Genomic stability in response to high versus low linear energy transfer radiation in Arabidopsis thaliana.

Low linear energy transfer (LET) gamma rays and high LET HZE (high atomic weight, high energy) particles act as powerful mutagens in both plants and animals. DNA damage generated by HZE particles is more densely clustered than that generated by gamma rays. To understand the genetic requirements for resistance to high versus low LET radiation, a series of Arabidopsis thaliana mutants were exposed to either 1GeV Fe nuclei or gamma radiation. A comparison of effects on the germination and subsequent growth of seedlings led us to conclude that the relative biological effectiveness (RBE) of the two types of radiation (HZE versus gamma) are roughly 3:1. Similarly, in wild-type lines, loss of somatic heterozygosity was induced at an RBE of about a 2:1 (HZE versus gamma). Checkpoint and repair defects, as expected, enhanced sensitivity to both agents. The "replication fork" checkpoint, governed by ATR, played a slightly more important role in resistance to HZE-induced mutagenesis than in resistance to gamma induced mutagenesis

Silicon-based three-dimensional microstructures for radiation dosimetry in hadrontherapy

In this work, we propose a solid-state-detector for use in radiation microdosimetry. This device improves the performance of existing dosimeters using customized 3D-cylindrical microstructures etched inside silicon. The microdosimeter consists of an array of micro-sensors that have 3D-cylindrical electrodes of 15 μm diameter and a depth of 5 μm within a silicon membrane, resulting in a well-defined micrometric radiation sensitive volume. These microdetectors have been characterized using an 241Am source to assess their performance as radiation detectors in a high-LET environment. This letter demonstrates the capability of this microdetector to be used to measure dose and LET in hadrontherapy centers for treatment plan verification as part of their patient-specific quality control program

Modulation of gene expression in endothelial cells in response to high LET nickel ion irradiation

Ionizing radiation can elicit harmful effects on the cardiovascular system at high doses. Endothelial cells are critical targets in radiation-induced cardiovascular damage. Astronauts performing a long-term deep space mission are exposed to consistently higher fluences of ionizing radiation that may accumulate to reach high effective doses. In addition, cosmic radiation contains high linear energy transfer (LET) radiation that is known to produce high values of relative biological effectiveness (RBE). The aim of this study was to broaden the understanding of the molecular response to high LET radiation by investigating the changes in gene expression in endothelial cells. For this purpose, a human endothelial cell line (EA.hy926) was irradiated with accelerated nickel ions (Ni) (LET, 183 keV/mu m) at doses of 0.5, 2 and 5 Gy. DNA damage was measured 2 and 24 h following irradiation by gamma-H2AX foci detection by fluorescence microscopy and gene expression changes were measured by microarrays at 8 and 24 h following irradiation. We found that exposure to accelerated nickel particles induced a persistent DNA damage response up to 24 h after treatment. This was accompanied by a downregulation in the expression of a multitude of genes involved in the regulation of the cell cycle and an upregulation in the expression of genes involved in cell cycle checkpoints. In addition, genes involved in DNA damage response, oxidative stress, apoptosis and cell-cell signaling (cytokines) were found to be upregulated. An in silico analysis of the involved genes suggested that the transcription factors, E2F and nuclear factor (NF)-kappa B, may be involved in these cellular responses

Parameterizations of the linear energy transfer spectrum for the CRaTER instrument during the LRO mission

[1] The Cosmic Ray Telescope for the Effects of Radiation (CRaTER) instrument was launched as part of the Lunar Reconnaissance Orbiter (LRO) spacecraft in June 2009. Its purpose is to measure the linear energy transfer (LET) spectrum in lunar orbit as an aid in determining risks to human crews on future lunar missions. Part of the preparations for the mission involved estimating the LET spectrum for the anticipated environment that the instrument is likely to see during the 1 year operational phase of the LRO mission. Detailed estimates of LET spectra in the six silicon detectors and two tissue equivalent plastic segments were made using the beta version of the HETC-HEDS Monte Carlo transport code. Tables of LET in each detector component, for incident particle elemental species from hydrogen through iron, were carried out at incident particle energies from 20 MeV per nucleon to 3 GeV per nucleon. The LET values in these tables have been parameterized by elemental species and energy for ease in quickly and accurately estimating the LET response for any input solar or galactic cosmic ray spectrum likely to be encountered during the lifetime of the instrument. The parameterized LET values are in excellent agreement with the HETC-HEDS calculations. Typical differences are on the order of a few percent. These parameterizations will also be useful in validation studies of the Earth-Moon-Mars Radiation Environment Module using CRaTER measurements in lunar orbit

Recruitment kinetics of DNA repair proteins Mdc1 and Rad52 but not 53BP1 depend on damage complexity.

The recruitment kinetics of double-strand break (DSB) signaling and repair proteins Mdc1, 53BP1 and Rad52 into radiation-induced foci was studied by live-cell fluorescence microscopy after ion microirradiation. To investigate the influence of damage density and complexity on recruitment kinetics, which cannot be done by UV laser irradiation used in former studies, we utilized 43 MeV carbon ions with high linear energy transfer per ion (LET = 370 keV/µm) to create a large fraction of clustered DSBs, thus forming complex DNA damage, and 20 MeV protons with low LET (LET = 2.6 keV/µm) to create mainly isolated DSBs. Kinetics for all three proteins was characterized by a time lag period T(0) after irradiation, during which no foci are formed. Subsequently, the proteins accumulate into foci with characteristic mean recruitment times τ(1). Mdc1 accumulates faster (T(0) = 17 ± 2 s, τ(1) = 98 ± 11 s) than 53BP1 (T(0) = 77 ± 7 s, τ(1) = 310 ± 60 s) after high LET irradiation. However, recruitment of Mdc1 slows down (T(0) = 73 ± 16 s, τ(1) = 1050 ± 270 s) after low LET irradiation. The recruitment kinetics of Rad52 is slower than that of Mdc1, but exhibits the same dependence on LET. In contrast, the mean recruitment time τ(1) of 53BP1 remains almost constant when varying LET. Comparison to literature data on Mdc1 recruitment after UV laser irradiation shows that this rather resembles recruitment after high than low LET ionizing radiation. So this work shows that damage quality has a large influence on repair processes and has to be considered when comparing different studies

A Review: Some biological effects of high LET radiations

There are qualitative and quantitative differences in the biological damage observed after exposure to high LET radiation as compared to that caused by low LET radiations. This review is concerned with these differences, which are ultimately reflected at the biochemical, cellular and even whole animal levels. In general, high LET radiations seem to produce biochemical damage which is more severe and possibly less repairable. Experimental data for those effects are presented in terms of biochemical RBE's with consideration of both early and late manifestations. An LET independent process by which significant biochemical damage may result from protons, neutrons and negative pion mesons is discussed

No increase in radiation-induced chromosome aberration complexity detected by m-FISH after culture in the presence of 5’-bromodeoxyuridine

The thymidine analogue, 5’-bromodeoxyuridine (BrdU), is a known mutagen that is routinely introduced into culture media for subsequent Harlequin stain analysis and determination of cell cycle status. Previously, we examined the induction of chromosome aberrations in human peripheral blood lymphocytes (PBL) known to be in their 1st cell division following exposure to a low dose (0.5 Gy, average one -particle per cell) of high-LET α-particles. We found complex chromosome aberrations to be characteristic of exposure to high-LET radiation and suggested the features of complex exchange to reflect qualitatively the spatial deposition of this densely ionising radiation. To exclude the possibility that BrdU addition post-irradiation influenced the complexity of chromosomal damage observed by m-FISH, the effect of increasing BrdU concentration on aberration complexity was investigated. Comparisons between BrdU concentration (0, 10, and 40 M) and between sham- and α-particle irradiated PBL, were made both independently and in combination to enable discrimination between BrdU and high-LET radiation effects. Aberration type, size, complexity and completeness were assessed by m-FISH, and the relative progression through cell division was evaluated. We found no evidence of any qualitative difference in the complexity of damage as visualized by m-FISH but did observe an increase in the frequency of complex exchanges with increasing BrdU concentration indicative of altered cell cycle kinetics. The parameters measured here are consistent with findings from previous in vitro and in vivo work, indicating that each complex aberration visualised by m-FISH is characteristic of the structure of the high-LET α-particle track and the geometry of cell irradiated

Radiation Due to Josephson Oscillations in Layered Superconductors

We derive the power of direct radiation into free space induced by Josephson oscillations in intrinsic Josephson junctions of highly anisotropic layered superconductors. We consider the super-radiation regime for a crystal cut in the form of a thin slice parallel to the c-axis. We find that the radiation correction to the current-voltage characteristic in this regime depends only on crystal shape. We show that at large enough number of junctions oscillations are synchronized providing high radiation power and efficiency in the THz frequency range. We discuss crystal parameters and bias current optimal for radiation power and crystal cooling.Comment: 4 pages, 1 figure, to be published in Phys. Rev. Let

Radiation-Induced Magnetoresistance Oscillations in a 2D Electron Gas

Recent measurements of a 2D electron gas subjected to microwave radiation reveal a magnetoresistance with an oscillatory dependence on the ratio of radiation frequency to cyclotron frequency. We perform a diagrammatic calculation and find radiation-induced resistivity oscillations with the correct period and phase. Results are explained via a simple picture of current induced by photo-excited disorder-scattered electrons. The oscillations increase with radiation intensity, easily exceeding the dark resistivity and resulting in negative-resistivity minima. At high intensity, we identify additional features, likely due to multi-photon processes, which have yet to be observed experimentally.Comment: 5 pages, 3 figures; final version as published in Phys Rev Let

Dependence of the thermoluminescent high-temperature ratio (HTR) of LiF:Mg,Ti detectors on proton energy and dose

The high-temperature ratio (HTR) is a parameter quantifying changes of the shape of the high-temperature part of the LiF:Mg,Ti glow-curve after exposure to densely ionizing radiation. It was introduced in order to estimate the effective LET of an unknown radiation field and to correct the decreased relative TL efficiency for high Linear Energy Transfer (LET) radiation. In the present work the dependence of HTR on proton energy (14.5 to 58 MeV) and dose (0.5 to 30 Gy) was investigated. All measured HTR values were at the level of 1.2 or higher, therefore significantly different from the respective value for gamma rays (HTR is equal to 1), but HTR was found to be insensitive to changes of proton energy above 20 MeV. As a result the relationship between HTR and relative TL efficiency is not unequivocal. The HTR was found to be dependent on absorbed dose even for the lowest studied doses.Comment: Manuscript has been presented at the 17th International Conference on Solid State Dosimetry, Recife, Brasil, September 22-27,201