Low Linear Energy Transfer Particles Research Articles

Estimations of relative biological effectiveness of secondary fragments in carbon ion irradiation of water using CR-39 plastic detector and microdosimetric kinetic model.

To estimate relative biological effectiveness (RBE) ascribed to secondary fragments in a lateral distribution of carbon ion irradiation. The RBE was estimated with the microdosimetric kinetic (MK) model and measured linear energy transfer (LET) obtained with CR-39 plastic detectors. A water phantom was irradiated by a 12 C pencil beam with energy of 380MeV/u at the Gunma University Heavy Ion Medical Center (GHMC), and CR-39 detectors were exposed to secondary fragments. Because CR-39 was insensitive to low LET, we conducted Monte Carlo simulations with Geant4 to calculate low LET particles. The spectra of low LET particleswere combined with experimental spectra to calculate RBE. To estimate accuracy of RBE, we calculated RBE by changing yield of low LET particles by±10% and±40%. At a small angle, maximum RBE by secondary fragments was 1.3 for 10% survival fractions. RBE values of fragments gradually decreased as the angle became larger. The shape of the LET spectra in the simulation reproduced the experimental spectra, but there was a discrepancy between the simulation and experiment for the relative yield of fragments. When the yield of low LET particles was changed by±40%, the change in RBE was smaller than 10%. An RBE of 1.3 was expected for secondary fragments emitted at a small angle. Although, we observed a discrepancy in the relative yield of secondary fragments between simulation and experiment, precision of RBE was not so sensitive to the yield of low LET particles.

Two distinct types of the inhibition of vasculogenesis by different species of charged particles.

BackgroundCharged particle radiation is known to be more biologically effective than photon radiation. One example of this is the inhibition of the formation of human blood vessels. This effect is an important factor influencing human health and is relevant to space travel as well as to cancer radiotherapy. We have previously shown that ion particles with a high energy deposition, or linear energy transfer (LET) are more than four times more effective at disrupting mature vessel tissue models than particles with a lower LET. For vasculogenesis however, the relative biological effectiveness between particles is the same. This unexpected result prompted us to investigate whether the inhibition of vasculogenesis was occurring by distinct mechanisms.MethodsUsing 3-Dimensional human vessel models, we developed assays that determine at what stage angiogenesis is inhibited. Vessel morphology, the presence of motile tip structures, and changes in the matrix architecture were assessed. To confirm that the mechanisms are distinct, stimulation of Protein Kinase C (PKC) with phorbol ester (PMA) was employed to selectively restore vessel formation in cultures where early motile tip activity was inhibited.ResultsEndothelial cells in 3-D culture exposed to low LET protons failed to make connections with other cells but eventually developed a central lumen. Conversely, cells exposed to high LET Fe charged particles extended cellular processes and made connections to other cells but did not develop a central lumen. The microtubule and actin cytoskeletons indicated that motility at the extending tips of endothelial cells is inhibited by low LET but not high LET particles. Actin-rich protrusive structures that contain bundled microtubules showed a 65% decrease when exposed to low LET particles but not high LET particles, with commensurate changes in the matrix architecture. Stimulation of PKC with PMA restored tip motility and capillary formation in low but not high LET particle treated cultures.ConclusionLow LET charged particles inhibit the early stages of vasculogenesis when tip cells have motile protrusive structures and are creating pioneer guidance tunnels through the matrix. High LET charged particles do not affect the early stages of vasculogenesis but they do affect the later stages when the endothelial cells migrate to form tubes.

Low LET protons focused to submicrometer shows enhanced radiobiological effectiveness

This study shows that enhanced radiobiological effectiveness (RBE) values can be generated focusing low linear energy transfer (LET) radiation and thus changing the microdose distribution. 20 MeV protons (LET = 2.65 keV µm−1) are focused to submicrometer diameter at the ion microprobe superconducting nanoprobe for applied nuclear (Kern) physics experiments of the Munich tandem accelerator. The RBE values, as determined by measuring micronuclei (RBEMN = 1.48 ± 0.07) and dicentrics (RBED = 1.92 ± 0.15), in human-hamster hybrid (AL) cells are significantly higher when 117 protons were focused to a submicrometer irradiation field within a 5.4 × 5.4 µm2 matrix compared to quasi homogeneous in a 1 × 1 µm2 matrix applied protons (RBEMN = 1.28 ± 0.07; RBED = 1.41 ± 0.14) at the same average dose of 1.7 Gy. The RBE values are normalized to standard 70 kV (dicentrics) or 200 kV (micronuclei) x-ray irradiation. The 117 protons applied per point deposit the same amount of energy like a 12C ion with 55 MeV total energy (4.48 MeV u−1). The enhancements are about half of that obtained for 12C ions (RBEMN = 2.20 ± 0.06 and RBED = 3.21 ± 0.10) and they are attributed to intertrack interactions of the induced damages. The measured RBE values show differences from predictions of the local effect model (LEM III) that is used to calculate RBE values for irradiation plans to treat tumors with high LET particles.

Hafnium and Uranium Contributions to Soft Error Rate at Ground Level

Current technologies are sensitive to low Linear Energy Transfer particles such as alphas. These particles can be spontaneously produced by some radioactive elements, called alpha-emitters. Here, we investigate two examples of emitters, Hafnium and Uranium. By calculating the disintegration rate in a modern technology with hafnium dioxide, we show that hafnium has no incidence on Soft Error Rate. Moreover, from Monte Carlo simulations, we point out that natural Uranium concentration in a silicon wafer lead to a Soft Error Rate comparable to that due to neutrons at ground level.

Formation of Clustered DNA Damage after High-LET Irradiation: A Review

Radiation can cause as well as cure cancer. The risk of developing radiation-induced cancer has traditionally been estimated from cancer incidence among survivors of the atomic bombs in Hiroshima and Nagasaki.(1)) These data provide the best estimate of human cancer risk over the dose range for low linear energy transfer (LET) radiations, such as X- or gamma-rays. The situation of estimating the real biological effects becomes even more difficult in the case of high LET particles encountered in space or as the result of domestic exposure to alpha-particles from radon gas emitters or other radioactive emitters like uranium-238. Complex DNA damage, i.e., the signature of high-LET radiations comprises of closely spaced DNA lesions forming a cluster of DNA damage. The two basic groups of complex DNA damage are double strand breaks (DSBs) and non-DSB oxidative clustered DNA lesions (OCDL). Theoretical analysis and experimental evidence suggest an increased complexity and severity of complex DNA damage with increasing LET (linear energy transfer) and a high mutagenic or carcinogenic potential. Data available on the formation of clustered DNA damage (DSBs and OCDL) by high-LET radiations are often controversial suggesting a variable response to dose and type of radiation. The chemical nature and cellular repair mechanisms of complex DNA damage have been much less characterized than those of isolated DNA lesions like an oxidized base or a single strand break especially in the case of high-LET radiation. This review will focus on the induction of clustered DNA damage by high-LET radiations presenting the earlier and recent relative data.

Synergism between gemcitabine and low LET (gamma-rays), but not high-let alpha-particles on multiple myeloma cell lines

Purpose/ObjectiveTo study the influence of Linear Energy Transfer (LET) on the radiosensitizing effects of gemcitabine, by comparing low LET (gamma-rays) and high LET particles (alpha-radioimmunotherapy).Materials/MethodsOn 3 multiple myeloma cell lines (LP1, RPMI 8226 and U266), we measured clonogenic survival after gamma-rays irradiation from Cobalt 60 (0 to 4 Gy) alone or combined with 10 nM gemcitabine after a 24h incubation prior to radiation. We also measured survival after alpha-radioimmunotherapy using B-B4 a monoclonal antibody that targets multiple myeloma cells radiolabeled with bismuth 213, alone or combined with 10 nM gemcitabine. Apoptosis was analyzed by apo 2.7 FACS staining.ResultsGemcitabine acted synergistically with gamma-rays on LP1 and U266 cell lines (Radiation Enhancement Ratio : 1.56 and 1.49 respectively), but not on RPMI 8226. Gemcitabine combined with alpha-radioimmunotherapy did not provoke a synergistic effect on all 3 cell lines. In order to explore the mechanisms of synergism we studied apoptosis 24h after irradiation combined with gemcitabine. Gemcitabine combined with gamma-rays increased apoptosis as compared with gemcitabine or gamma-rays alone on LP1 and U266 cell lines, but not on RPMI 8226. Gemcitabine combined with alpha-radioimmunotherapy increased apoptosis as compared with gemcitabine or alpha-radioimmunotherapy alone on U266 but not LP1 or RPMI 8226 cell lines.ConclusionsGemcitabine radiosensitization depended on the kind of radiation, and did not enhance high LET particles cellular effects. Gemcitabine acted synergistically with gamma-rays, but not with alpha-radioimmunotherapy on multiple myeloma cell lines. Gemcitabine enhanced the apoptotic effects of low LET particles, but this cannot be the only explanation of the observed synergistic effects Purpose/ObjectiveTo study the influence of Linear Energy Transfer (LET) on the radiosensitizing effects of gemcitabine, by comparing low LET (gamma-rays) and high LET particles (alpha-radioimmunotherapy). To study the influence of Linear Energy Transfer (LET) on the radiosensitizing effects of gemcitabine, by comparing low LET (gamma-rays) and high LET particles (alpha-radioimmunotherapy). Materials/MethodsOn 3 multiple myeloma cell lines (LP1, RPMI 8226 and U266), we measured clonogenic survival after gamma-rays irradiation from Cobalt 60 (0 to 4 Gy) alone or combined with 10 nM gemcitabine after a 24h incubation prior to radiation. We also measured survival after alpha-radioimmunotherapy using B-B4 a monoclonal antibody that targets multiple myeloma cells radiolabeled with bismuth 213, alone or combined with 10 nM gemcitabine. Apoptosis was analyzed by apo 2.7 FACS staining. On 3 multiple myeloma cell lines (LP1, RPMI 8226 and U266), we measured clonogenic survival after gamma-rays irradiation from Cobalt 60 (0 to 4 Gy) alone or combined with 10 nM gemcitabine after a 24h incubation prior to radiation. We also measured survival after alpha-radioimmunotherapy using B-B4 a monoclonal antibody that targets multiple myeloma cells radiolabeled with bismuth 213, alone or combined with 10 nM gemcitabine. Apoptosis was analyzed by apo 2.7 FACS staining. ResultsGemcitabine acted synergistically with gamma-rays on LP1 and U266 cell lines (Radiation Enhancement Ratio : 1.56 and 1.49 respectively), but not on RPMI 8226. Gemcitabine combined with alpha-radioimmunotherapy did not provoke a synergistic effect on all 3 cell lines. In order to explore the mechanisms of synergism we studied apoptosis 24h after irradiation combined with gemcitabine. Gemcitabine combined with gamma-rays increased apoptosis as compared with gemcitabine or gamma-rays alone on LP1 and U266 cell lines, but not on RPMI 8226. Gemcitabine combined with alpha-radioimmunotherapy increased apoptosis as compared with gemcitabine or alpha-radioimmunotherapy alone on U266 but not LP1 or RPMI 8226 cell lines. Gemcitabine acted synergistically with gamma-rays on LP1 and U266 cell lines (Radiation Enhancement Ratio : 1.56 and 1.49 respectively), but not on RPMI 8226. Gemcitabine combined with alpha-radioimmunotherapy did not provoke a synergistic effect on all 3 cell lines. In order to explore the mechanisms of synergism we studied apoptosis 24h after irradiation combined with gemcitabine. Gemcitabine combined with gamma-rays increased apoptosis as compared with gemcitabine or gamma-rays alone on LP1 and U266 cell lines, but not on RPMI 8226. Gemcitabine combined with alpha-radioimmunotherapy increased apoptosis as compared with gemcitabine or alpha-radioimmunotherapy alone on U266 but not LP1 or RPMI 8226 cell lines. ConclusionsGemcitabine radiosensitization depended on the kind of radiation, and did not enhance high LET particles cellular effects. Gemcitabine acted synergistically with gamma-rays, but not with alpha-radioimmunotherapy on multiple myeloma cell lines. Gemcitabine enhanced the apoptotic effects of low LET particles, but this cannot be the only explanation of the observed synergistic effects Gemcitabine radiosensitization depended on the kind of radiation, and did not enhance high LET particles cellular effects. Gemcitabine acted synergistically with gamma-rays, but not with alpha-radioimmunotherapy on multiple myeloma cell lines. Gemcitabine enhanced the apoptotic effects of low LET particles, but this cannot be the only explanation of the observed synergistic effects

Response of a tissue equivalent proportional counter to neutrons

The absorbed dose as a function of lineal energy was measured at the CERN-EC Reference-field Facility (CERF) using a 512-channel tissue equivalent proportional counter (TEPC), and neutron dose equivalent response evaluated. Although there are some differences, the measured dose equivalent is in agreement with that measured by the 16-channel HANDI tissue equivalent counter. Comparison of TEPC measurements with those made by a silicon solid-state detector for low linear energy transfer particles produced by the same beam, is presented. The measurements show that about 4% of dose equivalent is delivered by particles heavier than protons generated in the conducting tissue equivalent plastic.

Hydrogen production in ?-ray and helium-ion radiolysis of polyethylene, polypropylene, poly(methyl-methacrylate), and polystyrene

The production of molecular hydrogen in the radiolysis of high-density polyethylene, isotactic polypropylene (PP), poly(methyl-methacrylate) (PMMA), and polystyrene (PS) by y rays and 5-20-MeV helium ions was investigated. Molecular hydrogen is the dominant gaseous product from these polymers, and the yields with y rays are 3.3, 2.6, 0.24, and 0.033 molecules per 100 eV of energy absorbed for polyethylene, PP, PMMA, and PS, respectively. The decrease in observed hydrogen is due to increased branching and the chemical nature of the groups on the side chains. There is an increase in hydrogen production with increasing linear energy transfer (LET) from γ rays to helium ions, but the relative increase depends on the polymer type. With incident 5-MeV helium ions, the respective yields of molecular hydrogen are 4.6, 3.2, 0.62, and 0.15 molecules per 100 eV. The increase in molecular hydrogen with increasing LET may be due to changes in the kinetics of hydrogen precursors in the particle tracks. The differences in the relative increases in molecular hydrogen with increasing LET for each of the polymers suggests that self-scavenging reactions may be important for low LET particles.

Measurement of Distributions of Small-Scale Energy Depositions from Low-Linear Energy Transfer Particles Using the Superheated Drop Detector

We have developed a new detection method for measuring distributions of energy depositions from particles characterized by low linear energy transfers (LETs). In particular, we have developed a detection system to measure energy depositions produced by electrons and photons on nanometer scales. The detector is based upon the operational principles of the superheated drop detector (SDD). SDDs consist of tiny droplets of superheated liquid suspended within a gel-like emulsion. The SDDs in this study are fabricated using Freon-115 and a glycerol-based gel as the superheated liquid and host medium. This SDD configuration is operated as a threshold temperature-dependent detector for measuring nanoscopic distributions of energy depositions from low-LET particles. Measured results are compared to the calculated distributions of energy depositions along an electron track. A new electron track code, ESLOW3.1, is used to perform the computational study. Measurements show good agreement with computational results in the energy deposition range of 40-200 eV.

Space radiation enhancement linked to geomagnetic disturbances

Space radiation dosimetry measurements have been made on board the Space Shuttle. A newly developed active detector called “Real-time Radiation Monitoring Device (RRMD)” was used (Doke et al., 1995; Hayashi et al., 1995). The RRMD results indicate that low Linear Energy Transfer (LET) particles steadily penetrate around the South Atlantic Anomaly (SAA) without clear enhancement of dose equivalent and some daily periodic enhancements of dose equivalent due to high LET particles are seen at the lower geomagnetic cutoff regions (Doke et al., 1996). We also have been analyzing the space weather during the experiment, and found that the anomalous high-energy particle enhancement was linked to geomagnetic disturbance due to the high speed solar wind from a coronal hole. Additional analysis and other experiments are necessary for clarification of these phenomena. If a penetration of high-energy panicles into the low altitude occurs by common geomagnetic disturbances, the prediction of geomagnetic activity becomes more important in the next Space Station's era.

Space radiation enhancement linked to geomagnetic disturbances.

Space radiation dosimetry measurements have been made on board the Space Shuttle. A newly developed active detector called "Real-time Radiation Monitoring Device (RRMD)" was used (Doke et al., 1995; Hayashi et al., 1995). The RRMD results indicate that low Linear Energy Transfer (LET) particles steadily penetrate around the South Atlantic Anomaly (SAA) without clear enhancement of dose equivalent and some daily periodic enhancements of dose equivalent due to high LET particles are seen at the lower geomagnetic cutoff regions (Doke et al., 1996). We also have been analyzing the space weather during the experiment, and found that the anomalous high-energy particle enhancement was linked to geomagnetic disturbance due to the high speed solar wind from a coronal hole. Additional analysis and other experiments are necessary for clarification of these phenomena. If a penetration of high-energy particles into the low altitude occurs by common geomagnetic disturbances, the prediction of geomagnetic activity becomes more important in the next Space Station's era.