component contains mainly protons, a small amount of alpha particles and a smaller amount of heavier charged nuclei (ions). Although the fluxes of these heavier ions are very small in comparison to those of protons, they are able to originate a huge linear energy transfer (LET). This work studies the contribution of heavy ions from cosmic rays to the radiation hazard to which the crew of a manned long duration space flight might be exposed. The geometry of the energy deposition by a heavy ion is studied, and it is found that energies of the order of up to 10(23) J kg-1 are deposited.

Cosmic Radiation↗
PubMed1999

Recent European measurements inside Biorack.

The dosimetric package used inside Biorack on board STS76, STS81 and STS84 comprises passive detector stacks built from plastic nuclear track detectors (PNTDs), thermoluminescence detectors (TLDs) and one or two active DOSTEL (DOSimetric TELescope) units using planar silicon detectors. Five passive detector stacks were exposed at different places inside the BIORACK incubators and in different stowage positions. DOSTEL units were exposed inside the 22 degrees C incubator in all flights. Mission integrated dose measurements, particle fluence rates and neutron doses are obtained from the passive detector stacks. These results are complemented by time resolved particle counts and dose rates and linear energy transfer (LET) spectra separately for the contribution of the trapped particles and the galactic cosmic rays (GCR) as a result of the DOSTEL measurements. In addition, it was possible to investigate the anisotropy of the radiation field inside Biorack by the use of a second DOSTEL unit on STS84. Since all exposures are during a solar minimum period, the total radiation exposure is of a similar extent for all flights, although position differences in dose rate up to a factor of two are observed. Particle fluence rates show lower variations. Mission averaged mean quality factors (Q) determined from the LET spectra are 2.0+/-0.1; the deduced dose equivalent rates range from 631 to 716 microSv/day.

Analog-Digital Conversion↗
PubMed2006

On the biophysical interpretation of lethal DNA lesions induced by ionising radiation.

Although DNA damage is widely viewed as a critical target for the induction of cell killing by ionising radiation, the exact nature of DNA damage responsible for these effects is unknown. To address this issue, the probability of forming lethal damage by single proton tracks, derived from published survival data for Chinese hamster V79 cells irradiated by protons with energies from 0.57 to 5.01 MeV, has been compared to estimated yields of clustered DNA lesions and repair outcomes calculated with Monte Carlo models. The reported studies provide new information about the potential relationship between the induction and repair of clustered DNA damage and trends in the expected number of lethal events for protons with increasing linear energy transfer (LET). A good correlation was found between the number of lethal events in V79 cells and the induction of double-strand breaks (DSBs) consisting of three or more elementary DNA lesions. For the yields of other types of DNA damage, as well as point mutations formed through the misrepair of base damage and single-strand breaks, observed trends with increasing LET are not consistent with trends in the yields of lethal events. This observation suggests that the relative biological effectiveness (RBE) of protons of varying quality may be more closely related to the induction of complex DSBs rather than other forms of damage.

Animals↗
PubMed1997

Irradiation of mixed beam and design of spread-out Bragg peak for heavy-ion radiotherapy.

Data on cellular inactivation resulting from mixed irradiation with charged-particle beams of different linear energy transfer (LET) are needed to design a spread-out Bragg peak (SOBP) for heavy-ion radiotherapy. The present study was designed to study the relationship between the physical (LET) and biological (cell killing) properties by using different monoenergetic beams of 3He, 4He and 12C ions (12 and 18.5 MeV/nucleon) and to attempt to apply the experimental data in the design of the SOBP (3 cm width) with a 135 MeV/nucleon carbon beam. Experimental studies of the physical and biological measurements using sequentially combined irradiation were carried out to establish a close relationship between LET and cell inactivation. The results indicated that the dose-cell survival relationship for the combined high- and low-LET beams could be described by a linear-quadratic (LQ) model, in which new coefficients alpha and beta for the combined irradiation were obtained in terms of dose-averaged alpha and square root of beta for the single irradiation with monoenergetic beams. Based on the relationship obtained, the actual SOBP designed for giving a uniform biological effect at 3 cm depth was tested with the 135 MeV/nucleon carbon beam. The results of measurements of both physical (LET) and biological (90% level of cell killing, etc.) properties clearly demonstrated that the SOBP successfully and satisfactorily retained its high dose localization and uniform depth distribution of the biological effect. Based on the application of these results, more useful refinement and development can be expected for the heavy-ion radiotherapy currently under way at the National Institute of Radiological Sciences, Japan.

Animals↗
PubMed2004

Three-dimensional LET calculations for treatment planning of proton therapy.

The clinical impact of a variable relative biological effectiveness (RBE) in proton therapy is still under investigation. As the RBE depends on the linear energy transfer (LET), we present a fast method for three-dimensional calculations of the dose-averaged LET. The corresponding algorithm, based on an analytical expression for the LET and on Monte Carlo simulations, accounts for tissue inhomogeneities and allows LET calculations for realistic treatment plans and patient geometries given by computed tomography (CT) data sets. LET distributions were calculated for different proton spot scanning techniques, in particular for the full three-dimensional (3D) modulation and for the distal edge tracking technique (DET). In the case of 3D modulation, a more homogeneous distribution of LET in the planning target volume was observed than for the DET. Consequently, the proposed method allows to assess the impact of potential variations in RBE for various dose delivery techniques.

Humans↗
PubMed2006

Detailed analysis of the cell-inactivation mechanism by accelerated protons and light ions.

A detailed study of the biological effects of diverse quality radiations, addressing their biophysical interpretation, is presented. Published survival data for V79 cells irradiated by monoenergetic protons, helium-3, carbon and oxygen ions and for CHO cells irradiated by carbon ions have been analysed using the probabilistic two-stage model of cell inactivation. Three different classes of DNA damage formed by traversing particles have been distinguished, namely severe single-track lesions which might lead to cell inactivation directly, less severe lesions where cell inactivation is caused by their combinations and lesions of negligible severity that can be repaired easily. Probabilities of single ions forming these lesions have been assessed in dependence on their linear energy transfer (LET) values. Damage induction probabilities increase with atomic number and LET. While combined lesions play a crucial role at lower LET values, single-track damage dominates in high-LET regions. The yields of single-track lethal lesions for protons have been compared with Monte Carlo estimates of complex DNA lesions, indicating that lethal events correlate well with complex DNA double-strand breaks. The decrease in the single-track damage probability for protons of LET above approximately 30 keV microm(-1), suggested by limited experimental evidence, is discussed, together with the consequent differences in the mechanisms of biological effects between protons and heavier ions. Applications of the results in hadrontherapy treatment planning are outlined.

Animals↗
PubMed2004

Why it is advisable to keep wR = 1 and Q = 1 for photons and electrons.

It has been well known for a long time that the biological effectiveness of photons and electrons depends on the mean linear energy transfer (LET) of the radiation considered, e.g. (60)Co gamma rays are less effective than soft or hard X rays. Nevertheless, the protection and operational dose quantities applied in radiological protection include weighting factors, w(R) or Q, respectively, which were set to 1 for all low-LET radiations. Lack of precise information, simplicity and general practical considerations are the main arguments for this convention. However, a more detailed discussion on the practical aspects supporting this procedure is missing. The paper discusses in more detail some of these aspects regarding internal and external exposure situations, which may support the idea of continuing to use w(R) = 1 for photons and electrons and, correspondingly, using Q(L) = 1 for L < 10 keV microm(-1).

Electrons↗
PubMed1994

Molecular analysis of mutagenesis by high LET radiation.

Mutation induction by high linear energy transfer [LET] alpha particles and gamma-rays was scored in the human hamster hybrid [AL] cells. Southern blotting technique was used to analyse the molecular changes in the DNA from both the HGPRT- and S1- mutants. Dose dependent mutagenesis in the AL cells irradiated with the charged particles was higher by almost 20 fold at the S1 than the corresponding HGPRT locus. Southern analysis of the mutants induced by the high LET particles showed mostly multilocus deletion at both the HGPRT and S1 genes.

Alpha Particles↗
PubMed2004

Austrian dose measurements onboard space station MIR and the International Space Station--overview and comparison.

The Atominstitute of the Austrian Universities has conducted various space research missions in the last 12 years in cooperation with the Institute for Biomedical Problems in Moscow. They dealt with the exact determination of the radiation hazards for cosmonauts and the development of precise measurement devices. Special emphasis will be laid on the last experiment on space station MIR the goal of which was the determination of the depth distribution of absorbed dose and dose equivalent in a water filled Phantom. The first results from dose measurements onboard the International Space Station (ISS) will also be discussed. The spherical Phantom with a diameter of 35 cm was developed at the Institute for Biomedical Problems and had 4 channels where dosimeters can be exposed in different depths. The exposure period covered the timeframe from May 1997 to February 1999. Thermoluminescent dosimeters (TLDs) were exposed inside the Phantom, either parallel or perpendicular to the hull of the spacecraft. For the evaluation of the linear energy transfer (LET), the high temperature ratio (HTR) method was applied. Based on this method a mean quality factor and, subsequently, the dose equivalent is calculated according to the Q(LET infinity) relationship proposed in ICRP 26. An increased contribution of neutrons could be detected inside the Phantom. However the total dose equivalent did not increase over the depth of the Phantom. As the first Austrian measurements on the ISS dosimeter packages were exposed for 248 days, starting in February 2001 at six different locations onboard the ISS. The Austrian dosimeter sets for this first exposure on the ISS contained five different kinds of passive thermoluminescent dosimeters. First results showed a position dependent absorbed dose rate at the ISS.

Astronauts↗
PubMed1994

Real time dose rate and LET spectrum aboard MIR station during 1992.

Since the end of July 1992, the NAUSICAA system, a low gas pressured tissue equivalent proportional counter, recorded in real time the dose equivalent rate, the absorbed dose rate, the quality factor and the Linear Energy Transfer spectra, aboard the Russian orbital station MIR. The results since the ANTARES mission are presented. Some parameters like the proton flux, the previous solar cycles, the location of the NAUSICAA system inside the station and the South Atlantic Anomaly crossing seem to have an influence on these results. The total dose equivalent (H) during the ANTARES mission (between 1992 July the 30th and August the 10th) was 12 mSv and the total absorbed dose (D) 6.4 mGy with a quality factor (Q) equal to 1.9. The NAUSICAA system gives a good knowledge of LET spectra for the first time in space dosimetry.

Atlantic Ocean↗
PubMed2004

Instrumentation for investigation of the depth-dose distribution by the Liulin-5 instrument of a human phantom on the Russian segment of ISS for estimation of the radiation risk during long term space flights.

Described is the Liulin-5 experiment and instrumentation, developed for investigation of the space radiation doses depth distribution in a human phantom on the Russian Segment of the International Space Station (ISS). Liulin-5 experiment is a part of the international project MATROSHKA-R on ISS. The experiment MATROSHKA-R is aimed to study the depth dose distribution at the sites of critical organs of the human body, using models of human body-anthropomorphic and spherical tissue-equivalent phantoms. The aim of Liulin-5 experiment is long term (4-5 years) investigation of the radiation environment dynamics inside the spherical tissue-equivalent phantom, mounted in different places of the Russian Segment of ISS. Energy deposition spectra, linear energy transfer spectra, flux and dose rates for protons and the biologically-relevant heavy ion components of the galactic cosmic radiation will be measured simultaneously with near real time resolution at different depths of the phantom by a telescope of silicon detectors. Data obtained together with data from other active and passive dosimeters will be used to estimate the radiation risk to the crewmembers, verify the models of radiation environment in low Earth orbit, validate body transport model and correlate organ level dose to skin dose. Presented are the test results of the prototype unit. The spherical phantom will be flown on the ISS in 2004 year and Liulin-5 experiment is planned for 2005 year.

Cosmic Radiation↗
PubMed2005

Characterization of medium conditioned by irradiated cells using proteome-wide, high-throughput mass spectrometry.

Shedding, the release of cell surface proteins by regulated proteolysis, is a general cellular response to injury and is responsible for generating numerous bioactive molecules including growth factors and cytokines. The purpose of our work is to determine whether low doses of low-linear energy transfer (LET) radiation induce shedding of bioactive molecules. Using a mass spectrometry-based global proteomics method, we tested this hypothesis by analyzing for shed proteins in medium from irradiated human mammary epithelial cells (HMEC). Several hundred proteins were identified, including transforming growth factor beta (TGFB); however, no changes in protein abundances attributable to radiation exposure, based on immunoblotting methods, were observed. These results demonstrate that our proteomic-based approach has the sensitivity to identify the kinds of proteins believed to be released after low-dose radiation exposure but that improvements in mass spectrometry-based protein quantification will be required to detect the small changes in abundance associated with this type of insult.

Breast↗
PubMed2005

High LET-induced H2AX phosphorylation around the Bragg curve.

We investigated the spatial distribution of the induction of the phosphorylated form of the histone protein H2AX (gamma-H2AX), known to be activated by DSBs. Following irradiation of human fibroblast cells with 600 MeV/nucleon silicon and 600 MeV/nucleon iron ions we observed the formation of gamma-H2AX aggregates in the shape of streaks stretching over several micrometers in an x/y plane. Polyethylene shielding was used to achieve a Bragg curve distribution with beam geometry parallel to the monolayer of cells. We present data that highlights the formation of immunofluorescent gamma-H2AX tracks showing the ion trajectories across the Bragg peak of irradiated human fibroblast cells. Qualitative analyses of these distributions indicated potentially increased clustering of DNA damage before the Bragg peak, enhanced gamma-H2AX distribution at the peak, and provided visual evidence of high-linear energy transfer particle traversal of cells beyond the Bragg peak in agreement with one-dimensional transport approximations. Spatial assessment of gamma-H2AX fluorescence may provide direct insights into DNA damage across the Bragg curve for high charge and energy ions including the biological consequences of shielding and possible contributors to bystander effects.

Bystander Effect↗