WorldWideScience

Sample records for radiation damage genomic

  1. Genomic damage in children accidentally exposed to ionizing radiation

    DEFF Research Database (Denmark)

    Fucic, A; Brunborg, G; Lasan, R

    2007-01-01

    of children to environmental genotoxicants. Environmental research on children predominantly investigates the health effects of air pollution while effects from radiation exposure deserve more attention. The main sources of knowledge on genome damage of children exposed to radiation are studies performed...

  2. Radiation damage

    CERN Document Server

    Heijne, Erik H M; CERN. Geneva

    1998-01-01

    a) Radiation damage in organic materials. This series of lectures will give an overview of radiation effects on materials and components frequently used in accelerator engineering and experiments. Basic degradation phenomena will be presented for organic materials with comprehensive damage threshold doses for commonly used rubbers, thermoplastics, thermosets and composite materials. Some indications will be given for glass, scintillators and optical fibres. b) Radiation effects in semiconductor materials and devices. The major part of the time will be devoted to treat radiation effects in semiconductor sensors and the associated electronics, in particular displacement damage, interface and single event phenomena. Evaluation methods and practical aspects will be shown. Strategies will be developed for the survival of the materials under the expected environmental conditions of the LHC machine and detectors. I will describe profound revolution in our understanding of black holes and their relation to quantum me...

  3. Complex DNA Damage: A Route to Radiation-Induced Genomic Instability and Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Ifigeneia V. Mavragani

    2017-07-01

    Full Text Available Cellular effects of ionizing radiation (IR are of great variety and level, but they are mainly damaging since radiation can perturb all important components of the cell, from the membrane to the nucleus, due to alteration of different biological molecules ranging from lipids to proteins or DNA. Regarding DNA damage, which is the main focus of this review, as well as its repair, all current knowledge indicates that IR-induced DNA damage is always more complex than the corresponding endogenous damage resulting from endogenous oxidative stress. Specifically, it is expected that IR will create clusters of damage comprised of a diversity of DNA lesions like double strand breaks (DSBs, single strand breaks (SSBs and base lesions within a short DNA region of up to 15–20 bp. Recent data from our groups and others support two main notions, that these damaged clusters are: (1 repair resistant, increasing genomic instability (GI and malignant transformation and (2 can be considered as persistent “danger” signals promoting chronic inflammation and immune response, causing detrimental effects to the organism (like radiation toxicity. Last but not least, the paradigm shift for the role of radiation-induced systemic effects is also incorporated in this picture of IR-effects and consequences of complex DNA damage induction and its erroneous repair.

  4. How Magnetotactic Bacteria Respond to Radiation Induced Stress and Damage: Comparative Genomics Evidences for Evolutionary Adaptation

    Science.gov (United States)

    Wang, Y.; Pan, Y.

    2015-12-01

    Solar radiation and galactic cosmic radiation is believed to be major restriction factors influencing survival and evolution of life. On planet earth, geomagnetic field along with atmosphere protect living beings from the harmful radiation. During a geomagnetic reversal or excursion, however, the efflux of charged particles on earth surface would increase as the shielding effect of magnetic field decrease. The stratospheric ozone can also be partially stripped away by solar wind when the strength of the field is weak, leading to an increasing ultraviolet radiation penetration to the earth surface. However, studies on the mechanism of radiation induced stress and damage are focused only on bacteria that have no response to magnetic field. This study was motivated by the need to fill the gap upon knowledge of that on magnetic field sensitive microorganism. Magnetotactic bacteria (MTB) are a group of microbes that are able to synthesis intracellular nano-sized magnetic particles (named magnetosomes). These chain-arranged magnetosomes help MTB sense and swim along the magnetic field to find their optimal living environment efficiently. In this paper, in silico prediction of stress and damage repair genes in response to different radiation were carried out on the complete genome of four nonmagnetotactic and four magnetotactic spirilla. In silico analyses of the genomes of magnetic field sensitive and non-sensitive spirilla revealed: 1) all strains contain genes for regulate responses superoxide and peroxide stress, DNA pyrimidine dimer and string breaks; 2) non-magnetotactic spirilla have more genes dealing with oxidative stress, while magnetotactic spirilla may benefit from magnetotaxis by swimming into oxic-anoxic zone away from oxidative stress and direct radiation damage; yet, the lipid hydroperoxide peroxidase gene in MTB may be responsible for possible ROS generated by the membrane enveloped magnetite magnetosome; 3) magnetotactic spirilla possess SOS rec

  5. Protection of the genome and central protein-coding sequences by non-coding DNA against DNA damage from radiation.

    Science.gov (United States)

    Qiu, Guo-Hua

    2015-01-01

    Non-coding DNA comprises a very large proportion of the total genomic content in higher organisms, but its function remains largely unclear. Non-coding DNA sequences constitute the majority of peripheral heterochromatin, which has been hypothesized to be the genome's 'bodyguard' against DNA damage from chemicals and radiation for almost four decades. The bodyguard protective function of peripheral heterochromatin in genome defense has been strengthened by the results from numerous recent studies, which are summarized in this review. These data have suggested that cells and/or organisms with a higher level of heterochromatin and more non-coding DNA sequences, including longer telomeric DNA and rDNAs, exhibit a lower frequency of DNA damage, higher radioresistance and longer lifespan after IR exposure. In addition, the majority of heterochromatin is peripherally located in the three-dimensional structure of genome organization. Therefore, the peripheral heterochromatin with non-coding DNA could play a protective role in genome defense against DNA damage from ionizing radiation by both absorbing the radicals from water radiolysis in the cytosol and reducing the energy of IR. However, the bodyguard protection by heterochromatin has been challenged by the observation that DNA damage is less frequently detected in peripheral heterochromatin than in euchromatin, which is inconsistent with the expectation and simulation results. Previous studies have also shown that the DNA damage in peripheral heterochromatin is rarely repaired and moves more quickly, broadly and outwardly to approach the nuclear pore complex (NPC). Additionally, it has been shown that extrachromosomal circular DNAs (eccDNAs) are formed in the nucleus, highly detectable in the cytoplasm (particularly under stress conditions) and shuttle between the nucleus and the cytoplasm. Based on these studies, this review speculates that the sites of DNA damage in peripheral heterochromatin could occur more

  6. DNA repair efficiency in germ cells and early mouse embryos and consequences for radiation-induced transgenerational genomic damage

    Energy Technology Data Exchange (ETDEWEB)

    Marchetti, Francesco; Wyrobek, Andrew J.

    2009-01-18

    Exposure to ionizing radiation and other environmental agents can affect the genomic integrity of germ cells and induce adverse health effects in the progeny. Efficient DNA repair during gametogenesis and the early embryonic cycles after fertilization is critical for preventing transmission of DNA damage to the progeny and relies on maternal factors stored in the egg before fertilization. The ability of the maternal repair machinery to repair DNA damage in both parental genomes in the fertilizing egg is especially crucial for the fertilizing male genome that has not experienced a DNA repair-competent cellular environment for several weeks prior to fertilization. During the DNA repair-deficient period of spermatogenesis, DNA lesions may accumulate in sperm and be carried into the egg where, if not properly repaired, could result in the formation of heritable chromosomal aberrations or mutations and associated birth defects. Studies with female mice deficient in specific DNA repair genes have shown that: (i) cell cycle checkpoints are activated in the fertilized egg by DNA damage carried by the sperm; and (ii) the maternal genotype plays a major role in determining the efficiency of repairing genomic lesions in the fertilizing sperm and directly affect the risk for abnormal reproductive outcomes. There is also growing evidence that implicates DNA damage carried by the fertilizing gamete as a mediator of postfertilization processes that contribute to genomic instability in subsequent generations. Transgenerational genomic instability most likely involves epigenetic mechanisms or error-prone DNA repair processes in the early embryo. Maternal and embryonic DNA repair processes during the early phases of mammalian embryonic development can have far reaching consequences for the genomic integrity and health of subsequent generations.

  7. Novel synthetic (S,S) and (R,R)-secoisolariciresinol diglucosides (SDGs) protect naked plasmid and genomic DNA From gamma radiation damage.

    Science.gov (United States)

    Mishra, Om P; Pietrofesa, Ralph; Christofidou-Solomidou, Melpo

    2014-07-01

    Secoisolariciresinol diglucoside (SDG) is the major lignan in wholegrain flaxseed. However, extraction methods are complex and are associated with low yield and high costs. Using a novel synthetic pathway, our group succeeded in chemically synthesizing SDG (S,S and R,R enantiomers), which faithfully recapitulates the properties of their natural counterparts, possessing strong antioxidant and free radical scavenging properties. This study further extends initial findings by now investigating the DNA-radioprotective properties of the synthetic SDG enantiomers compared to the commercial SDG. DNA radioprotection was assessed by cell-free systems such as: (a) plasmid relaxation assay to determine the extent of the supercoiled (SC) converted to open-circular (OC) plasmid DNA (pBR322) after exposure of the plasmid to gamma radiation; and (b) determining the extent of genomic DNA fragmentation. Exposure of plasmid DNA to 25 Gy of γ radiation resulted in decreased supercoiled form and increased open-circular form, indicating radiation-induced DNA damage. Synthetic SDG (S,S) and SDG (R,R), and commercial SDG at concentrations of 25-250 μM significantly and equipotently reduced the radiation-induced supercoiled to open-circular plasmid DNA in a dose-dependent conversion. In addition, exposure of calf thymus DNA to 50 Gy of gamma radiation resulted in DNA fragments of low-molecular weight (SDGs are promising candidates for radioprotection for normal tissue damage as a result of accidental exposure during radiation therapy for cancer treatment.

  8. Radiation Damage of Quartz Fibers

    OpenAIRE

    Hagopian, V

    1999-01-01

    Quartz fibers are used in high energy physics experiments as the active medium in high radiation area calorimetry. Quartz fibers are also used in the transmission of optical signals. Even though quartz does not damage by moderate amounts of irradiation, the clad of the fibers and the protective coating ( buffer) do damage reducing light transmission. Various types of quartz fibers have been irradiated and measured for light transmission. The most radiation hard quartz fibers are those with qu...

  9. Radiation damage in biomolecular systems

    CERN Document Server

    Fuss, Martina Christina

    2012-01-01

    Since the discovery of X-rays and radioactivity, ionizing radiations have been widely applied in medicine both for diagnostic and therapeutic purposes. The risks associated with radiation exposure and handling led to the parallel development of the field of radiation protection. Pioneering experiments done by Sanche and co-workers in 2000 showed that low-energy secondary electrons, which are abundantly generated along radiation tracks, are primarily responsible for radiation damage through successive interactions with the molecular constituents of the medium. Apart from ionizing processes, which are usually related to radiation damage, below the ionization level low-energy electrons can induce molecular fragmentation via dissociative processes such as internal excitation and electron attachment. This prompted collaborative projects between different research groups from European countries together with other specialists from Canada,  the USA and Australia. This book summarizes the advances achieved by these...

  10. Strand-specific PCR of UV radiation-damaged genomic DNA revealed an essential role of DNA-PKcs in the transcription-coupled repair

    Directory of Open Access Journals (Sweden)

    Wang Yu

    2011-01-01

    Full Text Available Abstract Background In eukaryotic cells, there are two sub-pathways of nucleotide excision repair (NER, the global genome (gg NER and the transcription-coupled repair (TCR. TCR can preferentially remove the bulky DNA lesions located at the transcribed strand of a transcriptional active gene more rapidly than those at the untranscribed strand or overall genomic DNA. This strand-specific repair in a suitable restriction fragment is usually determined by alkaline gel electrophoresis followed by Southern blotting transfer and hybridization with an indirect end-labeled single-stranded probe. Here we describe a new method of TCR assay based on strand-specific-PCR (SS-PCR. Using this method, we have investigated the role of DNA-dependent protein kinase catalytic subunit (DNA-PKcs, a member of the phosphatidylinositol 3-kinase-related protein kinases (PIKK family, in the TCR pathway of UV-induced DNA damage. Results Although depletion of DNA-PKcs sensitized HeLa cells to UV radiation, it did not affect the ggNER efficiency of UV-induced cyclobutane pyrimidine dimers (CPD damage. We postulated that DNA-PKcs may involve in the TCR process. To test this hypothesis, we have firstly developed a novel method of TCR assay based on the strand-specific PCR technology with a set of smart primers, which allows the strand-specific amplification of a restricted gene fragment of UV radiation-damaged genomic DNA in mammalian cells. Using this new method, we confirmed that siRNA-mediated downregulation of Cockayne syndrome B resulted in a deficiency of TCR of the UV-damaged dihydrofolate reductase (DHFR gene. In addition, DMSO-induced silencing of the c-myc gene led to a decreased TCR efficiency of UV radiation-damaged c-myc gene in HL60 cells. On the basis of the above methodology verification, we found that the depletion of DNA-PKcs mediated by siRNA significantly decreased the TCR capacity of repairing the UV-induced CPDs damage in DHFR gene in HeLa cells

  11. Single Molecule Scanning of DNA Radiation Oxidative Damage Project

    Data.gov (United States)

    National Aeronautics and Space Administration — This proposal will develop an assay to map genomic DNA, at the single molecule level and in a nanodevice, for oxidative DNA damage arising from radiation exposure;...

  12. Radiation damage in electron cryomicroscopy.

    Science.gov (United States)

    Baker, Lindsay A; Rubinstein, John L

    2010-01-01

    In an electron microscope, the electron beam used to determine the structures of biological tissues, cells, and molecules destroys the specimen as the image is acquired. This destruction occurs before a statistically well-defined image can be obtained and is consequently the fundamental limit to resolution in biological electron cryomicroscopy (cryo-EM). Damage from the destructive interaction of electrons with frozen-hydrated specimens occurs in three stages: primary damage, as electrons ionize the sample, break bonds, and produce secondary electrons and free radicals; secondary damage, as the secondary electrons and free radicals migrate through the specimen and cause further chemical reactions; and tertiary damage, as hydrogen gas is evolved within the sample, causing gross morphological changes to the specimen. The deleterious effects of radiation are minimized in cryo-EM by limiting the exposure of the specimen to incident electrons and cooling the sample to reduce secondary damage. This review emphasizes practical considerations for minimizing radiation damage, including measurement of electron exposure, estimation of absorbed doses of energy, selection of microscope voltage and specimen temperature, and selection of electron exposure to optimize images. Copyright © 2010 Elsevier Inc. All rights reserved.

  13. Radiation Induced Genomic Instability

    Energy Technology Data Exchange (ETDEWEB)

    Morgan, William F.

    2011-03-01

    Radiation induced genomic instability can be observed in the progeny of irradiated cells multiple generations after irradiation of parental cells. The phenotype is well established both in vivo (Morgan 2003) and in vitro (Morgan 2003), and may be critical in radiation carcinogenesis (Little 2000, Huang et al. 2003). Instability can be induced by both the deposition of energy in irradiated cells as well as by signals transmitted by irradiated (targeted) cells to non-irradiated (non-targeted) cells (Kadhim et al. 1992, Lorimore et al. 1998). Thus both targeted and non-targeted cells can pass on the legacy of radiation to their progeny. However the radiation induced events and cellular processes that respond to both targeted and non-targeted radiation effects that lead to the unstable phenotype remain elusive. The cell system we have used to study radiation induced genomic instability utilizes human hamster GM10115 cells. These cells have a single copy of human chromosome 4 in a background of hamster chromosomes. Instability is evaluated in the clonal progeny of irradiated cells and a clone is considered unstable if it contains three or more metaphase sub-populations involving unique rearrangements of the human chromosome (Marder and Morgan 1993). Many of these unstable clones have been maintained in culture for many years and have been extensively characterized. As initially described by Clutton et al., (Clutton et al. 1996) many of our unstable clones exhibit persistently elevated levels of reactive oxygen species (Limoli et al. 2003), which appear to be due dysfunctional mitochondria (Kim et al. 2006, Kim et al. 2006). Interestingly, but perhaps not surprisingly, our unstable clones do not demonstrate a “mutator phenotype” (Limoli et al. 1997), but they do continue to rearrange their genomes for many years. The limiting factor with this system is the target – the human chromosome. While some clones demonstrate amplification of this chromosome and thus lend

  14. Radiation damage of structural materials

    CERN Document Server

    Koutsky, Jaroslav

    1994-01-01

    Maintaining the integrity of nuclear power plants is critical in the prevention or control of severe accidents. This monograph deals with both basic groups of structural materials used in the design of light-water nuclear reactors, making the primary safety barriers of NPPs. Emphasis is placed on materials used in VVER-type nuclear reactors: Cr-Mo-V and Cr-Ni-Mo-V steel for RPV and Zr-Nb alloys for fuel element cladding. The book is divided into 7 main chapters, with the exception of the opening one and the chapter providing a phenomenological background for the subject of radiation damage. Ch

  15. Studies on the Neutron Radiation Damage Equivalence

    Directory of Open Access Journals (Sweden)

    ZOU De-hui

    2015-01-01

    Full Text Available To establish a unified standard of the evaluation of different sources of radiation damage, the neutron radiation damage equivalent standard source was determined both at home and abroad, and a lot of equivalence research work was done for making weapons anti neutron radiation performance examination and acceptance basis. The theoretical research progress was combed according to the relationship between the displacement damage function and the radiation source spectra ,and the experimental research progress was combed from the basic experimental methods, the controlling trend of effect parameters and field parameters. The experiment method to reduce the uncertainty was discussed, and present the research directions of radiation damage equivalence.

  16. Elevated Rate of Genome Rearrangements in Radiation-Resistant Bacteria.

    Science.gov (United States)

    Repar, Jelena; Supek, Fran; Klanjscek, Tin; Warnecke, Tobias; Zahradka, Ksenija; Zahradka, Davor

    2017-04-01

    A number of bacterial, archaeal, and eukaryotic species are known for their resistance to ionizing radiation. One of the challenges these species face is a potent environmental source of DNA double-strand breaks, potential drivers of genome structure evolution. Efficient and accurate DNA double-strand break repair systems have been demonstrated in several unrelated radiation-resistant species and are putative adaptations to the DNA damaging environment. Such adaptations are expected to compensate for the genome-destabilizing effect of environmental DNA damage and may be expected to result in a more conserved gene order in radiation-resistant species. However, here we show that rates of genome rearrangements, measured as loss of gene order conservation with time, are higher in radiation-resistant species in multiple, phylogenetically independent groups of bacteria. Comparison of indicators of selection for genome organization between radiation-resistant and phylogenetically matched, nonresistant species argues against tolerance to disruption of genome structure as a strategy for radiation resistance. Interestingly, an important mechanism affecting genome rearrangements in prokaryotes, the symmetrical inversions around the origin of DNA replication, shapes genome structure of both radiation-resistant and nonresistant species. In conclusion, the opposing effects of environmental DNA damage and DNA repair result in elevated rates of genome rearrangements in radiation-resistant bacteria. Copyright © 2017 Repar et al.

  17. Common genomic signaling among initial DNA damage and radiation-induced apoptosis in peripheral blood lymphocytes from locally advanced breast cancer patients

    DEFF Research Database (Denmark)

    Henríquez-Hernández, Luis Alberto; Pinar, Beatriz; Carmona-Vigo, Ruth

    2013-01-01

    suffering from locally advanced breast cancer and treated with high-dose hyperfractionated radiotherapy were recruited. Initial DNA damage was measured by pulsed-field gel electrophoresis and radiation-induced apoptosis was measured by flow cytometry. Gene expression was assessed by DNA microarray. RESULTS...

  18. Simulation of radiation damage in zircon

    Energy Technology Data Exchange (ETDEWEB)

    Weber, W.J.; Maupin, G.D.

    1988-05-01

    Radiation damage in natural zircon minerals due to alpha decay over geologic time has been simulated in laboratory studies extending over 5.5 years using Pu-doped synthetic zircon. These studies confirm for the first time that laboratory testing of actinide-doped materials can accurately predict the radiation-damage behavior of radioactive waste forms over geologic time and also provide new insights into interpretation of radiation damage in natural minerals.

  19. Simulation of radiation damage in zircon

    Energy Technology Data Exchange (ETDEWEB)

    Weber, W.J.; Maupin, G.D.

    1987-06-01

    Radiation damage in natural zircon minerals due to alpha decay has been simulated in laboratory studies using Pu-doped synthetic zircon. These studies confirm that laboratory testing of actinide-doped materials can accurately predict the radiation-damage behavior of radioactive waste forms over geologic time, and also provide new insights into interpretation of radiation damage in natural minerals. 15 refs., 4 figs., 2 tabs.

  20. [Mechanisms of electromagnetic radiation damaging male reproduction].

    Science.gov (United States)

    Xue, Lei; Chen, Hao-Yu; Wang, Shui-Ming

    2012-08-01

    More and more evidence from over 50 years of researches on the effects of electromagnetic radiation on male reproduction show that a certain dose of electromagnetic radiation obviously damages male reproduction, particularly the structure and function of spermatogenic cells. The mechanisms of the injury may be associated with energy dysmetabolism, lipid peroxidation, abnormal expressions of apoptosis-related genes and proteins, and DNA damage.

  1. Repair of radiation damage in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Setlow, R.B.

    1981-01-01

    The responses, such as survival, mutation, and carcinogenesis, of mammalian cells and tissues to radiation are dependent not only on the magnitude of the damage to macromolecular structures - DNA, RNA, protein, and membranes - but on the rates of macromolecular syntheses of cells relative to the half-lives of the damages. Cells possess a number of mechanisms for repairing damage to DNA. If the repair systems are rapid and error free, cells can tolerate much larger doses than if repair is slow or error prone. It is important to understand the effects of radiation and the repair of radiation damage because there exist reasonable amounts of epidemiological data that permits the construction of dose-response curves for humans. The shapes of such curves or the magnitude of the response will depend on repair. Radiation damage is emphasized because: (a) radiation dosimetry, with all its uncertainties for populations, is excellent compared to chemical dosimetry; (b) a number of cancer-prone diseases are known in which there are defects in DNA repair and radiation results in more chromosomal damage in cells from such individuals than in cells from normal individuals; (c) in some cases, specific radiation products in DNA have been correlated with biological effects, and (d) many chemical effects seem to mimic radiation effects. A further reason for emphasizing damage to DNA is the wealth of experimental evidence indicating that damages to DNA can be initiating events in carcinogenesis.

  2. DNA Damage Signals and Space Radiation Risk

    Science.gov (United States)

    Cucinotta, Francis A.

    2011-01-01

    Space radiation is comprised of high-energy and charge (HZE) nuclei and protons. The initial DNA damage from HZE nuclei is qualitatively different from X-rays or gamma rays due to the clustering of damage sites which increases their complexity. Clustering of DNA damage occurs on several scales. First there is clustering of single strand breaks (SSB), double strand breaks (DSB), and base damage within a few to several hundred base pairs (bp). A second form of damage clustering occurs on the scale of a few kbp where several DSB?s may be induced by single HZE nuclei. These forms of damage clusters do not occur at low to moderate doses of X-rays or gamma rays thus presenting new challenges to DNA repair systems. We review current knowledge of differences that occur in DNA repair pathways for different types of radiation and possible relationships to mutations, chromosomal aberrations and cancer risks.

  3. The LHCb VELO: Performance and radiation damage

    Energy Technology Data Exchange (ETDEWEB)

    Snoek, H.L., E-mail: hella.snoek@nikhef.nl

    2014-11-21

    LHCb is a forward spectrometer experiment dedicated to the search for New Physics in the decays of beauty and charm hadrons produced by the proton–proton interactions at the Large Hadron Collider (LHC) at CERN. The measurement of the flight distance of these hadrons is critical for the physics program. The VErtex LOcator (VELO) is the silicon detector surrounding the LHCb interaction point and provides excellent resolution of charged tracks and vertex positions. The VELO has been run successfully since installation. The sensors have the first sensitive strips at a radius of 8.2 mm and are exposed to maximum radiation doses of ∼0.6×10{sup 14}1MeVn{sub eq}/cm{sup 2}perfb{sup −1} delivered integrated luminosity. The performance of the VELO during the first LHC run is described, together with methods to monitor radiation damage. Results from the radiation damage studies are presented showing interesting features, such as an unexpected charge coupling to the second metal layer routing lines after irradiation. The radiation damage has so far no impact on the track reconstruction performance. - Highlights: • We study the performance and radiation damage of the LHCb VELO detector. • The physics performance of the VELO detector is meeting its expectations. • Radiation damage is monitored through multiple developed methods. • An unexpected, radiation induced effect to the second metal layer has been observed.

  4. Animal Models of Ionizing Radiation Damage

    Science.gov (United States)

    1992-01-01

    level, some epithelial damage was observed (3). Michaelson, et al. (19) demonstrated that dogs developed hypothyroidism two to four years after expos... Pathophysiologic Signs of the Responses of the Nervous System to Ionizing Radiation, In Response of the Nervous System to Ionizing Radiation, Academic Press...Immunol. Ther. Exp., 10:416-459, 1962. 138. Krochak, R.J., and D.G. Baker, Radiation Nephritis. Clinical Manifestations and Pathophysiologic Mechanisms

  5. Nanofoams Response to Radiation Damage

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Engang [Los Alamos National Laboratory; Serrano De Caro, Magdalena [Los Alamos National Laboratory; Wang, Yongqiang [Los Alamos National Laboratory; Nastasi, Michael [Nebraska Center for Energy Sciences Research, University of Nebraska-Lincoln, NE 68508; Zepeda-Ruiz, Luis [PLS, Lawrence Livermore National Laboratory, Livermore, CA 94551; Bringa, Eduardo M. [CONICET and Inst. Ciencias Basicas, Universidad Nacional de Cuyo, Mendoza, 5500 Argentina; Baldwin, Jon K. [Los Alamos National Laboratory; Caro, Jose A. [Los Alamos National Laboratory

    2012-07-30

    Conclusions of this presentation are: (1) np-Au foams were successfully synthesized by de-alloying process; (2) np-Au foams remain porous structure after Ne ion irradiation to 1 dpa; (3) SFTs were observed in irradiated np-Au foams with highest and intermediate flux, while no SFTs were observed with lowest flux; (4) SFTs were observed in irradiated np-Au foams at RT, whereas no SFTs were observed at LNT irradiation; (5) The diffusivity of vacancies in Au at RT is high enough so that the vacancies have enough time to agglomerate and thus collapse. As a result, SFTs were formed; (6) The high flux created much more damage/time, vacancies don't have enough time to diffuse or recombine. As a result, SFTs were formed.

  6. Undulator Radiation Damage Experience at LCLS

    Energy Technology Data Exchange (ETDEWEB)

    Nuhn, H. D. [SLAC National Accelerator Lab., Menlo Park, CA (United States); Field, C. [SLAC National Accelerator Lab., Menlo Park, CA (United States); Mao, S. [SLAC National Accelerator Lab., Menlo Park, CA (United States); Levashov, Y. [SLAC National Accelerator Lab., Menlo Park, CA (United States); Santana, M. [SLAC National Accelerator Lab., Menlo Park, CA (United States); Welch, J. N. [SLAC National Accelerator Lab., Menlo Park, CA (United States); Wolf, Z. [SLAC National Accelerator Lab., Menlo Park, CA (United States)

    2015-01-06

    The SLAC National Accelerator Laboratory has been running the Linac Coherent Light Source (LCLS), the first x-ray Free Electron Laser since 2009. Undulator magnet damage from radiation, produced by the electron beam traveling through the 133-m long straight vacuum tube, has been and is a concern. A damage measurement experiment has been performed in 2007 in order to obtain dose versus damage calibrations. Radiation reduction and detection devices have been integrated into the LCLS undulator system. The accumulated radiation dose rate was continuously monitored and recorded. In addition, undulator segments have been routinely removed from the beamline to be checked for magnetic (50 ppm, rms) and mechanic (about 0.25 µm, rms) changes. A reduction in strength of the undulator segments is being observed, at a level, which is now clearly above the noise. Recently, potential sources for the observed integrated radiation levels have been investigated. The paper discusses the results of these investigation as well as comparison between observed damage and measured dose accumulations and discusses, briefly, strategies for the new LCLS-II upgrade, which will be operating at more than 300 times larger beam rate.

  7. Radiation damage of polymers in ultrasonic fields

    Energy Technology Data Exchange (ETDEWEB)

    Anbalagan, Poornnima

    2008-07-01

    Radiation damage has always been a topic of great interest in various fields of sciences. In this work, an attempt is made to probe into the effect of subthreshold ultrasonic waves on the radiation damage created by irradiation of deuterons in polymer samples wherein the polymer samples act as model systems. Two equal volumes of radiation damage were produced in a single polymer sample wherein a standing wave of ultrasound was introduced into one. Three polymers namely, Polycarbonate, Polymethylmethacrylate and Polyvinyl chloride were used in this work. Four independent techniques were used to analyze the irradiated samples and visualize the radiation damage. Interferometric measurements give a measure of the refractive index modulation in the irradiated sample. Polymers, being transparent, do not absorb in the visible region of the electromagnetic spectrum. UV-Vis absorption spectroscopy shows absorption peaks in the visible region in irradiated polymer samples. Ion irradiation causes coloration of polymers. The light microscope is used to measure the absorption of white light by the irradiated polymers. Positron annihilation spectroscopy is used to obtain a measure of the open volume created by irradiation in polymers. A comparison between the irradiated region and the region exposed to ultrasonic waves simultaneously with irradiation in a polymer sample shows the polymer specific influence of the ultrasonic standing wave. (orig.)

  8. The Status of Radiation Damage Experiments

    Energy Technology Data Exchange (ETDEWEB)

    Strachan, Denis M.; Scheele, Randall D.; Icenhower, Jonathan P.; Kozelisky, Anne E.; Sell, Richard L.; Legore, Virginia L.; Schaef, Herbert T.; O' Hara, Matthew J.; Brown, Christopher F.; Buchmiller, William C.

    2001-11-20

    Experiments have been on-going for about two years to determine the effects that radiation damage have on the physical and chemical properties of candidate titanate ceramics for the immobilization of plutonium. We summarize the results of these experiments in this document.

  9. Radiation damage in the LHCb VELO

    Science.gov (United States)

    Dossett, D.

    2013-08-01

    LHCb is a dedicated experiment to study new physics in the decays of beauty and charm hadrons at the Large Hadron Collider (LHC) at CERN. The Vertex Locator (VELO) is a silicon micro-strip detector which surrounds the LHCb interaction point and provides μm resolution of charged tracks and vertex positions. The tip of the VELO sensors is predicted to receive a dose of 0.5 ×1013 1-MeV neq /cm2 per fb of data. The highest fluence of any silicon tracker at the four major LHC experiments. Radiation damage studies have been carried out during the first two years of data taking at LHCb for all 88 sensors of the VELO. Radiation damage has been observed in all sensors, with those sensors in the highest fluence regions showing evidence of type inversion. Radiation induced charge loss due to the second metal layer on the sensors is also observed.

  10. Density Functional Theory Models for Radiation Damage

    Science.gov (United States)

    Dudarev, S. L.

    2013-07-01

    Density functional theory models developed over the past decade provide unique information about the structure of nanoscale defects produced by irradiation and about the nature of short-range interaction between radiation defects, clustering of defects, and their migration pathways. These ab initio models, involving no experimental input parameters, appear to be as quantitatively accurate and informative as the most advanced experimental techniques developed for the observation of radiation damage phenomena. Density functional theory models have effectively created a new paradigm for the scientific investigation and assessment of radiation damage effects, offering new insight into the origin of temperature- and dose-dependent response of materials to irradiation, a problem of pivotal significance for applications.

  11. The LHCb VELO: Performance and radiation damage

    Science.gov (United States)

    Snoek, H. L.

    2014-11-01

    LHCb is a forward spectrometer experiment dedicated to the search for New Physics in the decays of beauty and charm hadrons produced by the proton-proton interactions at the Large Hadron Collider (LHC) at CERN. The measurement of the flight distance of these hadrons is critical for the physics program. The VErtex LOcator (VELO) is the silicon detector surrounding the LHCb interaction point and provides excellent resolution of charged tracks and vertex positions. The VELO has been run successfully since installation. The sensors have the first sensitive strips at a radius of 8.2 mm and are exposed to maximum radiation doses of 0.6 ×1014 1 MeVneq /cm2 perfb-1 delivered integrated luminosity. The performance of the VELO during the first LHC run is described, together with methods to monitor radiation damage. Results from the radiation damage studies are presented showing interesting features, such as an unexpected charge coupling to the second metal layer routing lines after irradiation. The radiation damage has so far no impact on the track reconstruction performance.

  12. Radiation damage at LHCb, results and expectations

    CERN Multimedia

    Faerber, Christian

    2011-01-01

    The LHCb Detector is a single-arm spectrometer at the LHC designed to detect new physics through measuring CP violation and rare decays of heavy flavor mesons. The detector consists of vertex detector, tracking system, dipole magnet, 2 RICH detectors, em. calorimeter, hadron calorimeter, muon detector which all use different technologies and suffer differently from radiation damage. These radiation damage results and the investigation methods will be shown. The delivered luminosity till July 2011 was about 450 pb−1. The Vertex detector receives the highest particle flux at LHCb. The currents drawn by the silicon sensors are, as expected, increasing proportional to the integrated luminosity. The highest irradiaton regions of the n-bulk silicon sensors are observed to have recently undergone space charge sign inversion. The Silicon Trackers show increasing leakage currents comparable with earlier predictions. The electromagentic calorimeter and hadron calorimeter suffer under percent-level signal decrease whi...

  13. Radiation damage in the LHCb VELO1

    Science.gov (United States)

    Harrison, J.; Webber, A.; LHCb Collaboration1

    2013-01-01

    The VErtex LOcator (VELO) is a silicon strip detector designed to reconstruct particle tracks and vertices produced by proton-proton interactions near to the LHCb interaction point. The excellent track resolution and decay vertex separation provided by the VELO are essential to all LHCb analyses. For the integrated luminosity delivered by the LHC up to the end of 2011 the VELO is exposed to higher particle fluences than any other silicon detector of the four major LHC experiments. These proceedings present results from radiation damage studies carried out during the first two years of data taking at the LHC. Radiation damage has been observed in all of the 88 VELO silicon strip sensors, with many sensors showing evidence of type-inversion in the highest fluence regions. Particular attention has been given to the two n+-on-p sensors as this type of sensor is one of the leading candidates for the LHC silicon detector upgrades.

  14. Radiation Damage in the LHCb VELO

    CERN Multimedia

    Harrison, Jon

    2011-01-01

    The VErtex LOcator (VELO) is a silicon strip detector designed to reconstruct particle tracks and vertices produced by proton-proton interactions near to the LHCb interaction point. The excellent track resolution and decay vertex separation provided by the VELO are essential to all LHCb analyses. For the integrated luminosity delivered by the LHC up to the end of $2011$ the VELO is exposed to higher particle fluences than any other silicon detector of the four major LHC experiments. These proceedings present results from radiation damage studies carried out during the first two years of data taking at the LHC. Radiation damage has been observed in all of the $88$ VELO silicon strip sensors, with many sensors showing evidence of type-inversion in the highest fluence regions. Particular attention has been given to the two \

  15. Evaluation of radiation damage using nonlinear ultrasound

    Science.gov (United States)

    Matlack, K. H.; Wall, J. J.; Kim, J.-Y.; Qu, J.; Jacobs, L. J.; Viehrig, H.-W.

    2012-03-01

    Nonlinear ultrasound was used to monitor radiation damage in two reactor pressure vessel (RPV) steels. The microstructural changes associated with radiation damage include changes in dislocation density and the formation of precipitates, and nonlinear ultrasonic waves are known to be sensitive to such changes. Six samples each of two different RPV steels were previously irradiated in the Rheinsberg power reactor to two fluence levels, up to 1020 n/cm2 (E > 1 MeV). Longitudinal waves were used to measure the acoustic nonlinearity in these samples, and the results show a clear increase in the measured acoustic nonlinearity from the unirradiated state to the medium dose, and then a decrease from medium dose to high dose.

  16. Nonuniform radiation damage in permanent magnet quadrupoles.

    Science.gov (United States)

    Danly, C R; Merrill, F E; Barlow, D; Mariam, F G

    2014-08-01

    We present data that indicate nonuniform magnetization loss due to radiation damage in neodymium-iron-boron Halbach-style permanent magnet quadrupoles. The proton radiography (pRad) facility at Los Alamos uses permanent-magnet quadrupoles for magnifying lenses, and a system recently commissioned at GSI-Darmsdadt uses permanent magnets for its primary lenses. Large fluences of spallation neutrons can be produced in close proximity to these magnets when the proton beam is, intentionally or unintentionally, directed into the tungsten beam collimators; imaging experiments at LANL's pRad have shown image degradation with these magnetic lenses at proton beam doses lower than those expected to cause damage through radiation-induced reduction of the quadrupole strength alone. We have observed preferential degradation in portions of the permanent magnet quadrupole where the field intensity is highest, resulting in increased high-order multipole components.

  17. Radiation track, DNA damage and response—a review

    Science.gov (United States)

    Nikjoo, H.; Emfietzoglou, D.; Liamsuwan, T.; Taleei, R.; Liljequist, D.; Uehara, S.

    2016-11-01

    The purpose of this paper has been to review the current status and progress of the field of radiation biophysics, and draw attention to the fact that physics, in general, and radiation physics in particular, with the aid of mathematical modeling, can help elucidate biological mechanisms and cancer therapies. We hypothesize that concepts of condensed-matter physics along with the new genomic knowledge and technologies and mechanistic mathematical modeling in conjunction with advances in experimental DNA (Deoxyrinonucleic acid molecule) repair and cell signaling have now provided us with unprecedented opportunities in radiation biophysics to address problems in targeted cancer therapy, and genetic risk estimation in humans. Obviously, one is not dealing with ‘low-hanging fruit’, but it will be a major scientific achievement if it becomes possible to state, in another decade or so, that we can link mechanistically the stages between the initial radiation-induced DNA damage; in particular, at doses of radiation less than 2 Gy and with structural changes in genomic DNA as a precursor to cell inactivation and/or mutations leading to genetic diseases. The paper presents recent development in the physics of radiation track structure contained in the computer code system KURBUC, in particular for low-energy electrons in the condensed phase of water for which we provide a comprehensive discussion of the dielectric response function approach. The state-of-the-art in the simulation of proton and carbon ion tracks in the Bragg peak region is also presented. The paper presents a critical discussion of the models used for elastic scattering, and the validity of the trajectory approach in low-electron transport. Brief discussions of mechanistic and quantitative aspects of microdosimetry, DNA damage and DNA repair are also included as developed by the authors’ work.

  18. ACE inhibition attenuates radiation-induced cardiopulmonary damage

    NARCIS (Netherlands)

    van der Veen, Sonja J.; Ghobadi, Ghazaleh; de Boer, Rudolf A; Faber, Hette; Cannon, Megan V; Nagle, Peter W; Brandenburg, Sytze; Langendijk, Johannes A; van Luijk, Peter; Coppes, Robert P

    BACKGROUND AND PURPOSE: In thoracic irradiation, the maximum radiation dose is restricted by the risk of radiation-induced cardiopulmonary damage and dysfunction limiting tumor control. We showed that radiation-induced sub-clinical cardiac damage and lung damage in rats mutually interact and that

  19. Prevent Eye Damage: Protect Yourself from UV Radiation

    Science.gov (United States)

    PREVENT EYE DAMAGE Protect Yourself from UV Radiation M ost Americans understand the link between ultraviolet (UV) radiation and skin cancer. Many are less aware of the connection between UV radiation ...

  20. Studies on the strategies of minimizing radiation damage

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Hee Yong; Sohn, Young Sook

    1998-04-01

    We studied on the strategies of minimizing radiation damage in animal system. To this end we studied following areas of research (1) mechanisms involved in bone marrow damage after total body irradiation, (2) extraction of components that are useful in protecting hematopoietic system from radiation damage, (3) cell therapy approach in restoring the damaged tissue, (4) development of radioprotective chemical reagent, and (5) epidemiological study on the population that had been exposed to radiation.

  1. Thermal Decomposition of Radiation-Damaged Polystyrene

    Energy Technology Data Exchange (ETDEWEB)

    J Abrefah GS Klinger

    2000-09-26

    The radiation-damaged polystyrene material (''polycube'') used in this study was synthesized by mixing a high-density polystyrene (''Dylene Fines No. 100'') with plutonium and uranium oxides. The polycubes were used on the Hanford Site in the 1960s for criticality studies to determine the hydrogen-to-fissile atom ratios for neutron moderation during processing of spent nuclear fuel. Upon completion of the studies, two methods were developed to reclaim the transuranic (TRU) oxides from the polymer matrix: (1) burning the polycubes in air at 873 K; and (2) heating the polycubes in the absence of oxygen and scrubbing the released monomer and other volatile organics using carbon tetrachloride. Neither of these methods was satisfactory in separating the TRU oxides from the polystyrene. Consequently, the remaining polycubes were sent to the Hanford Plutonium Finishing Plant (PFP) for storage. Over time, the high dose of alpha and gamma radiation has resulted in a polystyrene matrix that is highly cross-linked and hydrogen deficient and a stabilization process is being developed in support of Defense Nuclear Facility Safety Board Recommendation 94-1. Baseline processes involve thermal treatment to pyrolyze the polycubes in a furnace to decompose the polystyrene and separate out the TRU oxides. Thermal decomposition products from this degraded polystyrene matrix were characterized by Pacific Northwest National Laboratory to provide information for determining the environmental impact of the process and for optimizing the process parameters. A gas chromatography/mass spectrometry (GC/MS) system coupled to a horizontal tube furnace was used for the characterization studies. The decomposition studies were performed both in air and helium atmospheres at 773 K, the planned processing temperature. The volatile and semi-volatile organic products identified for the radiation-damaged polystyrene were different from those observed for virgin

  2. Radiation Damage In Reactor Cavity Concrete

    Energy Technology Data Exchange (ETDEWEB)

    Field, Kevin G [ORNL; Le Pape, Yann [ORNL; Naus, Dan J [ORNL; Remec, Igor [ORNL; Busby, Jeremy T [ORNL; Rosseel, Thomas M [ORNL; Wall, Dr. James Joseph [Electric Power Research Institute (EPRI)

    2015-01-01

    License renewal up to 60 years and the possibility of subsequent license renewal to 80 years has established a renewed focus on long-term aging of nuclear generating stations materials, and recently, on concrete. Large irreplaceable sections of most nuclear generating stations include concrete. The Expanded Materials Degradation Analysis (EMDA), jointly performed by the Department of Energy, the Nuclear Regulatory Commission and Industry, identified the urgent need to develop a consistent knowledge base on irradiation effects in concrete. Much of the historical mechanical performance data of irradiated concrete does not accurately reflect typical radiation conditions in NPPs or conditions out to 60 or 80 years of radiation exposure. To address these potential gaps in the knowledge base, The Electric Power Research Institute and Oak Ridge National Laboratory are working to disposition radiation damage as a degradation mechanism. This paper outlines the research program within this pathway including: (i) defining the upper bound of the neutron and gamma dose levels expected in the biological shield concrete for extended operation (80 years of operation and beyond), (ii) determining the effects of neutron and gamma irradiation as well as extended time at temperature on concrete, (iii) evaluating opportunities to irradiate prototypical concrete under accelerated neutron and gamma dose levels to establish a conservative bound and share data obtained from different flux, temperature, and fluence levels, (iv) evaluating opportunities to harvest and test irradiated concrete from international NPPs, (v) developing cooperative test programs to improve confidence in the results from the various concretes and research reactors, (vi) furthering the understanding of the effects of radiation on concrete (see companion paper) and (vii) establishing an international collaborative research and information exchange effort to leverage capabilities and knowledge.

  3. Protection of DNA damage by radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jeong Ho; Kim, In Gyu; Lee, Kang Suk; Kim, Kug Chan; Oh, Tae Jung

    1998-12-01

    The SOS response of Escherichia coli is positively regulated by RecA. To examine the effects of polyamines on The SOS response of E. Coli, we investigated the expression of recA gene in polyamine-deficient mutant and wild type carrying recA'::lacZ fusion gene. As a result, recA expression by mitomycin C is higher in wild type than that of polyamine-deficient mutant, but recA expression by UV radiation is higher in wild type than of mutant. We also found that exogenous polyamines restored the recA expression in the polyamine-deficient mutant to the wild type level. These results proposed that polyamines play an important role in mechanism of intracellular DNA protection by DNA damaging agents.

  4. Thermal Decomposition of Radiation-Damaged Polystyrene

    Energy Technology Data Exchange (ETDEWEB)

    Abrefah, John; Klinger, George S.

    2000-09-26

    The radiation-damaged polystyrene (given the identification name of 'polycube') was fabricated by mixing high-density polystyrene material ("Dylene Fines # 100") with plutonium and uranium oxides. The polycubes were used in the 1960s for criticality studies during processing of spent nuclear fuel. The polycubes have since been stored for almost 40 years at the Hanford Plutonium Finishing Plant (PFP) after failure of two processes to reclaim the plutonium and uranium oxides from the polystyrene matrix. Thermal decomposition products from this highly cross-linked polystyrene matrix were characterized using Gas Chromatograph/Mass Spectroscopy (GC/MS) system coupled to a horizontal furnace. The decomposition studies were performed in air and helium atmospheres at about 773 K. The volatile and semi-volatile organic products for the radiation-damaged polystyrene were different compared to virgin polystyrene. The differences were in the number of organic species generated and their concentrations. In the inert (i.e., helium) atmosphere, the major volatile organic products identified (in order of decreasing concentrations) were styrene, benzene, toluene, ethylbenzene, xylene, nathphalene, propane, .alpha.-methylbenzene, indene and 1,2,3-trimethylbenzene. But in air, the major volatile organic species identified changed slightly. Concentrations of the organic species in the inert atmosphere were significantly higher than those for the air atmosphere processing. Overall, 38 volatile organic species were identified in the inert atmosphere compared to 49 species in air. Twenty of the 38 species in the inert conditions were also products in the air atmosphere. Twenty-two oxidized organic products were identified during thermal processing in air.

  5. Radiation damage limits to XPCS studies of protein dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Vodnala, Preeti, E-mail: preeti.vodnala@gmail.com; Karunaratne, Nuwan; Lurio, Laurence [Department of Physics, Northern Illinois University, DeKalb IL, 60115 (United States); Bera, Sambhunath [Amity Center for Spintronic Materials, Amity University UP, Sector 125, NOIDA 201313 (India); Thurston, George M. [School of Physics and Astronomy, Rochester Institute of Technology, Rochester, NY 14623-5603 (United States); Karonis, Nick [Department of Computer Science, Northern Illinois University, DeKalb, IL 60115 (United States); Mathematics and Computer Science, Argonne National Laboratory, Argonne, IL 60495 (United States); Winans, John [Department of Computer Science, Northern Illinois University, DeKalb, IL 60115 (United States); Sandy, Alec; Narayanan, Suresh [Advanced Photon Source, Argonne National Laboratory, Argonne, IL 60495 (United States); Yasui, Linda [Department of Biology, Northern Illinois University, DeKalb, IL 60115 (United States); Gaillard, Elizabeth; Karumanchi, Kalyan [Department of Chemistry and Biochemistry, Northern Illinois University, DeKalb IL, 60115 (United States)

    2016-07-27

    The limitations to x-ray photon correlation spectroscopy (XPCS) imposed by radiation damage have been evaluated for suspensions of alpha crystallin. We find that the threshold for radiation damage to the measured protein diffusion rate is significantly lower than the threshold for damage to the protein structure. We provide damage thresholds beyond which the measured diffusion coeffcients have been modified using both XPCS and dynamic light scattering (DLS).

  6. The study of radiation damage of EPROM 2764 memory

    Directory of Open Access Journals (Sweden)

    Domanski Grzegorz

    2016-01-01

    Full Text Available A simple statistical theory of radiation damage of semiconductor memory has been constructed. The radiation damage of EPROM memory has been investigated. The measured number of damaged bytes is significantly lower than the expected number resulting from the purely random distribution of the damaged bits. In this way it has been proven that there is a correlation between the failures of individual memory bits which are located in the same byte.

  7. Influence of radiation damage on plasma facing material erosion

    Energy Technology Data Exchange (ETDEWEB)

    Koidan, V.S. [Russian Research Centre ' Kurchatov Institute' (RRC KI), Moscow (Russian Federation)], E-mail: koidan@nfi.kiae.ru; Brukhanov, A.N.; Chugunov, O.K.; Gureev, V.M.; Khripunov, B.I.; Kornienko, S.N.; Kuteev, B.V.; Latushkin, S.T.; Muksunov, A.M.; Petrov, V.B.; Ryazanov, A.I.; Smirnov, V.P.; Stolyarova, V.G.; Unezhev, V.N. [Russian Research Centre ' Kurchatov Institute' (RRC KI), Moscow (Russian Federation)

    2009-04-30

    New experimental approach is developed to explore plasma facing materials accounting for neutron induced radiation damage on erosion of these materials in plasma. The radiation damage has been produced in carbon materials by 5 MeV {sup 12}C{sup +} ions accelerated on cyclotron of Kurchatov Institute. A high level of radiation damage (1-10 dpa) has been obtained on these materials. The erosion of irradiated materials including CFC under plasma impact was studied on the LENTA linear plasma simulator. Surface modification was analyzed and the erosion rate was evaluated. Enhancement of the erosion process was detected for the radiation-damaged materials.

  8. DNA Damage by Radiation in Tradescantia Leaf Cells

    Energy Technology Data Exchange (ETDEWEB)

    Han, Min; Hyun, Kyung Man; Ryu, Tae Ho; Kim, Jin Kyu [Korea Atomic Energy Research Institute, Advanced Radiation Technology Institute, Jeongeup (Korea, Republic of); Nili, Mohammad [Dawnesh Radiation Research Institute, Barcelona (Spain)

    2010-04-15

    The comet assay is currently used in different areas of biological sciences to detect DNA damage. The comet assay, due to its simplicity, sensitivity and need of a few cells, is ideal as a short-term genotoxicity test. The comet assay can theoretically be applied to every type of eukaryotic cell, including plant cells. Plants are very useful as monitors of genetic effects caused by pollution in the atmosphere, water and soil. Tradescantia tests are very useful tools for screening the mutagenic potential in the environment. Experiments were conducted to study the genotoxic effects of ionizing radiations on the genome integrity, particularly of Tradescantia. The increasingly frequent use of Tradescantia as a sensitive environmental bioindicator of genotoxic effects. This study was designed to assess the genotoxicity of ionizing radiation using Tradescnatia-comet assay. The development of comet assay has enabled investigators to detect DNA damage at the levels of cells. To adapt this assay to plant cells, nuclei were directly obtained from Tradescantia leaf samples. A significant dose-dependent increase in the average tail moment values over the negative control was observed. Recently the adaptation of this technique to plant cells opens new possibilities for studies in variety area. The future applications of the comet assay could impact some other important areas, certainly, one of the limiting factors to its utility is the imagination of the investigator.

  9. Radiation damage to DNA: the effect of LET

    Energy Technology Data Exchange (ETDEWEB)

    Ward, J.F.; Milligan, J.R. [California Univ., San Diego, La Jolla, CA (United States). School of Medicine

    1997-03-01

    Mechanisms whereby ionizing radiation induced damage are introduced into cellular DNA are discussed. The types of lesions induced are summarized and the rationale is presented which supports the statement that radiation induced singly damaged sites are biologically unimportant. The conclusion that multiply damaged sites are critical is discussed and the mechanisms whereby such lesions are formed are presented. Structures of multiply damaged sites are summarized and problems which they present to cellular repair systems are discussed. Lastly the effects of linear energy transfer on the complexity of multiply damaged sites are surveyed and the consequences of this increased complexity are considered in terms of cell survival and mutation. (author)

  10. Radiation damage measurements in room-temperature semiconductor radiation detectors

    CERN Document Server

    Franks, L A; Olsen, R W; Walsh, D S; Vizkelethy, G; Trombka, J I; Doyle, B L; James, R B

    1999-01-01

    The literature of radiation damage measurements on cadmium zinc telluride (CZT), cadmium telluride (CT), and mercuric iodide (HgI sub 2) is reviewed and in the case of CZT supplemented by new alpha particle data. CZT strip detectors exposed to intermediate energy (1.3 MeV) proton fluences exhibit increased interstrip leakage after 10 sup 1 sup 0 p/cm sup 2 and significant bulk leakage after 10 sup 1 sup 2 p/cm sup 2. CZT exposed to 200 MeV protons shows a two-fold loss in energy resolution after a fluence of 5x10 sup 9 p/cm sup 2 in thick (3 mm) planar devices but little effect in 2 mm devices. No energy resolution effects were noted from a moderated fission spectrum of neutrons after fluences up to 10 sup 1 sup 0 n/cm sup 2 , although activation was evident. Exposures of CZT to 5 MeV alpha particles at fluences up to 1.5x10 sup 1 sup 0 alpha/cm sup 2 produced a near linear decrease in peak position with fluence and increases in FWHM beginning at about 7.5x10 sup 9 alpha/cm sup 2. CT detectors show resolution...

  11. Follow-up studies on genome damage in children after Chernobyl nuclear power plant accident.

    Science.gov (United States)

    Fucic, Aleksandra; Aghajanyan, Anna; Druzhinin, Vladimir; Minina, Varvara; Neronova, Elizaveta

    2016-09-01

    As children are more susceptible to ionizing radiation than adults, each nuclear accident demands special attention and care of this vulnerable population. The Chernobyl nuclear disaster occurred in a region populated with a large number of children, but despite all efforts and expertise of nuclear specialists, it was not possible to avoid casualties. As vast regions of Ukraine, Belarus and Russia were exposed to doses of ionizing radiation, which are known to be related with different diseases, shortly after the accident medical surveillance was launched, which also included analysis of genome damage. Child population affected by internal and external radiation consisted of subjects exposed prenatally, postnatally (both evacuated and non-evacuated), born by irradiated fathers who worked as liquidators, and parents exposed environmentally. In all groups of children during the last 30 years who were exposed to doses which were significantly higher than that recommended for general population of 1 mSv per year, increased genome damage was detected. Increased genome damage includes statistically higher frequency of dicentric and ring chromosomes, chromated and chromosome breaks, acentric fragments, translocations, and micronuclei. The presence of rogue cells confirmed internal contamination. Genome instability and radiosensitivity in children was detected both in evacuated and continuously exposed children. Today the population exposed to ionizing radiation in 1986 is in reproductive period of life and follow-up of this population and their offspring is of great importance. This review aims to give insight in results of studies, which reported genome damage in children in journals without language restrictions.

  12. Genomic instability and bystander effects: a paradigm shift in radiation biology?

    Science.gov (United States)

    Morgan, William F.

    2002-01-01

    A basic paradigm in radiobiology is that, following exposure to ionizing radiation, the deposition of energy in the cell nucleus and the resulting damage to DNA, the principal target, are responsible for the radiation's deleterious biological effects. Findings in two rapidly expanding fields of research--radiation-induced genomic instability and bystander effects--have caused us to reevaluate these central tenets. In this article, the potential influence of induced genomic instability and bystander effects on cellular injury after exposure to low-level radiation will be reviewed.

  13. Activation and radiation damage in the environment of hadron accelerators

    CERN Document Server

    Kiselev, Daniela

    2013-01-01

    A component which suffers radiation damage usually also becomes radioactive, since the source of activation and radiation damage is the interaction of the material with particles from an accelerator or with reaction products. However, the underlying mechanisms of the two phenomena are different. These mechanisms are described here. Activation and radiation damage can have far-reaching consequences. Components such as targets, collimators, and beam dumps are the first candidates for failure as a result of radiation damage. This means that they have to be replaced or repaired. This takes time, during which personnel accumulate dose. If the dose to personnel at work would exceed permitted limits, remote handling becomes necessary. The remaining material has to be disposed of as radioactive waste, for which an elaborate procedure acceptable to the authorities is required. One of the requirements of the authorities is a complete nuclide inventory. The methods used for calculation of such inventories are presented,...

  14. Radiation damage to DNA: The importance of track structure

    CERN Document Server

    Hill, M A

    1999-01-01

    A wide variety of biological effects are induced by ionizing radiation, from cell death to mutations and carcinogenesis. The biological effectiveness is found to vary not only with the absorbed dose but also with the type of radiation and its energy, i.e., with the nature of radiation tracks. An overview is presented of some of the biological experiments using different qualities of radiation, which when compared with Monte Carlo track structure studies, have highlighted the importance of the localized spatial properties of stochastic energy deposition on the nanometer scale at or near DNA. The track structure leads to clustering of damage which may include DNA breaks, base damage etc., the complexity of the cluster and therefore its biological repairability varying with radiation type. The ability of individual tracks to produce clustered damage, and the subsequent biological response are important in the assessment of the risk associated with low-level human exposure. Recent experiments have also shown that...

  15. Radiation damage of the ILC positron source target

    Energy Technology Data Exchange (ETDEWEB)

    Ushakov, A.; Riemann, S.

    2007-11-15

    The radiation damage of the positron source target for the International Linear Collider (ILC) has been studied. The displacement damage in target material due to multi-MeV photons has been calculated by combining FLUKA simulations for secondary particle production, SPECTER data for neutron displacement cross-sections and the Lindhard model for estimations of displacement damage by ions. The radiation damage of a stationary Ti6Al4V target in units of displacements per atom (dpa) has been estimated for photons from an undulator with strength 0.92 and period 1.15 cm. The calculated damage is 7 dpa. Approximately 12.5% of displacement damage result from neutrons. (orig.)

  16. Radiation damage limitations for the Fermilab Energy Doubler/Saver

    Energy Technology Data Exchange (ETDEWEB)

    Sanger, P.A.

    1977-01-01

    One important factor determining the lifetime of particle accelerators using superconducting magnets is the accumulated radiation damage of the magnet components. Using existing damage studies and a measured correlation between the radiation levels with the beam-off and the beam-on, a reasonable assessment of magnet lifetimes can be made. On the basis of this assessment it is expected that damage to the magnet conductor will not limit the magnet performance. The proper choice of polymeric materials used in the magnet is necessary to avoid frequent refurbishing of the magnets.

  17. Radiation-induced DNA damage and chromatin structure

    Science.gov (United States)

    Rydberg, B.; Chatterjee, A. (Principal Investigator)

    2001-01-01

    DNA lesions induced by ionizing radiation in cells are clustered and not randomly distributed. For low linear energy transfer (LET) radiation this clustering occurs mainly on the small scales of DNA molecules and nucleosomes. For example, experimental evidence suggests that both strands of DNA on the nucleosomal surface can be damaged in single events and that this damage occurs with a 10-bp modulation because of protection by histones. For high LET radiation, clustering also occurs on a larger scale and depends on chromatin organization. A particularly significant clustering occurs when an ionizing particle traverses the 30 nm chromatin fiber with generation of heavily damaged DNA regions with an average size of about 2 kbp. On an even larger scale, high LET radiation can produce several DNA double-strand breaks in closer proximity than expected from randomness. It is suggested that this increases the probability of misrejoining of DNA ends and generation of lethal chromosome aberrations.

  18. Damage-tolerant nanotwinned metals with nanovoids under radiation environments

    Science.gov (United States)

    Chen, Y.; Yu, K. Y.; Liu, Y.; Shao, S.; Wang, H.; Kirk, M. A.; Wang, J.; Zhang, X.

    2015-04-01

    Material performance in extreme radiation environments is central to the design of future nuclear reactors. Radiation induces significant damage in the form of dislocation loops and voids in irradiated materials, and continuous radiation often leads to void growth and subsequent void swelling in metals with low stacking fault energy. Here we show that by using in situ heavy ion irradiation in a transmission electron microscope, pre-introduced nanovoids in nanotwinned Cu efficiently absorb radiation-induced defects accompanied by gradual elimination of nanovoids, enhancing radiation tolerance of Cu. In situ studies and atomistic simulations reveal that such remarkable self-healing capability stems from high density of coherent and incoherent twin boundaries that rapidly capture and transport point defects and dislocation loops to nanovoids, which act as storage bins for interstitial loops. This study describes a counterintuitive yet significant concept: deliberate introduction of nanovoids in conjunction with nanotwins enables unprecedented damage tolerance in metallic materials.

  19. Time scales of radiation damage decay in four optical materials

    Science.gov (United States)

    Grupp, Frank; Geis, Norbert; Katterloher, Reinhard; Bender, Ralf

    2017-09-01

    In the framework of the qualification campaigns for the near infrared spectrometer and photometer instrument (NISP) on board the ESA/EUCLID satellite six optical materials where characterized with respect to their transmission losses after a radiation dose representing the mission exposure to high energy particles in the outer Lagrange point L2. Data was taken between 500 and 2000nm on six 25mm thick coated probes. Thickness and coating being representative for the NISP flight configuration. With this paper we present results owing up the radiation damage shown in [1]. We where able to follow up the decay of the radiation damage over almost one year under ambient conditions. This allows us to distinguish between curing effects that happen on different time-scales. As for some of the materials no radiation damage and thus no curing was detected, all materials that showed significant radiation damage in the measured passband showed two clearly distinguished time scales of curing. Up to 70% of the transmission losses cured on half decay time scales of several tens of days, while the rest of the damage cures on time scales of years.

  20. Radiation induced oxidative damage modification by cholesterol in liposomal membrane

    Science.gov (United States)

    Pandey, B. N.; Mishra, K. P.

    1999-05-01

    Ionizing radiation induced structural and chemical alterations in egg lecithin liposomal membrane have been studied by measurements of lipid peroxides, conjugated diene and fluorescence polarization. Predominantly unilamellar phospholipid vesicles prepared by sonication procedure were subjected to radiation doses of γ-rays from Co-60 in aerated, buffered aqueous suspensions. The oxidative damage in irradiated lipid molecules of liposomes has been determined spectrophotometrically by diene conjugate formation and thiobarbituric acid reactive (TBAR) method as a function of radiation dose. A correlation was found between the radiation dose applied (0.1-1 kGy) and the consequent lipid oxidation. The damage produced in irradiated liposomal membrane was measured by 1,6-diphenyl-1,3,5-hexatriene (DPH) fluorescence decay and polarization. The observed decrease in DPH fluorescence and increase in polarization was found dependent on the radiation dose suggesting alterations in rigidity or organizational order in phospholipid bilayer after irradiation. Furthermore, irradiated liposome vesicles composed of cholesterol showed marked reduction in observed radiation mediated peroxide formation and significantly affected the DPH fluorescence parameters. The magnitude of these modifying effects were found dependent on the mole fraction of cholesterol. It is concluded that modulation of structural order in unilamellar vesicle membrane by variations in basic molecular components controlled the magnitude of lipid peroxidation and diene conjugate formation. These observations contribute to our understanding of mechanism of radical reaction mediated damage caused by ionizing radiation in phospholipid membrane.

  1. Radiation induced oxidative damage modification by cholesterol in liposomal membrane

    Energy Technology Data Exchange (ETDEWEB)

    Pandey, B.N. [Radiation Biology and Biochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai (India); Mishra, K.P. [Radiation Biology and Biochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai (India)

    1999-05-01

    Ionizing radiation induced structural and chemical alterations in egg lecithin liposomal membrane have been studied by measurements of lipid peroxides, conjugated diene and fluorescence polarization. Predominantly unilamellar phospholipid vesicles prepared by sonication procedure were subjected to radiation doses of {gamma}-rays from Co-60 in aerated, buffered aqueous suspensions. The oxidative damage in irradiated lipid molecules of liposomes has been determined spectrophotometrically by diene conjugate formation and thiobarbituric acid reactive (TBAR) method as a function of radiation dose. A correlation was found between the radiation dose applied (0.1-1 kGy) and the consequent lipid oxidation. The damage produced in irradiated liposomal membrane was measured by 1,6-diphenyl-1,3,5-hexatriene (DPH) fluorescence decay and polarization. The observed decrease in DPH fluorescence and increase in polarization was found dependent on the radiation dose suggesting alterations in rigidity or organizational order in phospholipid bilayer after irradiation. Furthermore, irradiated liposome vesicles composed of cholesterol showed marked reduction in observed radiation mediated peroxide formation and significantly affected the DPH fluorescence parameters. The magnitude of these modifying effects were found dependent on the mole fraction of cholesterol. It is concluded that modulation of structural order in unilamellar vesicle membrane by variations in basic molecular components controlled the magnitude of lipid peroxidation and diene conjugate formation. These observations contribute to our understanding of mechanism of radical reaction mediated damage caused by ionizing radiation in phospholipid membrane.

  2. Proton radiation damage in optical filter glass

    Science.gov (United States)

    Grillot, Patrick N.; Rosenberg, William J.

    1989-01-01

    Samples of Schott BG-39 and Hoya CM-500 blue-green filter glass were subjected to proton radiation to determine their acceptability for spaceflight. Initial testing done with 2.7 MeV protons showed negligible change in optical transmittance with doses as high as 5.2 x 10 to the 14th protons per sq cm. Irradiation with protons of energy up to 63 MeV caused a significant reduction in transmittance in the Schott samples at doses of 5.3 x 10 to the 12th protons per sq cm, while negligible change occurred in the Hoya samples.

  3. Radiation damage studies of silicon microstrip sensors

    CERN Document Server

    Nakayama, T; Hara, K; Shimojima, M; Ikegami, Y; Iwata, Y; Johansen, L G; Kobayashi, H; Kohriki, T; Kondo, T; Nakano, I; Ohsugi, T; Riedler, P; Roe, S; Stapnes, Steinar; Stugu, B; Takashima, R; Tanizaki, K; Terada, S; Unno, Y; Yamamoto, K; Yamamura, K

    2000-01-01

    Various types of large area silicon microstrip detectors were fabricated for the development of radiation-tolerant detectors that will operate in the LHC ATLAS SCT. The detectors were irradiated with 12-GeV protons at KEK to fluences of 1.7*10/sup 14/ and 4.2*10/sup 14 / protons/cm/sup 2/. Irradiated samples included n-on-n detectors with 4 k Omega cm bulk resistivity and p-on-n detectors with 1 k Omega cm and 4 k Omega cm bulk resistivities. Four patterns of p-stop structures are configured in the n-on-n detectors. Although Hamamatsu fabricated most of the detectors, p-on-n detectors by SINTEF are also included, as well as those fabricated in a modified process by Hamamatsu. The detector performances after irradiation that are compared are the probability of creation of faulty coupling capacitors, C-V characteristics, charge curves, and total leakage current. The p-on-n are similar to the n-on-n detectors in these performances, and will remain operational in the ATLAS radiation environment. (12 refs).

  4. Links between persistent DNA damage, genome instability, and aging

    Energy Technology Data Exchange (ETDEWEB)

    Dynan, William S. [Emory Univ., Atlanta, GA (United States). Dept. of Radiation Oncology

    2016-11-14

    The goal of this study was to examine long-term effects of low-dose radiation exposure. One of the hypotheses was that radiation exposure would accelerate the normal aging process. The study was jointly funded by NASA and examined both low-LET radiation (γ-rays) and high-LET radiation (1000 MeV/nucleon 56Fe ions) at doses of 0.1 Gy and up. The work used the Japanese medaka fish (Oryzias latipes), as a vertebrate model organism that can be maintained in large numbers at low cost for lifetime studies. Like other small laboratory fish, Japanese medaka share many anatomical and histological characteristics with other vertebrates, and a variety of genetic and genomic resources are available. Some work also used the zebrafish (Danio rerio), another widely used laboratory model organism.

  5. Gallium Arsenide solar cell radiation damage experiment

    Science.gov (United States)

    Maurer, R. H.; Kinnison, J. D.; Herbert, G. A.; Meulenberg, A.

    1991-01-01

    Gallium arsenide (GaAs) solar cells for space applications from three different manufactures were irradiated with 10 MeV protons or 1 MeV electrons. The electrical performance of the cells was measured at several fluence levels and compared. Silicon cells were included for reference and comparison. All the GaAs cell types performed similarly throughout the testing and showed a 36 to 56 percent power areal density advantage over the silicon cells. Thinner (8-mil versus 12-mil) GaAs cells provide a significant weight reduction. The use of germanium (Ge) substrates to improve mechanical integrity can be implemented with little impact on end of life performance in a radiation environment.

  6. A role for Lsmlp in response to ultraviolet-radiation damage in Saccharomyces cerevisiae.

    Science.gov (United States)

    Spicakova, Tatiana; McCann, Kelly; Brown, J Martin

    2008-10-01

    A genome-wide screen in Saccharomyces cerevisiae identified LSM1 as a new gene affecting sensitivity to ultraviolet (UV) radiation. Lsmlp is a member of a cytoplasmic complex composed of Lsmlp-7p that interacts with the yeast mRNA degradation machinery. To investigate the potential role of Lsmlp in response to UV radiation, we constructed double mutant strains in which LSM1 was deleted in combination with a representative gene from each of three known yeast DNA repair pathways. Our results show that lsm1delta increases the UV-radiation sensitivity of the rad1delta and rad51delta mutants, but not the radl8delta mutant, placing LSM1 within the post-replication repair/damage tolerance pathway (PRR). When combined with other deletions affecting PRR, lsm1delta increases the UV-radiation sensitivity of the rev3delta, rad30delta and pol30-K164R mutants but not rad5delta. Furthermore, the UV-radiation sensitivity phenotype of lsmldelta is partially rescued by mutations in genes involved in 3' to 5' mRNA degradation, and mutations predicted to function in RNA interactions confer the most UV-radiation sensitivity. Together, these results suggest that Lsmlp may confer protection against UV-radiation damage by protecting the 3' ends of mRNAs from exosome-dependent 3' to 5' degradation as part of a novel RAD5-mediated, PCNA-K164 ubiquitylation-independent subpathway of PRR.

  7. LHCb: Radiation Damage in the LHCb VELO

    CERN Multimedia

    Rodriguez Perez, P

    2012-01-01

    LHCb is a dedicated experiment to study new physics in the decays of beauty and charm hadrons at the Large Hadron Collider (LHC) at CERN. The beauty and charm hadrons are identified through their flight distance in the Vertex Locator (VELO), and hence the detector is critical for both the trigger and offline physics analyses. The 88 VELO sensors are all n-on-n type but one, which is made from n-on-p silicon, and is the only n-on-p module silicon sensor operated at the LHC. The sensors have an inner radius of only 7 mm from the LHC beam and an outer radius of 42 mm, consequently the sensors receive a large and non-uniform radiation dose. The LHCb is planned to record an integrated luminosity up to 5 $fb^{-1}$ with collision energies between 7 and 14 TeV before 2018. The leakage current in the sensors has increased significantly following the delivered luminosity, and decreased during shutdown periods due to annealing. The effective depletion voltage of the sensors is measured from the charge collection effi...

  8. Radiation damage on the LHCb-VELO

    Science.gov (United States)

    Casse, G.

    2013-12-01

    The LHCb Vertex Locator (VELO) is designed to reconstruct charged particle trajectories and vertices produced at the LHCb interaction region. This is a silicon strip detector system operating at the closest distance from the interaction region among all the currently installed detectors at the CERN LHC. The geometry of the sensors implies that every detector region is exposed to a different dose of radiation depending mainly on the radial distance from the beam line. In the first 2 years of operation they have been exposed to a range of fluences up to a maximum value of about 4.5×1013 1 MeV neutron equivalent (neq) cm-2. At the end of 2012 a maximum of about 1.5×1014 neq has been reached; data analysis is ongoing. Sensor currents, full depletion voltage and charge collection efficiencies have been studied at various fluences. Observation of type inversion of the n-type silicon sensors has been made (about after 10-15×1012 neq). The n-type bulk sensors have been compared with the only p-type bulk detectors installed in the LHC. A reduction in the charge collection efficiency due to charge losses to a second metal layer (used for routing the signal to the readout electronics in LHCb-VELO sensors) has been measured. Possible solutions to this undesirable effect are planned to be studied in the framework of the LHCb-VELO upgrade.

  9. Radiation damage on the LHCb-VELO

    Energy Technology Data Exchange (ETDEWEB)

    Casse, G., E-mail: gcasse@hep.ph.liv.ac.uk

    2013-12-01

    The LHCb Vertex Locator (VELO) is designed to reconstruct charged particle trajectories and vertices produced at the LHCb interaction region. This is a silicon strip detector system operating at the closest distance from the interaction region among all the currently installed detectors at the CERN LHC. The geometry of the sensors implies that every detector region is exposed to a different dose of radiation depending mainly on the radial distance from the beam line. In the first 2 years of operation they have been exposed to a range of fluences up to a maximum value of about 4.5×10{sup 13} 1 MeV neutron equivalent (n{sub eq}) cm{sup −2}. At the end of 2012 a maximum of about 1.5×10{sup 14} n{sub eq} has been reached; data analysis is ongoing. Sensor currents, full depletion voltage and charge collection efficiencies have been studied at various fluences. Observation of type inversion of the n-type silicon sensors has been made (about after 10–15×10{sup 12} n{sub eq}). The n-type bulk sensors have been compared with the only p-type bulk detectors installed in the LHC. A reduction in the charge collection efficiency due to charge losses to a second metal layer (used for routing the signal to the readout electronics in LHCb-VELO sensors) has been measured. Possible solutions to this undesirable effect are planned to be studied in the framework of the LHCb-VELO upgrade.

  10. Fluorescence studies on radiation oxidative damage to membranes ...

    Indian Academy of Sciences (India)

    Unknown

    Presence of structure modulating agents (e.g. cholesterol) or antioxidant molecules (e.g. tocopherol, ascorbic acid) in the membrane protected lipids against radiation, suggesting involvement of free radicals in the damage process. There seems to exist a relationship between generated ROS and permeability changes after.

  11. Radioprotective agents to prevent cellular damage due to ionizing radiation.

    Science.gov (United States)

    Smith, Tyler A; Kirkpatrick, Daniel R; Smith, Sean; Smith, Trevor K; Pearson, Tate; Kailasam, Aparna; Herrmann, Kortney Z; Schubert, Johanna; Agrawal, Devendra K

    2017-11-09

    Medical imaging has become a central component of patient care to ensure early and accurate diagnosis. Unfortunately, many imaging modalities use ionizing radiation to generate images. Ionizing radiation even in low doses can cause direct DNA damage and generate reactive oxygen species and free radicals, leading to DNA, protein, and lipid membrane damage. This cell damage can lead to apoptosis, necrosis, teratogenesis, or carcinogenesis. As many as 2% of cancers (and an associated 15,000 deaths annually) can be linked to computed tomography exposure alone. Radioprotective agents have been investigated using various models including cells, animals, and recently humans. The data suggest that radioprotective agents working through a variety of mechanisms have the potential to decrease free radical damage produced by ionizing radiation. Radioprotective agents may be useful as an adjunct to medical imaging to reduced patient morbidity and mortality due to ionizing radiation exposure. Some radioprotective agents can be found in high quantities in antioxidant rich foods, suggesting that a specific diet recommendation could be beneficial in radioprotection.

  12. Effect of Rosiglitazone on Radiation Damage in Bone Marrow Hemopoiesis

    Science.gov (United States)

    Benkő, Klára; Pintye, Éva; Szabó, Boglárka; Géresi, Krisztina; Megyeri, Attila; Benkő, Ilona

    2008-12-01

    To study radiobiological effects and drugs, which can modify radiation injury, has an importance if we would like to avoid harmful effects of radiation due to emergency situations or treat patients with malignant diseases by radiotherapy. During the long treatment schedules patients may be treated by not only anticancer but many other drugs because of accompanying diseases. These drugs may also modify radiobiological effects. Rosiglitazone pre-treatment proved to be myeloprotective and accelerated recovery of 5-fluorouracil-damaged bone marrow in our previous experiments. Our new studies are designed to evaluate whether rosiglitazone has similar beneficial effects in radiation-damaged hemopoiesis. Bone marrow damage was precipitated by total body irradiation (TBI) using single increasing doses (2-10 Gy) of γ—irradiation in groups of mice. Lethality was well correlated with damage in hemopoiesis measured by cellularity of bone marrow (LD50 values were 4.8 and 5.3 gray respectively). Rosiglitazone, an insulin-sensitizing drug, had no significant effect on bone marrow cellularity. Insulin resistance associated with obesity or diabetes mellitus type 2 is intensively growing among cancer patients requiring some kind of radiotherapy. Therefore it is important to know whether drugs used for their therapy can modify radiation effects.

  13. Radiation damage to multi-walled carbon nanotubes and their ...

    Indian Academy of Sciences (India)

    Home; Journals; Bulletin of Materials Science; Volume 38; Issue 7. Radiation damage to multi-walled carbon ... In this work, the Raman spectroscopy investigation of nanotube defects created by irradiation of Ar+ ions with various energies and doses was presented. In order to obtain more informative data, scanning electron ...

  14. Viral and Cellular Genomes Activate Distinct DNA Damage Responses

    Science.gov (United States)

    Shah, Govind A.; O’Shea, Clodagh C.

    2015-01-01

    Summary In response to cellular genome breaks, MRE11/RAD50/NBS1 (MRN) activates a global ATM DNA damage response (DDR) that prevents cellular replication. Here we show that MRN-ATM also has critical functions in defending the cell against DNA viruses. We reveal temporally distinct responses to adenovirus genomes: a critical MRN-ATM DDR that must be inactivated by E1B-55K/E4-ORF3 viral oncoproteins and a global MRN independent ATM DDR to viral nuclear domains that does not impact viral replication. We show that MRN binds to adenovirus genomes and activates a localized ATM response that specifically prevents viral DNA replication. In contrast to chromosomal breaks, ATM activation is not amplified by H2AX across megabases of chromatin to induce global signaling and replicative arrest. Thus, γH2AX foci discriminate ‘self’ and ‘non-self’ genomes and determine if a localized anti-viral or global ATM response is appropriate. This provides an elegant mechanism to neutralize viral genomes without jeopardizing cellular viability. PMID:26317467

  15. Influence of radiation damage on plasma-facing material erosion

    Energy Technology Data Exchange (ETDEWEB)

    Koidan, V.S.; Bruchanov, A.N.; Chugunov, O.K.; Gureev, V.M.; Khripunov, B.I.; Kornienko, S.N.; Kuteev, B.Y.; Latushkin, S.T.; Muksunov, A.M.; Petrov, V.B.; Ryazanov, A.; Smirnov, V.P.; Stolyarova, V.G.; Unezhev, V.N. [Russian Science Center ' Kurchatov Institute' , Ploshchad' Akademika Kurchatova 46, 123181 Moscow (Russian Federation)

    2007-07-01

    Full text of publication follows: Selection of structural materials for a fusion reactor is a very actual problem. Plasma-facing materials (PFM's) of the first wall and divertor of the fusion reactor will be affected by high heat, fast particle fluxes and 14 MeV neutron irradiation. All these factors are crucial for the lifetime of the fusion reactor components. Fast neutrons produce a high-level of radiation damage (estimated value is up to hundred dpa) in materials during long operation of fusion reactor. At the same time, PFM's will suffer erosion induced by the plasma as well. While important data on the plasma erosion have been collected for non-irradiated materials, it is difficult to qualify PFM's at present taking into account radiation damage effects. In this paper, we present the first experimental results on radiation-damage effects on erosion of materials under plasma impact. To obtain high level of radiation damage we simulate neutron irradiation by fast ions on the Cyclotron at Kurchatov Institute providing energies of 1-30 MeV. Using this method we can obtain the radiation damage equivalent in a few days that corresponds to fast neutron dose of irradiation {approx} 10{sup 26} neutron/m{sup 2}. Carbon materials were taken for the study as the targets: pyrolytic graphite (reference), MPG-8 (Russian graphite) and CFC SEP NB (ITER PFM candidate). Irradiation of these materials on the cyclotron has been performed with 5 MeV carbon ions. Plasma erosion was studied on the linear plasma simulator LENTA. Irradiated samples were exposed to steady-state deuterium plasma at 100 eV (D{sup +}ions) to dose {approx} 10{sup 25} ion/m{sup 2}.The microstructure modification was observed and comparison was made on damaged and non-irradiated materials. The experiments have been performed with 1-10 dpa of radiation damage. The results of the work appear to be an important step in further detailed characterization of PFM's in fusion reactor. (authors)

  16. Thermal annealing of natural, radiation-damaged pyrochlore

    Energy Technology Data Exchange (ETDEWEB)

    Zietlow, Peter; Mihailova, Boriana [Hamburg Univ. (Germany). Dept. of Earth Sciences; Beirau, Tobias [Hamburg Univ. (Germany). Dept. of Earth Sciences; Stanford Univ., CA (United States). Dept. of Geological Sciences; and others

    2017-03-01

    Radiation damage in minerals is caused by the α-decay of incorporated radionuclides, such as U and Th and their decay products. The effect of thermal annealing (400-1000 K) on radiation-damaged pyrochlores has been investigated by Raman scattering, X-ray powder diffraction (XRD), and combined differential scanning calorimetry/thermogravimetry (DSC/TG). The analysis of three natural radiation-damaged pyrochlore samples from Miass/Russia [6.4 wt% Th, 23.1.10{sup 18} α-decay events per gram (dpg)], Panda Hill/Tanzania (1.6 wt% Th, 1.6.10{sup 18} dpg), and Blue River/Canada (10.5 wt% U, 115.4.10{sup 18} dpg), are compared with a crystalline reference pyrochlore from Schelingen (Germany). The type of structural recovery depends on the initial degree of radiation damage (Panda Hill 28%, Blue River 85% and Miass 100% according to XRD), as the recrystallization temperature increases with increasing degree of amorphization. Raman spectra indicate reordering on the local scale during annealing-induced recrystallization. As Raman modes around 800 cm{sup -1} are sensitive to radiation damage (M. T. Vandenborre, E. Husson, Comparison of the force field in various pyrochlore families. I. The A{sub 2}B{sub 2}O{sub 7} oxides. J. Solid State Chem. 1983, 50, 362, S. Moll, G. Sattonnay, L. Thome, J. Jagielski, C. Decorse, P. Simon, I. Monnet, W. J. Weber, Irradiation damage in Gd{sub 2}Ti{sub 2}O{sub 7} single crystals: Ballistic versus ionization processes. Phys. Rev. 2011, 84, 64115.), the degree of local order was deduced from the ratio of the integrated intensities of the sum of the Raman bands between 605 and 680 cm{sup -1} divided by the sum of the integrated intensities of the bands between 810 and 860 cm{sup -1}. The most radiation damaged pyrochlore (Miass) shows an abrupt recovery of both, its short- (Raman) and long-range order (X-ray) between 800 and 850 K, while the weakly damaged pyrochlore (Panda Hill) begins to recover at considerably lower temperatures (near 500 K

  17. Laser annealing heals radiation damage in avalanche photodiodes

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Jin Gyu [University of Waterloo, Institute for Quantum Computing, Waterloo, ON (Canada); University of Waterloo, Department of Electrical and Computer Engineering, Waterloo, ON (Canada); Anisimova, Elena; Higgins, Brendon L.; Bourgoin, Jean-Philippe [University of Waterloo, Institute for Quantum Computing, Waterloo, ON (Canada); University of Waterloo, Department of Physics and Astronomy, Waterloo, ON (Canada); Jennewein, Thomas [University of Waterloo, Institute for Quantum Computing, Waterloo, ON (Canada); University of Waterloo, Department of Physics and Astronomy, Waterloo, ON (Canada); Canadian Institute for Advanced Research, Quantum Information Science Program, Toronto, ON (Canada); Makarov, Vadim [University of Waterloo, Institute for Quantum Computing, Waterloo, ON (Canada); University of Waterloo, Department of Electrical and Computer Engineering, Waterloo, ON (Canada); University of Waterloo, Department of Physics and Astronomy, Waterloo, ON (Canada)

    2017-12-15

    Avalanche photodiodes (APDs) are a practical option for space-based quantum communications requiring single-photon detection. However, radiation damage to APDs significantly increases their dark count rates and thus reduces their useful lifetimes in orbit. We show that high-power laser annealing of irradiated APDs of three different models (Excelitas C30902SH, Excelitas SLiK, and Laser Components SAP500S2) heals the radiation damage and several APDs are restored to typical pre-radiation dark count rates. Of nine samples we test, six APDs were thermally annealed in a previous experiment as another solution to mitigate the radiation damage. Laser annealing reduces the dark count rates further in all samples with the maximum dark count rate reduction factor varying between 5.3 and 758 when operating at -80 C. This indicates that laser annealing is a more effective method than thermal annealing. The illumination power to reach these reduction factors ranges from 0.8 to 1.6 W. Other photon detection characteristics, such as photon detection efficiency, timing jitter, and afterpulsing probability, fluctuate but the overall performance of quantum communications should be largely unaffected by these variations. These results herald a promising method to extend the lifetime of a quantum satellite equipped with APDs. (orig.)

  18. Radiation damage free ghost diffraction with atomic resolution

    Science.gov (United States)

    Li, Zheng; Medvedev, Nikita; Chapman, Henry N.; Shih, Yanhua

    2018-01-01

    The x-ray free electron lasers can enable diffractive structural determination of protein nanocrystals and single molecules that are too small and radiation-sensitive for conventional x-ray diffraction. However the electronic form factor may be modified during the ultrashort x-ray pulse due to photoionization and electron cascade caused by the intense x-ray pulse. For general x-ray imaging techniques, the minimization of the effects of radiation damage is of major concern to ensure reliable reconstruction of molecular structure. Here we show that radiation damage free diffraction can be achieved with atomic spatial resolution by using x-ray parametric down-conversion and ghost diffraction with entangled photons of x-ray and optical frequencies. We show that the formation of the diffraction patterns satisfies a condition analogous to the Bragg equation, with a resolution that can be as fine as the crystal lattice length scale of several Ångstrom. Since the samples are illuminated by low energy optical photons, they can be free of radiation damage.

  19. Positron annihilation lifetime study of radiation-damaged natural zircons

    Energy Technology Data Exchange (ETDEWEB)

    Roberts, J. [Centre for Antimatter-Matter Studies, Research School of Physics and Engineering, The Australian National University, Canberra (Australia); Gaugliardo, P. [Centre for Antimatter-Matter Studies, School of Physics, University of Western Australia (Australia); Farnan, I.; Zhang, M. [Department of Earth Sciences, University of Cambridge (United Kingdom); Vance, E.R.; Davis, J.; Karatchevtseva, I.; Knott, R.B. [Australian Nuclear Science and Technology Organisation (Australia); Mudie, S. [The Australian Synchrotron, Victoria (Australia); Buckman, S.J. [Centre for Antimatter-Matter Studies, Research School of Physics and Engineering, The Australian National University, Canberra (Australia); Institute for Mathematical Sciences, University of Malaya, Kuala Lumpur (Malaysia); Sullivan, J.P., E-mail: james.sullivan@anu.edu.au [Centre for Antimatter-Matter Studies, Research School of Physics and Engineering, The Australian National University, Canberra (Australia)

    2016-04-01

    Zircons are a well-known candidate waste form for actinides and their radiation damage behaviour has been widely studied by a range of techniques. In this study, well-characterised natural single crystal zircons have been studied using Positron Annihilation Lifetime Spectroscopy (PALS). In some, but not all, of the crystals that had incurred at least half of the alpha-event damage of ∼10{sup 19} α/g required to render them structurally amorphous, PALS spectra displayed long lifetimes corresponding to voids of ∼0.5 nm in diameter. The long lifetimes corresponded to expectations from published Small-Angle X-ray Scattering data on similar samples. However, the non-observation by PALS of such voids in some of the heavily damaged samples may reflect large size variations among the voids such that no singular size can be distinguished or. Characterisation of a range of samples was also performed using scanning electron microscopy, optical absorption spectroscopy, Raman scattering and X-ray scattering/diffraction, with the degree of alpha damage being inferred mainly from the Raman technique and X-ray diffraction. The observed void diameters and intensities of the long lifetime components were changed somewhat by annealing at 700 °C; annealing at 1200 °C removed the voids entirely. The voids themselves may derive from He gas bubbles or voids created by the inclusion of small quantities of organic and hydrous matter, notwithstanding the observation that no voidage was evidenced by PALS in two samples containing hydrous and organic matter. - Highlights: • Study of a range of naturally occurring zircons damaged by alpha radiation. • Characterised using a range of techniques, including PALS spectroscopy. • Effects on hydrous material appear important, rather than direct radiation damage. • Annealing is shown to remove the observed voids.

  20. Early and Late Damages in Chromosome 3 of Human Lymphocytes After Radiation Exposure

    Science.gov (United States)

    Sunagawa, Mayumi; Mangala, Lingegowda; Zhang, Ye; Kahdim, Munira; Wilson, Bobby; Cucinotta, Francis A.; Wu, Honglu

    2011-01-01

    Tumor formation in humans or animals is a multi-step process. An early stage of cancer development is believed to be genomic instability (GI) which accelerates the mutation rate in the descendants of the cells surviving radiation exposure. GI is defined as elevated or persistent genetic damages occurring many generations after the cells are exposed. While early studies have demonstrated radiation-induced GI in several cell types as detected in endpoints such as mutation, apoptosis and damages in chromosomes, the dependence of GI on the quality of radiation remains uncertain. To investigate GI in human lymphocytes induced by both low- and high-LET radiation, we initially exposed white blood cells collected from healthy subjects to gamma rays in vitro, and cultured the cells for multiple generations. Chromosome aberrations were analyzed in cells collected at first mitosis post irradiation and at several intervals during the culture period. Among a number of biological endpoints planned for the project, the multi-color banding fluorescent in situ hybridization (mBAND) allows identification of inversions that were expected to be stable. We present here early and late chromosome aberrations detected with mBAND in chromosome 3 after gamma exposure. Comparison of chromosome damages in between human lymphocytes and human epithelial cells is also discussed

  1. Measuring Radiation Damage from Heavy Energetic Ions in Aluminum

    Energy Technology Data Exchange (ETDEWEB)

    Kostin, M., PI-MSU; Ronningen, R., PI-MSU; Ahle, L., PI-LLNL; Gabriel, T., Scientific Investigation and Development; Mansur, L., PI-ORNL; Leonard, K., ORNL; Mokhov, N., FNAL; Niita, K., RIST, Japan

    2009-02-21

    An intense beam of 122 MeV/u (9.3 GeV) 76Ge ions was stopped in aluminum samples at the Coupled Cyclotron Facility at NSCL, MSU. Attempts were made at ORNL to measure changes in material properties by measuring changes in electrical resistivity and microhardness, and by transmission electron microscopy characterization, for defect density caused by radiation damage, as a function of depth and integrated ion flux. These measurements are relevant for estimating damage to components at a rare isotope beam facility.

  2. A Computational Study of Hadron Radiation Damage to DNA Nucleobases

    DEFF Research Database (Denmark)

    Milhøj, Birgitte Olai

    Radiation damage of biomolecules is a signicant contributor to both the onset and also possible curing of cancer. Such damage is largely the result of free radicals that can be created by the interaction of high-energetic photons or ions with water within cells. Understanding the details...... constants based on transition state theory. The investigations are performed with methods of increasing complexity ranging from pure gas-phase, through PCM solvation up to the very accurate and explicit QM/MM models of nucleobase water clusters through which also the importance of making conformational...

  3. Defective repair of ionizing radiation damage in Cockayne`s syndrome and xeroderma pigmentosum group G

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, P.K. [Lawrence Berkeley Lab., CA (United States); Leadon, S.A. [Univ. of North Carolina, Chapel Hill, NC (United States)

    1994-12-31

    Damage produced by ultraviolet light (UV) or certain chemical carcinogens is repaired more rapidly in transcriptionally active DNA than in the genome as a whole by an evolutionarily conserved process coupled to transcription and involving preferential repair of transcribed strands. The generality of strand-specific repair for damage other than UV has not been well-established, but it has generally been assumed to involve the nucleotide excision repair pathway for bulky lesions. There is little overlap in the spectrum of lesions induced by ionizing radiation and UV; consistent with the idea that to a large extent, the repair processes for these two types of damage are separable, there are very few mammalian cell mutants that are hypersensitive to the lethal effects of both.

  4. Acetylation dynamics of human nuclear proteins during the ionizing radiation-induced DNA damage response

    DEFF Research Database (Denmark)

    Bennetzen, Martin V; Larsen, Dorthe Helena; Dinant, Christoffel

    2013-01-01

    -dependent posttranslational modifications (PTMs). To complement our previous analysis of IR-induced temporal dynamics of nuclear phosphoproteome, we now identify a range of human nuclear proteins that are dynamically regulated by acetylation, and predominantly deacetylation, during IR-induced DDR by using mass spectrometry...... to genotoxic insults. Overall, these results present a resource of temporal profiles of a spectrum of protein acetylation sites during DDR and provide further insights into the highly dynamic nature of regulatory PTMs that help orchestrate the maintenance of genome integrity.......Genotoxic insults, such as ionizing radiation (IR), cause DNA damage that evokes a multifaceted cellular DNA damage response (DDR). DNA damage signaling events that control protein activity, subcellular localization, DNA binding, protein-protein interactions, etc. rely heavily on time...

  5. Non-Thermal Electromagnetic Radiation Damage to Lens Epithelium

    OpenAIRE

    Bormusov, Elvira; P.Andley, Usha; Sharon, Naomi; Sch?chter, Levi; Lahav, Assaf; Dovrat, Ahuva

    2008-01-01

    High frequency microwave electromagnetic radiation from mobile phones and other modern devices has the potential to damage eye tissues, but its effect on the lens epithelium is unknown at present. The objective of this study was to investigate the non-thermal effects of high frequency microwave electromagnetic radiation (1.1GHz, 2.22 mW) on the eye lens epithelium in situ. Bovine lenses were incubated in organ culture at 35?C for 10-15 days. A novel computer-controlled microwave source was us...

  6. Radiation Damage in Si Diodes from Short, Intense Ion Pulses

    Science.gov (United States)

    de Leon, S. J.; Ludewigt, B. A.; Persaud, A.; Seidl, P. A.; Schenkel, T.

    2017-10-01

    The Neutralized Drift Compression Experiment (NDCX-II) at Berkeley Lab is an induction accelerator studying the effects that concentrated ion beams have on various materials. Charged particle radiation damage was the focus of this research - we have characterized a series of Si diodes using an electrometer and calibrated the diodes response using an 241Am alpha source, both before and after exposing the diodes to 1 MeV He ions in the accelerator. The key part here is that the high intensity pulses from NDCX-II (>1010 ions/cm2 per pulse in accelerators, fusion energy experiments and space applications and results from short pulses can inform models of radiation damage evolution. This work was supported by the Office of Science of the US Department of Energy under contract DE-AC0205CH11231.

  7. Non-thermal electromagnetic radiation damage to lens epithelium.

    Science.gov (United States)

    Bormusov, Elvira; P Andley, Usha; Sharon, Naomi; Schächter, Levi; Lahav, Assaf; Dovrat, Ahuva

    2008-05-21

    High frequency microwave electromagnetic radiation from mobile phones and other modern devices has the potential to damage eye tissues, but its effect on the lens epithelium is unknown at present. The objective of this study was to investigate the non-thermal effects of high frequency microwave electromagnetic radiation (1.1GHz, 2.22 mW) on the eye lens epithelium in situ. Bovine lenses were incubated in organ culture at 35°C for 10-15 days. A novel computer-controlled microwave source was used to investigate the effects of microwave radiation on the lenses. 58 lenses were used in this study. The lenses were divided into four groups: (1) Control lenses incubated in organ culture for 10 to15 days. (2) Electromagnetic radiation exposure group treated with 1.1 GHz, 2.22 mW microwave radiation for 90 cycles of 50 minutes irradiation followed by 10 minutes pause and cultured up to 10 days. (3) Electromagnetic radiation exposure group treated as group 2 with 192 cycles of radiation and cultured for 15 days. (4) Lenses exposed to 39.5°C for 2 hours 3 times with 24 hours interval after each treatment beginning on the second day of the culture and cultured for 11 days. During the culture period, lens optical quality was followed daily by a computer-operated scanning laser beam. At the end of the culture period, control and treated lenses were analyzed morphologically and by assessment of the lens epithelial ATPase activity. Exposure to 1.1 GHz, 2.22 mW microwaves caused a reversible decrease in lens optical quality accompanied by irreversible morphological and biochemical damage to the lens epithelial cell layer. The effect of the electromagnetic radiation on the lens epithelium was remarkably different from those of conductive heat. The results of this investigation showed that electromagnetic fields from microwave radiation have a negative impact on the eye lens. The lens damage by electromagnetic fields was distinctly different from that caused by conductive heat.

  8. Ion-Induced Radiation Damage in Biomolecular Systems

    Science.gov (United States)

    Schlathölter, Thomas

    The interaction of keV ions with building blocks of DNA and proteins is of fundamental interest to proton and heavy ion therapy. During the last decade, ion-induced ionization and fragmentation was studied for isolated biomolecules, biomolecular clusters, nanosolvated isolated biomolecules and solid thin biomolecular films. This article gives a brief overview over the research on biomolecular mechanisms underlying ion-induced radiation damage with a focus on the different target systems.

  9. The effect of radiation damage on the vertex detector efficiency

    CERN Document Server

    Cooke, O

    1997-01-01

    97-023 This note describes a brief study into the effects of the radiation damage on the vertex detectorperformance. The noise increases as the detector is irradiated. Fixing the fraction of noise clusters to 0.1% by adjusting the thresholds brings about a loss in efficiency with increased irradiation. This loss in efficiency is parameterized, and some effects on the B->pi+pi- channel are shown.

  10. Radiation damage status of the ATLAS silicon strip detectors (SCT)

    CERN Document Server

    Kondo, Takahiko; The ATLAS collaboration

    2017-01-01

    The Silicon microstrip detector system (SCT) of the ATLAS experiment at LHC has been working well for about 7 years since 2010. The innermost layer has already received a few times of 10**13 1-MeV neutron-equivalent fluences/cm2. The evolutions of the radiation damage effects on strip sensors such as leakage current and full depletion voltages will be presented.

  11. Radiation damage and repair in cells and cell components. Progress report, 1978-1979

    Energy Technology Data Exchange (ETDEWEB)

    Fluke, D.J.; Pollard, E.C.

    1979-01-01

    Special work during the year concentrated on induced repair of cellular radiation damage in a number of strains of Escherchia coli. Ultraviolet and x-radiation are considered for induction of cell damage. (PCS)

  12. Low dose radiation damage effects in silicon strip detectors

    Science.gov (United States)

    Wiącek, P.; Dąbrowski, W.

    2016-11-01

    The radiation damage effects in silicon segmented detectors caused by X-rays have become recently an important research topic driven mainly by development of new detectors for applications at the European X-ray Free Electron Laser (E-XFEL). However, radiation damage in silicon strip is observed not only after extreme doses up to 1 GGy expected at E-XFEL, but also at doses in the range of tens of Gy, to which the detectors in laboratory instruments like X-ray diffractometers or X-ray spectrometers can be exposed. In this paper we report on investigation of radiation damage effects in a custom developed silicon strip detector used in laboratory diffractometers equipped with X-ray tubes. Our results show that significant degradation of detector performance occurs at low doses, well below 200 Gy, which can be reached during normal operation of laboratory instruments. Degradation of the detector energy resolution can be explained by increasing leakage current and increasing interstrip capacitance of the sensor. Another observed effect caused by accumulation of charge trapped in the surface oxide layer is change of charge division between adjacent strips. In addition, we have observed unexpected anomalies in the annealing process.

  13. Deoxyribonucleoprotein structure and radiation injury - Cellular radiosensitivity is determined by LET-infinity-dependent DNA damage in hydrated deoxyribonucleoproteins and the extent of its repair

    Science.gov (United States)

    Lett, J. T.; Peters, E. L.

    1992-01-01

    Until recently, OH radicals formed in bulk nuclear water were believed to be the major causes of DNA damage that results in cell death, especially for sparsely ionizing radiations. That hypothesis has now been challenged, if not refuted. Lethal genomic DNA damage is determined mainly by energy deposition in deoxyribonucleoproteins, and their hydration shells, and charge (energy) transfer processes within those structures.

  14. PREFACE: Radiation Damage in Biomolecular Systems (RADAM07)

    Science.gov (United States)

    McGuigan, Kevin G.

    2008-03-01

    The annual meeting of the COST P9 Action `Radiation damage in biomolecular systems' took place from 19-22 June 2007 in the Royal College of Surgeons in Ireland, in Dublin. The conference was structured into 5 Working Group sessions: Electrons and biomolecular interactions Ions and biomolecular interactions Radiation in physiological environments Theoretical developments for radiation damage Track structure in cells Each of the five working groups presented two sessions of invited talks. Professor Ron Chesser of Texas Tech University, USA gave a riveting plenary talk on `Mechanisms of Adaptive Radiation Responses in Mammals at Chernobyl' and the implications his work has on the Linear-No Threshold model of radiation damage. In addition, this was the first RADAM meeting to take place after the Alexander Litvenenko affair and we were fortunate to have one of the leading scientists involved in the European response Professor Herwig Paretzke of GSF-Institut für Strahlenschutz, Neuherberg, Germany, available to speak. The remaining contributions were presented in the poster session. A total of 72 scientific contributions (32 oral, 40 poster), presented by 97 participants from 22 different countries, gave an overview on the current progress in the 5 different subfields. A 1-day pre-conference `Early Researcher Tutorial Workshop' on the same topic kicked off on 19 June attended by more than 40 postgrads, postdocs and senior researchers. Twenty papers, based on these reports, are included in this volume of Journal of Physics: Conference Series. All the contributions in this volume were fully refereed, and they represent a sample of the courses, invited talks and contributed talks presented during RADAM07. The interdisciplinary RADAM07 conference brought together researchers from a variety of different fields with a common interest in biomolecular radiation damage. This is reflected by the disparate backgrounds of the authors of the papers presented in these proceedings

  15. Heavy ion linear accelerator for radiation damage studies of materials

    Energy Technology Data Exchange (ETDEWEB)

    Kutsaev, Sergey V.; Mustapha, Brahim; Ostroumov, Peter N.; Nolen, Jerry; Barcikowski, Albert; Pellin, Michael; Yacout, Abdellatif

    2017-03-01

    A new eXtreme MATerial (XMAT) research facility is being proposed at Argonne National Laboratory to enable rapid in situ mesoscale bulk analysis of ion radiation damage in advanced materials and nuclear fuels. This facility combines a new heavy-ion accelerator with the existing high-energy X-ray analysis capability of the Argonne Advanced Photon Source. The heavy-ion accelerator and target complex will enable experimenters to emulate the environment of a nuclear reactor making possible the study of fission fragment damage in materials. Material scientists will be able to use the measured material parameters to validate computer simulation codes and extrapolate the response of the material in a nuclear reactor environment. Utilizing a new heavy-ion accelerator will provide the appropriate energies and intensities to study these effects with beam intensities which allow experiments to run over hours or days instead of years. The XMAT facility will use a CW heavy-ion accelerator capable of providing beams of any stable isotope with adjustable energy up to 1.2 MeV/u for U-238(50+) and 1.7 MeV for protons. This energy is crucial to the design since it well mimics fission fragments that provide the major portion of the damage in nuclear fuels. The energy also allows damage to be created far from the surface of the material allowing bulk radiation damage effects to be investigated. The XMAT ion linac includes an electron cyclotron resonance ion source, a normal-conducting radio-frequency quadrupole and four normal-conducting multi-gap quarter-wave resonators operating at 60.625 MHz. This paper presents the 3D multi-physics design and analysis of the accelerating structures and beam dynamics studies of the linac.

  16. Molecular dynamics modelling of radiation damage in zircon

    Science.gov (United States)

    Grechanovsky, A. E.

    2009-04-01

    Zircon (ZrSiO4) is among actinide-bearing phases which has been proposed as a crystalline confinement matrix for nuclear waste management, especially for weapon-grade plutonium and UO2 spent fuel in the USA. Zircon is also widely used in geochronology. But, with accumulating α-decay damage, zircon undergoes a radiation induced transition to an amorphous (or metamict) state. So, in the present work molecular dynamics simulations (MD simulations) of zircon structure have been performed to study radiation damage in zircon. In this technique, one simulates the propagation of an energetic particle in a system of atoms interacting via model potentials, by integrating the Newton equations of motion. Author has used version 3.09 of the DL_POLY molecular simulation package. Zircon structure containing 181944 atoms (19x19x21 unit cells) was equilibrated at 300 K for 10 ps, and one Zr atom (usually called the primary knock-on atom, PKA) was given a velocity corresponding to an implantation energy of about 20 keV. MD simulations were performed in the microcanonical ensemble that is under conditions of constant particle number, volume and energy. Results of the MD simulations show that the number of interstitials is equal to 840 atoms. This is very close (4000-5000 atoms for 70 keV recoil atom 234Th) to what is measured in the diffuse x-ray scattering and NMR experiments on amorphous metamict samples (damaged by natural irradiation) of geological age. It has been shown that the damaged structure contains several depleted regions with characteristic sized up to 2,5 nm after single event and up to 4,5 nm after three overlapping events. Furthermore, these events produce channels of depleted matter between the overlapping damaged regions. These channels provide a high-diffusivity path for radiogenic Pb (percolation effect). Loss of radiogenic Pb may result in to incorrect dating of rocks.

  17. Heavy ion linear accelerator for radiation damage studies of materials

    Science.gov (United States)

    Kutsaev, Sergey V.; Mustapha, Brahim; Ostroumov, Peter N.; Nolen, Jerry; Barcikowski, Albert; Pellin, Michael; Yacout, Abdellatif

    2017-03-01

    A new eXtreme MATerial (XMAT) research facility is being proposed at Argonne National Laboratory to enable rapid in situ mesoscale bulk analysis of ion radiation damage in advanced materials and nuclear fuels. This facility combines a new heavy-ion accelerator with the existing high-energy X-ray analysis capability of the Argonne Advanced Photon Source. The heavy-ion accelerator and target complex will enable experimenters to emulate the environment of a nuclear reactor making possible the study of fission fragment damage in materials. Material scientists will be able to use the measured material parameters to validate computer simulation codes and extrapolate the response of the material in a nuclear reactor environment. Utilizing a new heavy-ion accelerator will provide the appropriate energies and intensities to study these effects with beam intensities which allow experiments to run over hours or days instead of years. The XMAT facility will use a CW heavy-ion accelerator capable of providing beams of any stable isotope with adjustable energy up to 1.2 MeV/u for 238U50+ and 1.7 MeV for protons. This energy is crucial to the design since it well mimics fission fragments that provide the major portion of the damage in nuclear fuels. The energy also allows damage to be created far from the surface of the material allowing bulk radiation damage effects to be investigated. The XMAT ion linac includes an electron cyclotron resonance ion source, a normal-conducting radio-frequency quadrupole and four normal-conducting multi-gap quarter-wave resonators operating at 60.625 MHz. This paper presents the 3D multi-physics design and analysis of the accelerating structures and beam dynamics studies of the linac.

  18. Ionizing radiation damage to cells: effects of cell cycle redistribution.

    Science.gov (United States)

    Chen, P L; Brenner, D J; Sachs, R K

    1995-04-01

    If a population of cycling cells is exposed to a fixed dose of ionizing radiation delivered over time T, it is sometimes observed that increasing T increases the amount of cell killing. This is essentially because at first the radiation preferentially kills cells in a sensitive portion of the cycle and the surviving, more resistant cells then have time to reach more sensitive stages. We refer to this effect as population resensitization, caused by redistribution within the cell cycle. We investigate the effect theoretically by employing the McKendrick-von Foerster equation for age-structured proliferating cell populations, generalized by introducing a radiation damage term. Within our formalism, we show that population resensitization occurs whenever: (a) prior to irradiation the cell population has the stable age-distribution approached asymptotically by an unirradiated population, and (b) T is sufficiently small. Examples and other cases are outlined. The methods of Volterra integral equations, renewal theory, and positive semigroup theory are applied. The effect of varying T is evaluated by considering the ultimate amplitude of the stable age-distribution population at times much greater than both the irradiation duration and the average cell-cycle time. The main biological limitations of the formalism are the following: considering only radiation damage which is not subject to enzymatic repair or quadratic misrepair, using an overly naive method of ensuring loss of cell cycle synchrony, neglecting nonlinear effects such as density inhibition of growth, and neglecting radiatively induced perturbations of the cell cycle. Possible methods for removing these limitations are briefly discussed.

  19. Modeling Radiation Damage to Pixel Sensors in the ATLAS Detector

    CERN Document Server

    Rossini, Lorenzo; The ATLAS collaboration

    2018-01-01

    Silicon pixel detectors are at the core of the current and planned upgrade of the ATLAS detector at the Large Hadron Collider (LHC). As the closest detector component to the interaction point, these detectors will be subjected to a significant amount of radiation over their lifetime: prior to the High-Luminosity LHC (HL-LHC), the innermost layers will receive a fluence in excess of 10^15 neq/cm^2 and the HL-HLC detector upgrades must cope with an order of magnitude higher fluence integrated over their lifetimes. Simulating radiation damage is critical in order to make accurate predictions for current and future detector performance that will enable searches for new particles and forces as well as precision measurements of Standard Model particles such as the Higgs boson. We present a digitization model that includes radiation damage effects to the ATLAS pixel sensors for the first time and considers both planar and 3D sensor designs. In addition to thoroughly describing the setup, we compare predictions for b...

  20. A radiation damage repair model for normal tissues

    Science.gov (United States)

    Partridge, Mike

    2008-07-01

    A cellular Monte Carlo model describing radiation damage and repair in normal epithelial tissues is presented. The deliberately simplified model includes cell cycling, cell motility and radiation damage response (cell cycle arrest and cell death) only. Results demonstrate that the model produces a stable equilibrium system for mean cell cycle times in the range 24-96 h. Simulated irradiation of these stable equilibrium systems produced a range of responses that are shown to be consistent with experimental and clinical observation, including (i) re-epithelialization of radiation-induced lesions by a mixture of cell migration into the wound and repopulation at the periphery; (ii) observed radiosensitivity that is quantitatively consistent with both rate of induction of irreparable DNA lesions and, independently, with the observed acute oral and pharyngeal mucosal reactions to radiotherapy; (iii) an observed time between irradiation and maximum toxicity that is consistent with experimental data for skin; (iv) quantitatively accurate predictions of low-dose hyper-radiosensitivity; (v) Gomperzian repopulation for very small lesions (~2000 cells) and (vi) a linear rate of re-epithelialization of 5-10 µm h-1 for large lesions (>15 000 cells).

  1. A radiation damage repair model for normal tissues

    Energy Technology Data Exchange (ETDEWEB)

    Partridge, Mike [Institute of Cancer Research, Downs Road, Sutton, SM2 5PT (United Kingdom)

    2008-07-07

    A cellular Monte Carlo model describing radiation damage and repair in normal epithelial tissues is presented. The deliberately simplified model includes cell cycling, cell motility and radiation damage response (cell cycle arrest and cell death) only. Results demonstrate that the model produces a stable equilibrium system for mean cell cycle times in the range 24-96 h. Simulated irradiation of these stable equilibrium systems produced a range of responses that are shown to be consistent with experimental and clinical observation, including (i) re-epithelialization of radiation-induced lesions by a mixture of cell migration into the wound and repopulation at the periphery; (ii) observed radiosensitivity that is quantitatively consistent with both rate of induction of irreparable DNA lesions and, independently, with the observed acute oral and pharyngeal mucosal reactions to radiotherapy; (iii) an observed time between irradiation and maximum toxicity that is consistent with experimental data for skin; (iv) quantitatively accurate predictions of low-dose hyper-radiosensitivity; (v) Gomperzian repopulation for very small lesions ({approx}2000 cells) and (vi) a linear rate of re-epithelialization of 5-10 {mu}m h{sup -1} for large lesions (>15 000 cells)

  2. Modeling radiation damage to pixel sensors in the ATLAS detector

    CERN Document Server

    Ducourthial, Audrey; The ATLAS collaboration

    2017-01-01

    Silicon pixel detectors are at the core of the current and planned upgrade of the ATLAS detector at the Large Hadron Collider (LHC). As the closest detector component to the interaction point, these detectors will be subjected to a significant amount of radiation over their lifetime: prior to the High-Luminosity LHC (HL-LHC), the innermost layers will receive a fluence in excess of $10^{15}n_{eq}/cm^2$ and the HL-HLC detector upgrades must cope with an order of magnitude higher fluence integrated over their lifetimes. Simulating radiation damage is critical in order to make accurate predictions for current future detector performance that will enable searches for new particles and forces as well as precision measurements of Standard Model particles such as the Higgs boson. We present a digitization model that includes radiation damage effects to the ATLAS pixel sensors for the first time. In addition to thoroughly describing the setup, we present first predictions for basic pixel cluster properties alongside ...

  3. Modeling Radiation Damage to Pixel Sensors in the ATLAS Detector

    CERN Document Server

    Ducourthial, Audrey; The ATLAS collaboration

    2017-01-01

    Silicon pixel detectors are at the core of the current and planned upgrade of the ATLAS detector at the Large Hadron Collider (LHC). As the closest detector component to the interaction point, these detectors will be subjected to a significant amount of radiation over their lifetime: prior to the High-Luminosity LHC (HL-LHC), the innermost layers will receive a fluence in excess of $10^{15} n_{eq}/cm^2$ and the HL-HLC detector upgrades must cope with an order of magnitude higher fluence integrated over their lifetimes. Simulating radiation damage is critical in order to make accurate predictions for current future detector performance that will enable searches for new particles and forces as well as precision measurements of Standard Model particles such as the Higgs boson. We present a digitization model that includes radiation damage effects to the ATLAS pixel sensors for the first time. In addition to thoroughly describing the setup, we present first predictions for basic pixel cluster properties alongside...

  4. A Role for Lsm1p in Response to Ultraviolet-Radiation Damage in Saccharomyces cerevisiae

    Science.gov (United States)

    Spicakova, Tatiana; McCann, Kelly; Brown, J. Martin

    2008-01-01

    A genome-wide screen in Saccharomyces cerevisiae identified LSM1 as a new gene affecting sensitivity to ultraviolet (UV) radiation. Lsm1p is a member of a cytoplasmic complex composed of Lsm1p–7p that interacts with the yeast mRNA degradation machinery. To investigate the potential role of Lsm1p in response to UV radiation, we constructed double mutant strains in which LSM1 was deleted in combination with a representative gene from each of three known yeast DNA repair pathways. Our results show that lsm1Δ increases the UV-radiation sensitivity of the rad1Δ and rad51Δ mutants, but not the rad18Δ mutant, placing LSM1 within the post-replication repair/damage tolerance pathway (PRR). When combined with other deletions affecting PRR, lsm1Δ increases the UV-radiation sensitivity of the rev3Δ, rad30Δ and pol30-K164R mutants but not rad5Δ. Furthermore, the UV-radiation sensitivity phenotype of lsm1Δ is partially rescued by mutations in genes involved in 3′ to 5′ mRNA degradation, and mutations predicted to function in RNA interactions confer the most UV-radiation sensitivity. Together, these results suggest that Lsm1p may confer protection against UV-radiation damage by protecting the 3′ ends of mRNAs from exosome-dependent 3′ to 5′ degradation as part of a novel RAD5-mediated, PCNA-K164 ubiquitylation-independent subpathway of PRR. PMID:19024647

  5. Long-term radiation damage to a spaceborne germanium spectrometer

    CERN Document Server

    Kurczynski, P; Hull, E L; Palmer, D; Harris, M J; Seifert, H; Teegarden, B J; Gehrels, N; Cline, T L; Ramaty, R; Sheppard, D; Madden, N W; Luke, P N; Cork, C P; Landis, D A; Malone, D F; Hurley, K

    1999-01-01

    The Transient Gamma-Ray Spectrometer aboard the Wind spacecraft in deep space has observed gamma-ray bursts and solar events for four years. The germanium detector in the instrument has gradually deteriorated from exposure to the approx 10 sup 8 p/cm sup 2 /yr(>100 MeV) cosmic-ray flux. Low-energy tailing and loss of efficiency, attributed to hole trapping and conversion of the germanium from n- to p-type as a result of crystal damage, were observed. Raising the detector bias voltage ameliorated both difficulties and restored the spectrometer to working operation. Together, these observations extend our understanding of the effects of radiation damage to include the previously unsuccessfully studied regime of long-term operation in space. (author)

  6. Modeling Radiation Damage to Pixel Sensors in the ATLAS Detector

    CERN Document Server

    Nachman, Benjamin Philip; The ATLAS collaboration

    2017-01-01

    Silicon Pixel detectors are at the core of the current and planned upgrade of the ATLAS detector. As the detector in closest proximity to the interaction point, these detectors will be subjected to a significant amount of radiation over their lifetime: prior to the HL-LHC, the innermost layers will receive a fluence in excess of $10^{15}$ 1 MeV $n_\\mathrm{eq}/\\mathrm{cm}^2$ and the HL-LHC detector upgrades must cope with an order of magnitude higher fluence integrated over their lifetimes. This talk presents a digitization model that includes radiation damage effects to the ATLAS Pixel sensors for the first time. After a thorough description of the setup, predictions for basic Pixel cluster properties are presented alongside first validation studies with Run 2 collision data.

  7. Molecular dynamics simulation of radiation damage cascades in diamond

    Energy Technology Data Exchange (ETDEWEB)

    Buchan, J. T. [Department of Physics and Astronomy, Curtin University, Perth, Western Australia 6845 (Australia); Robinson, M. [Nanochemistry Research Institute, Curtin University, Perth, Western Australia 6845 (Australia); Christie, H. J.; Roach, D. L.; Ross, D. K. [Physics and Materials Research Centre, School of Computing, Science and Engineering, University of Salford, Salford, Greater Manchester M5 4WT (United Kingdom); Marks, N. A. [Department of Physics and Astronomy, Curtin University, Perth, Western Australia 6845 (Australia); Nanochemistry Research Institute, Curtin University, Perth, Western Australia 6845 (Australia)

    2015-06-28

    Radiation damage cascades in diamond are studied by molecular dynamics simulations employing the Environment Dependent Interaction Potential for carbon. Primary knock-on atom (PKA) energies up to 2.5 keV are considered and a uniformly distributed set of 25 initial PKA directions provide robust statistics. The simulations reveal the atomistic origins of radiation-resistance in diamond and provide a comprehensive computational analysis of cascade evolution and dynamics. As for the case of graphite, the atomic trajectories are found to have a fractal-like character, thermal spikes are absent and only isolated point defects are generated. Quantitative analysis shows that the instantaneous maximum kinetic energy decays exponentially with time, and that the timescale of the ballistic phase has a power-law dependence on PKA energy. Defect recombination is efficient and independent of PKA energy, with only 50% of displacements resulting in defects, superior to graphite where the same quantity is nearly 75%.

  8. Compilation of radiation damage test data cable insulating materials

    CERN Document Server

    Schönbacher, H; CERN. Geneva

    1979-01-01

    This report summarizes radiation damage test data on commercially available organic cable insulation and jacket materials: ethylene- propylene rubber, Hypalon, neoprene rubber, polyethylene, polyurethane, polyvinylchloride, silicone rubber, etc. The materials have been irradiated in a nuclear reactor to integrated absorbed doses from 5*10/sup 5/ to 5*10/sup 6/ Gy. Mechanical properties, e.g. tensile strength, elongation at break, and hardness, have been tested on irradiated and non-irradiated samples. The results are presented in the form of tables and graphs, to show the effect of the absorbed dose on the measured properties. (13 refs).

  9. Simulation of neutron radiation damage in silicon semiconductor devices.

    Energy Technology Data Exchange (ETDEWEB)

    Shadid, John Nicolas; Hoekstra, Robert John; Hennigan, Gary Lee; Castro, Joseph Pete Jr.; Fixel, Deborah A.

    2007-10-01

    A code, Charon, is described which simulates the effects that neutron damage has on silicon semiconductor devices. The code uses a stabilized, finite-element discretization of the semiconductor drift-diffusion equations. The mathematical model used to simulate semiconductor devices in both normal and radiation environments will be described. Modeling of defect complexes is accomplished by adding an additional drift-diffusion equation for each of the defect species. Additionally, details are given describing how Charon can efficiently solve very large problems using modern parallel computers. Comparison between Charon and experiment will be given, as well as comparison with results from commercially-available TCAD codes.

  10. Covariances for the 56Fe radiation damage cross sections

    Science.gov (United States)

    Simakov, Stanislav P.; Koning, Arjan; Konobeyev, Alexander Yu.

    2017-09-01

    The energy-energy and reaction-reaction covariance matrices were calculated for the n + 56Fe damage cross-sections by Total Monte Carlo method using the TENDL-2013 random files. They were represented in the ENDF-6 format and added to the unperturbed evaluation file. The uncertainties for the spectrum averaged radiation quantities in the representative fission, fusion and spallation facilities were first time assessed as 5-25%. Additional 5 to 20% have to be added to the atom displacement rate uncertainties to account for accuracy of the primary defects simulation in materials. The reaction-reaction correlation were shown to be 1% or less.

  11. Effects of radiation damage on the silicon lattice

    Science.gov (United States)

    Dumas, Katherine A.; Lowry, Lynn; Russo, O. Louis

    1987-01-01

    Silicon was irradiated with both proton and electron particle beams in order to investigate changes in the structural and optical properties of the lattice as a result of the radiation damage. Lattice expansions occurred when large strain fields (+0.34 percent) developed after 1- and 3-MeV proton bombardment. The strain was a factor of three less after 1-MeV electron irradiation. Average increases of approximately 22 meV in the 3.46-eV interband energy gap and 14 meV in the Lorentz broadening parameter were measured after the electron irradiation.

  12. Damages by radiation in glasses; Danos por radiacion en vidrios

    Energy Technology Data Exchange (ETDEWEB)

    Olguin, F.; Gutierrez, C.; Cisniega, G.; Flores, J.H.; Golzarri, J.I.; Espinoza, G. [Instituto Nacional de Investigaciones Nucleares, A.P. 18-1027, 11801 Mexico D.F. (Mexico)

    1997-07-01

    As a part of the works carried out to characterize the electrons beam from the Pelletron accelerator of the Mexican Nuclear Center aluminium-silicate glass samples were irradiated. The purpose of these irradiations is to cause alterations in the amorphous microstructure of the material by means of the creation of color centers. The population density of these defects, consequence to the irradiation, is function of the exposure time which varied from 1 to 30 minutes, with an electronic beam energy of 400 keV, doing the irradiations at free atmosphere. the obtained spectra are correlated by damage which the radiation produced. (Author)

  13. Multiscale physics of ion-induced radiation damage.

    Science.gov (United States)

    Surdutovich, Eugene; Solov'yov, A V

    2014-01-01

    This is a review of a multiscale approach to the physics of ion-beam cancer therapy, an approach suggested in order to understand the interplay of a large number of phenomena involved in the radiation damage scenario occurring on a range of temporal, spatial, and energy scales. We describe different effects that take place on different scales and play major roles in the scenario of interaction of ions with tissue. The understanding of these effects allows an assessment of relative biological effectiveness that relates the physical quantities, such as dose, to the biological values, such as the probability of cell survival. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Role of Oxidative Damage in Radiation-Induced Bone Loss

    Science.gov (United States)

    Schreurs, Ann-Sofie; Alwood, Joshua S.; Limoli, Charles L.; Globus, Ruth K.

    2014-01-01

    During prolonged spaceflight, astronauts are exposed to both microgravity and space radiation, and are at risk for increased skeletal fragility due to bone loss. Evidence from rodent experiments demonstrates that both microgravity and ionizing radiation can cause bone loss due to increased bone-resorbing osteoclasts and decreased bone-forming osteoblasts, although the underlying molecular mechanisms for these changes are not fully understood. We hypothesized that excess reactive oxidative species (ROS), produced by conditions that simulate spaceflight, alter the tight balance between osteoclast and osteoblast activities, leading to accelerated skeletal remodeling and culminating in bone loss. To test this, we used the MCAT mouse model; these transgenic mice over-express the human catalase gene targeted to mitochondria, the major organelle contributing free radicals. Catalase is an anti-oxidant that converts reactive species, hydrogen peroxide into water and oxygen. This animal model was selected as it displays extended lifespan, reduced cardiovascular disease and reduced central nervous system radio-sensitivity, consistent with elevated anti-oxidant activity conferred by the transgene. We reasoned that mice overexpressing catalase in mitochondria of osteoblast and osteoclast lineage cells would be protected from the bone loss caused by simulated spaceflight. Over-expression of human catalase localized to mitochondria caused various skeletal phenotypic changes compared to WT mice; this includes greater bone length, decreased cortical bone area and moment of inertia, and indications of altered microarchitecture. These findings indicate mitochondrial ROS are important for normal bone-remodeling and skeletal integrity. Catalase over-expression did not fully protect skeletal tissue from structural decrements caused by simulated spaceflight; however there was significant protection in terms of cellular oxidative damage (MDA levels) to the skeletal tissue. Furthermore, we

  15. Creative deaminases, self-inflicted damage, and genome evolution.

    Science.gov (United States)

    Conticello, Silvestro G

    2012-09-01

    Organisms minimize genetic damage through complex pathways of DNA repair. Yet a gene family--the AID/APOBECs--has evolved in vertebrates with the sole purpose of producing targeted damage in DNA/RNA molecules through cytosine deamination. They likely originated from deaminases involved in A>I editing in tRNAs. AID, the archetypal AID/APOBEC, is the trigger of the somatic diversification processes of the antibody genes. Its homologs may have been associated with the immune system even before the evolution of the antibody genes. The APOBEC3s, arising from duplication of AID, are involved in the restriction of exogenous/endogenous threats such as retroviruses and mobile elements. Another family member, APOBEC1, has (re)acquired the ability to target RNA while maintaining its ability to act on DNA. The AID/APOBECs have shaped the evolution of vertebrate genomes, but their ability to mutate nucleic acids is a double-edged sword: AID is a key player in lymphoproliferative diseases by triggering mutations and chromosomal translocations in B cells, and there is increasing evidence suggesting that other AID/APOBECs could be involved in cancer development as well. © 2012 New York Academy of Sciences.

  16. Clinical and experimental studies on effects of chemotherapeutic agents on radiation-induced pulmonary damage

    Energy Technology Data Exchange (ETDEWEB)

    Wadasaki, Kouichi

    1988-12-01

    Clinical and experimental studies were undertaken to evaluate the effects of chemotherapeutic agents on radiation-induced pulmonary damage. In a clinical study, one hundred patients with lung cancer were retrospectively reviewed in terms of the development of radiation pneumonitis. In the patients treated with radiation and chemotherapy except for cisplatinum, radiation pneumonitis occurred more frequently and severely than patients with radiation alone. In an experimental study, male SD rats received 15 Gy radiation to the right lungs with or without injection of chemotherapeutic agents including cisplatinum, adriamycin or peplomycin. Histological changes and hydroxyproline contents of the lungs were evaluated at 2 or 5 months after treatment. Pulmonary damage was severer in rats with radiation and drugs than those with radiation alone. However, rats with cisplatinum had less damage than those with other drugs. In conclusion, radiation-induced pulmonary damage was enhanced by administration of several chemotherapeutic agents. However, cisplatinum seemed to enhance pulmonary damage less than other drugs. (author) 77 refs.

  17. Properties and recrystallization of radiation damaged pyrochlore and titanite

    Energy Technology Data Exchange (ETDEWEB)

    Zietlow, Peter

    2016-11-02

    Radiation damage in minerals is caused by the alpha-decay of incorporated radionuclides, such as U and Th and their decay products. The effect of thermal annealing (400-1400 K) on radiation-damaged pyrochlores has been investigated by Raman scattering, X-ray powder diffraction (XRD), and combined differential scanning calorimetry/thermogravimetry (DSC/TG) (Zietlow et al., in print). The analysis of three natural radiation-damaged pyrochlore samples from Miass/Russia (6.4 wt% Th, 23.1.10{sup 18} a-decay events per gram (dpg)), Zlatoust/Russia (6.3 wt% Th, 23.1.10{sup 18} dpg), Panda Hill/Tanzania (1.6 wt% Th, 1.6.10{sup 18} dpg), and Blue River/Canada (10.5 wt% U, 115.4.10{sup 18} dpg), are compared with a crystalline reference pyrochlore from Schelingen (Germany). The type of structural recovery depends on the initial degree of radiation damage (Panda Hill 28 %, Blue River 85 %, Zlatoust and Miass 100 % according to XRD), as the recrystallization temperature increases with increasing degree of amorphization. Raman spectra indicate reordering on the local scale during annealing-induced recrystallization. As Raman modes around 800 cm{sup -1} are sensitive to radiation damage (Vandenborre and Husson 1983, Moll et al. 2011), the degree of local order was deduced from the ratio of the integrated intensities of the sum of the Raman bands between 605 and 680 cm{sup -1} devided by the sum of the integrated intensities of the bands between 810 and 860 cm{sup -1}. The most radiation damaged pyrochlores (Miass and Zlatoust) show an abrupt recovery of both, its short- (Raman) and long-range order (X-ray) between 800 and 850 K. The volume decrease upon recrystallization in Zlatoust pyrochlore was large enough to crack the sample repeatedly. In contrast, the weakly damaged pyrochlore (Panda Hill) begins to recover at considerably lower temperatures (near 500 K), extending over a temperature range of ca. 300 K, up to 800 K (Raman). The pyrochlore from Blue River shows in its

  18. Grad-Level Radiation Damage of SIO2 Detectors

    Energy Technology Data Exchange (ETDEWEB)

    Simos, N.; Atoian, G.; Ludewig, H; White, S; O' Conor, J; Mokhov, N.V.

    2009-05-04

    Radiation effects and levels to detectors. SiO{sub 2} quartz fibers of the LHC ATLAS Zero-degree Calorimeter (ZDC) anticipated to experience integrated doses of a few Grad at their closest position were exposed to 200 MeV protons and neutrons at the Brookhaven National Laboratory (BNL) Linac. Specifically, 1 mm- and 2mm-diameter quartz (GE 124) rods were exposed to direct 200 MeV protons during the first phase of exposure leading to peak integrated dose of {approx}28 Grad. Exposure to a primarily neutron flux of 1mm-diameter SiO{sub 2} fibers was also achieved with a special neutron source arrangement. In a post-irradiation analysis the quartz fiber transmittance was evaluated as a function of the absorbed dose. Dramatic degradation of the transmittance property was observed with increased radiation damage. In addition, detailed evaluation of the fibers under the microscope revealed interesting micro-structural damage features and irradiation-induced defects.

  19. Self-radiation damage in plutonium and uranium mixed dioxide

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Masato, E-mail: kato.masato@jaea.go.j [Japan Atomic Energy Agency, 4-33 Muramatu, Tokai-Mura, Naka-gun, Ibaraki 319-1194 (Japan); Komeno, Akira [Japan Atomic Energy Agency, 4-33 Muramatu, Tokai-Mura, Naka-gun, Ibaraki 319-1194 (Japan); Uno, Hiroki; Sugata, Hiromasa [Inspection Development Company, 4-33 Muramatu, Tokai-Mura, Naka-gun, Ibaraki 319-1194 (Japan); Nakae, Nobuo [Japan Atomic Energy Agency, 4-33 Muramatu, Tokai-Mura, Naka-gun, Ibaraki 319-1194 (Japan); Japan Nuclear Energy Safety Organization, TOKYU REIT Toranomon Bldg, 3-17-1, Toranomon, Minato-ku, Tokyo 105-0001 (Japan); Konashi, Kenji [Tohoku University, 2145-2, Narita, Oarai-machi, Ibaraki 311-1313 (Japan); Kashimura, Motoaki [Japan Atomic Energy Agency, 4-33 Muramatu, Tokai-Mura, Naka-gun, Ibaraki 319-1194 (Japan)

    2009-08-15

    In plutonium compounds, the lattice parameter increases due to self-radiation damage by alpha-decay of plutonium isotopes. The lattice parameter change and its thermal recovery in plutonium and uranium mixed dioxide (MOX) were studied. The lattice parameter for samples of MOX powders and pellets that had been left in the air for up to 32 years was measured. The lattice parameter increased and was saturated at about 0.29%. The change in lattice parameter was formulated as a function of self-radiation dose. Three stages in the thermal recovery of the damage were observed in temperature ranges of below 673 K, 673-1073 K and above 1073 K. The activation energies in each recovery stage were estimated to be 0.12, 0.73 and 1.2 eV, respectively, and the corresponding mechanism for each stage was considered to be the recovery of the anion Frenkel defect, the cation Frenkel defect and a defect connected with helium, respectively.

  20. Biomolecular damage induced by ionizing radiation: the direct and indirect effects of low-energy electrons on DNA.

    Science.gov (United States)

    Alizadeh, Elahe; Orlando, Thomas M; Sanche, Léon

    2015-04-01

    Many experimental and theoretical advances have recently allowed the study of direct and indirect effects of low-energy electrons (LEEs) on DNA damage. In an effort to explain how LEEs damage the human genome, researchers have focused efforts on LEE interactions with bacterial plasmids, DNA bases, sugar analogs, phosphate groups, and longer DNA moieties. Here, we summarize the current understanding of the fundamental mechanisms involved in LEE-induced damage of DNA and complex biomolecule films. Results obtained by several laboratories on films prepared and analyzed by different methods and irradiated with different electron-beam current densities and fluencies are presented. Despite varied conditions (e.g., film thicknesses and morphologies, intrinsic water content, substrate interactions, and extrinsic atmospheric compositions), comparisons show a striking resemblance in the types of damage produced and their yield functions. The potential of controlling this damage using molecular and nanoparticle targets with high LEE yields in targeted radiation-based cancer therapies is also discussed.

  1. Facilities for studying radiation damage in nonmetals during irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Levy, P.W.

    1984-08-01

    Two facilities have been developed for making optical absorption, luminescence and other measurements on a single sample before, during and after irradiation. One facility uses /sup 60/Co gamma rays and the other 0.5 to 3 MeV electrons from an accelerator. Optical relays function as spectrophotometers, luminescenc detectors, etc. All radiation sensitive components are outside of walk-in irradiation chambers; all measurement control and data recording is computerized. Irradiations are made at controlled temperatures between 5K and 900/sup 0/C. The materials studied include glasses, quartz, alkali halides (especially natural rock salt), organic crystals, etc. As determined from color center measurements the damage formation rate in all materials studied at 25/sup 0/C or above is strongly temperature dependent. The defect concentration during irradiation is usually much greater than that measured after irradiation. The fraction of defects annealing after irradiation and the annealing rate usually increases as the irradiation temperature increases. The completed studies demonstrate that, in most cases, the extent of maximum damage and the damage formation and annealing kinetics can be determined only by making measurements during irradiation.

  2. Radiation damage of hollandite in multiphase ceramic waste forms

    Science.gov (United States)

    Clark, Braeden M.; Tumurgoti, Priyatham; Sundaram, S. K.; Amoroso, Jake W.; Marra, James C.; Shutthanandan, Vaithiyalingam; Tang, Ming

    2017-10-01

    Radiation damage was simulated in multiphase titanate-based ceramic waste forms using an ion accelerator to generate high energy alpha particles (He+) and an ion implanter to generate 7 MeV gold (Au3+) particles. X-ray diffraction and transmission electron microscopy were used to characterize the damaged surfaces and nearby regions. Simulated multiphase ceramic waste forms were prepared using two processing methods: spark plasma sintering and melt-processing. Both processing methods produced ceramics with similar phase assemblages consisting of hollandite-, zirconolite/pyrochlore-, and perovskite-type phases. The measured heavy ion (Au3+) penetration depth was less in spark plasma sintered samples than in melt-processed samples. Structural breakdown of the hollandite phase occurred under He+ irradiation indicated by the presence of x-ray diffraction peaks belonging to TiO2, BaTiO5, and other hollandite related phases (Ba2Ti9O20). The composition of the constituent hollandite phase affected the extent of damage induced by Au3+ ions.

  3. Imperfection and radiation damage in protein crystals studied with coherent radiation

    Energy Technology Data Exchange (ETDEWEB)

    Nave, Colin, E-mail: colin.nave@diamond.ac.uk [Diamond Light Source Ltd, Harwell Science and Innovation Campus, Didcot OX11 0DE (United Kingdom); Sutton, Geoff [Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Evans, Gwyndaf; Owen, Robin; Rau, Christoph [Diamond Light Source Ltd, Harwell Science and Innovation Campus, Didcot OX11 0DE (United Kingdom); Robinson, Ian [University College London, 17–19 Gordon Street, London WC1H 0AH (United Kingdom); Stuart, David Ian [Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Diamond Light Source Ltd, Harwell Science and Innovation Campus, Didcot OX11 0DE (United Kingdom)

    2016-01-01

    Coherent diffraction observations from polyhedra crystals at cryotemperature are reported. Information is obtained about the lattice strain and the changes with radiation damage. Fringes and speckles occur within diffraction spots when a crystal is illuminated with coherent radiation during X-ray diffraction. The additional information in these features provides insight into the imperfections in the crystal at the sub-micrometre scale. In addition, these features can provide more accurate intensity measurements (e.g. by model-based profile fitting), detwinning (by distinguishing the various components), phasing (by exploiting sampling of the molecular transform) and refinement (by distinguishing regions with different unit-cell parameters). In order to exploit these potential benefits, the features due to coherent diffraction have to be recorded and any change due to radiation damage properly modelled. Initial results from recording coherent diffraction at cryotemperatures from polyhedrin crystals of approximately 2 µm in size are described. These measurements allowed information about the type of crystal imperfections to be obtained at the sub-micrometre level, together with the changes due to radiation damage.

  4. The repair mechanism for radiation damages by inorganic elements

    Energy Technology Data Exchange (ETDEWEB)

    Ogata, Hiromitsu; Yamaguchi, Ichiro; Izumo, Yoshiro [Institute of Public Health, Tokyo (Japan). Dept. of Radiological Health

    2000-02-01

    Previous studies of the authors showed that the death rate for mice after radiation exposure at a sub-lethal dose was significantly decreased by administration of a large amount of inorganic element such as Zn, Co, Mn, Mg, etc. Here, the cellular metabolism of Co element was investigated to elucidate the mechanism of such repair of radiation damages. The incorporation of {sup 57}-Co into the mouse spleen and bone marrow cells in vitro exposed to X-ray was compared to that into both cells from the mouse in vivo exposed to X-ray. The administration of Co carrier into the cells from unexposed mice increased the incorporation of Co into these cells and there were no differences in Co-incorporation between the cells exposed to radiation in vitro and in vivo. The Co-incorporation into the bone marrow cells was dose-dependently increased by either of in vitro and in vivo exposure, suggesting that there exists some cellular defense mechanism. For in vivo exposure, the amount of Co incorporation and also DNA synthesizing activity in spleen and bone marrow cells both decreased as increasing the amount of Co subcutaneously injected, but not given to the culture medium. To clarify cellular distribution of Co incorporated, the cells suspension was homogenized and centrifuged for cell fractionation. About 80% of incorporated Co was found in the cytoplasmic fraction and the other was in the membrane fraction, suggesting that Co element might be incorporated into some cellular components. (M.N.)

  5. Mitigating radiation damage of single photon detectors for space applications

    Energy Technology Data Exchange (ETDEWEB)

    Anisimova, Elena; Higgins, Brendon L.; Bourgoin, Jean-Philippe [University of Waterloo, Institute for Quantum Computing, Waterloo, ON (Canada); University of Waterloo, Department of Physics and Astronomy, Waterloo, ON (Canada); Cranmer, Miles [University of Waterloo, Institute for Quantum Computing, Waterloo, ON (Canada); Choi, Eric [University of Waterloo, Institute for Quantum Computing, Waterloo, ON (Canada); Magellan Aerospace, Ottawa, ON (Canada); Hudson, Danya; Piche, Louis P.; Scott, Alan [Honeywell Aerospace (formerly COM DEV Ltd.), Ottawa, ON (Canada); Makarov, Vadim [University of Waterloo, Institute for Quantum Computing, Waterloo, ON (Canada); University of Waterloo, Department of Physics and Astronomy, Waterloo, ON (Canada); University of Waterloo, Department of Electrical and Computer Engineering, Waterloo, ON (Canada); Jennewein, Thomas [University of Waterloo, Institute for Quantum Computing, Waterloo, ON (Canada); University of Waterloo, Department of Physics and Astronomy, Waterloo, ON (Canada); Canadian Institute for Advanced Research, Quantum Information Science Program, Toronto, ON (Canada)

    2017-12-15

    Single-photon detectors in space must retain useful performance characteristics despite being bombarded with sub-atomic particles. Mitigating the effects of this space radiation is vital to enabling new space applications which require high-fidelity single-photon detection. To this end, we conducted proton radiation tests of various models of avalanche photodiodes (APDs) and one model of photomultiplier tube potentially suitable for satellite-based quantum communications. The samples were irradiated with 106 MeV protons at doses approximately equivalent to lifetimes of 0.6, 6, 12 and 24 months in a low-Earth polar orbit. Although most detection properties were preserved, including efficiency, timing jitter and afterpulsing probability, all APD samples demonstrated significant increases in dark count rate (DCR) due to radiation-induced damage, many orders of magnitude higher than the 200 counts per second (cps) required for ground-to-satellite quantum communications. We then successfully demonstrated the mitigation of this DCR degradation through the use of deep cooling, to as low as -86 C. This achieved DCR below the required 200 cps over the 24 months orbit duration. DCR was further reduced by thermal annealing at temperatures of +50 to +100 C. (orig.)

  6. Rosiglitazone attenuates pulmonary fibrosis and radiation-induced intestinal damage

    Energy Technology Data Exchange (ETDEWEB)

    Mangoni, M.; Gerini, C.; Sottili, M.; Cassani, S.; Stefania, G.; Biti, G. [Radiotherapy Unit, Clinical Physiopathology Department, University of Florence, Firenze (Italy); Castiglione, F. [Department of Human Pathology and Oncology, University of Florence, Firenze (Italy); Vanzi, E.; Bottoncetti, A.; Pupi, A. [Nuclear Medicine Unit, Clinical Physiopathology Department, University of Florence, Firenze (Italy)

    2011-10-15

    Full text of publication follows: Purpose.-The aim of the study was to evaluate radioprotective effect of rosiglitazone (RGZ) on a murine model of late pulmonary damage and of acute intestinal damage. Methods.- Lung fibrosis: C57 mice were treated with the radiomimetic agent bleomycin, with or without rosiglitazone (5 mg/kg/day). To obtain an independent qualitative and quantitative measure for lung fibrosis we used high resolution CT, performed twice a week during the entire observation period. Hounsfield Units (HU) of section slides from the upper and lower lung region were determined. On day 31 lungs were collected for histological analysis. Acute intestinal damage: mice underwent 12 Gy total body irradiation with or without rosiglitazone. Mice were sacrificed 24 or 72 h after total body irradiation and ileum and colon were collected. Results.- Lung fibrosis: after bleomycin treatment, mice showed typical CT features of lung fibrosis, including irregular septal thickening and patchy peripheral reticular abnormalities. Accordingly, HU lung density was dramatically increased. Rosiglitazone markedly attenuated the radiological signs of fibrosis and strongly inhibited HU lung density increase (60% inhibition at the end of the observation period). Histological analysis revealed that in bleomycin-treated mice, fibrosis involved 50-55% of pulmonary parenchyma and caused an alteration of the alveolar structures in 10% of parenchyma, while in rosiglitazone-treated mice, fibrosis involved only 20-25% of pulmonary parenchyma, without alterations of the alveolar structures. Acute intestinal damage: 24 h after 12 Gy of total body irradiation intestinal mucosa showed villi shortening, mucosal thickness and crypt necrotic changes. Rosiglitazone showed a histological improvement of tissue structure, with villi and crypts normalization and oedema reduction. Conclusion.- These results demonstrate that rosiglitazone displays a protective effect on pulmonary fibrosis and radiation

  7. Chromatin Dynamics in Genome Stability: Roles in Suppressing Endogenous DNA Damage and Facilitating DNA Repair

    Directory of Open Access Journals (Sweden)

    Nidhi Nair

    2017-07-01

    Full Text Available Genomic DNA is compacted into chromatin through packaging with histone and non-histone proteins. Importantly, DNA accessibility is dynamically regulated to ensure genome stability. This is exemplified in the response to DNA damage where chromatin relaxation near genomic lesions serves to promote access of relevant enzymes to specific DNA regions for signaling and repair. Furthermore, recent data highlight genome maintenance roles of chromatin through the regulation of endogenous DNA-templated processes including transcription and replication. Here, we review research that shows the importance of chromatin structure regulation in maintaining genome integrity by multiple mechanisms including facilitating DNA repair and directly suppressing endogenous DNA damage.

  8. Computer simulations of radiation damage in protein crystals; Simulationsrechnungen zu Strahlenschaeden an Proteinkristallen

    Energy Technology Data Exchange (ETDEWEB)

    Zehnder, M.

    2007-03-15

    The achievable resolution and the quality of the dataset of an intensity data collection for structure analysis of protein crystals with X-rays is limited among other factors by radiation damage. The aim of this work is to obtain a better quantitative understanding of the radiation damage process in proteins. Since radiation damage is unavoidable it was intended to look for the optimum ratio between elastically scattered intensity and radiation damage. Using a Monte Carlo algorithm physical processes after an inelastic photon interaction are studied. The main radiation damage consists of ionizations of the atoms through the electron cascade following any inelastic photon interaction. Results of the method introduced in this investigation and results of an earlier theoretical studies of the influence of Auger-electron transport in diamond are in a good agreement. The dependence of the radiation damage as a function of the energy of the incident photon was studied by computer-aided simulations. The optimum energy range for diffraction experiments on the protein myoglobin is 10-40 keV. Studies of radiation damage as a function of crystal volume and shape revealed that very small plate or rod shaped crystals suffer less damage than crystals formed like a cube with the same volume. Furthermore the influence of a few heavy atoms in the protein molecule on radiation damage was examined. Already two iron atoms in the unit cell of myoglobin increase radiation damage significantly. (orig.)

  9. Non-targeted and delayed effects of exposure to ionizing radiation: II. Radiation-induced genomic instability and bystander effects in vivo, clastogenic factors and transgenerational effects

    Science.gov (United States)

    Morgan, William F.

    2003-01-01

    The goal of this review is to summarize the evidence for non-targeted and delayed effects of exposure to ionizing radiation in vivo. Currently, human health risks associated with radiation exposures are based primarily on the assumption that the detrimental effects of radiation occur in irradiated cells. Over the years a number of non-targeted effects of radiation exposure in vivo have been described that challenge this concept. These include radiation-induced genomic instability, bystander effects, clastogenic factors produced in plasma from irradiated individuals that can cause chromosomal damage when cultured with nonirradiated cells, and transgenerational effects of parental irradiation that can manifest in the progeny. These effects pose new challenges to evaluating the risk(s) associated with radiation exposure and understanding radiation-induced carcinogenesis.

  10. Application to radiation damage simulation calculation of Monte Carlo method

    Energy Technology Data Exchange (ETDEWEB)

    Aruga, Takeo [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    2001-01-01

    Recent progress in Monte Carlo calculation for radiation damage simulation of structural materials to be used in fast breeder reactors or thermonuclear fusion reactors under energetic neutron or charged particle bombardment is reviewed. Specifically usefulness of employing Monte Carlo methods in molecular dynamics calculations to understand mechanical properties change such as dimensional change, strength, creep, fatigue, corrosion, and crack growth of materials under irradiation on the basis of atomic collision processes is stressed. Structure and spatial distribution of point defects in iron, gold, or cooper as demonstrative examples at several hundreds of ps after the movement of primary knock-on atom (PKA) takes place are calculated as a function of PKA energy. The results are compared with those obtained by the method developed by Norgett, Robinson and Torrens and the usefulness is discussed. (S. Ohno)

  11. Ultraviolet radiation-mediated damage to cellular DNA

    Energy Technology Data Exchange (ETDEWEB)

    Cadet, Jean [Laboratoire Lesions des Acides Nucleiques, Service de Chimie Inorganique et Biologique, CEA/DSM/Departement de Recherche Fondamentale sur la Matiere Condensee, CEA-Grenoble, 17, Av. des Martyrs, Grenoble Cedex 9 F-38054 (France)]. E-mail: jcadet@cea.fr; Sage, Evelyne [Institut Curie, CNRS/IC UMR 2027, Centre Universitaire, Orsay (France); Douki, Thierry [Laboratoire Lesions des Acides Nucleiques, Service de Chimie Inorganique et Biologique, CEA/DSM/Departement de Recherche Fondamentale sur la Matiere Condensee, CEA-Grenoble, 17, Av. des Martyrs, Grenoble Cedex 9 F-38054 (France)

    2005-04-01

    Emphasis is placed in this review article on recent aspects of the photochemistry of cellular DNA in which both the UVB and UVA components of solar radiation are implicated individually or synergistically. Interestingly, further mechanistic insights into the UV-induced formation of DNA photoproducts were gained from the application of new accurate and sensitive chromatographic and enzymic assays aimed at measuring base damage. Thus, each of the twelve possible dimeric photoproducts that are produced at the four main bipyrimidine sites can now be singled out as dinucleoside monophosphates that are enzymatically released from UV-irradiated DNA. This was achieved using a recently developed high-performance liquid chromatography-tandem mass spectrometry assay (HPLC-MS/MS) assay after DNA extraction and appropriate enzymic digestion. Interestingly, a similar photoproduct distribution pattern is observed in both isolated and cellular DNA upon exposure to low doses of either UVC or UVB radiation. This applies more specifically to the DNA of rodent and human cells, the cis-syn cyclobutadithymine being predominant over the two other main photolesions, namely thymine-cytosine pyrimidine (6-4) pyrimidone adduct and the related cyclobutyl dimer. UVA-irradiation was found to generate cyclobutane dimers at TT and to a lower extent at TC sites as a likely result of energy transfer mechanism involving still unknown photoexcited chromophore(s). Oxidative damage to DNA is also induced although less efficiently by UVA-mediated photosensitization processes that mostly involved {sup 1}O{sub 2} together with a smaller contribution of hydroxyl radical-mediated reactions through initially generated superoxide radicals.

  12. Evaluating experimental molecular physics studies of radiation damage in DNA*

    Science.gov (United States)

    Śmiałek, Małgorzata A.

    2016-11-01

    The field of Atomic and Molecular Physics (AMP) is a mature field exploring the spectroscopy, excitation, ionisation of atoms and molecules in all three phases. Understanding of the spectroscopy and collisional dynamics of AMP has been fundamental to the development and application of quantum mechanics and is applied across a broad range of disparate disciplines including atmospheric sciences, astrochemistry, combustion and environmental science, and in central to core technologies such as semiconductor fabrications, nanotechnology and plasma processing. In recent years the molecular physics also started significantly contributing to the area of the radiation damage at molecular level and thus cancer therapy improvement through both experimental and theoretical advances, developing new damage measurement and analysis techniques. It is therefore worth to summarise and highlight the most prominent findings from the AMP community that contribute towards better understanding of the fundamental processes in biologically-relevant systems as well as to comment on the experimental challenges that were met for more complex investigation targets. Contribution to the Topical Issue "Low-Energy Interactions related to Atmospheric and Extreme Conditions", edited by S. Ptasinska, M. Smialek-Telega, A. Milosavljevic, B. Sivaraman.

  13. Radiation damage in proton-irradiated epitaxial silicon detectors

    Energy Technology Data Exchange (ETDEWEB)

    Lange, Joern

    2009-07-15

    In this work radiation hardness of 75 {mu}m, 100 {mu}m and 150 {mu}m thick epitaxial silicon pad diodes of both standard and oxygenated material was investigated. Damage after 24 GeV/c proton irradiation in a 1MeV neutron equivalent fluence range between 10{sup 14} cm{sup -2} and 10{sup 16} cm{sup -2} was studied and isothermal annealing experiments at 80 C were carried out. Standard CV/IV measurements could be performed up to 4 x 10{sup 15} cm{sup -2}. The volume-normalised reverse current was found to increase linearly with fluence with a slope independent of the thickness and impurity concentration. However, due to large fluctuations the fluences had to be renormalised using the current-related damage parameter. Concerning the depletion voltage, nearly all materials remained at a moderate level up to 4 x 10{sup 15} cm{sup -2}. During short-term annealing acceptors annealed out, whereas others were introduced during the long-term annealing. The stable damage was characterised by donor removal at low fluences and fluence-proportional predominant donor introduction for highly irradiated diodes, depending on the oxygen level. No type inversion was observed. Time-resolved measurements with a new 670 nm laser-TCT setup made the determination of the trapping time constant with the charge correction method possible. The results agreed with expectations and showed a linear increase of trapping probability with fluence. The electric field exhibited a double peak structure in highly irradiated diodes. Charge collection efficiency measurements with {alpha}-particles were independent of oxygen concentration, but showed an improved efficiency for thinner diodes. A comparison to simulation revealed systematic discrepancies. A non-constant trapping time parameter was proposed as possible solution. (orig.)

  14. Study of the radiation damage of silicon photomultipliers

    Energy Technology Data Exchange (ETDEWEB)

    Nitschke, Michael; Chmill, Valery; Garutti, Erika; Klanner, Robert; Schwandt, Joern [Institute for Experimental Physics, Hamburg University, Luruper Chaussee 149, D-22761 Hamburg (Germany)

    2016-07-01

    Radiation damage significantly changes the performance of silicon photomultipliers (SiPM). In this work, we first have characterized KETEK SiPMs with a pixel size of 15 x 15 μm{sup 2} using I-V (current-voltage), C/G-V/f (capacitance/impedance-voltage/frequency) and Q-V (charge-voltage) measurements with and without illumination with blue light of 470 nm from an LED. The SiPM parameters determined are DCR (dark count rate), relative PDE (photon detection efficiency), G (Gain), XT (cross-talk), Geiger breakdown characteristics, C{sub pix} (pixel capacitance) and R{sub q} (quenching resistance). Following this first characterization, the SiPMs were irradiated using reactor neutrons with fluences of 10{sup 9}, 10{sup 10}, 10{sup 11}, 5 . 10{sup 11}, and 10{sup 12} n/cm{sup 2}. Afterwards, the same measurements were repeated, and the dependence of the SiPM parameters on neutron fluence was determined. The results are used to optimize the radiation tolerance of SiPMs.

  15. Energy Dependence of Proton Radiation Damage in Si-Sensors

    CERN Document Server

    AUTHOR|(CDS)2084399; Neubüser, C.

    2014-01-01

    Irradiation experiments on silicon sensors are used to mimic the radiation environment at collider experiments with the aim to forecast the change of the electrical properties of a detector with irradiation. Measurements on irradiated sensors are invaluable in choosing a material well suited for a silicon tracking detector. This is especially true for the upgraded detectors to be used in the high-luminosity phase of the LHC (HL-LHC), where silicon sensors as currently used would suffer severe loss in signal from irradiation with charged and neutral hadrons.\\\\ The CMS Tracker Collaboration has initiated irradiation studies with protons with energies ranging from 23 MeV to 23 GeV. They are often used instead of charged hadrons, their radiation induced damage to the silicon being rather similar. However, in oxygen rich silicon, NIEL violation concerning the full depletion voltage has been observed.\\\\ In this paper results from investigations on bulk defects compared to the change of the electrical properties of ...

  16. Effects of lactic bacteria on immunological activation and radiation damage

    Energy Technology Data Exchange (ETDEWEB)

    Monzen, Hajime; Yuki, Rumio [Otsu Red Cross Hospital, Shiga (Japan); Gu, Yeunhwa; Hasegawa, Takeo [Suzuka Univ. of Medical Science, Mie (Japan). Graduate School

    2003-03-01

    Although some studies have suggested that certain substances, such as vitamins and glucan, found in natural food products may have protective effect against radiation injuries, no substance is used practically as radioprotectors. Safe radioprotectors without side effects are, however, yet to see. Enterococcus faecalis (Ef) in intestines is known to enhance immunity of the host as a biological response modifier. In this report, we have examined the radiation protection effect of Ef using C3H mice and assessed the effect of Ef on the natural killer (NK) cells activity of the splenic cells in the mice. Less body weight losses after irradiation were observed among Ef injection groups, in comparison with control groups. Our data showed a strong tendency to prolong the surviving fraction among the groups with the Ef injection. Hence, the Ef treatment appeared to have protected mucosal damage caused by the X-ray irradiation. The NK cells activities were markedly enhanced after the Ef injection as well. With the evidence mentioned above, we conclude that the Ef may have positive effect on patients who undergo a radiotherapy. (author)

  17. Radiation Damage and Fission Product Release in Zirconium Nitride

    Energy Technology Data Exchange (ETDEWEB)

    Egeland, Gerald W. [New Mexico Inst. of Mining and Technology, Socorro, NM (United States)

    2005-08-29

    Zirconium nitride is a material of interest to the AFCI program due to some of its particular properties, such as its high melting point, strength and thermal conductivity. It is to be used as an inert matrix or diluent with a nuclear fuel based on transuranics. As such, it must sustain not only high temperatures, but also continuous irradiation from fission and decay products. This study addresses the issues of irradiation damage and fission product retention in zirconium nitride through an assessment of defects that are produced, how they react, and how predictions can be made as to the overall lifespan of the complete nuclear fuel package. Ion irradiation experiments are a standard method for producing radiation damage to a surface for observation. Cryogenic irradiations are performed to produce the maximum accumulation of defects, while elevated temperature irradiations may be used to allow defects to migrate and react to form clusters and loops. Cross-sectional transmission electron microscopy and grazing-incidence x-ray diffractometry were used in evaluating the effects that irradiation has on the crystal structure and microstructure of the material. Other techniques were employed to evaluate physical effects, such as nanoindentation and helium release measurements. Results of the irradiations showed that, at cryogenic temperatures, ZrN withstood over 200 displacements per atom without amorphization. No significant change to the lattice or microstructure was observed. At elevated temperatures, the large amount of damage showed mobility, but did not anneal significantly. Defect clustering was possibly observed, yet the size was too small to evaluate, and bubble formation was not observed. Defects, specifically nitrogen vacancies, affect the mechanical behavior of ZrN dramatically. Current and previous work on dislocations shows a distinct change in slip plane, which is evidence of the bonding characteristics. The stacking-fault energy changes dramatically with

  18. Influence of XRCC1 Genetic Polymorphisms on Ionizing Radiation-Induced DNA Damage and Repair

    Directory of Open Access Journals (Sweden)

    Silvia Sterpone

    2010-01-01

    Full Text Available It is well known that ionizing radiation (IR can damage DNA through a direct action, producing single- and double-strand breaks on DNA double helix, as well as an indirect effect by generating oxygen reactive species in the cells. Mammals have evolved several and distinct DNA repair pathways in order to maintain genomic stability and avoid tumour cell transformation. This review reports important data showing a huge interindividual variability on sensitivity to IR and in susceptibility to developing cancer; this variability is principally represented by genetic polymorphisms, that is, DNA repair gene polymorphisms. In particular we have focussed on single nucleotide polymorphisms (SNPs of XRCC1, a gene that encodes for a scaffold protein involved basically in Base Excision Repair (BER. In this paper we have reported and presented recent studies that show an influence of XRCC1 variants on DNA repair capacity and susceptibility to breast cancer.

  19. An update on the mechanisms and pathophysiological consequences of genomic instability with a focus on ionizing radiation

    Directory of Open Access Journals (Sweden)

    Streffer C

    2015-12-01

    Full Text Available Christian Streffer Institute for Medical Radiobiology, University Clinics Essen, Essen, Germany Abstract: The genome of eukaryotic cells is generally instable. DNA damage occurs by endogenous processes and exogenous toxic agents. The efficient DNA repair pathways conserve the genetic information to a large extent throughout the life. However, exposure to genotoxic agents can increase the genomic instability. This phenomenon develops in a delayed manner after approximately 20 and more cell generations. It is comparatively thoroughly investigated after the exposure to ionizing radiation. The increase of genomic instability has been observed after exposures to ionizing radiation in vitro and in vivo as well as with many different types of radiation. The effect is induced over a wide dose range, and it has been found with cell death, chromosomal damage, cell transformations, mutations, double-strand breaks, malformations, and cancers. No specific chromosomes or genomic sites have been observed for such events. The increased genomic instability can be transmitted to the next generation. Possible mechanisms such as oxidative stress (mitochondria may be involved, reduced DNA repair, changes in telomeres, epigenetic effects are discussed. A second wave of oxidative stress has been observed after radiation exposures with considerably high doses as well as with cytotoxic agents at time periods when an increased genomic instability was seen. However, the increase of genomic instability also happens to much lower radiation doses. Hypoxia induces an increase of genomic instability. This effect is apparently connected with a reduction of DNA repair. Changes of telomeres appear as the most probable mechanisms for the increase of genomic instability. Syndromes have been described with a genetic predisposition for high radiosensitivity. These individuals show an increase of cancer, a deficient DNA repair, a disturbed regulation of the cell cycle, and an

  20. Radiation damage to DNA in DNA-protein complexes

    Energy Technology Data Exchange (ETDEWEB)

    Spotheim-Maurizot, M. [Centre de Biophysiqe Moleculaire, CNRS, rue C. Sadron, 45071 Orleans (France); Davidkova, M., E-mail: davidkova@ujf.cas.cz [Dept. of Radiation Dosimetry, Nuclear Physics Institute AS CR, Na Truhlarce 39/64, 18086 Prague 8 (Czech Republic)

    2011-06-03

    Graphical abstract: RADACK model: studied biomolecules of known molecular structure are located in a water volume where OH{center_dot} radicals are randomly generated. The radicals diffuse and either react with the encountered target atom or escape from the box. The model allows to assess the yields and distributions of radiolytic attack. Research highlights: {yields} Radiation-induced lesions are inhomogeneously distributed along DNA. {yields} The distribution is modulated by DNA sequence and structure. {yields} DNA radiosensitivity is modified by positively charged molecules or by proteins. {yields} Our original model RADACK accounts for these observations. - Abstract: The most aggressive product of water radiolysis, the hydroxyl (OH{center_dot}) radical, is responsible for the indirect effect of ionizing radiations on DNA in solution and aerobic conditions. According to radiolytic footprinting experiments, the resulting strand breaks and base modifications are inhomogeneously distributed along the DNA molecule irradiated free or bound to ligands (polyamines, thiols, proteins). A Monte-Carlo based model of simulation of the reaction of OH{center_dot} radicals with the macromolecules, called RADACK, allows calculating the relative probability of damage of each nucleotide of DNA irradiated alone or in complexes with proteins. RADACK calculations require the knowledge of the three dimensional structure of DNA and its complexes (determined by X-ray crystallography, NMR spectroscopy or molecular modeling). The confrontation of the calculated values with the results of the radiolytic footprinting experiments together with molecular modeling calculations show that: (1) the extent and location of the lesions are strongly dependent on the structure of DNA, which in turns is modulated by the base sequence and by the binding of proteins and (2) the regions in contact with the protein can be protected against the attack by the hydroxyl radicals via masking of the binding

  1. A FLUORESCENCE BASED ASSAY FOR DNA DAMAGE: INDUCED BY RADIATION, CHEMICALS AND ENZYMES

    Science.gov (United States)

    A simple and rapid assay to detect DNA damage is reported. This assay is based on the ability of certain dyes to fluoresce upon intercalation with dsDNA. Damage caused by ultraviolet (UV) radiation, chemicals or restriction enzymes is detected using this assay. UV radiation at...

  2. [Cellphone electromagnetic radiation damages the testicular ultrastructure of male rats].

    Science.gov (United States)

    Gao, Xiao-Hui; Hu, Hui-Rong; Ma, Xue-Lian; Chen, Jie; Zhang, Guo-Hong

    2016-06-01

    To investigate the influence of cellphone electromagnetic radiation (CER) on the testicular ultrastructure and the apoptosis of spermatogenic cells in male rats.atability, feasibility, applicability, and controllability in the construction of experimental animal models, we compared the major anatomic features of the penis of 20 adult beagle dogs with those of 10 adult men. Using microsurgical techniques, we performed cross-transplantation of the penis in the 20 (10 pairs) beagle dogs and observed the survival rate of the transplanted penises by FK506+MMF+MP immune induction. We compared the relevant indexes with those of the 10 cases of microsurgical replantation of the amputated penis. Thirty adult male SD rats were equally randomized into a 2 h CER, a 4 h CER, and a normal control group, the former two groups exposed to 30 days of 900 MHz CER for 2 and 4 hours a day, respectively, while the latter left untreated. Then the changes in the ultrastructure of the testis tissue were observed under the transmission electron microscope and the apoptosis of the spermatogenic cells was determined by TUNEL. Compared with the normal controls, the rats of the 2 h CER group showed swollen basement membrane of seminiferous tubules, separated tight junction of Sertoli cells, increased cell intervals, apparent vacuoles and medullization in some mitochondria, and increased apoptosis of spermatogenic cells, mainly the apoptosis of primary spermatocytes (P<0.05 ). In comparison with the 2 h CER group, the animals of the 4 h CER group exhibited swollen basement membrane of seminiferous tubules, more separated tight junction of Sertoli cells, wider cell intervals, incomplete membrane of spermatogonial cells, fragments of cytoplasm, nuclear pyknosis and notch, slight dilation of perinuclear space, abnormalities of intracellular mitochondria with vacuoles, fuzzy structure, and fusion or disappearance of some cristae, and increased damage of mitochondria and apoptosis of spermatogenic

  3. Development of radiation biological dosimetry and treatment of radiation-induced damaged tissue

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Chul Koo; Kim, Tae Hwan; Lee, Yun Sil [and others

    2000-04-01

    Util now, only a few methods have been developed for radiation biological dosimetry such as conventional chromosome aberration and micronucleus in peripheral blood cell. However, because these methods not only can be estimated by the expert, but also have a little limitation due to need high technique and many times in the case of radiation accident, it is very difficult to evaluate the absorbed dose of victims. Therefore, we should develop effective, easy, simple and rapid biodosimetry and its guideline(triage) to be able to be treated the victims as fast as possible. We established the apoptotic fragment assay, PCC, comet assay, and micronucleus assay which was the significant relationship between dose and cell damages to evaluate the irradiated dose as correct and rapid as possible using lymphocytes and crypt cells, and compared with chromosome dosimetry and micronucleus assay.

  4. PWO crystals for CMS electromagnetic calorimeter studies of the radiation damage kinetics

    CERN Document Server

    Drobychev, G Yu; Dormenev, V; Korzhik, M; Lecoq, P; Lopatic, A; Nédélec, P; Peigneux, J P; Sillou, D

    2005-01-01

    Kinetics of radiation damage of the PWO crystals under irradiation and recovery were studied. Crystals were irradiated with dose corresponding to average one expected in the electromagnetic calorimeter (working dose irradiation). Radiation damage and recovery were monitored through measurements of PWO optical transmission. An approach is proposed which allows evaluating the influence of the PWO crystals properties on the statistical term in the energy resolution of the electromagnetic calorimeter. The analysis also gives important information about the nature of the radiation damage mechanism in scintillation crystals. The method was used during development of technology of the mass production of radiation hard crystals and during development of methods for crystals certification

  5. Monitoring radiation damage in the LHCb Silicon Tracker

    CERN Multimedia

    Graverini, Elena

    2018-01-01

    The purpose of LHCb is to search for indirect evidence of new physics in decays of heavy hadrons. The LHCb detector is a single-arm forward spectrometer with precise silicon-strip detectors in the regions with highest particle occupancies. The non-uniform exposure of the LHCb sensors makes it an ideal laboratory to study radiation damage effects in silicon detectors. The LHCb Silicon Tracker is composed of an upstream tracker, the TT, and of the inner part of the downstream tracker (IT). Dedicated scans are regularly taken, which allow a precise measurement of the charge collection efficiency (CCE) and the calibration of the operational voltages. The measured evolution of the effective depletion voltage $V_{depl}$ is shown, and compared with the Hamburg model prediction. The magnitudes of the sensor leakage current are also analysed and compared to their expected evolution according to phenomenological models. Our results prove that both the TT and the IT will withstand normal operation until the end of the L...

  6. Unraveling Fungal Radiation Resistance Regulatory Networks through the Genome-Wide Transcriptome and Genetic Analyses of Cryptococcus neoformans

    Directory of Open Access Journals (Sweden)

    Kwang-Woo Jung

    2016-11-01

    Full Text Available The basidiomycetous fungus Cryptococcus neoformans has been known to be highly radiation resistant and has been found in fatal radioactive environments such as the damaged nuclear reactor at Chernobyl. To elucidate the mechanisms underlying the radiation resistance phenotype of C. neoformans, we identified genes affected by gamma radiation through genome-wide transcriptome analysis and characterized their functions. We found that genes involved in DNA damage repair systems were upregulated in response to gamma radiation. Particularly, deletion of recombinase RAD51 and two DNA-dependent ATPase genes, RAD54 and RDH54, increased cellular susceptibility to both gamma radiation and DNA-damaging agents. A variety of oxidative stress response genes were also upregulated. Among them, sulfiredoxin contributed to gamma radiation resistance in a peroxiredoxin/thioredoxin-independent manner. Furthermore, we found that genes involved in molecular chaperone expression, ubiquitination systems, and autophagy were induced, whereas genes involved in the biosynthesis of proteins and fatty acids/sterols were downregulated. Most importantly, we discovered a number of novel C. neoformans genes, the expression of which was modulated by gamma radiation exposure, and their deletion rendered cells susceptible to gamma radiation exposure, as well as DNA damage insults. Among these genes, we found that a unique transcription factor containing the basic leucine zipper domain, named Bdr1, served as a regulator of the gamma radiation resistance of C. neoformans by controlling expression of DNA repair genes, and its expression was regulated by the evolutionarily conserved DNA damage response protein kinase Rad53. Taken together, the current transcriptome and functional analyses contribute to the understanding of the unique molecular mechanism of the radiation-resistant fungus C. neoformans.

  7. Current ideas to reduce or salvage radiation damage to salivary glands

    NARCIS (Netherlands)

    Vissink, A; van Luijk, P; Langendijk, J A; Coppes, R P

    Radiation-induced hyposalivation is still a major problem after radiotherapy for head and neck cancer. Current and promising new thoughts to reduce or salvage radiation damage to salivary gland tissue are explored. The main cause underlying radiation-induced hyposalivation is a lack of functional

  8. Next generation testing strategy for assessment of genomic damage: A conceptual framework and considerations.

    Science.gov (United States)

    Dearfield, Kerry L; Gollapudi, B Bhaskar; Bemis, Jeffrey C; Benz, R Daniel; Douglas, George R; Elespuru, Rosalie K; Johnson, George E; Kirkland, David J; LeBaron, Matthew J; Li, Albert P; Marchetti, Francesco; Pottenger, Lynn H; Rorije, Emiel; Tanir, Jennifer Y; Thybaud, Veronique; van Benthem, Jan; Yauk, Carole L; Zeiger, Errol; Luijten, Mirjam

    2017-06-01

    For several decades, regulatory testing schemes for genetic damage have been standardized where the tests being utilized examined mutations and structural and numerical chromosomal damage. This has served the genetic toxicity community well when most of the substances being tested were amenable to such assays. The outcome from this testing is usually a dichotomous (yes/no) evaluation of test results, and in many instances, the information is only used to determine whether a substance has carcinogenic potential or not. Over the same time period, mechanisms and modes of action (MOAs) that elucidate a wider range of genomic damage involved in many adverse health outcomes have been recognized. In addition, a paradigm shift in applied genetic toxicology is moving the field toward a more quantitative dose-response analysis and point-of-departure (PoD) determination with a focus on risks to exposed humans. This is directing emphasis on genomic damage that is likely to induce changes associated with a variety of adverse health outcomes. This paradigm shift is moving the testing emphasis for genetic damage from a hazard identification only evaluation to a more comprehensive risk assessment approach that provides more insightful information for decision makers regarding the potential risk of genetic damage to exposed humans. To enable this broader context for examining genetic damage, a next generation testing strategy needs to take into account a broader, more flexible approach to testing, and ultimately modeling, of genomic damage as it relates to human exposure. This is consistent with the larger risk assessment context being used in regulatory decision making. As presented here, this flexible approach for examining genomic damage focuses on testing for relevant genomic effects that can be, as best as possible, associated with an adverse health effect. The most desired linkage for risk to humans would be changes in loci associated with human diseases, whether in somatic

  9. Lack of Genomic Instability in Bone Marrow Cells of SCID Mice Exposed Whole-Body to Low-Dose Radiation

    Directory of Open Access Journals (Sweden)

    Elbert Whorton

    2013-04-01

    Full Text Available It is clear that high-dose radiation is harmful. However, despite extensive research, assessment of potential health-risks associated with exposure to low-dose radiation (at doses below or equal to 0.1 Gy is still challenging. Recently, we reported that 0.05 Gy of 137Cs gamma rays (the existing limit for radiation-exposure in the workplace was incapable of inducing significant in vivo genomic instability (measured by the presence of late-occurring chromosomal damage at 6 months post-irradiation in bone marrow (BM cells of two mouse strains, one with constitutively high and one with intermediate levels of the repair enzyme DNA-dependent protein-kinase catalytic-subunit (DNA-PKcs. In this study, we present evidence for a lack of genomic instability in BM cells of the severely combined-immunodeficiency (SCID/J mouse (which has an extremely low-level of DNA-PKcs activity exposed whole-body to low-dose radiation (0.05 Gy. Together with our previous report, the data indicate that low-dose radiation (0.05 Gy is incapable of inducing genomic instability in vivo (regardless of the levels of DNA-PKcs activity of the exposed mice, yet higher doses of radiation (0.1 and 1 Gy do induce genomic instability in mice with intermediate and extremely low-levels of DNA-PKcs activity (indicating an important role of DNA-PKcs in DNA repair.

  10. Silymarin protects epidermal keratinocytes from ultraviolet radiation-induced apoptosis and DNA damage by nucleotide excision repair mechanism.

    Directory of Open Access Journals (Sweden)

    Santosh K Katiyar

    Full Text Available Solar ultraviolet (UV radiation is a well recognized epidemiologic risk factor for melanoma and non-melanoma skin cancers. This observation has been linked to the accumulation of UVB radiation-induced DNA lesions in cells, and that finally lead to the development of skin cancers. Earlier, we have shown that topical treatment of skin with silymarin, a plant flavanoid from milk thistle (Silybum marianum, inhibits photocarcinogenesis in mice; however it is less understood whether chemopreventive effect of silymarin is mediated through the repair of DNA lesions in skin cells and that protect the cells from apoptosis. Here, we show that treatment of normal human epidermal keratinocytes (NHEK with silymarin blocks UVB-induced apoptosis of NHEK in vitro. Silymarin reduces the amount of UVB radiation-induced DNA damage as demonstrated by reduced amounts of cyclobutane pyrimidine dimers (CPDs and as measured by comet assay, and that ultimately may lead to reduced apoptosis of NHEK. The reduction of UV radiation-induced DNA damage by silymarin appears to be related with induction of nucleotide excision repair (NER genes, because UV radiation-induced apoptosis was not blocked by silymarin in NER-deficient human fibroblasts. Cytostaining and dot-blot analysis revealed that silymarin repaired UV-induced CPDs in NER-proficient fibroblasts from a healthy individual but did not repair UV-induced CPD-positive cells in NER-deficient fibroblasts from patients suffering from xeroderma pigmentosum complementation-A disease. Similarly, immunohistochemical analysis revealed that silymarin did not reduce the number of UVB-induced sunburn/apoptotic cells in the skin of NER-deficient mice, but reduced the number of sunburn cells in their wild-type counterparts. Together, these results suggest that silymarin exert the capacity to reduce UV radiation-induced DNA damage and, thus, prevent the harmful effects of UV radiation on the genomic stability of epidermal cells.

  11. Recent radiation damage studies and developments of the Marlowe code

    Science.gov (United States)

    Ortiz, C. J.; Souidi, A.; Becquart, C. S.; Domain, C.; Hou, M.

    2014-07-01

    Radiation damage in materials relevant to applications evolves over time scales spanning from the femtosecond - the characteristic time for an atomic collision - to decades - the aging time expected for nuclear materials. The relevant kinetic energies of atoms span from thermal motion to the MeV range.The question motivating this contribution is to identify the relationship between elementary atomic displacements triggered by irradiation and the subsequent microstructural evolution of metals in the long term. The Marlowe code, based on the binary collision approximation (BCA) is used to simulate the sequences of atomic displacements generated by energetic primary recoils and the Object Kinetic Monte Carlo code LAKIMOCA, parameterized on a range of ab initio calculations, is used to predict the subsequent long-term evolution of point defect and clusters thereof. In agreement with full Molecular Dynamics, BCA displacement cascades in body-centered cubic (BCC) Fe and a face-centered cubic (FCC) Febond Nibond Cr alloy display recursive properties that are found useful for predictions in the long term.The case of defects evolution in W due to external irradiation with energetic H and He is also discussed. To this purpose, it was useful to extend the inelastic energy loss model available in Marlowe up to the Bethe regime. The last version of the Marlowe code (version 15) was delivered before message passing instructions softwares (such as MPI) were available but the structure of the code was designed in such a way to permit parallel executions within a distributed memory environment. This makes possible to obtain N different cascades simultaneously using N independent nodes without any communication between processors. The parallelization of the code using MPI was recently achieved by one author of this report (C.J.O.). Typically, the parallelized version of Marlowe allows simulating millions of displacement cascades using a limited number of processors (CPU time.

  12. Radiation-Induced Liver Damage: Correlation of Histopathology with Hepatobiliary Magnetic Resonance Imaging, a Feasibility Study

    Energy Technology Data Exchange (ETDEWEB)

    Seidensticker, Max, E-mail: max.seidensticker@med.ovgu.de [Universitätsklinik Magdeburg, Klinik für Radiologie und Nuklearmedizin (Germany); Burak, Miroslaw [Pomeranian Medical University, Department of Diagnostic Imaging and Interventional Radiology (Poland); Kalinski, Thomas [Universitätsklinik Magdeburg, Institut für Pathologie (Germany); Garlipp, Benjamin [Universitätsklinik Magdeburg, Klinik für Allgemein-, Viszeral- und Gefäßchirurgie (Germany); Koelble, Konrad [Philipps Universität Marburg, Fachbereich Medizin der, Abteilung für Neuropathologie (Germany); Wust, Peter [Charité Universitätsmedizin Berlin, Klinik für Radioonkologie und Strahlentherapie (Germany); Antweiler, Kai [Universitätsklinik Magdeburg, Institut für Biometrie und Medizinische Informatik (Germany); Seidensticker, Ricarda; Mohnike, Konrad; Pech, Maciej; Ricke, Jens [Universitätsklinik Magdeburg, Klinik für Radiologie und Nuklearmedizin (Germany)

    2015-02-15

    PurposeRadiotherapy of liver malignancies shows promising results (radioembolization, stereotactic irradiation, interstitial brachytherapy). Regardless of the route of application, a certain amount of nontumorous liver parenchyma will be collaterally damaged by radiation. The functional reserve may be significantly reduced with an impact on further treatment planning. Monitoring of radiation-induced liver damage by imaging is neither established nor validated. We performed an analysis to correlate the histopathological presence of radiation-induced liver damage with functional magnetic resonance imaging (MRI) utilizing hepatobiliary contrast media (Gd-BOPTA).MethodsPatients undergoing local high-dose-rate brachytherapy for whom a follow-up hepatobiliary MRI within 120 days after radiotherapy as well as an evaluable liver biopsy from radiation-exposed liver tissue within 7 days before MRI were retrospectively identified. Planning computed tomography (CT)/dosimetry was merged to the CT-documentation of the liver biopsy and to the MRI. Presence/absence of radiation-induced liver damage (histopathology) and Gd-BOPTA uptake (MRI) as well as the dose applied during brachytherapy at the site of tissue sampling was determined.ResultsFourteen biopsies from eight patients were evaluated. In all cases with histopathological evidence of radiation-induced liver damage (n = 11), no uptake of Gd-BOPTA was seen. In the remaining three, cases no radiation-induced liver damage but Gd-BOPTA uptake was seen. Presence of radiation-induced liver damage and absence of Gd-BOPTA uptake was correlated with a former high-dose exposition.ConclusionsAbsence of hepatobiliary MRI contrast media uptake in radiation-exposed liver parenchyma may indicate radiation-induced liver damage. Confirmatory studies are warranted.

  13. Molecular mechanisms of radiation-induced genomic instability in human cells

    Energy Technology Data Exchange (ETDEWEB)

    Liber, Howard L.

    2003-02-13

    The overall strategy was to create a series of isogenic human cell lines that differ in key elements of cell cycle checkpoint, apoptosis, or DNA repair in response to radiation-induced damage. The goal then was to quantify the fractions of cells within a population that exhibit reduced telomere lengths and relate this to the genetic background of the cell, as well as to the response to ionizing radiation. Association between telomere length and degree of genomic instability in the population is being examined for seven closely related cell lines, that vary in p53 status, bcl-2 status, or ability to repair double strand breaks. Experiments utilize gamma rays at doses of 0, 10, and 200 cGy. During this time period the effort concentrated on generating data with two cell lines. Approximately one-third of the required clones were isolated, and analyses for mutagenesis and chromosome aberrations were undertaken.

  14. Preferential repair of ionizing radiation-induced damage in the transcribed strand of an active human gene is defective in Cockayne syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Leadon, S.A. (Univ. of North Carolina, Chapel Hill, NC (United States)); Copper, P.K. (Lawrence Berkeley Lab., CA (United States))

    1993-11-15

    Cells from patients with Cockayne syndrome (CS), which are sensitive to killing by UV although overall damage removal appears normal, are specifically defective in repair of UV damage in actively transcribe genes. Because several CS strains display cross-sensitivity to killing by ionizing radiation, the authors examined whether ionizing radiation-induced damage in active genes is preferentially repaired by normal cells and whether the radiosensitivity of CS cells can be explained by a defect in this process. They found that ionizing radiation-induced damage was repaired more rapidly in the transcriptionally active metallothionein IIA (MTIIA) gene than in the inactive MTIIB gene or in the genome overall in normal cells as a result of faster repair on the transcribed strand of MTIIA. Cells of the radiosensitive CS strain CS1AN are completely defective in this strand-selective repair of ionizing radiation-induced damage, although their overall repair rate appears normal. CS3BE cells, which are intermediate in radiosensitivity, do exhibit more rapid repair of the transcribed strand but at a reduced rate compared to normal cells. Xeroderma pigmentosum complementation group A cells, which are hypersensitive to UV light because of a defect in the nucleotide excision repair pathway but do not show increased sensitivity to ionizing radiation, preferentially repair ionizing radiation-induced damage on the transcribed strand of MTIIA. Thus, the ability to rapidly repair ionizing radiation-induced damage in actively transcribing genes correlates with cell survival. The results extend the generality of preferential repair in active genes to include damage other than bulky lesions.

  15. Preferential repair of ionizing radiation-induced damage in the transcribed strand of an active human gene is defective in Cockayne syndrome.

    Science.gov (United States)

    Leadon, S A; Cooper, P K

    1993-11-15

    Cells from patients with Cockayne syndrome (CS), which are sensitive to killing by UV although overall damage removal appears normal, are specifically defective in repair of UV damage in actively transcribed genes. Because several CS strains display cross-sensitivity to killing by ionizing radiation, we examined whether ionizing radiation-induced damage in active genes is preferentially repaired by normal cells and whether the radiosensitivity of CS cells can be explained by a defect in this process. We found that ionizing radiation-induced damage was repaired more rapidly in the transcriptionally active metallothionein IIA (MTIIA) gene than in the inactive MTIIB gene or in the genome overall in normal cells as a result of faster repair on the transcribed strand of MTIIA. Cells of the radiosensitive CS strain CS1AN are completely defective in this strand-selective repair of ionizing radiation-induced damage, although their overall repair rate appears normal. CS3BE cells, which are intermediate in radiosensitivity, do exhibit more rapid repair of the transcribed strand but at a reduced rate compared to normal cells. Xeroderma pigmentosum complementation group A cells, which are hypersensitive to UV light because of a defect in the nucleotide excision repair pathway but do not show increased sensitivity to ionizing radiation, preferentially repair ionizing radiation-induced damage on the transcribed strand of MTIIA. Thus, the ability to rapidly repair ionizing radiation-induced damage in actively transcribing genes correlates with cell survival. Our results extend the generality of preferential repair in active genes to include damage other than bulky lesions.

  16. Non-Destructive Detection and Separation of Radiation Damaged Cells in Miniaturized, Inexpensive Device Project

    Data.gov (United States)

    National Aeronautics and Space Administration — There is a clear and well-identified need for rapid, efficient, non-destructive detection and isolation of radiation damaged cells. Available commercial technologies...

  17. Non-Destructive Detection and Separation of Radiation Damaged Cells in Miniaturized, Inexpensive Device Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Our objective is to develop and demonstrate a novel microfluidic device for non-destructive identification, sorting and counting of radiation damaged cells. A major...

  18. Several pathways of hydrogen peroxide action that damage the E. coli genome

    Directory of Open Access Journals (Sweden)

    Nasser Ribeiro Asad

    2004-01-01

    Full Text Available Hydrogen peroxide is an important reactive oxygen species (ROS that arises either during the aerobic respiration process or as a by-product of water radiolysis after exposure to ionizing radiation. The reaction of hydrogen peroxide with transition metals imposes on cells an oxidative stress condition that can result in damage to cell components such as proteins, lipids and principally to DNA, leading to mutagenesis and cell death. Escherichia coli cells are able to deal with these adverse events via DNA repair mechanisms, which enable them to recover their genome integrity. These include base excision repair (BER, nucleotide excision repair (NER and recombinational repair. Other important defense mechanisms present in Escherichia coli are OxyR and SosRS anti-oxidant inducible pathways, which are elicited by cells to avoid the introduction of oxidative lesions by hydrogen peroxide. This review summarizes the phenomena of lethal synergism between UV irradiation (254 nm and H2O2, the cross-adaptive response between different classes of genotoxic agents and hydrogen peroxide, and the role of copper ions in the lethal response to H2O2 under low-iron conditions.

  19. Implantation of keV-energy argon clusters and radiation damage in diamond

    DEFF Research Database (Denmark)

    Popok, Vladimir; Samela, Juha; Nordlund, Kai

    2012-01-01

    We show that for impacting argon clusters, both mean projected ranges of the constituents and depths of radiation damage in diamond scale linearly with momentum. The same dependence was earlier found for keV-energy cluster implantation in graphite, thus suggesting the universality of this scaling...... law. For diamond, a good agreement for the value of displacement energy for the case of cluster impact is found by comparing the calculated target sputtering and experimentally measured depth of radiation damage....

  20. Cranial Radiation Therapy and Damage to Hippocampal Neurogenesis

    Science.gov (United States)

    Monje, Michelle

    2008-01-01

    Cranial radiation therapy is associated with a progressive decline in cognitive function, prominently memory function. Impairment of hippocampal neurogenesis is thought to be an important mechanism underlying this cognitive decline. Recent work has elucidated the mechanisms of radiation-induced failure of neurogenesis. Potential therapeutic…

  1. DNA Oncogenic Virus-Induced Oxidative Stress, Genomic Damage, and Aberrant Epigenetic Alterations

    Directory of Open Access Journals (Sweden)

    Mankgopo Magdeline Kgatle

    2017-01-01

    Full Text Available Approximately 20% of human cancers is attributable to DNA oncogenic viruses such as human papillomavirus (HPV, hepatitis B virus (HBV, and Epstein-Barr virus (EBV. Unrepaired DNA damage is the most common and overlapping feature of these DNA oncogenic viruses and a source of genomic instability and tumour development. Sustained DNA damage results from unceasing production of reactive oxygen species and activation of inflammasome cascades that trigger genomic changes and increased propensity of epigenetic alterations. Accumulation of epigenetic alterations may interfere with genome-wide cellular signalling machineries and promote malignant transformation leading to cancer development. Untangling and understanding the underlying mechanisms that promote these detrimental effects remain the major objectives for ongoing research and hope for effective virus-induced cancer therapy. Here, we review current literature with an emphasis on how DNA damage influences HPV, HVB, and EBV replication and epigenetic alterations that are associated with carcinogenesis.

  2. Radiation damage in indium tin oxide (ITO) layers

    Energy Technology Data Exchange (ETDEWEB)

    Morgan, D.V. [University Coll. of Wales, Cardiff (United Kingdom). School of Electric, Electronic and System Engineering; Salehi, A. [University Coll. of Wales, Cardiff (United Kingdom). School of Electric, Electronic and System Engineering; Aliyu, Y.H. [University Coll. of Wales, Cardiff (United Kingdom). School of Electric, Electronic and System Engineering; Bunce, R.W. [University Coll. of Wales, Cardiff (United Kingdom). School of Electric, Electronic and System Engineering; Diskett, D. [Applied Physics and Electro-optics Group, Cranfield University RMCS, Shrivenham, Swindon SN6 8LA (United Kingdom)

    1995-03-15

    The effects of proton damage on transparent conducting indium tin oxide (ITO) layers were investigated by electrical and optical techniques. ITO layers were found to be highly resistant to proton damage for fluences up to 10{sup 16} ions cm{sup -2}. For fluences greater than 10{sup 16} cm{sup -2} the resistivity rises rapidly with a corresponding degradation of the transmittance. ((orig.))

  3. Nanocrystal ghosting: Extensive radiation damage in MgO induced by low-energy electrons

    Energy Technology Data Exchange (ETDEWEB)

    Frankenfield, Zackery [Department of Physics, West Chester University of PA, West Chester, PA 19382 (United States); Kane, Kenneth [Department of Physics, West Chester University of PA, West Chester, PA 19382 (United States); Current address: Department of Physics, Virginia Commonwealth University, Richmond, VA 23228 (United States); Sawyer, William H., E-mail: wsawyer@wcupa.edu [Department of Physics, West Chester University of PA, West Chester, PA 19382 (United States)

    2017-03-15

    We report direct evidence of extensive radiation damage in MgO nanocrystals due to intense bombardment (2 × 10 electrons/nm sec) by electrons with beam energies between 60 keV and 120 keV. Based upon a minimum intensity necessary to produce the observed damage, we present an explanation based on the Knotek-Feibelman process.

  4. Current ideas to reduce or salvage radiation damage to salivary glands.

    Science.gov (United States)

    Vissink, A; van Luijk, P; Langendijk, J A; Coppes, R P

    2015-01-01

    Radiation-induced hyposalivation is still a major problem after radiotherapy for head and neck cancer. Current and promising new thoughts to reduce or salvage radiation damage to salivary gland tissue are explored. The main cause underlying radiation-induced hyposalivation is a lack of functional saliva-producing acinar cells resulting from radiation-induced stem cell sterilization. Current methods to prevent that damage are radiation techniques to reduce radiation-injury to salivary gland tissue, surgical techniques to relocate salivary glands to a region receiving a lower cumulative radiation dose, and techniques to make salivary gland cells more resistant to radiation injury. These preventive techniques cannot be applied in all cases, also reduce tumor sensitivity, or do not result in a sufficient amelioration of the dryness-related complaints. Therefore, alternative methods on techniques to salvage salivary glands that are damaged by radiation are explored with promising results, such as stem cell therapies and gene transfer techniques to allow the radiation-injured salivary gland tissue to secrete water. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Genomic Damage in Endstage Renal Disease—Contribution of Uremic Toxins

    Directory of Open Access Journals (Sweden)

    Helga Stopper

    2010-10-01

    Full Text Available Patients with end-stage renal disease (ESRD, whether on conservative, peritoneal or hemodialysis therapy, have elevated genomic damage in peripheral blood lymphocytes and an increased cancer incidence, especially of the kidney. The damage is possibly due to accumulation of uremic toxins like advanced glycation endproducts or homocysteine. However, other endogenous substances with genotoxic properties, which are increased in ESRD, could be involved, such as the blood pressure regulating hormones angiotensin II and aldosterone or the inflammatory cytokine TNF-a. This review provides an overview of genomic damage observed in ESRD patients, focuses on possible underlying causes and shows modulations of the damage by modern dialysis strategies and vitamin supplementation.

  6. Integrated Microarray-based Tools for Detection of Genomic DNA Damage and Repair Mechanisms.

    Science.gov (United States)

    van Eijk, Patrick; Teng, Yumin; Bennet, Mark R; Evans, Katie E; Powell, James R; Webster, Richard M; Reed, Simon H

    2018-01-01

    The genetic information contained within the DNA molecule is highly susceptible to chemical and physical insult, caused by both endogenous and exogenous sources that can generate in the order of thousands of lesions a day in each of our cells (Lindahl, Nature 362(6422):709-715, 1993). DNA damages interfere with DNA metabolic processes such as transcription and replication and can be potent inhibitors of cell division and gene expression. To combat these regular threats to genome stability, a host of DNA repair mechanisms have evolved. When DNA lesions are left unrepaired due to defects in the repair pathway, mutations can arise that may alter the genetic information of the cell. DNA repair is thus fundamental to genome stability and defects in all the major repair pathways can lead to cancer predisposition. Therefore, the ability to accurately measure DNA damage at a genomic scale and determine the level, position, and rates of removal by DNA repair can contribute greatly to our understanding of how DNA repair in chromatin is organized throughout the genome. For this reason, we developed the 3D-DIP-Chip protocol described in this chapter. Conducting such measurements has potential applications in a variety of other fields, such as genotoxicity testing and cancer treatment using DNA damage inducing chemotherapy. Being able to detect and measure genomic DNA damage and repair patterns in individuals following treatment with chemotherapy could enable personalized medicine by predicting response to therapy.

  7. From electrons to stars : modelling and mitigation of radiation damage effects on astronomical CCDs

    NARCIS (Netherlands)

    Prod'homme, Thibaut

    2011-01-01

    The work presented in this thesis is part of an on-going effort to understand and mitigate the effects of radiation damage in astronomical CCDs. My research was motivated by and took place in the challenging context of the European Space Agency’s (ESA) astrometric mission, Gaia, for which radiation

  8. Compilation of radiation damage test data part III: materials used around high-energy accelerators

    CERN Document Server

    Beynel, P; Schönbacher, H; CERN. Geneva

    1982-01-01

    For pt.II see CERN report 79-08 (1979). This handbook gives the results of radiation damage tests on various engineering materials and components intended for installation in radiation areas of the CERN high-energy particle accelerators. It complements two previous volumes covering organic cable-insulating materials and thermoplastic and thermosetting resins.

  9. DETECTION OF LOW DOSE RADIATION INDUCED DNA DAMAGE USING TEMPERATURE DIFFERENNTIAL FLUORESENCE ASSAY

    Science.gov (United States)

    A rapid and sensitive fluorescence assay for radiation-induced DNA damage is reported. Changes in temperature-induced strand separation in both calf thymus DNA and plasmid DNA (puc 19 plasmid from Escherichia coli) were measured after exposure to low doses of radiation. Exposures...

  10. DETECTION OF LOW DOSE RADIATION INDUCED DNA DAMAGE USING TEMPERATURE DIFFERENTIAL FLUORESCENCE ASSAY

    Science.gov (United States)

    A rapid and sensitive fluorescence assay for radiation-induced DNA damage is reported. Changes in temperature-induced strand separation in both calf thymus DNA and plasmid DNA (puc 19 plasmid from Escherichia coli) were measured after exposure to low doses of radiation. Exposur...

  11. Evidence of Dopant Type-Inversion and Other Radiation Damage Effects of the CDF Silicon Detectors

    Energy Technology Data Exchange (ETDEWEB)

    Martinez-Ballarin, Roberto [Univ. of the Basque Country, Leioa (Spain)

    2010-06-01

    The aim of this document is to study the effect of radiation damage on the silicon sensors. The reflection of the effect of radiation can be observed in two fundamental parameters of the detector: the bias current and the bias voltage. The leakage current directly affects the noise, while the bias voltage is required to collect the maximum signal deposited by the charged particle.

  12. Investigations in silicate glasses. I. Radiation damage. II. Optical nonlinearity. [Gamma rays and electrons

    Energy Technology Data Exchange (ETDEWEB)

    Moran, M.J.

    1976-11-15

    The investigation of two poorly understood but technologically important physical properties of silicate glasses and related materials is described. The use of Electron Paramagnetic Resonance to investigate the nature of radiation-induced damage in glasses exposed to a variety of high-energy radiation sources is discussed first. Second, the measurement of the nonlinear index of refraction coefficient in a variety of optical materials related to the design of high-power laser systems is described. The radiation damage investigations rely heavily on the comparison of experimental results for different experimental situations. The comparison of EPR lineshapes, absolute spin densities and power saturation behavior is used to probe a variety of microscopic and macroscopic aspects of radiation damage in glasses. Comparison of radiation damage associated with exposure to gamma rays and fast neutrons (and combinations thereof) are interpreted in terms of the microscopic damage mechanisms which are expected to be associated with the specific radiations. Comparison of radiation damage behavior in different types of glasses is also interpreted in terms of the behavior expected for the specific materials. The body of data which is generated is found to be internally self-consistent and is also generally consistent with the radiation damage behavior expected for specific situations. A new and versatile technique for measuring the nonlinear index of refraction coefficient, n/sub 2/, in optical materials is described. The technique utilizes a 1 ns pulsed neodymium-glass laser system and time-resolved interferometry to determine the ratio of the coefficient n/sub 2/ of sample materials to the n/sub 2/ of CS/sub 2/. This method avoids some of the complications associated with performing absolute measurements of n/sub 2/ and allows the use of a relatively simple experimental technique. The measurements determine the nonlinear index ratios of the samples with an accuracy of about

  13. [Association of genetic polymorphism of XPD with chromosomal damage in workers exposed to radiation].

    Science.gov (United States)

    Fan, Xue-Yun; Jin, Yu-Lan; Yao, San-Qiao; Bai, Yu-Ping; Wu, Xu-Mei; Ren, Da-Wei; Pen, Jian

    2007-12-01

    To explore association genetic polymorphism of XPD with chromosomal damage in workers exposed to radiation. 182 workers exposed to radiation for at least one year with chromosomal damage were selected as cases based on a general health examination for all workers exposed to radiation in Tangshan city. The control group without chromosomal damage was matched to case by age (within 5 years), sex, work unit, type of exposed to radiation, cumulate serve length (within 1 year) according to 1:1. The micro whole blood cultivation was used for the chromosome analysis. The chromosome aberration type and rate were observed and counted. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to examine the genotype of three XPD loci (751, 312 and 156). The frequency of XPD 751 AA in cases was higher than that in controls (P 0.05). 156 mutant gene type in case group was higher than that in the control groups. The frequency of 156 A allele in case group were higher than that of the control groups (P < 0.05). The frequency of genotype with both 751AA and 156CA or 751AA and 156AA was higher in cases than that of controls (P < 0.05). XPD 751AA genotype is a possible risk factor for radiation-induced chromosomal damage. XPD 156 mutant gene type is a possible risk factor for radiation-induced chromosomal damage. Individuals with both XPD 751AA and 156 (CA+AA) genotypes are susceptible to radiation-induced chromosomal damage. No association of XPD 312 polymorphism with radiation-induced chromosomal damage is found.

  14. Proton irradiation of stem cells: Radiation damage and chemical radioprotection

    Science.gov (United States)

    Riley, R. C.; Montour, J. L.; Gurney, C. W.

    1972-01-01

    Effects of high energy protons on erythropoietic stem cells and radioprotection by chemicals were investigated in NASA Space Radiation Effects Laboratory. The effects of a parallel beam of 600 MeV protons. The fluence, when converted to dose, were referenced to the synchrocyclotron beam monitors which were then used to administer radiation exposures. Mice were given graded doses to 300 rads to determine dose-response curve. Other mice received saline, AET, or 5-hydroxytryptamine 10 to 15 minutes before exposure.

  15. Genomic instability and bystander effects induced by high-LET radiation.

    Science.gov (United States)

    Hall, Eric J; Hei, Tom K

    2003-10-13

    An understanding of the radiobiological effects of high-linear energy transfer (LET) radiation is essential for radiation protection and human risk assessment. Ever since the discovery of X-rays was made by Röntgen more than a century ago, it has always been accepted that the deleterious effects of ionizing radiation, such as mutation and carcinogenesis, are due mainly to direct damage to DNA. With the availability of a precision single-particle microbeam, it is possible to demonstrate, unequivocally, the presence of a bystander effect with many biological end points. These studies provide clear evidence that irradiated cells can induce a bystander mutagenic response in neighboring cells not directly traversed by alpha-particles, and that cell-cell communication processes play a critical role in mediating the bystander phenomenon. Following exposure to high-LET radiation, immortalized human bronchial (BEP2D) and breast (MCF-10F) cells have been shown to undergo malignant transformation through a series of successive steps, before becoming tumorigenic in nude mice. There is a progressive increase in genomic instability, determined either by gene amplification or allelic imbalance, with the highest incidence observed among established tumor cell lines, relative to transformed, nontumorigenic and control cell lines.

  16. Radiation damage in plastic detectors; Dano por radiacion en detectores plasticos

    Energy Technology Data Exchange (ETDEWEB)

    Balcazar, M. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico); Tavera, L. [UAEM, Facultad de Quimica, 50000 Toluca, Estado de Mexico (Mexico)

    2007-07-01

    Full text: The damage induced by ionizing radiation in plastics produce a wide diversity of changes in the either the whole polymer structure or a localized high destruction. The first effect is achieved by using gamma and/or electron irradiation, whereas the second is carry out by employing positive ions irradiation. The damage intensity can be controlled by the dose delivery to the plastic, in the first case and by the rate of energy loss of the incident ion in the second case. Damage deepness in the thickness of the plastic, depends of radiation energy, although, attenuation effects have to be considered for gamma and electron irradiation. This paper presents an overview of those effects, the applications for radiation dosimetry and the production of micro and nano pores, as well as the methodology for control all parameters involved in the damage. Techniques for visualization the localized high destruction in the plastics are also presented. (Author)

  17. \\title{Development of Radiation Damage Models for Irradiated Silicon Sensors Using TCAD Tools}

    CERN Document Server

    Bhardwaj, Ashutosh; Lalwani, Kavita; Ranjan, Kirti; Printz, Martin; Ranjeet, Ranjeet; Eber, Robert; Eichhorn, Thomas; Peltola, Timo Hannu Tapani

    2014-01-01

    Abstract. During the high luminosity upgrade of the LHC (HL-LHC) the CMS tracking system will face a more intense radiation environment than the present system was designed for. In order to design radiation tolerant silicon sensors for the future CMS tracker upgrade it is fundamental to complement the measurement with device simulation. This will help in both the understanding of the device performance and in the optimization of the design parameters. One of the important ingredients of the device simulation is to develop a radiation damage model incorporating both bulk and surface damage. In this paper we will discuss the development of a radiation damage model by using commercial TCAD packages (Silvaco and Synopsys), which successfully reproduce the recent measurements like leakage current, depletion voltage, interstrip capacitance and interstrip resistance, and provides an insight into the performance of irradiated silicon strip sensors.

  18. Time-scale invariances in preseismic electromagnetic radiation, magnetization and damage evolution of rocks

    Directory of Open Access Journals (Sweden)

    Y. Kawada

    2007-10-01

    Full Text Available We investigate the time-scale invariant changes in electromagnetic and mechanical energy releases prior to a rock failure or a large earthquake. The energy release processes are caused by damage evolutions such as crack propagation, motion of charged dislocation, area-enlargement of sheared asperities and repetitive creep-rate changes. Damage mechanics can be used to represent the time-scale invariant evolutions of both brittle and plastic damages. Irreversible thermodynamics applied to the damage mechanics reveals that the damage evolution produces the variations in charge, dipole and electromagnetic signals in addition to mechanical energy release, and yields the time-scale invariant patterns of Benioff electromagnetic radiation and cumulative Benioff strain-release. The irreversible thermodynamic framework of damage mechanics is also applicable to the seismo-magnetic effect, and the time-scale invariance is recognized in the remanent magnetization change associated with damage evolution prior to a rock failure.

  19. Moderate acute intake of de-alcoholised red wine, but not alcohol, is protective against radiation-induced DNA damage ex vivo-Results of a comparative in vivo intervention study in younger men

    Energy Technology Data Exchange (ETDEWEB)

    Greenrod, W. [CSIRO Health Sciences and Nutrition, Genome Health and Nutrigenomics Laboratory, PO Box 10041, Adelaide BC, SA 5000 (Australia); Department of Clinical and Experimental Pharmacology, University of Adelaide, South Australia (Australia); Stockley, C.S. [Australian Wine Research Institute, South Australia (Australia); Burcham, P. [Department of Clinical and Experimental Pharmacology, University of Adelaide, South Australia (Australia); Abbey, M. [CSIRO Health Sciences and Nutrition, Genome Health and Nutrigenomics Laboratory, PO Box 10041, Adelaide BC, SA 5000 (Australia); Fenech, M. [CSIRO Health Sciences and Nutrition, Genome Health and Nutrigenomics Laboratory, PO Box 10041, Adelaide BC, SA 5000 (Australia)]. E-mail: michael.fenech@hsn.csiro.au

    2005-12-11

    Moderate intake of wine is associated with reduced risk of cardiovascular disease and possibly cancer however it remains unclear whether the potential health benefits of wine intake are due to alcohol or the non-alcoholic fraction of wine. We therefore tested the hypothesis that the non-alcoholic fraction of wine protects against genome damage induced by oxidative stress in a crossover intervention study involving six young adult males aged 21-26 years. The participants adhered to a low plant phenolic compound diet for 48 h prior to consuming 300 mL of complete red wine, dealcoholised red wine or ethanol on separate occasions 1 week apart. Blood samples were collected 0.5, 1.0 and 2.0 h after beverage consumption. Baseline and radiation-induced genome damage was measured using the cytokinesis-block micronucleus assay and total plasma catechin concentration was measured. Consumption of dealcoholised red wine significantly decreased the gamma radiation-induced DNA damage at 1 and 2 h post-consumption by 20%. In contrast alcohol tended to increase radiation-induced genome damage and complete wine protected against radiation-induced genome damage relative to alcohol. The observed effects were only weakly correlated with the concentration of total plasma catechin (R = -0.23). These preliminary data suggest that only the non-alcoholic fraction of red wine protects DNA from oxidative damage but this effect cannot be explained solely by plasma catechin.

  20. Ionizing radiation, antioxidant response and oxidative damage: A meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Einor, D., E-mail: daniel@einor.com [Department of Biological Sciences, University of South Carolina, Columbia, SC 29208 (United States); Bonisoli-Alquati, A., E-mail: andreabonisoli@gmail.com [Department of Biological Sciences, University of South Carolina, Columbia, SC 29208 (United States); School of Renewable Natural Resources, Louisiana State University AgCenter, Baton Rouge, LA 70803 (United States); Costantini, D., E-mail: davidcostantini@libero.it [Department of Biology, University of Antwerp, Wilrijk, B-2610, Antwerp (Belgium); Mousseau, T.A., E-mail: mousseau@sc.edu [Department of Biological Sciences, University of South Carolina, Columbia, SC 29208 (United States); Faculty of Bioscience and Biotechnology, Chubu University, Kasugai (Japan); Møller, A.P., E-mail: anders.moller@u-psud.fr [Laboratoire d' Ecologie, Systématique et Evolution, CNRS UMR 8079, Université Paris-Sud, Bâtiment 362, F-91405 Orsay Cedex (France)

    2016-04-01

    One mechanism proposed as a link between exposure to ionizing radiation and detrimental effects on organisms is oxidative damage. To test this hypothesis, we surveyed the scientific literature on the effects of chronic low-dose ionizing radiation (LDIR) on antioxidant responses and oxidative damage. We found 40 publications and 212 effect sizes for antioxidant responses and 288 effect sizes for effects of oxidative damage. We performed a meta-analysis of signed and unsigned effect sizes. We found large unsigned effects for both categories (0.918 for oxidative damage; 0.973 for antioxidant response). Mean signed effect size weighted by sample size was 0.276 for oxidative damage and − 0.350 for antioxidant defenses, with significant heterogeneity among effects for both categories, implying that ionizing radiation caused small to intermediate increases in oxidative damage and small to intermediate decreases in antioxidant defenses. Our estimates are robust, as shown by very high fail-safe numbers. Species, biological matrix (tissue, blood, sperm) and age predicted the magnitude of effects for oxidative damage as well as antioxidant response. Meta-regression models showed that effect sizes for oxidative damage varied among species and age classes, while effect sizes for antioxidant responses varied among species and biological matrices. Our results are consistent with the description of mechanisms underlying pathological effects of chronic exposure to LDIR. Our results also highlight the importance of resistance to oxidative stress as one possible mechanism associated with variation in species responses to LDIR-contaminated areas. - Highlights: • There is interest in variation in metabolic effects of chronic low-dose ionizing radiation • A random effect meta-analysis of effect sizes of radioactive contamination was performed • We found significant effects of radiation on oxidative damage and antioxidant response • We found significant heterogeneity among

  1. Ion induced radiation damage on the molecular level

    NARCIS (Netherlands)

    Alvarado Chacon, Fresia

    2007-01-01

    Throughout our lives we are exposed to ionizing radiation from cosmic and environmental sources or from medical diagnostics and treatments. In conventional therapy of malignant tumors, photons or electrons are used. Nowadays we witness the introduction of proton and heavy ion beams which have a

  2. Radiation damage measurements on CZT drift strip detectors

    DEFF Research Database (Denmark)

    Kuvvetli, Irfan; Budtz-Jørgensen, Carl; Korsbech, Uffe C C

    2003-01-01

    At DSRI, in collaboration with the cyclotron facility at Copenhagen University Hospital, we have performed a study of radiation effects exposing a 2.7 mm thick CZT drift strip detector to 30 MeV protons. The detector characteristics were evaluated after exposure to a number of fluences in the ran...

  3. Unraveling Fungal Radiation Resistance Regulatory Networks through the Genome-Wide Transcriptome and Genetic Analyses of Cryptococcus neoformans.

    Science.gov (United States)

    Jung, Kwang-Woo; Yang, Dong-Hoon; Kim, Min-Kyu; Seo, Ho Seong; Lim, Sangyong; Bahn, Yong-Sun

    2016-11-29

    The basidiomycetous fungus Cryptococcus neoformans has been known to be highly radiation resistant and has been found in fatal radioactive environments such as the damaged nuclear reactor at Chernobyl. To elucidate the mechanisms underlying the radiation resistance phenotype of C. neoformans, we identified genes affected by gamma radiation through genome-wide transcriptome analysis and characterized their functions. We found that genes involved in DNA damage repair systems were upregulated in response to gamma radiation. Particularly, deletion of recombinase RAD51 and two DNA-dependent ATPase genes, RAD54 and RDH54, increased cellular susceptibility to both gamma radiation and DNA-damaging agents. A variety of oxidative stress response genes were also upregulated. Among them, sulfiredoxin contributed to gamma radiation resistance in a peroxiredoxin/thioredoxin-independent manner. Furthermore, we found that genes involved in molecular chaperone expression, ubiquitination systems, and autophagy were induced, whereas genes involved in the biosynthesis of proteins and fatty acids/sterols were downregulated. Most importantly, we discovered a number of novel C. neoformans genes, the expression of which was modulated by gamma radiation exposure, and their deletion rendered cells susceptible to gamma radiation exposure, as well as DNA damage insults. Among these genes, we found that a unique transcription factor containing the basic leucine zipper domain, named Bdr1, served as a regulator of the gamma radiation resistance of C. neoformans by controlling expression of DNA repair genes, and its expression was regulated by the evolutionarily conserved DNA damage response protein kinase Rad53. Taken together, the current transcriptome and functional analyses contribute to the understanding of the unique molecular mechanism of the radiation-resistant fungus C. neoformans IMPORTANCE: Although there are no natural environments under intense radiation, some living organisms

  4. Compensation for damage to workers health exposed to ionizing radiation in Argentina

    CERN Document Server

    Sobehart, L J

    2003-01-01

    The objective of this report is to analyze the possibility to establish a scheme to compensate damage to workers health exposed to ionizing radiation in Argentina for those cases in which it is possible to assume that the exposure to ionizing radiation is the cause of the cancer suffered by the worker. The proposed scheme is based on the recommendations set out in the 'International Conference on Occupational Radiation Protection: Protecting Workers against Exposure to Ionization Radiation, held in Geneva, Switzerland, August 26-30, 2002. To this end, the study analyzes the present state of scientific knowledge on cancer causation due to genotoxic factors, and the accepted form of the doses-response curve, for the human beings exposure to ionization radiation at low doses with low doses rates. Finally, the labor laws and regulations related to damage compensation; in particular the present Argentine Labor Law; the National Russian Federal Occupational Radiological Health Impairment and Workmen Compensation, t...

  5. X-radiation damage of hydrated lecithin membranes detected by real-time X-ray diffraction using wiggler-enhanced synchrotron radiation as the ionizing radiation source

    Science.gov (United States)

    Caffrey, Martin

    1984-05-01

    Radiation damage of hydrated lecithin membranes brought about by exposure to wiggler-derived synchrotron radiation at 8.3 keV (1.5 Å) is reported. Considerable damage was observed with exposures under 1 h at an incident flux density of 3 × 10 10 photon s -1 mm -2, corresponding to a cumulative radiation dose of ≦10 MRad. Damage was so dramatic as to be initially observed while making real-time X-ray diffraction measurements on the sample. The damaging effects of 8.3 keV X-rays on dispersions of dipalmitoyllecithin and lecithin derived from hen egg yolk are as follows: (1) marked changes were noted in the X-ray diffraction behaviour, indicating disruption of membrane stacking. (2) Chemical breakdown of lecithin was observed. (3) The X-ray beam visibly damaged the sample and changed the appearance of the lipid dispersion, when viewed under the light microscope. Considering the importance of X-ray diffraction as a structural probe and the anticipated use of synchrotron radiation in studies involving membranes, the problem of radiation damage must be duly recognized. Furthermore, since dipalmitoyllecithin, the major lipid used in the present study, is a relatively stable compound, it is not unreasonable to expect that X-ray damage may be a problem with other less stable biological and non-biological materials. These results serve to emphasize that whenever a high intensity X-ray source is used, radiation damage can be a problem and that the sensitivity of the sample must always be evaluated under the conditions of measurement.

  6. BGO radiation damage effects optical absorption, thermoluminescence and thermoconductivity

    CERN Document Server

    Lecoq, P; Rostaing, B

    1991-01-01

    After irradiation, the light transmission of bismuth germanate monocrystals decreases, mainly in the blue, as a consequence of the formation of colour centres. The absorption, thermoluminescence and thermoconductivity spectra were studied for different kinds of irradiation, different doses and at different temperatures. Doped samples were also tested, showing the role of impurities, mainly iron, in the process of damage. Finally a model is proposed which explains all the experimental results.

  7. Radiation damage in silicon. Defect analysis and detector properties

    Energy Technology Data Exchange (ETDEWEB)

    Hoenniger, F.

    2008-01-15

    Silicon microstrip and pixel detectors are vital sensor-components as particle tracking detectors for present as well as future high-energy physics (HEP) experiments. All experiments at the large Hadron Collider (LHC) are equipped with such detectors. Also for experiments after the upgrade of the LHC (the so-called Super-LHC), with its ten times higher luminosity, or the planned International Linear Collider (ILC) silicon tracking detectors are forseen. Close to the interaction region these detectors have to face harsh radiation fields with intensities above the presently tolerable level. defect engineering of the used material, e. g. oxygen enrichment of high resistivity float zone silicon and growing of thin low resistivityepitaxial layers on Czochralski silicon substrates has been established to improve the radiation hardness of silicon sensors. This thesis focuses mainly on the investigation of radiation induced defects and their differences observed in various kinds of epitaxial silicon material. Comparisons with other materials like float zone or Czochralski silicon are added. Deep Level Transient Spectroscopy (DLTS) and Thermally Stimulated Current (TSC) measurements have been performed after {gamma}-, electron-, proton- and neutron-irradiation. The differenced in the formation of vacancy and interstitial related defects as well as so-called clustered regions were investigated for various types of irradiation. In addition to the well known defects VO{sub i}, C{sub i}O{sub i}, C{sub i}C{sub s}, VP or V{sub 2} several other defect complexes have been found and investigated. Also the material dependence of the defect introduction rates and the defect annealing behavior has been studied by isothermal and isochronal annealing experiments. Especially the IO{sub 2} defect which is an indicator for the oxygen-dimer content of the material has been investigated in detail. On the basis of radiation induced defects like the bistable donor (BD) defect and a deep

  8. Genome-Wide Identification and 3D Modeling of Proteins involved in DNA Damage Recognition and Repair (Final Report)

    Energy Technology Data Exchange (ETDEWEB)

    Ruben A. Abagyan, PhD

    2004-04-15

    OAK-B135 DNA Damage Recognition and Repair (DDR and R) proteins play a critical role in cellular responses to low-dose radiation and are associated with cancer. the authors have performed a systematic, genome-wide computational analysis of genomic data for human genes involved in the DDR and R process. The significant achievements of this project include: (1) Construction of the computational pipeline for searching DDR and R genes, building and validation of 3D models of proteins involved in DDR and R; (2) Functional and structural annotation of the 3D models and generation of comprehensive lists of suggested knock-out mutations; (3) Important improvement of macromolecular docking technology and its application to predict the DNA-Protein complex conformation; (4) Development of a new algorithm for improved analysis of high-density oligonucleotide arrays for gene expression profiling; (5) Construction and maintenance of the DNA Damage Recognition and Repair Database; and (6) Producing 14 research papers (10 published and 4 in preparation).

  9. Genome-Wide Identification and 3D Modeling of Proteins involved in DNA Damage Recognition and Repair (Final Report)

    Energy Technology Data Exchange (ETDEWEB)

    Abagyan, Ruben; An, Jianghong

    2005-08-12

    DNA Damage Recognition and Repair (DDR&R) proteins play a critical role in cellular responses to low-dose radiation and are associated with cancer. We have performed a systematic, genome-wide computational analysis of genomic data for human genes involved in the DDR&R process. The significant achievements of this project include: 1) Construction of the computational pipeline for searching DDR&R genes, building and validation of 3D models of proteins involved in DDR&R; 2) Functional and structural annotation of the 3D models and generation of comprehensive lists of suggested knock-out mutations; and the development of a method to predict the effects of mutations. Large scale testing of technology to identify novel small binding pockets in protein structures leading to new DDRR inhibitor strategies 3) Improvements of macromolecular docking technology (see the CAPRI 1-3 and 4-5 results) 4) Development of a new algorithm for improved analysis of high-density oligonucleotide arrays for gene expression profiling; 5) Construction and maintenance of the DNA Damage Recognition and Repair Database; 6) Producing 15 research papers (12 published and 3 in preparation).

  10. Radiation damage in diagnostic window materials for the TFTR

    Energy Technology Data Exchange (ETDEWEB)

    Primak, W.

    1981-07-01

    The general problem of evaluating diagnostic window materials for the TFTR at the tank wall location is described. Specific evaluations are presented for several materials: vitreous silica, crystal quartz, sapphire, zinc selenide, and several fluorides: lithium fluoride, magnesium fluoride, and calcium fluoride; and seal glasses are discussed. The effects of the neutrons will be minimal. The major problems arise from the high flux of ionizing radiation, mainly the soft x rays which are absorbed near the surface of the materials. Additionally, this large energy deposition causes a significant thermal pulse with attendant thermal stresses. It is thus desirable to protect the windows with cover slips where this is feasible or to reduce the incident radiation by mounting the windows on long pipes. A more detailed summary is given at the end of this report.

  11. The 2100MHz radiofrequency radiation of a 3G-mobile phone and the DNA oxidative damage in brain.

    Science.gov (United States)

    Sahin, Duygu; Ozgur, Elcin; Guler, Goknur; Tomruk, Arın; Unlu, Ilhan; Sepici-Dinçel, Aylin; Seyhan, Nesrin

    2016-09-01

    We aimed to evaluate the effect of 2100MHz radiofrequency radiation emitted by a generator, simulating a 3G-mobile phone on the brain of rats during 10 and 40 days of exposure. The female rats were randomly divided into four groups. Group I; exposed to 3G modulated 2100MHz RFR signal for 6h/day, 5 consecutive days/wk for 2 weeks, group II; control 10 days, were kept in an inactive exposure set-up for 6h/day, 5 consecutive days/wk for 2 weeks, group III; exposed to 3G modulated 2100MHz RFR signal for 6h/day, 5 consecutive days/wk for 8 weeks and group IV; control 40 days, were kept in an inactive exposure set-up for 6h/day, 5 consecutive days/wk for 8 weeks. After the genomic DNA content of brain was extracted, oxidative DNA damage (8-hydroxy-2'deoxyguanosine, pg/mL) and malondialdehyde (MDA, nmoL/g tissue) levels were determined. Our main finding was the increased oxidative DNA damage to brain after 10 days of exposure with the decreased oxidative DNA damage following 40 days of exposure compared to their control groups. Besides decreased lipid peroxidation end product, MDA, was observed after 40 days of exposure. The measured decreased quantities of damage during the 40 days of exposure could be the means of adapted and increased DNA repair mechanisms. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Effects of radiation damage in studies of protein-DNA complexes by cryo-EM.

    Science.gov (United States)

    Mishyna, M; Volokh, O; Danilova, Ya; Gerasimova, N; Pechnikova, E; Sokolova, O S

    2017-05-01

    Nucleic acids are responsible for the storage, transfer and realization of genetic information in the cell, which provides correct development and functioning of organisms. DNA interaction with ligands ensures the safety of this information. Over the past 10 years, advances in electron microscopy and image processing allowed to obtain the structures of key DNA-protein complexes with resolution below 4Å. However, radiation damage is a limiting factor to the potentially attainable resolution in cryo-EM. The prospect and limitations of studying protein-DNA complex interactions using cryo-electron microscopy are discussed here. We reviewed the ways to minimize radiation damage in biological specimens and the possibilities of using radiation damage (so-called 'bubblegrams') to obtain additional structural information. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Evidence of radiation damage impact on material erosion in plasma environment

    Energy Technology Data Exchange (ETDEWEB)

    Khripunov, B.I., E-mail: boris@nfi.kiae.r [Russian Research Center ' Kurchatov Institute' , 123182 Kurchatov Sq., 1 Moscow (Russian Federation); Brukhanov, A.N.; Chugunov, O.K.; Gureev, V.M.; Koidan, V.S.; Kornienko, S.N.; Kuteev, B.V.; Latushkin, S.T.; Muksunov, A.M.; Petrov, V.B.; Ryazanov, A.I.; Semenov, E.V.; Smirnov, V.P.; Stolyarova, V.G.; Unezhev, V.N. [Russian Research Center ' Kurchatov Institute' , 123182 Kurchatov Sq., 1 Moscow (Russian Federation)

    2009-06-15

    Plasma facing materials in a fusion reactor will suffer from both plasma fluxes and DT-neutron irradiations. Experimental investigations have been initiated aiming at assessment of the combined effect of high-level radiation damage and plasma induced erosion on these materials. Complex modeling studies were performed on the ion cyclotron and LENTA plasma simulator at Kurchatov Institute. Carbon materials and tungsten have been irradiated with 3-5 MeV ions to reach 1-10 dpa of radiation damage. The features of irradiated materials are described. Irradiated materials response to deuterium plasma (100-250 eV D{sup +} ions) at fluence 10{sup 25} ion/m{sup 2} was studied. Deformation effect and surface microstructure modification have been observed. Evaluation of erosion rate indicated erosion enhancement for radiation-damaged materials.

  14. Radiation Damage of Polypropylene Fiber Targets in Storage Rings

    CERN Document Server

    Rohdjess, H; Bisplinghoff, J; Bollmann, R; Büsser, K; Diehl, O; Dohrmann, F; Engelhardt, H P; Eversheim, P D; Greiff, J; Gross, A; Gross-Hardt, R; Hinterberger, F; Igelbrink, M; Langkau, R; Maier, R; Mosel, F; Müller, M; Muenstermann, M; Prasuhn, D; Von Rossen, P; Scheid, H; Schirm, N; Schwandt, F; Scobel, W; Trelle, H J; Wellinghausen, A; Wiedmann, W; Woller, K; Ziegler, R

    2004-01-01

    Thin polypropylene (CH$_2$) fibers have been used for internal experiments in storage rings as an option for hydrogen targets. The change of the hydrogen content due to the radiation dose applied by the circulating proton beam has been investigated in the range $1\\cdot10^6$ to $2\\cdot10^8$~Gy at beam momenta of 1.5 to 3 GeV/c by comparing the elastic pp-scattering yield to that from inelastic p-carbon reactions. It is found that the loss of hydrogen as a function of applied dose receives contributions from a fast and a slow component.

  15. Radiation damage of polypropylene fiber targets in storage rings

    Science.gov (United States)

    Rohdjeß, H.; Albers, D.; Bisplinghoff, J.; Bollmann, R.; Büßer, K.; Diehl, O.; Dohrmann, F.; Engelhardt, H.-P.; Eversheim, P. D.; Greiff, J.; Groß, A.; Groß-Hardt, R.; Hinterberger, F.; Igelbrink, M.; Langkau, R.; Maier, R.; Mosel, F.; Müller, M.; Münstermann, M.; Prasuhn, D.; von Rossen, P.; Scheid, H.; Schirm, N.; Schwandt, F.; Scobel, W.; Trelle, H. J.; Wellinghausen, A.; Wiedmann, W.; Woller, K.; Ziegler, R.

    2006-01-01

    Thin polypropylene fibers have been used for internal experiments in storage rings as an option for hydrogen targets. The change of the hydrogen content due to the radiation dose applied by the circulating proton beam has been investigated in the range 1 × 106-2 × 108 Gy at beam momenta of 1.5-3 GeV/c by comparing the elastic pp-scattering yield to that from inelastic p-carbon reactions. It is found that the loss of hydrogen as a function of applied dose receives contributions from a fast and a slow component.

  16. Higher-Density Culture in Human Embryonic Stem Cells Results in DNA Damage and Genome Instability

    Science.gov (United States)

    Jacobs, Kurt; Zambelli, Filippo; Mertzanidou, Afroditi; Smolders, Ilse; Geens, Mieke; Nguyen, Ha Thi; Barbé, Lise; Sermon, Karen; Spits, Claudia

    2016-01-01

    Summary Human embryonic stem cells (hESC) show great promise for clinical and research applications, but their well-known proneness to genomic instability hampers the development to their full potential. Here, we demonstrate that medium acidification linked to culture density is the main cause of DNA damage and genomic alterations in hESC grown on feeder layers, and this even in the short time span of a single passage. In line with this, we show that increasing the frequency of the medium refreshments minimizes the levels of DNA damage and genetic instability. Also, we show that cells cultured on laminin-521 do not present this increase in DNA damage when grown at high density, although the (long-term) impact on their genomic stability remains to be elucidated. Our results explain the high levels of genome instability observed over the years by many laboratories worldwide, and show that the development of optimal culture conditions is key to solving this problem. PMID:26923824

  17. Complete genome sequence of Hymenobacter sp. strain PAMC26554, an ionizing radiation-resistant bacterium isolated from an Antarctic lichen.

    Science.gov (United States)

    Oh, Tae-Jin; Han, So-Ra; Ahn, Do-Hwan; Park, Hyun; Kim, Augustine Yonghwi

    2016-06-10

    A Gram-negative, rod-shaped, red-pink in color, and UV radiation-resistant bacterium Hymenobacter sp. strain PAMC26554 was isolated from Usnea sp., an Antarctic lichen, and belongs to the class of Cytophagia and the phylum of Bacteroidetes. The complete genome of Hymenobacter sp. PAMC26554 consists of one chromosome (5,244,843bp) with two plasmids (199,990bp and 6421bp). The genomic sequence indicates that Hymenobacter sp. strain PAMC26554 possesses several genes involved in the nucleotide excision repair pathway that protects damaged DNA. This complete genome information will help us to understand its adaptation and novel survival strategy in the Antarctic extreme cold environment. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Radiation Damage in Silicon Detectors Caused by Hadronic and Electromagnetic Irradiation

    CERN Document Server

    Fretwurst, E.; Stahl, J.; Pintilie, I.

    2002-01-01

    The report contains various aspects of radiation damage in silicon detectors subjected to high intensity hadron and electromagnetic irradiation. It focuses on improvements for the foreseen LHC applications, employing oxygenation of silicon wafers during detector processing (result from CERN-RD48). An updated survey on hadron induced damage is given in the first article. Several improvements are outlined especially with respect to antiannealing problems associated with detector storage during LHC maintenance periods. Open questions are outlined in the final section, among which are a full understanding of differences found between proton and neutron induced damage, process related effects changing the radiation tolerance in addition to the oxygen content and the lack of understanding the changed detector properties on the basis of damage induced point and cluster defects. In addition to float zone silicon, so far entirely used for detector fabrication,Czochralski silicon was also studied and first promising re...

  19. Graphene damage effects on radiation-resistance and configuration of copper?graphene nanocomposite under irradiation: A molecular dynamics study

    OpenAIRE

    Huang, Hai; Tang, Xiaobin; Chen, Feida; Liu, Jian; Li, Huan; Chen, Da

    2016-01-01

    Metal?graphene nanocomposite is a kind of potential radiation tolerant material. Graphene damage of the composite is inevitable within radiation environments. In this paper, two kinds of copper?graphene nanocomposite (CGNC) systems containing perfect graphene and prefabricated damage graphene, respectively, were adopted to expound the influences of graphene damage on the properties (radiation-resistance and configuration) of CGNC under irradiation by atomistic simulations. In the CGNC contain...

  20. Sestrin2 protects the myocardium against radiation-induced damage

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Yue-Can; Chi, Feng; Xing, Rui; Gao, Song; Chen, Jia-Jia; Duan, Qiong-Yu; Sun, Yu-Nan; Niu, Nan; Tang, Mei-Yue; Wu, Rong [Shengjing Hospital of China Medical University, Department of Medical Oncology, Cancer Center, Shenyang (China); Zeng, Jing [University of Washington School of Medicine, Department of Radiation Oncology, Seattle, WA (United States); Wang, Hong-Mei [Nanfang Hospital of Southern Medical University, Department of Radiation Oncology, Guangzhou (China)

    2016-05-15

    The purpose of this study was to investigate the role of Sestrin2 in response to radiation-induced injury to the heart and on the cardiomyopathy development in the mouse. Mice with genetic deletion of the Sestrin2 (Sestrin2 knockout mice [Sestrin2 KO]) and treatment with irradiation (22 or 15 Gy) were used as independent approaches to determine the role of Sestrin2. Echocardiography (before and after isoproterenol challenge) and left ventricular (LV) catheterization were performed to evaluate changes in LV dimensions and function. Masson's trichrome was used to assess myocardial fibrosis. Immunohistochemistry and Western blot were used to detect the capillary density. After 22 or 15 Gy irradiation, the LV ejection fraction (EF) was impaired in wt mice at 1 week and 4 months after irradiation when compared with sham irradiation. Compared to wt mice, Sestrin2 KO mice had significant reduction in reduced LVEF at 1 week and 4 months after irradiation. A significant increase in LV end-diastolic pressure and myocardial fibrosis and a significant decrease in capillary density were observed in irradiation-wt mice, as well as in irradiation-Sestrin2 KO mice. Sestrin2 involved in the regulation of cardiomyopathy (such as myocardial fibrosis) after irradiation. Overexpression of Sestrin2 might be useful in limiting radiation-induced myocardial injury. (orig.)

  1. Nonlinear Ultrasonic Techniques to Monitor Radiation Damage in RPV and Internal Components

    Energy Technology Data Exchange (ETDEWEB)

    Jacobs, Laurence [Georgia Inst. of Technology, Atlanta, GA (United States); Kim, Jin-Yeon [Georgia Inst. of Technology, Atlanta, GA (United States); Qu, Jisnmin [Northwestern Univ., Evanston, IL (United States); Ramuhalli, Pradeep [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Wall, Joe [Electric Power Research Inst. (EPRI), Knoxville, TN (United States)

    2015-11-02

    The objective of this research is to demonstrate that nonlinear ultrasonics (NLU) can be used to directly and quantitatively measure the remaining life in radiation damaged reactor pressure vessel (RPV) and internal components. Specific damage types to be monitored are irradiation embrittlement and irradiation assisted stress corrosion cracking (IASCC). Our vision is to develop a technique that allows operators to assess damage by making a limited number of NLU measurements in strategically selected critical reactor components during regularly scheduled outages. This measured data can then be used to determine the current condition of these key components, from which remaining useful life can be predicted. Methods to unambiguously characterize radiation related damage in reactor internals and RPVs remain elusive. NLU technology has demonstrated great potential to be used as a material sensor – a sensor that can continuously monitor a material’s damage state. The physical effect being monitored by NLU is the generation of higher harmonic frequencies in an initially monochromatic ultrasonic wave. The degree of nonlinearity is quantified with the acoustic nonlinearity parameter, β, which is an absolute, measurable material constant. Recent research has demonstrated that nonlinear ultrasound can be used to characterize material state and changes in microscale characteristics such as internal stress states, precipitate formation and dislocation densities. Radiation damage reduces the fracture toughness of RPV steels and internals, and can leave them susceptible to IASCC, which may in turn limit the lifetimes of some operating reactors. The ability to characterize radiation damage in the RPV and internals will enable nuclear operators to set operation time thresholds for vessels and prescribe and schedule replacement activities for core internals. Such a capability will allow a more clear definition of reactor safety margins. The research consists of three tasks: (1

  2. Atomic-scale modelling of primary damage and properties of radiation defects in metals

    CERN Document Server

    Osetsky, Y N

    2003-01-01

    Considerable success has been achieved in recent years in the understanding of radiation damage production in high-energy displacement cascades, the properties of the defects and evolution of radiation damage in metals. Two main reasons form the basis of this success. First, the significant increase in computing power has allowed simulation of realistic cascade energies with good statistics and relatively long-time evolution of defects to be carried out. Second, new experimental findings and corresponding theoretical calculations have allowed interpretation of a number of mechanisms and phenomena crucial for understanding and prediction of practically important radiation effects, such as void swelling, radiation growth, matrix hardening and plastic flow localisation. In this paper we review the most significant results in atomic-scale computer modelling related to these issues, mainly focusing on new achievements such as the formation of extended defect clusters, the dynamic properties of defect clusters, int...

  3. Comparison of radiation damage in silicon induced by proton and neutron irradiation

    CERN Document Server

    Ruzin, A; Glaser, M; Zanet, A; Lemeilleur, F; Watts, S

    1999-01-01

    The subject of radiation damage to Si detectors induced by 24-GeV/c protons and nuclear reactor neutrons has been studied. Detectors fabricated on single-crystal silicon enriched with various impurities have been tested. Significant differences in electrically active defects have been found between the various types of material. The results of the study suggest for the first time that the widely used nonionizing energy loss (NIEL) factors are insufficient for normalization of the electrically active damage in case of oxygen- and carbon-enriched silicon detectors. It has been found that a deliberate introduction of impurities into the semiconductor can affect the radiation hardness of silicon detectors. (16 refs).

  4. The influence of neutron radiation damage on the optical properties of plastic scintillator UPS 923A

    Science.gov (United States)

    Mthembu, Skhathisomusa; Davydov, Yuri; Baranov, Vladimir; Mellado Garcia, Bruce; Mdhluli, Joyful; Sideras-Haddad, Elias

    2017-09-01

    Plastic scintillators are vital in the reconstruction of hadronic particle energy and tracks resulting from the collision of high energy particles in the Large Hadron Collider (LHC) at CERN. These plastic scintillators are exposed to harsh radiation environments and are susceptible to radiation damage. The effects of radiation damage on the transmittance, luminescence and light yield of Ukraine polystyrene-based scintillator UPS 923A were studied. Samples were irradiated with fast neutrons, of varying energies and fluences, using the IBR-2 reactor FLNP (Frank Laboratory for Nuclear Problems) at the Joint Institute for Nuclear Research. Results show a small change in the transmittance of the higher energy visible spectrum, and a noticeable change in the light yield of the samples as a result of the damage. There is no change observed on the luminescence as a result of radiation damage at studied fluences. The doses and uences of the neutrons shall be increased and changes in optical properties as a result of the radiation shall be further studied.

  5. Spectromicroscopy of Polymers: Comparison of Radiation Damage with Electron and Photon Core Excitation Spectroscopy Techniques

    Science.gov (United States)

    Ade, H.; Smith, A. P.; Rightor, E. G.; Hitchcock, A. P.; Urquhart, S.; Leapman, R.

    1997-03-01

    Core excitation microspectroscopy has become a powerful tool for the characterization of polymeric materials due to its sensitivity to chemical functionality. However, the excitations utilized in electron energy loss spectroscopy performed in a scanning transmission electron microscope (TEM-EELS) and near edge x-ray absorption fine structure (NEXAFS) spectroscopy can introduce radiation damage and chemically modify the sample. In order to understand the radiation damage associated with TEM-EELS and NEXAFS spectroscopy we have studied the radiation damage of the common polymer poly(ethylene terephthalate) (PET) as exhibited by changes in the acquired C K-edge excitation spectra. By fitting gaussian functions to the spectral intensity changes as a function of dose, we have determined the critical radiation dose of PET for both NEXAFS spectroscopy and TEM-EELS under typical operating conditions. This critical radiation dose for TEM-EELS is found to be 1.7 ± 0.2 x 10^8 grey (1.7 ± 0.2 x 10^4 Mrad) compared to a critical radiation dose for NEXAFS spectroscopy of 1.4 ± 0.7 x 10^9 grey (1.4 ± 0.7 x 10^5 Mrad). By considering the G factors of the two techniques and the critical radiation dose, a rule of thumb was derived that indicates that with typical present operating conditions, NEXAFS spectroscopy can analyze areas 500 times smaller than TEM-EELS given the same amount of radiation damage. Work supported by: NSF Young Investigator Award (DMR-9458060) and Dow Chemical

  6. Human umbilical cord mesenchymal stem cells alleviate nasal mucosa radiation damage in a guinea pig model.

    Science.gov (United States)

    Duan, Hong-Gang; Ji, Fang; Zheng, Chun-Quan; Wang, Chun-Hua; Li, Jing

    2015-02-01

    Nasal complications after radiotherapy severely affect the quality of life of nasopharyngeal carcinoma patients, and there is a compelling need to find novel therapies for nasal epithelial cell radiation damage. Therefore, we investigated the therapeutic effect of human umbilical cord mesenchymal stem cells (hUC-MSCs) in guinea pig model of nasal mucosa radiation damage and explored its therapeutic mechanism. Cultured hUC-MSCs were injected intravenously immediately after radiation in the nasal mucosa-radiation-damage guinea pig model. Migration of hUC-MSCs into the nasal mucosa and the potential for differentiation into nasal epithelial cells were evaluated by immunofluorescence. The therapeutic effects of hUC-MSCs were evaluated by mucus clearance time (MCT), degree of nasal mucosa edema, and the nasal mucosa cilia form and coverage ratio. Results indicate that the hUC-MSCs migrated to the nasal mucosa lamina propria and did not differentiate into nasal epithelial cells in this model. The MCT and degree of mucosal edema were improved at 1 week and 1 month after radiation, respectively, but no difference was found at 3 months and 6 months after radiation. The nasal mucosa cilia form and coverage ratio was not improved 6 months after radiation. Thus, hUC-MSCs can migrate to the nasal mucosa lamina propria and improve MCT and mucosa edema within a short time period, but these cells are unable to differentiate into nasal epithelial cells and improve nasal epithelial regeneration in the nasal mucosa radiation damage guinea pig model. © 2014 Wiley Periodicals, Inc.

  7. Dose-rate effect of ultrashort electron beam radiation on DNA damage and repair in vitro.

    Science.gov (United States)

    Babayan, Nelly; Hovhannisyan, Galina; Grigoryan, Bagrat; Grigoryan, Ruzanna; Sarkisyan, Natalia; Tsakanova, Gohar; Haroutiunian, Samvel; Aroutiounian, Rouben

    2017-11-01

    Laser-generated electron beams are distinguished from conventional accelerated particles by ultrashort beam pulses in the femtoseconds to picoseconds duration range, and their application may elucidate primary radiobiological effects. The aim of the present study was to determine the dose-rate effect of laser-generated ultrashort pulses of 4 MeV electron beam radiation on DNA damage and repair in human cells. The dose rate was increased via changing the pulse repetition frequency, without increasing the electron energy. The human chronic myeloid leukemia K-562 cell line was used to estimate the DNA damage and repair after irradiation, via the comet assay. A distribution analysis of the DNA damage was performed. The same mean level of initial DNA damages was observed at low (3.6 Gy/min) and high (36 Gy/min) dose-rate irradiation. In the case of low-dose-rate irradiation, the detected DNA damages were completely repairable, whereas the high-dose-rate irradiation demonstrated a lower level of reparability. The distribution analysis of initial DNA damages after high-dose-rate irradiation revealed a shift towards higher amounts of damage and a broadening in distribution. Thus, increasing the dose rate via changing the pulse frequency of ultrafast electrons leads to an increase in the complexity of DNA damages, with a consequent decrease in their reparability. Since the application of an ultrashort pulsed electron beam permits us to describe the primary radiobiological effects, it can be assumed that the observed dose-rate effect on DNA damage/repair is mainly caused by primary lesions appearing at the moment of irradiation. © The Author 2017. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

  8. Radiation-induced damage to mitochondrial D-. beta. -hydroxybutyrate dehydrogenase and lipid peroxidation

    Energy Technology Data Exchange (ETDEWEB)

    Yukawa, O.; Nakazawa, T. (National Inst. of Radiological Sciences, Chiba (Japan)); Miyahara, M.; Shiraishi, N. (Kochi Medical School (Japan). Dept. of Medical Biology)

    1985-07-01

    Radiation-induced damage to the reconstituted system of membrane-bound enzyme, D-..beta.. hydroxybutyrate dehydrogenase obtained from rat liver mitochondria, was investigated in relation to the lipid peroxidation of membranes. The D-..beta.. hydroxybutyrate dehydrogenase in fresh mitochondria was very low in general and not affected by irradiation because of little incorporation of substrates into mitochondria. Enzyme activity in one-day-aged mitochondria or submitochondrial particles was five times higher than that of fresh mitochondria and decreased with increasing radiation dose accompanying the increase in peroxidation of membrane lipids. D-..beta..-hydroxyl-butyrate dehydrogenase activity in the reconstituted system of the purified enzyme with irradiated liver microsomes or irradiated liposomes was decreased considerably in comparison with either unirradiated control or irradiated enzyme. Radiation-induced decrease in the enzyme activity was thought to be caused mainly by peroxidation of membrane lipids and not due to direct damage by radiation to the enzyme molecule itself. Irradiation of microsomes caused decreases in phosphatidylcholine and phosphatidylethanolamine content and an increase in lysophosphatidylcholine content. Arachidonic acid contents in phosphatidylcholine, phosphatidylinositol and phosphatidylethanolamine were also markedly decreased with increasing radiation dose. These results are discussed in terms of a mechanism involving radiation-induced damage to membrane function and structures.

  9. Modification of radiation-induced oxidative damage in liposomal and microsomal membrane by eugenol

    Energy Technology Data Exchange (ETDEWEB)

    Pandey, B.N. [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India); Lathika, K.M. [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India); Mishra, K.P. [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India)]. E-mail: kpm@magnum.barc.ernet.in

    2006-03-15

    Radiation-induced membrane oxidative damage, and their modification by eugenol, a natural antioxidant, was investigated in liposomes and microsomes. Liposomes prepared with DPH showed decrease in fluorescence after {gamma}-irradiation, which was prevented significantly by eugenol and correlated with magnitude of oxidation of phospholipids. Presence of eugenol resulted in substantial inhibition in MDA formation in irradiated liposomes/microsomes, which was less effective when added after irradiation. Similarly, the increase in phospholipase C activity observed after irradiation in microsomes was inhibited in samples pre-treated with eugenol. Results suggest association of radio- oxidative membrane damage with alterations in signaling molecules, and eugenol significantly prevented these membrane damaging events.

  10. Modification of radiation-induced oxidative damage in liposomal and microsomal membrane by eugenol

    Science.gov (United States)

    Pandey, B. N.; Lathika, K. M.; Mishra, K. P.

    2006-03-01

    Radiation-induced membrane oxidative damage, and their modification by eugenol, a natural antioxidant, was investigated in liposomes and microsomes. Liposomes prepared with DPH showed decrease in fluorescence after γ-irradiation, which was prevented significantly by eugenol and correlated with magnitude of oxidation of phospholipids. Presence of eugenol resulted in substantial inhibition in MDA formation in irradiated liposomes/microsomes, which was less effective when added after irradiation. Similarly, the increase in phospholipase C activity observed after irradiation in microsomes was inhibited in samples pre-treated with eugenol. Results suggest association of radio- oxidative membrane damage with alterations in signaling molecules, and eugenol significantly prevented these membrane damaging events.

  11. Pathological study on the mucosal damage of gastric replacement of the esophagus after the postoperative radiation

    Energy Technology Data Exchange (ETDEWEB)

    Iwata, Takashi; Kuniyasu, Hiroki; Hirai, Toshihiro; Yamashita, Yoshinori; Yoshimoto, Akihiro; Kuwahara, Masaki; Toge, Tetsuya [Hiroshima Univ. (Japan). Research Inst. for Radiation Biology and Medicine

    1997-12-01

    Mucosal damage to the whole stomach as an esohageal substitute, via the postmediastinal route, was pathologically investigated to elucidate the influence of postoperative radiation therapy. Subjects were 26 and 16 operated cases of esophageal cancer with and without postoperative radiation therapy, respectively. Endoscopic biopsy of the replaced stomach was performed preoperatively, before and after the radiation, and then at various different times for 2 years. The biopsy specimens obtained by endoscopic examination from the upper, middle and lower sites of the stomach were evaluated for the following pathological factors; atrophy, intestinal metaplasia, neutrophil infiltration, edema, erosion, necrosis and atypia. These findings were rated in score and changes in scores were studied. In both radiation and non-radiation groups, the degree of inflammatory change was strongest in the upper site, following middle and lower site in this order, in that some hematogenic involvement was considered. When the both groups compared for the inflammatory change, the changes in the radiation group were stronger than the other group in all sites. Necrosis and especially atypia were seen only in the upper and middle sites of radiated patients. Chronological inflammatory changes in each patient revealed that, as the site went up, the inflammation became stronger and was intensified by radiation therapy. But these inflammatory changes and atypia disappeared within a year after radiation therapy. These results suggest that postoperative radiation therapy would not be contraindicated for patients undergoing an esophageal substitution. (author)

  12. Ectopic expression of cancer/testis antigen SSX2 induces DNA damage and promotes genomic instability

    DEFF Research Database (Denmark)

    Greve, Katrine Buch Vidén; Lindgreen, Jonas; Terp, Mikkel Green

    2015-01-01

    of senescence (i.e. an irregular and enlarged cell shape, enhanced β-galactosidase activity and DNA double-strand breaks). Since replication defects, DNA damage and senescence are interconnected and well-documented effects of oncogene expression, we tested the oncogenic potential of SSX2. Importantly, knockdown...... in an increased DNA content and enlargement of cell nuclei, suggestive of replication aberrations. The cells further displayed signs of DNA damage and genomic instability, associated with p53-mediated G1 cell cycle arrest and a late apoptotic response. These results suggest a model wherein SSX2-mediated...... replication stress translates into mitotic defects and genomic instability. Arrest of cell growth and induction of DNA double-strand breaks was also observed in MCF7 breast cancer cells in response to SSX2 expression. Additionally, MCF7 cells with ectopic SSX2 expression demonstrated typical signs...

  13. Study of terahertz-radiation-induced DNA damage in human blood leukocytes

    Energy Technology Data Exchange (ETDEWEB)

    Angeluts, A A; Esaulkov, M N; Kosareva, O G; Solyankin, P M; Shkurinov, A P [International Laser Center, M. V. Lomonosov Moscow State University, Moscow (Russian Federation); Gapeyev, A B; Pashovkin, T N [Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region (Russian Federation); Matyunin, S N [Section of Applied Problems at the Presidium of the Russian Academy of Sciences, Moscow (Russian Federation); Nazarov, M M [Institute on Laser and Information Technologies, Russian Academy of Sciences, Shatura, Moscow Region (Russian Federation); Cherkasova, O P [Institute of Laser Physics, Siberian Branch, Russian Academy of Sciences, Novosibirsk (Russian Federation)

    2014-03-28

    We have carried out the studies aimed at assessing the effect of terahertz radiation on DNA molecules in human blood leukocytes. Genotoxic testing of terahertz radiation was performed in three different oscillation regimes, the blood leukocytes from healthy donors being irradiated for 20 minutes with the mean intensity of 8 – 200 μW cm{sup -2} within the frequency range of 0.1 – 6.5 THz. Using the comet assay it is shown that in the selected regimes such radiation does not induce a direct DNA damage in viable human blood leukocytes. (biophotonics)

  14. Study of terahertz-radiation-induced DNA damage in human blood leukocytes

    Science.gov (United States)

    Angeluts, A. A.; Gapeyev, A. B.; Esaulkov, M. N.; Kosareva, O. G.; Matyunin, S. N.; Nazarov, M. M.; Pashovkin, T. N.; Solyankin, P. M.; Cherkasova, O. P.; Shkurinov, A. P.

    2014-03-01

    We have carried out the studies aimed at assessing the effect of terahertz radiation on DNA molecules in human blood leukocytes. Genotoxic testing of terahertz radiation was performed in three different oscillation regimes, the blood leukocytes from healthy donors being irradiated for 20 minutes with the mean intensity of 8 - 200 μW cm-2 within the frequency range of 0.1 - 6.5 THz. Using the comet assay it is shown that in the selected regimes such radiation does not induce a direct DNA damage in viable human blood leukocytes.

  15. Radiation damage induced by neutrons in CMS silicon sensors

    CERN Document Server

    Forton, Eric

    Les expériences conduites auprès du futur accélérateur LHC au CERN nécessitent la construction des détecteurs les plus grands et les plus complexes jamais conçus. En particulier, le trajectographe de la collaboration CMS utilisera uniquement des détecteurs micropiste silicium et ce, en très grandes quantités. Ce dernier dépend donc de manière capitale de la qualité de toute la production des senseurs et la collaboration CMS a ainsi décidé de mettre en place un vaste programme de contrôle de cette qualité. Cette thèse présente une partie des travaux réalisés à l'UCL dans ce cadre. La discussion porte en particulier sur résistance aux radiations des senseurs en silicium, testée de manière routinière à Louvain-la-Neuve. Le texte débute par une présentation du détecteur CMS et des dégâts radiatifs subits par les détecteurs micropiste silicium. Les dispositifs expérimentaux mis en place auprès des cyclotrons et dans le laboratoire de l'institut de Physique nucléaire sont ensuite...

  16. Computational determination of radiation damage effects on DNA structure

    Science.gov (United States)

    Pinak, Miroslav

    2003-03-01

    Molecular dynamics (MD) studies of several radiation originated lesions on the DNA molecules are presented. The pyrimidine lesions (cytosinyl radical, thymine dimer, thymine glycol) and purine lesion (8-oxoguanine) were subjected to the MD simulations for several hundred picoseconds using MD simulation code AMBER 5.0 (4.0). The simulations were performed for fully dissolved solute molecules in water. Significant structural changes in the DNA double helical structure were observed in all cases which may be categorized as: a) the breaking of hydrogen bonds network between complementary bases and resulted opening of the double helix (cytosinyl, radical, 8-oxoguanine); b) the sharp bending of the DNA helix centered at the lesion site (thymine dimer, thymine glycol); and c) the flippingout of adenine on the strand complementary to the lesion (8-oxoguanine). These changes related to the overall collapsing of the double helical structure around the lesion, are expected to facilitate the docking of the repair enzyme into the DNA in the formation of DNA-enzyme complex. The stable DNA-enzyme complex is a necessary condition for the onset of the enzymatic repair process. In addition to structural changes, specific values of electrostatic interaction energy were determined at several lesion sites (thymine dimer, thymine glycol and 8-oxoguanine). This lesion-specific electrostatic energy is a factor that enables repair enzyme to discriminate lesion from the native site during the scanning of the DNA surface.

  17. Bystander effects in UV-induced genomic instability: Antioxidants inhibit delayed mutagenesis induced by ultraviolet A and B radiation

    Directory of Open Access Journals (Sweden)

    Dahle Jostein

    2005-01-01

    Full Text Available Abstract Background Genomic instability is characteristic of many types of human cancer. Recently, we reported that ultraviolet radiation induced elevated mutation rates and chromosomal instability for many cell generations after ultraviolet irradiation. The increased mutation rates of unstable cells may allow them to accumulate aberrations that subsequently lead to cancer. Ultraviolet A radiation, which primarily acts by oxidative stress, and ultraviolet B radiation, which initially acts by absorption in DNA and direct damage to DNA, both produced genomically unstable cell clones. In this study, we have determined the effect of antioxidants on induction of delayed mutations by ultraviolet radiation. Delayed mutations are indicative of genomic instability. Methods Delayed mutations in the hypoxanthine phosphoribosyl transferase (hprt gene were detected by incubating the cells in medium selectively killing hprt mutants for 8 days after irradiation, followed by a 5 day period in normal medium before determining mutation frequencies. Results The UVB-induced delayed hprt mutations were strongly inhibited by the antioxidants catalase, reduced glutathione and superoxide dismutase, while only reduced glutathione had a significant effect on UVA-induced delayed mutations. Treatment with antioxidants had only minor effects on early mutation frequenies, except that reduced glutathione decreased the UVB-induced early mutation frequency by 24 %. Incubation with reduced glutathione was shown to significantly increase the intracellular amount of reduced glutathione. Conclusion The strong effects of these antioxidants indicate that genomic instability, which is induced by the fundamentally different ultraviolet A and ultraviolet B radiation, is mediated by reactive oxygen species, including hydrogen peroxide and downstream products. However, cells take up neither catalase nor SOD, while incubation with glutathione resulted in increased intracellular levels of

  18. The impact of locally multiply damaged sites (LMDS) induced by ionizing radiation in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Averbeck, D.; Boucher, D. [Institut Curie-Section de Recherche, UMR2027 CNRS, LCR-V28 du CEA, Centre Universitaire, 91405 Orsay Cedex (France)

    2006-07-01

    Monte Carlo calculations have shown that ionising radiations produce a specific type of clustered cell damage called locally multiply damaged sites or LMDS. These lesions consist of closely positioned single-strand breaks, (oxidative) base damage and DNA double-strand breaks (DSB) in between one helical turn of DNA. As specific markers of radiation-induced damage these lesions are likely to condition biological responses and are thus of great interest for radiation protection. Calculations indicate that there should be more LMDS induced by high than by low LET radiation, and they should be absent in un-irradiated cells. Processes like K-shell activation and local Auger electron emission can be expected to add complex DSB or LMDS, producing significant chromosomal damage. In the discussion of the specificity of ionising radiation in comparison to other genotoxic agents, many arguments have been put forward that these lesions should be particularly deleterious for living cells. Complex lesions of that type should represent big obstacles for DNA repair and give rise to high lethality. Moreover, cellular attempts to repair them could accentuate harm, leading to mutations, genetic instability and cancer. In vitro experiments with oligonucleotides containing an artificially introduced set of base damage and SSB in different combinations have shown that depending on the close positioning of the damage on DNA, repair enzymes, and even whole cell extracts, are unable to repair properly and may stimulate mis-repair. Pulsed field gel electrophoresis (PFGE) in conjunction with enzymatic treatments has been used to detect LMDS in mammalian cells after high and low LET radiation. In order to further define the importance of LMDS for radiation induced cellular responses, we studied the induction of LMDS as a function of radiation dose and dose rate in mammalian cells (CHO and MRC5) using {sup 137}Cs gamma-radiation. Using PFGE and specific glycosylases to convert oxidative damage

  19. Assessment of DNA damage and oxidative stress induced by radiation in Eisenia fetida

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Tae Ho; Kim, Jin Kyu [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Nili, Mohammad [Dawnesh Radiation Research Institute, Barcelona (Spain)

    2012-04-15

    Exposure of eukaryotic cells to ionizing radiation results in the immediate formation of free radicals and the occurrence of oxidative cell damage. Recently International Commission on Radiological Protection (ICRP) requires the effect data of ionizing radiation on non-human biota for the radiological protection of the environment. Based on their radioecological properties and their important role in the soil ecosystem, earthworms have been identified by the ICRP as one of the reference animals and plants (RAPs) to be used in environmental radiation protection. The investigation shows that oxidative stress is closely related to the exposed dose of radiation in the environment. To evaluate oxidative stress by ionizing radiation in the earthworm, we performed several experiments. The comet assay is known as a measurement which is one of the best techniques in assessing the DNA damage by oxidative stress. The SOD is a key enzyme in protecting cells against oxidative stress. An increase in the level of antioxidant enzyme such as SOD indicated that the exposure to radiation caused stress responses. Glutathione oxidation is considered as a maker for detection of reactive oxygen species (ROS). The GSSG levels increased progressively with increased exposure dose of ionizing radiation, which suggested a dose-dependent ROS generation.

  20. Stem Cell Therapy to Reduce Radiation-Induced Normal Tissue Damage

    NARCIS (Netherlands)

    Coppes, Rob P.; van der Goot, Annemieke; Lombaert, Isabelle M. A.

    Normal tissue damage after radiotherapy is still a major problem in cancer treatment. Stem cell therapy may provide a means to reduce radiation-induced side effects and improve the quality of life of patients. This review discusses the current status in stem cell research with respect to their

  1. Strongly Reduced Penetration of Atomic Deuterium in Radiation-Damaged Tungsten

    NARCIS (Netherlands)

    't Hoen, M. H. J.; Mayer, M.; Kleyn, A.W.; van Emmichoven, P.A.Z.

    2013-01-01

    Radiation-damaged tungsten is exposed to high-flux, low-energy deuterium plasmas at self-bias conditions. We observe that the fraction of deuterium that penetrates is only 10(-5)-10(-7) of the plasma flux and strongly dependent on the local surface temperature. We propose that deuterium does not

  2. Retinal damage by optical radiation. An alternative approach to current, ACGIH-inspired guidelines

    NARCIS (Netherlands)

    Vos, J.J.; Norren, D. van

    2005-01-01

    Background: The ACGIH guidelines for protection against retinal damage by optical radiation are often difficult to apply due to their lack of transparency. The less known guidelines by the Netherlands Health Council (HCN), dating from 1978 and updated in 1993, might offer a way out in many cases.

  3. Bystander effects in radiation-induced genomic instability

    Science.gov (United States)

    Morgan, William F.; Hartmann, Andreas; Limoli, Charles L.; Nagar, Shruti; Ponnaiya, Brian

    2002-01-01

    Exposure of GM10115 hamster-human hybrid cells to X-rays can result in the induction of chromosomal instability in the progeny of surviving cells. This instability manifests as the dynamic production of novel sub-populations of cells with unique cytogenetic rearrangements involving the "marker" human chromosome. We have used the comet assay to investigate whether there was an elevated level of endogenous DNA breaks in chromosomally unstable clones that could provide a source for the chromosomal rearrangements and thus account for the persistent instability observed. Our results indicate no significant difference in comet tail measurement between non-irradiated and radiation-induced chromosomally unstable clones. Using two-color fluorescence in situ hybridization we also investigated whether recombinational events involving the interstitial telomere repeat-like sequences in GM10115 cells were involved at frequencies higher than random processes would otherwise predict. Nine of 11 clones demonstrated a significantly higher than expected involvement of these interstitial telomere repeat-like sequences at the recombination junction between the human and hamster chromosomes. Since elevated levels of endogenous breaks were not detected in unstable clones we propose that epigenetic or bystander effects (BSEs) lead to the activation of recombinational pathways that perpetuate the unstable phenotype. Specifically, we expand upon the hypothesis that radiation induces conditions and/or factors that stimulate the production of reactive oxygen species (ROS). These reactive intermediates then contribute to a chronic pro-oxidant environment that cycles over multiple generations, promoting chromosomal recombination and other phenotypes associated with genomic instability.

  4. Impact of DNA damaging agents on genome-wide transcriptional profiles in two marine Synechococcus species

    Directory of Open Access Journals (Sweden)

    Sasha Gabrielle Tetu

    2013-08-01

    Full Text Available Marine microorganisms, particularly those residing in coastal areas, may come in contact with any number of chemicals of environmental or xenobiotic origin. The sensitivity and response of marine cyanobacteria to such chemicals is, at present, poorly understood. We have looked at the transcriptional response of well characterised Synechococcus open ocean (WH8102 and coastal (CC9311 isolates to two DNA damaging agents, mitomycin C and ethidium bromide, using whole-genome expression microarrays. The coastal strain showed differential regulation of a larger proportion of its genome following ‘shock’ treatment with each agent. Many of the orthologous genes in these strains, including those encoding sensor kinases, showed different transcriptional responses, with the CC9311 genes more likely to show significant changes in both treatments. While the overall response of each strain was considerably different, there were distinct transcriptional responses common to both strains observed for each DNA damaging agent, linked to the mode of action of each chemical. In both CC9311 and WH8102 there was evidence of SOS response induction under mitomycin C treatment, with genes recA, lexA and umuC significantly upregulated in this experiment but not under ethidium bromide treatment. Conversely, ethidium bromide treatment tended to result in upregulation of the DNA-directed RNA polymerase genes, not observed following mitomycin C treatment. Interestingly, a large number of genes residing on putative genomic island regions of each genome also showed significant upregulation under one or both chemical treatments.

  5. Protecting the radiation-damaged skin from friction: a mini review

    Energy Technology Data Exchange (ETDEWEB)

    Herst, Patries M [Department of Radiation Therapy, University of Otago, Wellington (New Zealand)

    2014-06-15

    Radiation-induced skin reactions are an unavoidable side effect of external beam radiation therapy, particularly in areas prone to friction and excess moisture such as the axilla, head and neck region, perineum and skin folds. Clinical studies investigating interventions for preventing or managing these reactions have largely focussed on formulations with moisturising, anti-inflammatory, anti-microbial and wound healing properties. However, none of these interventions has emerged as a consistent candidate for best practice. Much less emphasis has been placed on evaluating ways to protect the radiation-damaged skin from friction and excess moisture. This mini review analyses the clinical evidence for barrier products that form a protective layer by adhering very closely to the skin folds and do not cause further trauma to the radiation-damaged skin upon removal. A database search identified only two types of barrier products that fitted these criteria and these were tested in two case series and six controlled clinical trials. Friction protection was most effective when the interventions were used from the start of treatment and continued for several weeks after completion of treatment. Soft silicone dressings (Mepilex Lite and Mepitel Film) and Cavilon No Sting Barrier Film, but not Cavilon Moisturizing Barrier Cream, decreased skin reaction severity, most likely due to differences in formulation and skin build-up properties. It seems that prophylactic use of friction protection of areas at risk could be a worthwhile addition to routine care of radiation-damaged skin.

  6. DNA bending facilitates the error-free DNA damage tolerance pathway and upholds genome integrity

    Science.gov (United States)

    Gonzalez-Huici, Victor; Szakal, Barnabas; Urulangodi, Madhusoodanan; Psakhye, Ivan; Castellucci, Federica; Menolfi, Demis; Rajakumara, Eerappa; Fumasoni, Marco; Bermejo, Rodrigo; Jentsch, Stefan; Branzei, Dana

    2014-01-01

    DNA replication is sensitive to damage in the template. To bypass lesions and complete replication, cells activate recombination-mediated (error-free) and translesion synthesis-mediated (error-prone) DNA damage tolerance pathways. Crucial for error-free DNA damage tolerance is template switching, which depends on the formation and resolution of damage-bypass intermediates consisting of sister chromatid junctions. Here we show that a chromatin architectural pathway involving the high mobility group box protein Hmo1 channels replication-associated lesions into the error-free DNA damage tolerance pathway mediated by Rad5 and PCNA polyubiquitylation, while preventing mutagenic bypass and toxic recombination. In the process of template switching, Hmo1 also promotes sister chromatid junction formation predominantly during replication. Its C-terminal tail, implicated in chromatin bending, facilitates the formation of catenations/hemicatenations and mediates the roles of Hmo1 in DNA damage tolerance pathway choice and sister chromatid junction formation. Together, the results suggest that replication-associated topological changes involving the molecular DNA bender, Hmo1, set the stage for dedicated repair reactions that limit errors during replication and impact on genome stability. PMID:24473148

  7. Genome-Wide Requirements for Resistance to Functionally Distinct DNA-Damaging Agents.

    Directory of Open Access Journals (Sweden)

    2005-08-01

    Full Text Available The mechanistic and therapeutic differences in the cellular response to DNA-damaging compounds are not completely understood, despite intense study. To expand our knowledge of DNA damage, we assayed the effects of 12 closely related DNA-damaging agents on the complete pool of ~4,700 barcoded homozygous deletion strains of Saccharomyces cerevisiae. In our protocol, deletion strains are pooled together and grown competitively in the presence of compound. Relative strain sensitivity is determined by hybridization of PCR-amplified barcodes to an oligonucleotide array carrying the barcode complements. These screens identified genes in well-characterized DNA-damage-response pathways as well as genes whose role in the DNA-damage response had not been previously established. High-throughput individual growth analysis was used to independently confirm microarray results. Each compound produced a unique genome-wide profile. Analysis of these data allowed us to determine the relative importance of DNA-repair modules for resistance to each of the 12 profiled compounds. Clustering the data for 12 distinct compounds uncovered both known and novel functional interactions that comprise the DNA-damage response and allowed us to define the genetic determinants required for repair of interstrand cross-links. Further genetic analysis allowed determination of epistasis for one of these functional groups.

  8. Genome-wide requirements for resistance to functionally distinct DNA-damaging agents.

    Directory of Open Access Journals (Sweden)

    William Lee

    2005-08-01

    Full Text Available The mechanistic and therapeutic differences in the cellular response to DNA-damaging compounds are not completely understood, despite intense study. To expand our knowledge of DNA damage, we assayed the effects of 12 closely related DNA-damaging agents on the complete pool of approximately 4,700 barcoded homozygous deletion strains of Saccharomyces cerevisiae. In our protocol, deletion strains are pooled together and grown competitively in the presence of compound. Relative strain sensitivity is determined by hybridization of PCR-amplified barcodes to an oligonucleotide array carrying the barcode complements. These screens identified genes in well-characterized DNA-damage-response pathways as well as genes whose role in the DNA-damage response had not been previously established. High-throughput individual growth analysis was used to independently confirm microarray results. Each compound produced a unique genome-wide profile. Analysis of these data allowed us to determine the relative importance of DNA-repair modules for resistance to each of the 12 profiled compounds. Clustering the data for 12 distinct compounds uncovered both known and novel functional interactions that comprise the DNA-damage response and allowed us to define the genetic determinants required for repair of interstrand cross-links. Further genetic analysis allowed determination of epistasis for one of these functional groups.

  9. An Automated Method to Quantify Radiation Damage in Human Blood Cells

    Energy Technology Data Exchange (ETDEWEB)

    Gordon K. Livingston, Mark S. Jenkins and Akio A. Awa

    2006-07-10

    Cytogenetic analysis of blood lymphocytes is a well established method to assess the absorbed dose in persons exposed to ionizing radiation. Because mature lymphocytes circulate throughout the body, the dose to these cells is believed to represent the average whole body exposure. Cytogenetic methods measure the incidence of structural aberrations in chromosomes as a means to quantify DNA damage which occurs when ionizing radiation interacts with human tissue. Methods to quantify DNA damage at the chromosomal level vary in complexity and tend to be laborious and time consuming. In a mass casualty scenario involving radiological/nuclear materials, the ability to rapidly triage individuals according to radiation dose is critically important. For high-throughput screening for dicentric chromosomes, many of the data collection steps can be optimized with motorized microscopes coupled to automated slide scanning platforms.

  10. A simple model of space radiation damage in GaAs solar cells

    Science.gov (United States)

    Wilson, J. W.; Stith, J. J.; Stock, L. V.

    1983-01-01

    A simple model is derived for the radiation damage of shallow junction gallium arsenide (GaAs) solar cells. Reasonable agreement is found between the model and specific experimental studies of radiation effects with electron and proton beams. In particular, the extreme sensitivity of the cell to protons stopping near the cell junction is predicted by the model. The equivalent fluence concept is of questionable validity for monoenergetic proton beams. Angular factors are quite important in establishing the cell sensitivity to incident particle types and energies. A fluence of isotropic incidence 1 MeV electrons (assuming infinite backing) is equivalent to four times the fluence of normal incidence 1 MeV electrons. Spectral factors common to the space radiations are considered, and cover glass thickness required to minimize the initial damage for a typical cell configuration is calculated. Rough equivalence between the geosynchronous environment and an equivalent 1 MeV electron fluence (normal incidence) is established.

  11. Beclin 1 and UVRAG confer protection from radiation-induced DNA damage and maintain centrosome stability in colorectal cancer cells.

    Directory of Open Access Journals (Sweden)

    Jae Myung Park

    Full Text Available Beclin 1 interacts with UV-irradiation-resistance-associated gene (UVRAG to form core complexes that induce autophagy. While cells with defective autophagy are prone to genomic instability that contributes to tumorigenesis, it is unknown whether Beclin1 or UVRAG can regulate the DNA damage/repair response to cancer treatment in established tumor cells. We found that siRNA knockdown of Beclin 1 or UVRAG can increase radiation-induced DNA double strand breaks (DSBs, shown by pATM and γH2Ax, and promote colorectal cancer cell death. Furthermore, knockdown of Beclin 1, UVRAG or ATG5 increased the percentage of irradiated cells with nuclear foci expressing 53BP1, a marker of nonhomologous end joining but not RAD51 (homologous recombination, compared to control siRNA. Beclin 1 siRNA was shown to attenuate UVRAG expression. Cells with a UVRAG deletion mutant defective in Beclin 1 binding showed increased radiation-induced DSBs and cell death compared to cells with ectopic wild-type UVRAG. Knockdown of Beclin 1 or UVRAG, but not ATG5, resulted in a significant increase in centrosome number (γ-tubulin staining in irradiated cells compared to control siRNA. Taken together, these data indicate that Beclin 1 and UVRAG confer protection against radiation-induced DNA DSBs and may maintain centrosome stability in established tumor cells.

  12. Ultraviolet radiation-specific DNA damage and embryonic viability in sea urchins from Kasitsna Bay, Alaska

    Energy Technology Data Exchange (ETDEWEB)

    Theodorakis, C. [Oak Ridge Associated Universities, TN (United States); Anderson, S. [Lawrence Berkeley National Lab., CA (United States); Shugart, L.R. [Oak Ridge National Lab., TN (United States)

    1995-12-31

    Ripe ova and sperm were obtained from Green Sea Urchins (Strongvlocentrotus drochbachiensis) collected from Kasitsna Bay, Alaska, and ova were fertilized in vitro. Embryos were immediately placed in plastic bags secured to floating racks deployed in the bay. The bags were suspended just below the surface of the water and at 1 and 2 meter depths for up to 120 hours. Bags were either left uncovered, covered with Mylar plastic (which blocks out UV-B but not UV-A radiations), or covered with dark plastic. The number of damaged DNA sites was determined by digesting the DNA with enzymes isolated from the bacterium Micrococcus luteus which cleave the DNA at damaged sites. It was found that DNA damage was present in a dose-dependent fashion with the amount of damage in embryos from the uncovered bags > Mylar covered bags > dark covered bags. No dimers were detected from embryos at 1 or 2 m. depths. Also, the number of damaged sites varied from day to day. Finally, the number of damaged sites was positively correlated with percent abnormal embryos in each bag. The results are discussed with relation to monitoring UV-B effects and ecological consequences of enhanced UV-B radiation.

  13. Comparing simulations and test data of a radiation damaged CCD for the Euclid mission

    Science.gov (United States)

    Skottfelt, Jesper; Hall, David; Gow, Jason; Murray, Neil; Holland, Andrew; Prod'homme, Thibaut

    2016-07-01

    The radiation damage effects from the harsh radiative environment outside the Earth's atmosphere can be a cause for concern for most space missions. With the science goals becoming ever more demanding, the requirements on the precision of the instruments on board these missions also increases, and it is therefore important to investigate how the radiation induced damage affects the Charge-Coupled Devices (CCDs) that most of these instruments rely on. The primary goal of the Euclid mission is to study the nature of dark matter and dark energy using weak lensing and baryonic acoustic oscillation techniques. The weak lensing technique depends on very precise shape measurements of distant galaxies obtained by a large CCD array. It is anticipated that over the 6 year nominal lifetime of mission, the CCDs will be degraded to an extent that these measurements will not be possible unless the radiation damage effects are corrected. We have therefore created a Monte Carlo model that simulates the physical processes taking place when transferring signal through a radiation damaged CCD. The software is based on Shockley-Read-Hall theory, and is made to mimic the physical properties in the CCD as close as possible. The code runs on a single electrode level and takes charge cloud size and density, three dimensional trap position, and multi-level clocking into account. A key element of the model is that it takes device specific simulations of electron density as a direct input, thereby avoiding to make any analytical assumptions about the size and density of the charge cloud. This paper illustrates how test data and simulated data can be compared in order to further our understanding of the positions and properties of the individual radiation-induced traps.

  14. A Combination of Pre- and Post-Exposure Ascorbic Acid Rescues Mice from Radiation-Induced Lethal Gastrointestinal Damage

    Science.gov (United States)

    Ito, Yasutoshi; Kinoshita, Manabu; Yamamoto, Tetsuo; Sato, Tomohito; Obara, Takeyuki; Saitoh, Daizoh; Seki, Shuhji; Takahashi, Yukihiro

    2013-01-01

    The development of an effective therapy for radiation-induced gastrointestinal damage is important, because it is currently a major complication of treatment and there are few effective therapies available. Although we have recently demonstrated that pretreatment with ascorbic acid attenuates lethal gastrointestinal damage in irradiated mice, more than half of mice eventually died, thus indicating that better approach was needed. We then investigated a more effective therapy for radiation-induced gastrointestinal damage. Mice receiving abdominal radiation at 13 Gy were orally administered ascorbic acid (250 mg/kg/day) for three days before radiation (pretreatment), one shot of engulfment (250 mg/kg) at 8 h before radiation, or were administered the agent for seven days after radiation (post-treatment). None of the control mice survived the abdominal radiation at 13 Gy due to severe gastrointestinal damage (without bone marrow damage). Neither pretreatment with ascorbic acid (20% survival), engulfment (20%), nor post-treatment (0%) was effective in irradiated mice. However, combination therapy using ascorbic acid, including pretreatment, engulfment and post-treatment, rescued all of the mice from lethal abdominal radiation, and was accompanied by remarkable improvements in the gastrointestinal damage (100% survival). Omitting post-treatment from the combination therapy with ascorbic acid markedly reduced the mouse survival (20% survival), suggesting the importance of post-treatment with ascorbic acid. Combination therapy with ascorbic acid may be a potent therapeutic tool for radiation-induced gastrointestinal damage. PMID:24084715

  15. Opposite roles for p38MAPK-driven responses and reactive oxygen species in the persistence and resolution of radiation-induced genomic instability.

    Directory of Open Access Journals (Sweden)

    Erica Werner

    Full Text Available We report the functional and temporal relationship between cellular phenotypes such as oxidative stress, p38MAPK-dependent responses and genomic instability persisting in the progeny of cells exposed to sparsely ionizing low-Linear Energy Transfer (LET radiation such as X-rays or high-charge and high-energy (HZE particle high-LET radiation such as (56Fe ions. We found that exposure to low and high-LET radiation increased reactive oxygen species (ROS levels as a threshold-like response induced independently of radiation quality and dose. This response was sustained for two weeks, which is the period of time when genomic instability is evidenced by increased micronucleus formation frequency and DNA damage associated foci. Indicators for another persisting response sharing phenotypes with stress-induced senescence, including beta galactosidase induction, increased nuclear size, p38MAPK activation and IL-8 production, were induced in the absence of cell proliferation arrest during the first, but not the second week following exposure to high-LET radiation. This response was driven by a p38MAPK-dependent mechanism and was affected by radiation quality and dose. This stress response and elevation of ROS affected genomic instability by distinct pathways. Through interference with p38MAPK activity, we show that radiation-induced stress phenotypes promote genomic instability. In contrast, exposure to physiologically relevant doses of hydrogen peroxide or increasing endogenous ROS levels with a catalase inhibitor reduced the level of genomic instability. Our results implicate persistently elevated ROS following exposure to radiation as a factor contributing to genome stabilization.

  16. The contribution of co-transcriptional RNA:DNA hybrid structures to DNA damage and genome instability

    Science.gov (United States)

    Hamperl, Stephan; Cimprich, Karlene A.

    2014-01-01

    Accurate DNA replication and DNA repair are crucial for the maintenance of genome stability, and it is generally accepted that failure of these processes is a major source of DNA damage in cells. Intriguingly, recent evidence suggests that DNA damage is more likely to occur at genomic loci with high transcriptional activity. Furthermore, loss of certain RNA processing factors in eukaryotic cells is associated with increased formation of co-transcriptional RNA:DNA hybrid structures known as R-loops, resulting in double-strand breaks (DSBs) and DNA damage. However, the molecular mechanisms by which R-loop structures ultimately lead to DNA breaks and genome instability is not well understood. In this review, we summarize the current knowledge about the formation, recognition and processing of RNA:DNA hybrids, and discuss possible mechanisms by which these structures contribute to DNA damage and genome instability in the cell. PMID:24746923

  17. The contribution of co-transcriptional RNA:DNA hybrid structures to DNA damage and genome instability.

    Science.gov (United States)

    Hamperl, Stephan; Cimprich, Karlene A

    2014-07-01

    Accurate DNA replication and DNA repair are crucial for the maintenance of genome stability, and it is generally accepted that failure of these processes is a major source of DNA damage in cells. Intriguingly, recent evidence suggests that DNA damage is more likely to occur at genomic loci with high transcriptional activity. Furthermore, loss of certain RNA processing factors in eukaryotic cells is associated with increased formation of co-transcriptional RNA:DNA hybrid structures known as R-loops, resulting in double-strand breaks (DSBs) and DNA damage. However, the molecular mechanisms by which R-loop structures ultimately lead to DNA breaks and genome instability is not well understood. In this review, we summarize the current knowledge about the formation, recognition and processing of RNA:DNA hybrids, and discuss possible mechanisms by which these structures contribute to DNA damage and genome instability in the cell. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Protection of DPPC phospholipid liposomal membrane against radiation oxidative damage by antioxidants

    Energy Technology Data Exchange (ETDEWEB)

    Marathe, D.L.; Pandey, B.N.; Mishra, K.P [Bhabha Atomic Research Centre, Mumbai (India)

    2000-05-01

    Investigations in our laboratory on egg lecithin liposomes have recently showed a marked protection against damage by gamma radiation when cholesterol was present in the composition of vesicles suggesting a role of bilayer molecular architecture in the mechanism of free radical mediated lipid peroxidation. Present study was designed to determine the changes in bilayer permeability in DPPC unilamelar vesicles after exposure to gamma radiation by monitoring the leakage of pre-loaded carboxyfluorescein (CF), a marker loaded in aqueous interior of vesicle and fluidity alterations in the bilayer using fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH), a membrane bilayer probe. It was found that radiation doses of an order of magnitude higher were required to produce detectable changes in vesicles of DPPC than in the vesicles of egg lecithin suggesting a modulating role of chemical nature of composition in the membrane radiation sensitivity. It was significant to find that the leakage of CF from and incorporation of DPH into vesicle bilayer showed similar response pattern to radiation doses (0.1-6 kGy) which was also found to be dose rate dependent. Presence of antioxidants; alpha-tocopherol (0.15 mole %) in the bilayer membrane or ascorbic acid (0.1 mM) in the aqueous region significantly protected DPPC vesicles from radiation damage as determined from DPH uptake kinetics suggesting involvement of reactive free radicals of lipids as well as water radicals in the mechanism of membrane peroxidative damage. The magnitude of protection was found to increase with the increasing concentration of both these antioxidants but comparisons showed that {alpha}-tocopherol was far more effective in protecting the vesicles than ascorbic acid. These results contribute to our understanding of the mechanism of radiation oxidative damage and its modification by radical scavenging and/or organizational modulation which emphasize the importance of structure and composition of

  19. Radiation damage of polyethylene exposed in the stratosphere at an altitude of 40 km

    CERN Document Server

    Kondyurin, Alexey; Bilek, Marcela

    2011-01-01

    Low Density Polyethylene (LDPE) films were exposed at an altitude of 40 km over a 3 day NASA stratospheric balloon mission from Alice Springs, Australia. The radiation damage, oxidation and nitration in the LDPE films exposed in stratosphere were measured using ESR, FTIR and XPS spectroscopy. The results were compared with those from samples stored on the ground and exposed in a laboratory plasma. The types of free radicals, unsaturated hydrocarbon groups, oxygen-containing and nitrogen-containing groups in LDPE film exposed in the stratosphere and at the Earth's surface are different. The radiation damage in films exposed in the stratosphere are observed in the entire film due to the penetration of high energy cosmic rays through their thickness, while the radiation damage in films exposed on the ground is caused by sunlight penetrating into only a thin surface layer. A similarly thin layer of the film is damaged by exposure to plasma due to the low energy of the plasma particles. The intensity of oxidation ...

  20. The interaction of melanin with ionizing and UVC radiations: Characterization of thymine damage

    Energy Technology Data Exchange (ETDEWEB)

    Huselton, C.A.

    1988-01-01

    These studies were undertaken to determine whether melanin could protect DNA against the harmful effects of ionizing or UVC radiations. A simple, in vitro, model system was developed to evaluate eumelanin (Sigma melanin) as a radioprotector of solutions of 0.1 mM thymine or thymidine exposed to 570Gy of ionizing radiation. Sigma melanin was compared to several amino acids, other biomolecules or to other forms of melanin. To investigate the role of melanin as a passive screen of UVC radiation, melanotic (I{sub 3}), amelanotic (AMEL) cells (both derived from a Cloudman S91 melanoma) and non-melanotic (EMT6) cells were labelled with radioactive dTHd and exposed to 0, 1, 5 or 10KJ/m{sup 2} of UVC. The DNA was extracted; the bases hydrolyzed with concentrated HCl. Thymine bases were separated by reverse phase HPLC. No difference in dimer content was observed between I{sub 3} and AMEL cells, but EMT6 cells had nearly twice the amount of dimer. Overall thymine degradation was more pronounced in I{sub 3} cells than in the other two cell lines, due to the production of non-dimer thymine damage. This damage was identified as thymine glycol by HPLC and mass spectrometry. Melanin, upon exposure to UVC, appears to enhance thymine damage by producing oxidative damage.

  1. Radiation damage studies of mineral apatite, using fission tracks and thermoluminescence techniques

    Energy Technology Data Exchange (ETDEWEB)

    Al-Khalifa, I.J.M. (Arabian Gulf Univ., Manama, Bahrain); James, K.; Durrani, S.A. (Birmingham Univ. (UK). Dept. of Physics); Khalifa, M.S. (Tajoura Research Centre, Tripoli (Libya))

    1988-01-01

    In a uranium (/thorium)-rich mineral sample which has not suffered a recent geological high-temperature excursion, the fossil fission track density (FFTD) will give a good indication of its natural radiation damage, provided that its U/Th ratio is known. From our studies of FFTD and thermoluminescence (TL) properties of several samples of apatite from different locations, and containing varying degrees of natural-radiation damage, an anti-correlation is observed between FFTD and TL sensitivity. It is also found that an anti-correlation exists between TL sensitivity and the amount of damage produced artificially by bombarding apatite crystals with different fluences of approx30 MeV alpha-particles from a cyclotron. These results indicate that the presence of radiation damage in this mineral (viz., fluorapatite) can severely affect its TL sensitivity (i.e. TL output per unit test dose). The effect of crystal composition on the thermoluminescence and fission track annealing properties of mineral apatite is also reported. We have found that fission track annealing sensitivity and TL sensitivity are both significantly lower in samples of chlorapatite than in samples consisting predominantly of fluorapatite. (author).

  2. DNA damage response and spindle assembly checkpoint function throughout the cell cycle to ensure genomic integrity.

    Directory of Open Access Journals (Sweden)

    Katherine S Lawrence

    2015-04-01

    Full Text Available Errors in replication or segregation lead to DNA damage, mutations, and aneuploidies. Consequently, cells monitor these events and delay progression through the cell cycle so repair precedes division. The DNA damage response (DDR, which monitors DNA integrity, and the spindle assembly checkpoint (SAC, which responds to defects in spindle attachment/tension during metaphase of mitosis and meiosis, are critical for preventing genome instability. Here we show that the DDR and SAC function together throughout the cell cycle to ensure genome integrity in C. elegans germ cells. Metaphase defects result in enrichment of SAC and DDR components to chromatin, and both SAC and DDR are required for metaphase delays. During persistent metaphase arrest following establishment of bi-oriented chromosomes, stability of the metaphase plate is compromised in the absence of DDR kinases ATR or CHK1 or SAC components, MAD1/MAD2, suggesting SAC functions in metaphase beyond its interactions with APC activator CDC20. In response to DNA damage, MAD2 and the histone variant CENPA become enriched at the nuclear periphery in a DDR-dependent manner. Further, depletion of either MAD1 or CENPA results in loss of peripherally associated damaged DNA. In contrast to a SAC-insensitive CDC20 mutant, germ cells deficient for SAC or CENPA cannot efficiently repair DNA damage, suggesting that SAC mediates DNA repair through CENPA interactions with the nuclear periphery. We also show that replication perturbations result in relocalization of MAD1/MAD2 in human cells, suggesting that the role of SAC in DNA repair is conserved.

  3. A Role for Lsm1p in Response to Ultraviolet-Radiation Damage in Saccharomyces cerevisiae

    OpenAIRE

    Spicakova, Tatiana; McCann, Kelly; Brown, J. Martin

    2008-01-01

    A genome-wide screen in Saccharomyces cerevisiae identified LSM1 as a new gene affecting sensitivity to ultraviolet (UV) radiation. Lsm1p is a member of a cytoplasmic complex composed of Lsm1p–7p that interacts with the yeast mRNA degradation machinery. To investigate the potential role of Lsm1p in response to UV radiation, we constructed double mutant strains in which LSM1 was deleted in combination with a representative gene from each of three known yeast DNA repair pathways. Our results sh...

  4. Radiation damage and sensitization effects on thermoluminescence of LiF:Mg,Ti (TLD-700)

    Science.gov (United States)

    Farag, M. A.; Sadek, A. M.; Shousha, Hany. A.; El-Hagg, A. A.; Atta, M. R.; Kitis, G.

    2017-09-01

    The radiation damage effects and enhancement the thermoluminescence (TL) efficiency of LiF:Mg,Ti (TLD-700)dosimeters via sensitization method were discussed. Attempts to eliminate the effects of damage and sensitization were made using different types of annealing processes. The results showed that after irradiating the dosimeters with dose > 250 Gy of 60Co gamma source, damage effects were observed. The sensitivity of the total area under the curve was decreased by a factor of ∼0.5 after irradiation at a pre-test dose of 2 kGy. However, the effects of radiation damage on each glow-peak are different. The glow-peak 2 was the only peak that was not affected by the high-dose irradiation. It has been shown that the degree of the radiation damage effect is related to the maximum dose-response function, f(D)max of the glow-peak. In general, significant radiation damage effects were observed for the glow-peaks of high f(D)max . Post-irradiation anneal at 280 °C for 30 min causes dramatic effects on the shape of the glow-curve and as well as on the sensitivity of the dosimeters. An increasing by a factor of ∼35 in the sensitivity of the total area under the curve was observed at a pre-test dose of 2 kGy. Improving the sensitivity of peak 7 by a factor of∼22 was the dominant factor in increasing the sensitivity of the dosimeters. On the other hand, an increasing by factors of ∼2.5 and ∼4 was found for peaks 2 and 5 respectively. On the other hand, a decreasing by a factor ∼0.5 was observed for peaks 3 and 4. At pre-test dose levels >250 Gy, a very strange and high intensity tail was observed in the high-temperature region of the glow-curves. The readout anneal was not enough to remove this tail. While, the furnace anneal could eliminate the sensitization effects but not the radiation damage effects on the sensitivity of the dosimeters.

  5. Genome-wide analysis of radiation-induced mutations in rice (Oryza sativa L. ssp. indica).

    Science.gov (United States)

    Cheng, Zuxin; Lin, Juncheng; Lin, Tongxiang; Xu, Ming; Huang, Zhiwei; Yang, Zhijian; Huang, Xinying; Zheng, Jingui

    2014-04-01

    Radiation has been efficiently used for rice germplasm innovation. However, the molecular mechanisms by which radiation induces mutations are still unclear. In this study, we performed whole genome sequencing to reveal the comprehensive mutations in rice treated with radiation. Red-1 (a rice rich in beneficial ingredients for human health) was derived from rice 9311 after γ-radiation. Solexa sequencing technology was applied to uncover the mutations. Compared with the 9311 genome, 9.19% of genome sequences were altered in the Red-1 genome. Among these alterations, there were 381,403 SNPs, 50,116 1-5 bp Indels, 1279 copy number variations, and 10,026 presence/absence variations. These alterations were located in 14,493 genes, the majority of which contained a kinase domain, leucine rich repeats, or Cyt_P450. Point mutations were the main type of variation in the Red-1 genome. Gene ontology clustering revealed that genes that are associated with cell components, binding function, catalytic activity and metabolic processes were susceptible to γ-radiation. It was also predicted that 8 mutated genes were involved in the biosynthetic pathways of beneficial products or pigment accumulation. We conclude that genome-wide analysis of mutations provides novel insights into the mechanisms by which radiation improves the beneficial ingredients in rice Red-1.

  6. Study of radiation damage in metals by positron annihilation. [Neutron irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Gauster, W.B

    1977-01-01

    Positron annihilation is a sensitive technique for probing defects in metals and it has recently been shown to be a valuable tool for the study of radiation damage. After an introduction to the three basic experimental methods (angular correlation, Doppler broadening, and lifetime measurements), the interaction of positrons with lattice defects is reviewed. Results for the annealing of damage after low temperature irradiation are used to show that positron annihilation has provided new information on annealing kinetics. The role of positron techniques in characterizing complex defect structures resulting from high-temperature neutron irradiation is reviewed and the possible utility of positron annihilation as a nondestructive monitor of property changes is pointed out.

  7. Radiation damage study of thin YAG:Ce scintillator using low-energy protons

    Science.gov (United States)

    Novotný, P.; Linhart, V.

    2017-07-01

    Radiation hardness of a 50 μ m thin YAG:Ce scintillator in a form of dependence of a signal efficiency on 3.1 MeV proton fluence was measured and analysed using X-ray beam. The signal efficiency is a ratio of signals given by a CCD chip after and before radiation damage. The CCD chip was placed outside the primary beam because of its protection from damage which could be caused by radiation. Using simplified assumptions, the 3.1 MeV proton fluences were recalculated to: ṡ 150 MeV proton fluences with intention to estimate radiation damage of this sample under conditions at proton therapy centres during medical treatment, ṡ 150 MeV proton doses with intention to give a chance to compare radiation hardness of the studied sample with radiation hardness of other detectors used in medical physics, ṡ 1 MeV neutron equivalent fluences with intention to compare radiation hardness of the studied sample with properties of position sensitive silicon and diamond detectors used in nuclear and particle physics. The following results of our research were obtained. The signal efficiency of the studied sample varies slightly (± 3%) up to 3.1 MeV proton fluence of c. (4 - 8) × 1014 cm-2. This limit is equivalent to 150 MeV proton fluence of (5 - 9) × 1016 cm-2, 150 MeV proton dose of (350 - 600) kGy and 1 MeV neutron fluence of (1 - 2) × 1016 cm-2. Beyond the limit, the signal efficiency goes gradually down. Fifty percent decrease in the signal efficiency is reached around 3.1 MeV fluence of (1 - 2) × 1016 cm-2 which is equivalent to 150 MeV proton fluence of around 2 × 1018 cm-2, 150 MeV proton dose of around 15 MGy and 1 MeV neutron equivalent fluence of (4 - 8) × 1017 cm-2. In contrast with position sensitive silicon and diamond radiation detectors, the studied sample has at least two order of magnitude greater radiation resistance. Therefore, YAG:Ce scintillator is a suitable material for monitoring of primary beams of particles of ionizing radiation.

  8. Radiation Tolerant Interfaces: Influence of Local Stoichiometry at the Misfit Dislocation on Radiation Damage Resistance of Metal/Oxide Interfaces

    Energy Technology Data Exchange (ETDEWEB)

    Shutthanandan, Vaithiyalingam [Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland WA 99352 USA; Choudhury, Samrat [Materials Science and Technology Division, Los Alamos National Laboratory, Los Alamos NM 87545 USA; Manandhar, Sandeep [Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland WA 99352 USA; Kaspar, Tiffany C. [Physical and Computational Sciences Directorate, Pacific Northwest National Laboratory, Richland WA 99352 USA; Wang, Chongmin [Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland WA 99352 USA; Devaraj, Arun [Physical and Computational Sciences Directorate, Pacific Northwest National Laboratory, Richland WA 99352 USA; Wirth, Brian D. [Department of Nuclear Engineering, University of Tennessee, Knoxville TN 37996 USA; Thevuthasan, Suntharampilli [Physical and Computational Sciences Directorate, Pacific Northwest National Laboratory, Richland WA 99352 USA; Hoagland, Richard G. [Materials Science and Technology Division, Los Alamos National Laboratory, Los Alamos NM 87545 USA; Dholabhai, Pratik P. [Materials Science and Technology Division, Los Alamos National Laboratory, Los Alamos NM 87545 USA; Uberuaga, Blas P. [Materials Science and Technology Division, Los Alamos National Laboratory, Los Alamos NM 87545 USA; Kurtz, Richard J. [Energy and Environment Directorate, Pacific Northwest National Laboratory, Richland WA 99352 USA

    2017-04-24

    To understand how variations in interface properties such as misfit-dislocation density and local chemistry affect radiation-induced defect absorption and recombination, we have explored a model system of CrxV1-x alloy epitaxial films deposited on MgO single crystals. By controlling film composition, the lattice mismatch with MgO was adjusted so that the misfit-dislocation density varies at the interface. These interfaces were exposed to irradiation and in situ results show that the film with a semi-coherent interface (Cr) withstands irradiation while V film, which has similar semi-coherent interface like Cr, showed the largest damage. Theoretical calculations indicate that, unlike at metal/metal interfaces, the misfit dislocation density does not dominate radiation damage tolerance at metal/oxide interfaces. Rather, the stoichiometry, and the precise location of the misfit-dislocation density relative to the interface, drives defect behavior. Together, these results demonstrate the sensitivity of defect recombination to interfacial chemistry and provide new avenues for engineering radiation-tolerant nanomaterials.

  9. ON01210.Na (Ex-RAD® mitigates radiation damage through activation of the AKT pathway.

    Directory of Open Access Journals (Sweden)

    Anthony D Kang

    Full Text Available Development of radio-protective agents that are non-toxic is critical in light of ever increasing threats associated with proliferation of nuclear materials, terrorism and occupational risks associated with medical and space exploration. In this communication, we describe the discovery, characterization and mechanism of action of ON01210.Na, which effectively protects mouse and human bone marrow cells from radiation-induced damage both in vitro and in vivo. Our results show that treatment of normal fibroblasts with ON01210.Na before and after exposure to ionizing radiation provides dose dependent protection against radiation-induced damage. Treatment of mice with ON01210.Na prior to radiation exposure was found to result in a more rapid recovery of their hematopoietic system. The mechanistic studies described here show that ON01210.Na manifests its protective effects through the up-regulation of PI3-Kinase/AKT pathways in cells exposed to radiation. These results suggest that ON 01210.Na is a safe and effective radioprotectant and could be a novel agent for use in radiobiological disasters.

  10. Modeling Radiation Damage Effects in 3D Pixel Digitization for the ATLAS Detector

    CERN Document Server

    Giugliarelli, Gilberto; The ATLAS collaboration

    2017-01-01

    Silicon Pixel detectors are at the core of the current and planned upgrade of the ATLAS detector. As the detector in closest proximity to the interaction point, these detectors will be subjected to a significant amount of radiation over their lifetime: prior to the HL-LHC, the innermost layers will receive a fluence in excess of 10^15 neq/cm2 and the HL-LHC detector upgrades must cope with an order of magnitude higher fluence integrated over their lifetimes. This poster presents the details of a new digitization model that includes radiation damage effects to the 3D Pixel sensors for the ATLAS Detector.

  11. Radiation damage to bull sperm motility. III. Further x-ray studies

    Energy Technology Data Exchange (ETDEWEB)

    Rikmenspoel, R.

    1975-08-01

    The results of previous radiation experiments, which indicated that the centriole serves as a control center for bull sperm motility, appear to be in conflict with experiments showing that the bull sperm flagellum is an autonomous oscillator. To resolve this conflict experiments were conducted to calibrate absolutely the dose-response curves for the radiation damage, and to measure the force production and the mechanochemical energy conversion after irradiation in bull sperm. The results indicate that the centriole acts as a mechanical anchor for the contractile fibers. (auth)

  12. Study of Radiation Damage of Silicon Drift Detectors Induced by Fast Neutrons

    CERN Document Server

    Kugler, A; CERN. Geneva; Hanzal, V

    1995-01-01

    We report results of radiation hardness tests of linear Silicon Drift Detectors (SDDs). Non-biased SDDs wre irradiated using flux of fast neutrons with fluency up to 3.5 x 1013 neutrons/cm2. Neutrons were generated due to the stopping of 20 MeV deuteron beam in thick Be target. We have found that electron drift is still possible. However substantional increase in the leakage current of SDDs was observed. Hence, radiation damage will result in corresponding increase of heat generation, which has to be taken into account designing the cooling system of ALICE ITS.

  13. Modeling Radiation Damage Effects in 3D Pixel Digitization for the ATLAS Detector

    CERN Document Server

    Wallangen, Veronica; The ATLAS collaboration

    2017-01-01

    Silicon Pixel detectors are at the core of the current and planned upgrade of the ATLAS detector. As the detector in closest proximity to the interaction point, these detectors will be subjected to a significant amount of radiation over their lifetime: prior to the HL-LHC, the innermost layers will receive a fluence in excess of 10$^{15}$ n$_\\mathrm{eq}$/cm$^2$ and the HL-LHC detector upgrades must cope with an order of magnitude higher fluence integrated over their lifetimes. This work presents the details of a new digitization model that includes radiation damage effects to the 3D Pixel sensors for the ATLAS detector.

  14. Radiation Damage Modeling for 3D Pixel Sensors in the ATLAS Detector

    CERN Document Server

    Wallangen, Veronica; The ATLAS collaboration

    2017-01-01

    Silicon Pixel detectors are at the core of the current and planned upgrade of the ATLAS detector. As the detector in closest proximity to the interaction point, these detectors will be subjected to a significant amount of radiation over their lifetime: prior to the HL-LHC, the innermost layers will receive a fluence in excess of 10^15 neq/cm2 and the HL-LHC detector upgrades must cope with an order of magnitude higher fluence integrated over their lifetimes. This poster presents the details of a new digitization model that includes radiation damage effects to the 3D Pixel sensors for the ATLAS Detector.

  15. DNA damage checkpoint kinase ATM regulates germination and maintains genome stability in seeds.

    Science.gov (United States)

    Waterworth, Wanda M; Footitt, Steven; Bray, Clifford M; Finch-Savage, William E; West, Christopher E

    2016-08-23

    Genome integrity is crucial for cellular survival and the faithful transmission of genetic information. The eukaryotic cellular response to DNA damage is orchestrated by the DNA damage checkpoint kinases ATAXIA TELANGIECTASIA MUTATED (ATM) and ATM AND RAD3-RELATED (ATR). Here we identify important physiological roles for these sensor kinases in control of seed germination. We demonstrate that double-strand breaks (DSBs) are rate-limiting for germination. We identify that desiccation tolerant seeds exhibit a striking transcriptional DSB damage response during germination, indicative of high levels of genotoxic stress, which is induced following maturation drying and quiescence. Mutant atr and atm seeds are highly resistant to aging, establishing ATM and ATR as determinants of seed viability. In response to aging, ATM delays germination, whereas atm mutant seeds germinate with extensive chromosomal abnormalities. This identifies ATM as a major factor that controls germination in aged seeds, integrating progression through germination with surveillance of genome integrity. Mechanistically, ATM functions through control of DNA replication in imbibing seeds. ATM signaling is mediated by transcriptional control of the cell cycle inhibitor SIAMESE-RELATED 5, an essential factor required for the aging-induced delay to germination. In the soil seed bank, seeds exhibit increased transcript levels of ATM and ATR, with changes in dormancy and germination potential modulated by environmental signals, including temperature and soil moisture. Collectively, our findings reveal physiological functions for these sensor kinases in linking genome integrity to germination, thereby influencing seed quality, crucial for plant survival in the natural environment and sustainable crop production.

  16. Archaeal Genome Guardians Give Insights into Eukaryotic DNA Replication and Damage Response Proteins

    Directory of Open Access Journals (Sweden)

    David S. Shin

    2014-01-01

    Full Text Available As the third domain of life, archaea, like the eukarya and bacteria, must have robust DNA replication and repair complexes to ensure genome fidelity. Archaea moreover display a breadth of unique habitats and characteristics, and structural biologists increasingly appreciate these features. As archaea include extremophiles that can withstand diverse environmental stresses, they provide fundamental systems for understanding enzymes and pathways critical to genome integrity and stress responses. Such archaeal extremophiles provide critical data on the periodic table for life as well as on the biochemical, geochemical, and physical limitations to adaptive strategies allowing organisms to thrive under environmental stress relevant to determining the boundaries for life as we know it. Specifically, archaeal enzyme structures have informed the architecture and mechanisms of key DNA repair proteins and complexes. With added abilities to temperature-trap flexible complexes and reveal core domains of transient and dynamic complexes, these structures provide insights into mechanisms of maintaining genome integrity despite extreme environmental stress. The DNA damage response protein structures noted in this review therefore inform the basis for genome integrity in the face of environmental stress, with implications for all domains of life as well as for biomanufacturing, astrobiology, and medicine.

  17. Empirical constraints on the effects of radiation damage on helium diffusion in zircon

    Science.gov (United States)

    Anderson, Alyssa J.; Hodges, Kip V.; van Soest, Matthijs C.

    2017-12-01

    In this study, we empirically evaluate the impact of radiation damage on zircon (U-Th)/He closure temperatures for a suite of zircon crystals from the slowly cooled McClure Mountain syenite of south-central Colorado, USA. We present new zircon, titanite, and apatite conventional (U-Th)/He dates, zircon laser ablation (U-Th)/He and U-Pb dates, and zircon Raman spectra for crystals from the syenite. Titanite and apatite (U-Th)/He dates range from 447 to 523 Ma and 88.0 to 138.9 Ma, respectively, and display no clear correlation between (U-Th)/He date and effective uranium concentration. Conventional zircon (U-Th)/He dates range from 230.3 to 474 Ma, while laser ablation zircon (U-Th)/He dates show even greater dispersion, ranging from 5.31 to 520 Ma. Dates from both zircon (U-Th)/He datasets decrease with increasing alpha dose, indicating that most of the dispersion can be attributed to radiation damage. Alpha dose values for the dated zircon crystals range from effectively zero to 2.15 × 1019 α /g, spanning the complete damage spectrum. We use an independently constrained thermal model to empirically assign a closure temperature to each dated zircon grain. If we assume that this thermal model is robust, the zircon radiation damage accumulation and annealing model of Guenthner et al. (2013) does not accurately predict closure temperatures for many of the analyzed zircon crystals. Raman maps of the zircons dated by laser ablation document complex radiation damage zoning, sometimes revealing crystalline zones in grains with alpha dose values suggestive of amorphous material. Such zoning likely resulted in heterogeneous intra-crystalline helium diffusion and may help explain some of the discrepancies between our empirical findings and the Guenthner et al. (2013) model predictions. Because U-Th zoning is a common feature in zircon, radiation damage zoning is likely to be a concern for most ancient, slowly cooled zircon (U-Th)/He datasets. Whenever possible, multiple

  18. TRAIP promotes DNA damage response during genome replication and is mutated in primordial dwarfism.

    Science.gov (United States)

    Harley, Margaret E; Murina, Olga; Leitch, Andrea; Higgs, Martin R; Bicknell, Louise S; Yigit, Gökhan; Blackford, Andrew N; Zlatanou, Anastasia; Mackenzie, Karen J; Reddy, Kaalak; Halachev, Mihail; McGlasson, Sarah; Reijns, Martin A M; Fluteau, Adeline; Martin, Carol-Anne; Sabbioneda, Simone; Elcioglu, Nursel H; Altmüller, Janine; Thiele, Holger; Greenhalgh, Lynn; Chessa, Luciana; Maghnie, Mohamad; Salim, Mahmoud; Bober, Michael B; Nürnberg, Peter; Jackson, Stephen P; Hurles, Matthew E; Wollnik, Bernd; Stewart, Grant S; Jackson, Andrew P

    2016-01-01

    DNA lesions encountered by replicative polymerases threaten genome stability and cell cycle progression. Here we report the identification of mutations in TRAIP, encoding an E3 RING ubiquitin ligase, in patients with microcephalic primordial dwarfism. We establish that TRAIP relocalizes to sites of DNA damage, where it is required for optimal phosphorylation of H2AX and RPA2 during S-phase in response to ultraviolet (UV) irradiation, as well as fork progression through UV-induced DNA lesions. TRAIP is necessary for efficient cell cycle progression and mutations in TRAIP therefore limit cellular proliferation, providing a potential mechanism for microcephaly and dwarfism phenotypes. Human genetics thus identifies TRAIP as a component of the DNA damage response to replication-blocking DNA lesions.

  19. Molecular dynamics study of radiation damage and microstructure evolution of zigzag single-walled carbon nanotubes under carbon ion incidence

    Energy Technology Data Exchange (ETDEWEB)

    Li, Huan [Department of Nuclear Science & Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing (China); Tang, Xiaobin, E-mail: tangxiaobin@nuaa.edu.cn [Department of Nuclear Science & Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing (China); Jiangsu Key Laboratory of Nuclear Energy Equipment Materials Engineering, Nanjing (China); Chen, Feida; Huang, Hai; Liu, Jian [Department of Nuclear Science & Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing (China); Chen, Da [Department of Nuclear Science & Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing (China); Jiangsu Key Laboratory of Nuclear Energy Equipment Materials Engineering, Nanjing (China)

    2016-07-01

    Highlights: • Various incident sites of CNTs are classified into three types for the first time. • Different ion energies and fluences are considered to study the radiation damage. • CNTs have ability to heal the radiation-induced damage at higher temperature. • Stability of a large-diameter tube excels in a slim one under the same conditions. - Abstract: The radiation damage and microstructure evolution of different zigzag single-walled carbon nanotubes (SWCNTs) were investigated under incident carbon ion by molecular dynamics (MD) simulations. The radiation damage of SWCNTs under incident carbon ion with energy ranging from 25 eV to 1 keV at 300 K showed many differences at different incident sites, and the defect production increased to the maximum value with the increase in incident ion energy, and slightly decreased but stayed fairly stable within the majority of the energy range. The maximum damage of SWCNTs appeared when the incident ion energy reached 200 eV and the level of damage was directly proportional to incident ion fluence. The radiation damage was also studied at 100 K and 700 K and the defect production decreased distinctly with rising temperature because radiation-induced defects would anneal and recombine by saturating dangling bonds and reconstructing carbon network at the higher temperature. Furthermore, the stability of a large-diameter tube surpassed that of a thin one under the same radiation environments.

  20. The influence of various factors on the radiation induced structural damage and leakage of liposomes

    Science.gov (United States)

    Sprinz, H.; Franck, U.; Winkler, E.; Schäfer, H.; Kuroptera, Z. V.

    Liposomes from egg yolk lecithin are a membrane model possessing various properties of natural lipids. The modification of chemical groups and the increase of the penetration of europium ions into liposomes after irradiation was measured by means of NMR methods. It is shown that nitrofuraldehyde as well as sodium chloride in physiological concentration may protect against radiation damage. The chloride ion is the ion responsible for the protection effect. The influence of the variation of some irradiation conditions is discussed.

  1. Space Photovoltaic Research and Technology 1983. High Efficiency, Radiation Damage, and Blanket Technology

    Science.gov (United States)

    1984-01-01

    This three day conference, sixth in a series that began in 1974, was held at the NASA Lewis Research Center on October 18-20, 1983. The conference provided a forum for the discussion of space photovoltaic systems, their research status, and program goals. Papers were presented and workshops were held in a variety of technology areas, including basic cell research, advanced blanket technology, and radiation damage.

  2. Prevention of radiation damages with antioxidative nutritional factors and analysis of the modification

    Energy Technology Data Exchange (ETDEWEB)

    Umegaki, Keizo; Esashi, Takatoshi [National Inst. of Health and Nutrition, Tokyo (Japan)

    1998-02-01

    The effects of dietary vitamine E, C and carotene on the damages of bone marrow DNA were investigated with mice exposed to X-ray radiation as the functions of radiation dose and time after the radiation. The administrations of vit E and vit C had little preventive effects on the generation of DNA damages due to X-ray irradiation. This may be attributed to small intake of those vitamines by bone marrow. On the contrary, the administration of {beta}-carotene from donaliella, a green algae at a dose of 300 mg/kg of body weight for two weeks significantly repressed the production of DNA damages by X-ray irradiation at 0.3 Gy, whereas the administration of carotene from palm oil had no effects. The vitamine E level was markedly reduced by either administration of the two carotenes to a level nearly 1/100-1/50 of the normal level. This study suggests that to investigate the effects of an antioxidant in vivo, it is important to consider its concentration in the region concerned as well as the effects of other antioxidants. (M.N.)

  3. Femtoradical events in aqueous molecular environments: the tenuous borderline between direct and indirect radiation damages

    Energy Technology Data Exchange (ETDEWEB)

    Gauduel, Y; Glinec, Y; Malka, V [Laboratoire d' Optique Appliquee, CNRS UMR 7639, Ecole Polytechnique - ENS Techniques Avancees, 91761 Palaiseau Cedex (France)], E-mail: yann.gauduel@ensta.fr

    2008-02-01

    The complex links existing between radiation physics and radiobiology concern the complete understanding of spatio-temporal events triggered by an initial energy deposition in confined spaces called spurs. Microscopic radiation effects (photons or relativistic particles) on integrated biological targets such as water 'the solvent of life' and biomolecular architectures (DNA, histones, enzymes) cannot be satisfactorily described from an absorbed dose delivery profile or a linear energy transfer (LET) approach. Primary radiation damages on biological targets being dependent on the survival probability of secondary electrons and short-lived radicals inside nascent nanometric clusters of ionisation, a thorough knowledge of these processes require the real-time probing of early events on sub-micrometric scale, in the temporal range 10{sup -15} - 10{sup -10} s. Major strides concern early water damages: primary water cation formation (H{sub 2}O{sup .+} or positive hole), concerted electron-proton couplings, attachment dynamics of p-like excited prehydrated electron on biomolecule, short-lived radical pairs involving water-bridged radical OH{sup .} and hydronium ion H{sub 3}O{sup +}. The deactivation frequency of electron-radical pairs is comparable to an H-OH deactivation of excited water molecules (v{sub H2O}* {approx} 0.33 x 10{sup 13} s{sup -1}). These short-lived events take place in the prethermal regime of delocalized secondary electrons and represent a tenuous borderline between direct and indirect molecular damages.

  4. Palliative effects of lutein intervention in gamma-radiation-induced cellular damages in Swiss albino mice.

    Science.gov (United States)

    Vasudeva, Vidya; Tenkanidiyoor, Yogish Somayaji; Radhakrishna, Vishakh; Shivappa, Pooja; Lakshman, Srikanth Patil; Fernandes, Ronald; Patali, Krishna Ananthapura

    2017-01-01

    Radiation-induced hematological, biochemical, and cytogenetic damages to the normal cells are major concerns in the field of radiotherapy. The carotenoids and their derivatives have been the source of antioxidants with wide range of medicinal applications. The objective is to evaluate the protective effects of lutein, a carotenoid, against radiation-induced cellular and tissue damages. Swiss albino mice were grouped into 5, 50, 250, and 500 mg/kg b.wt. of lutein treatment groups, a sham and vehicle control group. The groups were irradiated with a lethal dose of 10 Gy y'-radiation. The mortality was recorded for 30 days to optimize the protective dose against radiation. The mice were administered with the compound orally for 15 consecutive days and irradiated with a sublethal dose of 6Gy. The hematological changes in blood and antioxidant parameters were determined in liver, kidney homogenates, and hemolysate/serum. The hematological parameters were recorded using an automated cell counter. The antioxidants such as malondialdehyde (MDA), glutathione (GSH), superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase were spectrophotometrically determined. The red blood cell, white blood cell count, lymphocyte count, hemoglobin, platelet levels, and hematocrit value were found to be decreased in the irradiated groups. Lutein pretreatment maintains near-normal levels of these parameters indicating resistance/recovery from the radiation-induced damages. The antioxidant levels were found to be reduced in all the irradiated groups. However, lutein pretreatment (50 mg/kg b.wt.) has increased the catalase activity of hemolysate. Lutein pretreatment has reduced the MDA levels in hemolysate, when administered at doses of 5, 250, and 500 mg/kg b.wt. in comparison to its control. The study demonstrates the radioprotective potential of lutein by maintaining the hematological and antioxidant homeostasis.

  5. Protection against radiation-induced hematopoietic damage in bone marrow by hepatocyte growth factor gene transfer.

    Science.gov (United States)

    Li, Qingfang; Sun, Huiyan; Xiao, Fengjun; Wang, Xiaojie; Yang, Yuefeng; Liu, Yingxia; Zhang, Qunwei; Wu, Chutse; Wang, Hua; Wang, Li-Sheng

    2014-01-01

    To investigate whether adenovirus-mediated delivery of the human hepatocyte growth factor (HGF) gene could prevent radiation-induced hematopoietic damage. Thirty C57BL/6 mice were randomized into three groups, in which phosphate buffer saline (PBS), mock adenovirus vector (Ad-null) or adenovirus vector containing HGF (Ad-HGF) were injected into the tail vein of each group, respectively. After 48 hours, the mice received a single irradiation dose of 6.5 Gy (60)Co gamma rays. Blood samples were extracted via the tail vein at day 0, 4, 7, 10, 14, 21, 24 and 30 after irradiation, for red blood cell (RBC) and white blood cell (WBC) and cluster of differentiation4 (CD4)/cluster of differentiation8 (CD8) ratio assessment. At weekly intervals following irradiation, serum erythropoietin (EPO), Interleukin-6 (IL-6) and Interferon-gamma (IFN-γ) levels were measured using enzyme-linked immunosorbent assay (ELISA). On post-irradiation day 30, the mice were autopsied and erythroid burst-forming units (BFU-E) were evaluated. Adenovirus-mediated HGF gene transfer could increase human HGF level in serum and have a significant elevation in RBC and WBC count. Ad-HGF increased EPO and IL-6 levels and prompted BFU-E formation. Ad-HGF decreased radiation- induced micronucleus frequency in the mouse bone marrow (BM). Most evidence of radiation-induced hematopoietic damage was observed morphologically in bone marrow specimen four weeks after irradiation. Ad-HGF protected against radiation-induced BM failure and increased survival. Finally, Ad-HGF increased the thymic index and enhanced immune function in the irradiated C57BL/6 mice. This is the first report to date that demonstrates the potential of HGF gene transfer to prevent radiation-induced hematopoietic damage.

  6. Low doses of ionizing radiation to mammalian cells may rather control than cause DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Feinendegen, L.E. [Brookhaven National Lab., Upton, NY (United States). Medical Dept.; Bond, V.P. [Washington State Univ., Richland, WA (United States); Sondhaus, C.A. [Univ. of Arizona, Tucson, AZ (United States). Dept. of Radiology and Radiation Control Office; Altman, K.I. [Univ. of Rochester Medical Center, NY (United States). Dept. of Biochemistry and Biophysics

    1998-12-31

    This report examines the origin of tissue effects that may follow from different cellular responses to low-dose irradiation, using published data. Two principal categories of cellular responses are considered. One response category relates to the probability of radiation-induced DNA damage. The other category consists of low-dose induced metabolic changes that induce mechanisms of DNA damage mitigation, which do not operate at high levels of exposure. Modeled in this way, tissue is treated as a complex adaptive system. The interaction of the various cellular responses results in a net tissue dose-effect relation that is likely to deviate from linearity in the low-dose region. This suggests that the LNT hypothesis should be reexamined. This paper aims at demonstrating tissue effects as an expression of cellular responses, both damaging and defensive, in relation to the energy deposited in cell mass, by use of microdosimetric concepts.

  7. Radiation damage and nuclear heating studies in selected functional materials during the JET DT campaign

    Energy Technology Data Exchange (ETDEWEB)

    Lengar, Igor, E-mail: igor.lengar@ijs.si [Jozef Stefan Institute, Reactor Physics Department, Jamova 39, SI-1000 Ljubljana (Slovenia); EUROfusion Consortium, JET, Culham Science Centre, Abingdon OX14 3DB (United Kingdom); Čufar, Aljaž [Jozef Stefan Institute, Reactor Physics Department, Jamova 39, SI-1000 Ljubljana (Slovenia); EUROfusion Consortium, JET, Culham Science Centre, Abingdon OX14 3DB (United Kingdom); Conroy, Sean [Department of Physics and Astronomy, Uppsala University, SE-75120 Uppsala (Sweden); EUROfusion Consortium, JET, Culham Science Centre, Abingdon OX14 3DB (United Kingdom); Batistoni, Paola [ENEA, via E. Fermi 45, 00044 Frascati, Roma (Italy); EUROfusion Consortium, JET, Culham Science Centre, Abingdon OX14 3DB (United Kingdom); Popovichev, Sergey [CCFE, Culham Science Centre, Abingdon OX14 3DB, Oxon (United Kingdom); EUROfusion Consortium, JET, Culham Science Centre, Abingdon OX14 3DB (United Kingdom); Snoj, Luka [Jozef Stefan Institute, Reactor Physics Department, Jamova 39, SI-1000 Ljubljana (Slovenia); EUROfusion Consortium, JET, Culham Science Centre, Abingdon OX14 3DB (United Kingdom); Syme, Brian [CCFE, Culham Science Centre, Abingdon OX14 3DB, Oxon (United Kingdom); EUROfusion Consortium, JET, Culham Science Centre, Abingdon OX14 3DB (United Kingdom); Vila, Rafael [Laboratorio Nacional de Fusión, CIEMAT, Madrid (Spain); EUROfusion Consortium, JET, Culham Science Centre, Abingdon OX14 3DB (United Kingdom); Stankunas, Gediminas [Lithuanian Energy Institute, Laboratory of Nuclear Installation Safety, Breslaujos str. 3, LT-44403 Kaunas (Lithuania); EUROfusion Consortium, JET, Culham Science Centre, Abingdon OX14 3DB (United Kingdom)

    2016-11-01

    Highlights: • Material damage calculation in during the JET DT campaign nuclear heating ratio of the damage due to 14 MeV neutronsgamma activity and dose rates. - Abstract: A new Deuterium-Tritium campaign (DTE2) is planned at JET in the next years, with a proposed 14 MeV neutron budget of 1.7 × 10{sup 21}, which is nearly an order of magnitude higher than any previous DT campaigns. The neutron and gamma ray fields inside the JET device during DT plasma operations at specific locations have previously been evaluated. It is estimated that a total neutron fluence on the first wall of JET of up to 10{sup 20} n/m{sup 2} could be achieved, which is comparable to the fluence occurring in ITER at the end of life in the rear part of the port plug, where several diagnostic components will be located. The purpose of the present work is to evaluate the radiation damage and nuclear heating in selected functional materials to be irradiated at JET during DT plasma operation. These quantities are calculated with the use of the MCNP6 code and the FISPACT II code. In particular the neutron and gamma ray fields at specific locations inside the JET device, dedicated to material damage studies, were characterized. The emphasis is on a potential long term irradiation station located close to the first wall at outboard midplane, offering the opportunity to irradiate samples of functional materials used in ITER diagnostics, to assess the degradation of the physical properties. The radiation damage and the nuclear heating were calculated for selected materials irradiated in these positions and for the neutron flux and fluence expected in DTE2. The studied candidate functional materials include, among others, Sapphire, YAG, ZnS, Spinel, Diamond. In addition the activation of the internal irradiation holder itself was calculated with FISPACT. Damage levels in the range of 10{sup −5} dpa were found.

  8. Ionizing radiation-induced DNA injury and damage detection in patients with breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Borrego-Soto, Gissela; Ortiz-Lopez, Rocio; Rojas-Martinez, Augusto, E-mail: arojasmtz@gmail.com, E-mail: augusto.rojasm@uanl.mx [Departamento de Bioquímica y Medicina Molecular, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León (Mexico)

    2015-10-15

    Breast cancer is the most common malignancy in women. Radiotherapy is frequently used in patients with breast cancer, but some patients may be more susceptible to ionizing radiation, and increased exposure to radiation sources may be associated to radiation adverse events. This susceptibility may be related to deficiencies in DNA repair mechanisms that are activated after cell-radiation, which causes DNA damage, particularly DNA double strand breaks. Some of these genetic susceptibilities in DNA-repair mechanisms are implicated in the etiology of hereditary breast/ovarian cancer (pathologic mutations in the BRCA 1 and 2 genes), but other less penetrant variants in genes involved in sporadic breast cancer have been described. These same genetic susceptibilities may be involved in negative radiotherapeutic outcomes. For these reasons, it is necessary to implement methods for detecting patients who are susceptible to radiotherapy-related adverse events. This review discusses mechanisms of DNA damage and repair, genes related to these functions, and the diagnosis methods designed and under research for detection of breast cancer patients with increased radiosensitivity. (author)

  9. Study on radiation damage to high energy accelerator components by irradiation in a nuclear reactor

    CERN Document Server

    Schönbacher, Helmut; Casta, J; Van de Voorde, M H

    1975-01-01

    The structural and other components used in high energy accelerators are continuously exposed to a wide spectrum of high energy particles and electromagnetic radiation. The resulting radiation damage may severely influence the functional capability of accelerator facilities. In order to arrive at an estimate of the service life of various materials in the radiation field, simulating experiments have to be carried out in a nuclear reactor. A large number of organic and inorganic materials, electronic components, metals, etc., intended specifically for use in 400 GeV proton synchrotron of CERN near Geneva, were irradiated in the ASTRA reactor in Seibersdorf near Vienna. The paper reports on the irradiation facilities available in this reactor for this purpose, on the dosimetry methods used, on the most important materials irradiated and on the results obtained in these experiments. (14 refs).

  10. Spatiotemporal characterization of ionizing radiation induced DNA damage foci and their relation to chromatin organization

    Energy Technology Data Exchange (ETDEWEB)

    Costes, Sylvain V; Chiolo, Irene; Pluth, Janice M.; Barcellos-Hoff, Mary Helen; Jakob, Burkhard

    2009-09-15

    DNA damage sensing proteins have been shown to localize to the sites of DSB within seconds to minutes following ionizing radiation (IR) exposure, resulting in the formation of microscopically visible nuclear domains referred to as radiation-induced foci (RIF). This review characterizes the spatio-temporal properties of RIF at physiological doses, minutes to hours following exposure to ionizing radiation, and it proposes a model describing RIF formation and resolution as a function of radiation quality and nuclear densities. Discussion is limited to RIF formed by three interrelated proteins ATM (Ataxia telangiectasia mutated), 53BP1 (p53 binding protein 1) and ?H2AX (phosphorylated variant histone H2AX). Early post-IR, we propose that RIF mark chromatin reorganization, leading to a local nuclear scaffold rigid enough to keep broken DNA from diffusing away, but open enough to allow the repair machinery. We review data indicating clear kinetic and physical differences between RIF emerging from dense and uncondensed regions of the nucleus. At later time post-IR, we propose that persistent RIF observed days following exposure to ionizing radiation are nuclear ?scars? marking permanent disruption of the chromatin architecture. When DNA damage is resolved, such chromatin modifications should not necessarily lead to growth arrest and it has been shown that persistent RIF can replicate during mitosis. Thus, heritable persistent RIF spanning over tens of Mbp may affect the transcriptome of a large progeny of cells. This opens the door for a non DNA mutation-based mechanism of radiation-induced phenotypes.

  11. THE ONE CINETIC MODEL DAMAGE OF CELL BY SMALL DOSES OF RADIATION

    Directory of Open Access Journals (Sweden)

    A. T. Gubin

    2015-01-01

    Full Text Available To explain the known differences in the dose and age dependences of radiogenic mortality from leukemia and solid tumors after single exposure, a model was developed, which is a modification of the Kellerer-Rossi theory of dual radiation action. The model assumes formation in a cell of both single and double primary damages due to radiation and other carcinogens, while the recovery rate of single damages (φ significantly exceeds that for double ones (ψ. Upon achieving a certain stage of the cell cycle (the critical age of cell – T, double damages become permanent and with probability of А can be inherited to daughter cells as “premalignant” defects. In contrast, in the Kellerer-Rossi theory, permanent damage is formed immediately after formation of the second damage at the next energy absorption event in the cell, i.e. ψ=0 .On the assumption that the premalignant defects only occur based on the double primary damages, i.e. φ>>ψ, the expressions for А were derived for the prompt radiation exposure and radiation exposure at a constant dose rate. They reproduce the effect increasing with decreasing of T, whereas the influence of T on the linear term of the dose expression in both cases is the same, but with decreasing of T the quadratic term increases faster for exposure at a constant dose rate than that for the prompt one. Thus, presence of the quadratic term in the dose expression for leukemia and its virtual complete absence for solid tumors may be due to lower T-value for hemopoietic stem cells. Predicted by the model dose rate influence on the quadratic term does not depend on the dose, so the reduction factor should be only applied to the quadratic term of the dose expression. This follows as well from the original version of the Kellerer-Rossi theory.

  12. Lipid peroxidation, detoxification capacity, and genome damage in mice after transplacental exposure to pharmaceutical drugs

    Directory of Open Access Journals (Sweden)

    D. Markovic

    2013-12-01

    Full Text Available Data on genome damage, lipid peroxidation, and levels of glutathione peroxidase (GPX in newborns after transplacental exposure to xenobiotics are rare and insufficient for risk assessment. The aim of the current study was to analyze, in an animal model, transplacental genotoxicity, lipid peroxidation, and detoxification disturbances caused by the following drugs commonly prescribed to pregnant women: paracetamol, fluconazole, 5-nitrofurantoin, and sodium valproate. Genome damage in dams and their newborn pups transplacentally exposed to these drugs was investigated using the in vivo micronucleus (MN assay. The drugs were administered to dams intraperitoneally in three consecutive daily doses between days 12 and 14 of pregnancy. The results were correlated, with detoxification capacity of the newborn pups measured by the levels of GPX in blood and lipid peroxidation in liver measured by malondialdehyde (HPLC-MDA levels. Sodium valproate and 5-nitrofurantoin significantly increased MN frequency in pregnant dams. A significant increase in the MN frequency of newborn pups was detected for all drugs tested. This paper also provides reference levels of MDA in newborn pups, according to which all drugs tested significantly lowered MDA levels of newborn pups, while blood GPX activity dropped significantly only after exposure to paracetamol. The GPX reduction reflected systemic oxidative stress, which is known to occur with paracetamol treatment. The reduction of MDA in the liver is suggested to be an unspecific metabolic reaction to the drugs that express cytotoxic, in particular hepatotoxic, effects associated with oxidative stress and lipid peroxidation.

  13. Detection of DNA damage by space radiation in human fibroblasts flown on the International Space Station

    Science.gov (United States)

    Lu, Tao; Zhang, Ye; Wong, Michael; Feiveson, Alan; Gaza, Ramona; Stoffle, Nicholas; Wang, Huichen; Wilson, Bobby; Rohde, Larry; Stodieck, Louis; Karouia, Fathi; Wu, Honglu

    2017-02-01

    Although charged particles in space have been detected with radiation detectors on board spacecraft since the discovery of the Van Allen Belts, reports on the effects of direct exposure to space radiation in biological systems have been limited. Measurement of biological effects of space radiation is challenging due to the low dose and low dose rate nature of the radiation environment, and due to the difficulty in distinguishing the radiation effects from microgravity and other space environmental factors. In astronauts, only a few changes, such as increased chromosome aberrations in their lymphocytes and early onset of cataracts, are attributed primarily to their exposure to space radiation. In this study, cultured human fibroblasts were flown on the International Space Station (ISS). Cells were kept at 37 °C in space for 14 days before being fixed for analysis of DNA damage with the γ-H2AX assay. The 3-dimensional γ-H2AX foci were captured with a laser confocal microscope. Quantitative analysis revealed several foci that were larger and displayed a track pattern only in the Day 14 flight samples. To confirm that the foci data from the flight study was actually induced from space radiation exposure, cultured human fibroblasts were exposed to low dose rate γ rays at 37 °C. Cells exposed to chronic γ rays showed similar foci size distribution in comparison to the non-exposed controls. The cells were also exposed to low- and high-LET protons, and high-LET Fe ions on the ground. Our results suggest that in G1 human fibroblasts under the normal culture condition, only a small fraction of large size foci can be attributed to high-LET radiation in space.

  14. Hesperidin as radioprotector against radiation-induced lung damage in rat: A histopathological study

    Directory of Open Access Journals (Sweden)

    Gholam Hassan Haddadi

    2017-01-01

    Full Text Available Reactive oxygen species (ROS are generated by ionizing radiation, and one of the organs commonly affected by ROS is the lung. Radiation-induced lung injury including pneumonia and lung fibrosis is a dose-limiting factor in radiotherapy (RT of patients with thorax irradiation. Administration of antioxidants has been proved to protect against ROS. The present study was aimed to assess the protective effect of hesperidin (HES against radiation-induced lung injury of male rats. Fifty rats were divided into three groups. G1: Received no HES and radiation (sham. G2: Underwent γ-irradiation to the thorax. G3: Received HES and underwent γ-irradiation. The rats were exposed to a single dose of 18 Gy using cobalt-60 unit and were administered HES (100 mg/kg for 7 days before irradiation. Histopathological analysis was performed 24 h and 8 weeks after RT. Histopathological results in 24 h showed radiation-induced inflammation and presence of more inflammatory cells as compared to G1 (P < 0.05. Administration of HES significantly decreased such an effect when compared to G2 (P < 0.05. Histopathological evaluation in 8 weeks showed a significant increase in mast cells, inflammation, inflammatory cells, alveolar thickness, vascular thickness, pulmonary edema, and fibrosis in G2 when compared to G1 (P < 0.05. HES significantly decreased inflammatory response, fibrosis, and mast cells when compared to G2 (P < 0.05. Administration of HES resulted in decreased radiation pneumonitis and radiation fibrosis in the lung tissue. Thus, the present study showed HES to be an efficient radioprotector against radiation-induced damage in the lung of tissue rats.

  15. Detection of DNA Damage by Space Radiation in Human Fibroblasts Flown on the International Space Station

    Science.gov (United States)

    Lu, Tao; Zhang, Ye; Wong, Michael; Feiveson, Alan; Gaza, Ramona; Stoffle, Nicholas; Wang, Huichen; Wilson, Bobby; Rohde, Larry; Stodieck, Louis; hide

    2017-01-01

    Although charged particles in space have been detected with radiation detectors on board spacecraft since the discovery of the Van Allen Belts, reports on the effects of direct exposure to space radiation in biological systems have been limited. Measurement of biological effects of space radiation is challenging due to the low dose and low dose rate nature of the radiation environment, and due to the difficulty in distinguishing the radiation effects from microgravity and other space environmental factors. In astronauts, only a few changes, such as increased chromosome aberrations in their lymphocytes and early onset of cataracts, are attributed primarily to their exposure to space radiation. In this study, cultured human fibroblasts were flown on the International Space Station (ISS). Cells were kept at 37 degrees Centigrade in space for 14 days before being fixed for analysis of DNA damages with the gamma-H2AX assay. The 3-dimensional gamma-H2AX foci were captured with a laser confocal microscope. Quantitative analysis revealed several foci that were larger and displayed a track pattern only in the Day 14 flight samples. To confirm that the foci data from the flight study was actually induced from space radiation exposure, cultured human fibroblasts were exposed to low dose rate gamma rays at 37 degrees Centigrade. Cells exposed to chronic gamma rays showed similar foci size distribution in comparison to the non-exposed controls. The cells were also exposed to low- and high-LET (Linear Energy Transfer) protons, and high-LET Fe ions on the ground. Our results suggest that in G1 human fibroblasts under the normal culture condition, only a small fraction of large size foci can be attributed to high-LET radiation in space.

  16. In vivo and in vitro evaluation of corneal damage induced by 1573 nm laser radiation

    Energy Technology Data Exchange (ETDEWEB)

    Courant, D.; Chapel, C. [CEA Fontenay-aux-Roses (DSV/DRR/SRBF), 92 (France). Dept. de Radiobiologie et de Radiopathologie; Pothier, C. [DGA-DCE/CTA/LOT, 94 - Arcueil (France); Sales, N. [CEA Fontenay-aux-Roses (DSV/DRM/SNV), 92 (France)

    2006-07-01

    Recent developments in laser technology have originated a variety of infrared laser sources between 1500-1700 nm called as 'eye-safe' which are gaining widespread use in industry, medicine and military applications. This spectral region has been called 'eye safe' because the cornea and aqueous humor absorb sufficient radiation to prevent nearly all potentially damaging radiation from reaching the retina whereas the lens does not absorb this spectral range and remains undamaged. However, in providing protection for the deeper layers of the eye, the cornea itself is susceptible to thermal damage. Previous studies, performed at 1540 nm with exposures less than 1 s, are inconsistent in the quantity of energy required to cause corneal damage. The purpose of this study was first, to determine the threshold damage exposure (E.D.{sub 50}) on rabbit cornea induced by a 3 ns single pulse emitted at 1573 nm, using clinical observations and histology and to compare the results to the limit values recommended by I.C.N.I.R.P. guidelines or international standards. Secondly, it was suggested to investigate the cellular effects of infrared radiation with biochemical techniques on cell cultures in order to specify a cellular damage threshold and a better understanding of the laser - tissue interaction and the corneal injury. The minimal damage criterion was defined by a shallow, very small depression of the epithelial surface with a mild fluorescein staining. The E.D.{sub 50} obtained with corneal beam diameter of 400 mm is 26.6 J.cm{sup -2}. The corresponding radiant exposure, calculated with the 1 mm aperture diameter recommended by I.C.N.I.R.P. guidelines or standards, is 4.3 J.cm{sup -2}. In vitro experiments have been carried out on primary keratocytes and H.T. 1080 epithelial cell line, using an expanded beam of 3.5 mm diameter on plates or Lab Tek holders. Cells were irradiated with 10 Hz pulse ratio frequency during 1, 2 or 3 s. The S A

  17. Stability of Radiation Induced Chromosome Damage in Human Peripheral Blood Lymphocytes

    Science.gov (United States)

    Cucinotta, F. A.; George, K.; Willingham, V.

    2006-01-01

    Chromosome damage in an individual's peripheral blood lymphocytes can be an indicator of radiation exposure and this data can be used to evaluate dose after accidental or occupational exposure. Evidence suggests that the yield of chromosome damage in lymphocytes is also a relevant biomarker of cancer risk in humans that reflects individual cancer susceptibility. It follows that biomonitoring studies can be used to uncover subjects who are particularly susceptible to radiation damage and therefore at higher risk of cancer. Translocations and other stable aberrations are commonly believed to persist in peripheral blood cells for many years after exposure, and it has been suggested that translocations can be used for assessing retrospective radiation doses or chronic exposures. However, recent investigations suggest that translocations might not always persist indefinitely. We measured chromosome aberrations in the blood lymphocytes of six astronauts before their respective missions of approximately 3 to 6 months onboard the international space station, and again at various intervals up to 5 years after flight. In samples collected a few days after return to earth, the yield of chromosome translocations had significantly increased compared with preflight values, and results indicate that biodosimetry estimates lie within the range expected from physical dosimetry. However, for five of the astronauts, follow up analysis revealed a temporal decline in translocations with half-lives ranging from 10 to 58 months. The yield of exchanges remained unchanged for the sixth astronaut during an observation period of 5 months post-flight. These results may indicate complications with the use of stable aberrations for retrospective dose reconstruction and could affect cancer risk predictions that are estimated from yields of chromosome damage obtained shortly after exposure.

  18. Repair of base damage and genome maintenance in the nucleo-cytoplasmic large DNA viruses.

    Science.gov (United States)

    Redrejo-Rodríguez, Modesto; Salas, María L

    2014-01-22

    Among the DNA viruses, the so-called nucleo-cytoplasmic large DNA viruses (NCLDV) constitute a monophyletic group that currently consists of seven families of viruses infecting a very broad variety of eukaryotes, from unicellular marine protists to humans. Many recent papers have analyzed the sequence and structure of NCLDV genomes and their phylogeny, providing detailed analysis about their genomic structure and evolutionary history and proposing their inclusion in a new viral order named Megavirales that, according to some authors, should be considered as a fourth domain of life, aside from Bacteria, Archaea and Eukarya. The maintenance of genetic information protected from environmental attacks and mutations is essential not only for the survival of cellular organisms but also viruses. In cellular organisms, damaged DNA bases are removed in two major repair pathways: base excision repair (BER) and nucleotide incision repair (NIR) that constitute the major pathways responsible for repairing most endogenous base lesions and abnormal bases in the genome by precise repair procedures. Like cells, many NCLDV encode proteins that might constitute viral DNA repair pathways that would remove damages through BER/NIR pathways. However, the molecular mechanisms and, specially, the biological roles of those viral repair pathways have not been deeply addressed in the literature so far. In this paper, we review viral-encoded BER proteins and the genetic and biochemical data available about them. We propose and discuss probable viral-encoded DNA repair mechanisms and pathways, as compared with the functional and molecular features of known homologs proteins. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Characterization of genomic alterations in radiation-associated breast cancer among childhood cancer survivors, using comparative genomic hybridization (CGH arrays.

    Directory of Open Access Journals (Sweden)

    Xiaohong R Yang

    Full Text Available Ionizing radiation is an established risk factor for breast cancer. Epidemiologic studies of radiation-exposed cohorts have been primarily descriptive; molecular events responsible for the development of radiation-associated breast cancer have not been elucidated. In this study, we used array comparative genomic hybridization (array-CGH to characterize genome-wide copy number changes in breast tumors collected in the Childhood Cancer Survivor Study (CCSS. Array-CGH data were obtained from 32 cases who developed a second primary breast cancer following chest irradiation at early ages for the treatment of their first cancers, mostly Hodgkin lymphoma. The majority of these cases developed breast cancer before age 45 (91%, n = 29, had invasive ductal tumors (81%, n = 26, estrogen receptor (ER-positive staining (68%, n = 19 out of 28, and high proliferation as indicated by high Ki-67 staining (77%, n = 17 out of 22. Genomic regions with low-copy number gains and losses and high-level amplifications were similar to what has been reported in sporadic breast tumors, however, the frequency of amplifications of the 17q12 region containing human epidermal growth factor receptor 2 (HER2 was much higher among CCSS cases (38%, n = 12. Our findings suggest that second primary breast cancers in CCSS were enriched for an "amplifier" genomic subgroup with highly proliferative breast tumors. Future investigation in a larger irradiated cohort will be needed to confirm our findings.

  20. ATM Deficiency Generating Genomic Instability Sensitizes Pancreatic Ductal Adenocarcinoma Cells to Therapy-Induced DNA Damage.

    Science.gov (United States)

    Perkhofer, Lukas; Schmitt, Anna; Romero Carrasco, Maria Carolina; Ihle, Michaela; Hampp, Stephanie; Ruess, Dietrich Alexander; Hessmann, Elisabeth; Russell, Ronan; Lechel, André; Azoitei, Ninel; Lin, Qiong; Liebau, Stefan; Hohwieler, Meike; Bohnenberger, Hanibal; Lesina, Marina; Algül, Hana; Gieldon, Laura; Schröck, Evelin; Gaedcke, Jochen; Wagner, Martin; Wiesmüller, Lisa; Sipos, Bence; Seufferlein, Thomas; Reinhardt, Hans Christian; Frappart, Pierre-Olivier; Kleger, Alexander

    2017-10-15

    Pancreatic ductal adenocarcinomas (PDAC) harbor recurrent functional mutations of the master DNA damage response kinase ATM, which has been shown to accelerate tumorigenesis and epithelial-mesenchymal transition. To study how ATM deficiency affects genome integrity in this setting, we evaluated the molecular and functional effects of conditional Atm deletion in a mouse model of PDAC. ATM deficiency was associated with increased mitotic defects, recurrent genomic rearrangements, and deregulated DNA integrity checkpoints, reminiscent of human PDAC. We hypothesized that altered genome integrity might allow synthetic lethality-based options for targeted therapeutic intervention. Supporting this possibility, we found that the PARP inhibitor olaparib or ATR inhibitors reduced the viability of PDAC cells in vitro and in vivo associated with a genotype-selective increase in apoptosis. Overall, our results offered a preclinical mechanistic rationale for the use of PARP and ATR inhibitors to improve treatment of ATM-mutant PDAC. Cancer Res; 77(20); 5576-90. ©2017 AACR. ©2017 American Association for Cancer Research.

  1. XPD localizes in mitochondria and protects the mitochondrial genome from oxidative DNA damage.

    Science.gov (United States)

    Liu, Jing; Fang, Hongbo; Chi, Zhenfen; Wu, Zan; Wei, Di; Mo, Dongliang; Niu, Kaifeng; Balajee, Adayabalam S; Hei, Tom K; Nie, Linghu; Zhao, Yongliang

    2015-06-23

    Xeroderma pigmentosum group D (XPD/ERCC2) encodes an ATP-dependent helicase that plays essential roles in both transcription and nucleotide excision repair of nuclear DNA, however, whether or not XPD exerts similar functions in mitochondria remains elusive. In this study, we provide the first evidence that XPD is localized in the inner membrane of mitochondria, and cells under oxidative stress showed an enhanced recruitment of XPD into mitochondrial compartment. Furthermore, mitochondrial reactive oxygen species production and levels of oxidative stress-induced mitochondrial DNA (mtDNA) common deletion were significantly elevated, whereas capacity for oxidative damage repair of mtDNA was markedly reduced in both XPD-suppressed human osteosarcoma (U2OS) cells and XPD-deficient human fibroblasts. Immunoprecipitation-mass spectrometry analysis was used to identify interacting factor(s) with XPD and TUFM, a mitochondrial Tu translation elongation factor was detected to be physically interacted with XPD. Similar to the findings in XPD-deficient cells, mitochondrial common deletion and oxidative damage repair capacity in U2OS cells were found to be significantly altered after TUFM knock-down. Our findings clearly demonstrate that XPD plays crucial role(s) in protecting mitochondrial genome stability by facilitating an efficient repair of oxidative DNA damage in mitochondria. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  2. Dysregulation of Mitochondrial Calcium Signaling and Superoxide Flashes Cause Mitochondrial Genomic DNA Damage in Huntington Disease*

    Science.gov (United States)

    Wang, Jiu-Qiang; Chen, Qian; Wang, Xianhua; Wang, Qiao-Chu; Wang, Yun; Cheng, He-Ping; Guo, Caixia; Sun, Qinmiao; Chen, Quan; Tang, Tie-Shan

    2013-01-01

    Huntington disease (HD) is an inherited, fatal neurodegenerative disorder characterized by the progressive loss of striatal medium spiny neurons. Indications of oxidative stress are apparent in brain tissues from both HD patients and HD mouse models; however, the origin of this oxidant stress remains a mystery. Here, we used a yeast artificial chromosome transgenic mouse model of HD (YAC128) to investigate the potential connections between dysregulation of cytosolic Ca2+ signaling and mitochondrial oxidative damage in HD cells. We found that YAC128 mouse embryonic fibroblasts exhibit a strikingly higher level of mitochondrial matrix Ca2+ loading and elevated superoxide generation compared with WT cells, indicating that both mitochondrial Ca2+ signaling and superoxide generation are dysregulated in HD cells. The excessive mitochondrial oxidant stress is critically dependent on mitochondrial Ca2+ loading in HD cells, because blocking mitochondrial Ca2+ uptake abolished elevated superoxide generation. Similar results were obtained using neurons from HD model mice and fibroblast cells from HD patients. More importantly, mitochondrial Ca2+ loading in HD cells caused a 2-fold higher level of mitochondrial genomic DNA (mtDNA) damage due to the excessive oxidant generation. This study provides strong evidence to support a new causal link between dysregulated mitochondrial Ca2+ signaling, elevated mitochondrial oxidant stress, and mtDNA damage in HD. Our results also indicate that reducing mitochondrial Ca2+ uptake could be a therapeutic strategy for HD. PMID:23250749

  3. Radiation damage of all-silica fibers in the UV region

    Science.gov (United States)

    Gombert, Joerg; Ziegler, M.; Assmus, J.; Klein, Karl-Friedrich; Nelson, Gary W.; Clarkin, James P.; Pross, H.; Kiefer, J.

    1999-04-01

    Since several years, UVI-fibers having higher solarization- resistance are well known stimulating new fiber-optic applications in the UV-region below 250 nm. Besides the description of the improved transmission properties of UV- light from different UV-sources, the mechanisms of improvement have been discussed in detail. The UV-defects, mainly the E'- center with the UV-absorption band around 215 nm, were passivated by using hydrogen-doping. Besides DUV-light, ionizing radiation like Gamma-radiation or X-rays can create similar defects in the UV-region. In the past, the radiation- damage in the UV-region was studied on silica bulk samples: again, E'-centers were generated. Up to now, no UV- transmission through a 1 m long fiber during or after Gamma- radiation had been observed. However, the hydrogen in the UVI- fibers behaves the same for Gamma-irradiation, leading to a passivation of the radiation-induced defects and an improved transmission in the UV-C region below 250 nm. On this report, the influence of total dose and fiber diameter on the UV- damage after irradiation will be described and discussed. In addition, we will include annealing studies, with and without UV-light. Based on our results, the standard process of Gamma- sterilization with a total dose of approx. 2 Mrad can be used for UVI-fibers resulting in a good UV-transmission below 320 nm. Excimer-laser light at 308 nm (XeCl) and 248 nm (KrF) and deuterium-lamp light with the full spectrum starting at 200 nm can also be transmitted.

  4. Influence of complex impurity centres on radiation damage in wide-gap metal oxides

    Energy Technology Data Exchange (ETDEWEB)

    Lushchik, A., E-mail: aleksandr.lushchik@ut.ee [Institute of Physics, University of Tartu, Ravila 14c, 50411 Tartu (Estonia); Lushchik, Ch. [Institute of Physics, University of Tartu, Ravila 14c, 50411 Tartu (Estonia); Popov, A.I. [Institute of Solid State Physics, University of Latvia, Kengaraga 8, Riga LV-1063 (Latvia); Schwartz, K. [GSI Helmholtzzentrum für Schwerionenforschung (GSI), Planckstr. 1, 64291 Darmstadt (Germany); Shablonin, E.; Vasil’chenko, E. [Institute of Physics, University of Tartu, Ravila 14c, 50411 Tartu (Estonia)

    2016-05-01

    Different mechanisms of radiation damage of wide-gap metal oxides as well as a dual influence of impurity ions on the efficiency of radiation damage have been considered on the example of binary ionic MgO and complex ionic–covalent Lu{sub 3}Al{sub 5}O{sub 12} single crystals. Particular emphasis has been placed on irradiation with ∼2 GeV heavy ions ({sup 197}Au, {sup 209}Bi, {sup 238}U, fluence of 10{sup 12} ions/cm{sup 2}) providing extremely high density of electronic excitations within ion tracks. Besides knock-out mechanism for Frenkel pair formation, the additional mechanism through the collapse of mobile discrete breathers at certain lattice places (e.g., complex impurity centres) leads to the creation of complex defects that involve a large number of host atoms. The experimental manifestations of the radiation creation of intrinsic and impurity antisite defects (Lu|{sub Al} or Ce|{sub Al} – a heavy ion in a wrong cation site) have been detected in LuAG and LuAG:Ce{sup 3+} single crystals. Light doping of LuAG causes a small enhancement of radiation resistance, while pair impurity centres (for instance, Ce|{sub Lu}–Ce|{sub Al} or Cr{sup 3+}–Cr{sup 3+} in MgO) are formed with a rise of impurity concentration. These complex impurity centres as well as radiation-induced intrinsic antisite defects (Lu|{sub Al} strongly interacting with Lu in a regular site) tentatively serve as the places for breathers collapse, thus decreasing the material resistance against dense irradiation.

  5. Persistence of Space Radiation Induced Cytogenetic Damage in the Blood Lymphocytes of Astronauts

    Science.gov (United States)

    George, Kerry; Cucinotta, Francis A.

    2008-01-01

    Cytogenetic damage in astronaut's peripheral blood lymphocytes is a useful in vivo marker of space radiation induced damage. Moreover, if radiation induced chromosome translocations persist in peripheral blood lymphocytes for many years, as has been assumed, they could potentially be used to measure retrospective doses or prolonged low dose rate exposures. However, as more data becomes available, evidence suggests that the yield of translocations may decline with time after exposure, at least in the case of space radiation exposures. We present our latest follow-up measurements of chromosome aberrations in astronauts blood lymphocytes assessed by FISH painting and collected a various times beginning directly after return from space to several years after flight. For most individuals the analysis of individual time-courses for translocations revealed a temporal decline of yields with different half-lives. Since the level of stable aberrations depends on the interplay between natural loss of circulating T-lymphocytes and replenishment from the stem or progenitor cells, the differences in the rates of decay could be explained by inter-individual variation in lymphocyte turn over. Biodosimetry estimates derived from cytogenetic analysis of samples collected a few days after return to earth lie within the range expected from physical dosimetry. However, a temporal decline in yields may indicate complications with the use of stable aberrations for retrospective dose reconstruction, and the differences in the decay time may reflect individual variability in risk from space radiation exposure. In addition, limited data on multiple flights show a lack of correlation between time in space and translocation yields. Data from one crewmember who has participated in two separate long-duration space missions and has been followed up for over 10 years provides limited information on the effect of repeat flights and show a possible adaptive response to space radiation exposure.

  6. Space Radiation Induced Cytogenetic Damage in the Blood Lymphocytes of Astronauts

    Science.gov (United States)

    George, K.; Cucinotta, F. A.

    2008-01-01

    Cytogenetic analysis of astronauts blood lymphocytes provides a direct in vivo measurement of space radiation damage, which takes into account individual radiosensitivity and considers the influence of microgravity and other stress conditions. We present our latest analyses of chromosome damage in astronauts blood lymphocytes assessed by fluorescence in situ hybridization (FISH) chromosome painting and collected at various times beginning directly after return from space to several years after flight. Dose was derived from frequencies of chromosome exchanges using preflight calibration curves, and the Relative Biological Effect (RBE) was estimated by comparison with individually measured physically absorbed doses. Values for average RBE were compared to the average quality factor (Q), from direct measurements of the lineal energy spectra using a tissue-equivalent proportional counter (TEPC) and radiation transport codes. Results prove that cytogenetic biodosimetry analyses on blood collected within a week or two of return from space provides a reliable estimate of equivalent radiation dose and risk after protracted exposure to space radiation of a few months or more. However, data collected several months or years after flight suggests that the yield of chromosome translocations may decline with time after the mission, indicating that retrospective doses may be more difficult to estimate. In addition, limited data on multiple flights show a lack of correlation between time in space and translocation yields. Data from one crewmember, who has participated in two separate long-duration space missions and has been followed up for over 10 years, provide limited information on the effect of repeat flights and show a possible adaptive response to space radiation exposure.

  7. Automated analysis of damages for radiation in plastics surfaces; Analisis automatizado de danos por radiacion en superficies plasticas

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, C.; Camacho M, E.; Tavera, L.; Balcazar, M. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico)

    1990-02-15

    Analysis of damages done by the radiation in a polymer characterized by optic properties of polished surfaces, of uniformity and chemical resistance that the acrylic; resistant until the 150 centigrade grades of temperature, and with an approximate weight of half of the glass. An objective of this work is the development of a method that analyze in automated form the superficial damages induced by radiation in plastic materials means an images analyst. (Author)

  8. Detection of radiation-induced myocardial damage by technetium-99m sestamibi scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Gyenes, G. [Southern Hospital, Stockholm (Sweden). Dept. of Oncology; Fornander, T. [Southern Hospital, Stockholm (Sweden). Dept. of Oncology; Carlens, P, [Southern Hospital, Stockholm (Sweden). Dept. of Clinical Physiology; Glas, U. [Southern Hospital, Stockholm (Sweden). Dept. of Oncology; Rutqvist, L.E. [Oncologic Center, Radiumhemmet, Karolinska Hospital, Stockholm (Sweden)

    1997-03-01

    A prospective study was initiated to assess the side-effects of postoperative adjuvant radiotherapy in patients with left-sided early breast cancer. Twelve patients with early breast cancer were examined before and a year after radiotherapy. Echocardiography, ECG and bicycle ergometry stress test with technetium-99m sestamibi myocardial perfusion scintigraphic were carried out to assess changes in regional myocardial blood flow. Six of the 12 patients had new fixed scintigraphic defects after radiotherapy (as compared with the preradiation examination). The localization of the defects corresponded well with the irradiated volume of the left ventricle. These defects were probably due to microvascular damage to the myocardium. Neither ECG changes nor left ventricular segmental wall motion abnormalities could be detected by echocardiography. To our knowledge this study is the first to show that radiation-induced microvascular damage to the myocardium may be detected by perfusion scintigraphy. This may limit the use of scintigraphy in diagnosing coronary artery disease in patients treated with thoracic radiotherapy. Long-term follow-up is necessary to assess whether the presence of microvascular damage is a prognostic sign for the development of radiation-induced coronary artery disease. (orig.)

  9. Radiation damage to alkyl chain monolayers on semiconductor substrates investigated by electron spectroscopy.

    Science.gov (United States)

    Amy, Fabrice; Chan, Calvin K; Zhao, Wei; Hyung, Jaehyung; Ono, Masaki; Sueyoshi, Tomoki; Kera, Satoshi; Nesher, Guy; Salomon, Adi; Segev, Lior; Seitz, Oliver; Shpaisman, Hagay; Schöll, Achim; Haeming, Marc; Böcking, Till; Cahen, David; Kronik, Leeor; Ueno, Nobuo; Umbach, Eberhard; Kahn, Antoine

    2006-11-02

    Monolayers of alkyl chains, attached through direct Si-C bonds to Si(111), via phosphonates to GaAs(100) surfaces, or deposited as alkyl-silane monolayers on SiO2, are investigated by ultraviolet and inverse photoemission spectroscopy and X-ray absorption spectroscopy. Exposure to ultraviolet radiation from a He discharge lamp, or to a beam of energetic electrons, leads to significant damage, presumably associated with radiation- or electron-induced H-abstraction leading to carbon-carbon double-bond formation in the alkyl monolayer. The damage results in an overall distortion of the valence spectrum, in the appearance of (occupied) states above the highest occupied molecular orbital of the alkyl molecule, and in a characteristic (unoccupied state) pi resonance at the edge of the carbon absorption peak. These distortions present a serious challenge for the interpretation of the electronic structure of the monolayer system. We show that extrapolation to zero damage at short exposure times eliminates extrinsic features and allows a meaningful extraction of the density of state of the pristine monolayer from spectroscopy measurements.

  10. Radiation hybrid maps of D-genome of Aegilops tauschii and their application in sequence assembly of large and complex plant genomes

    Science.gov (United States)

    The large and complex genome of bread wheat (Triticum aestivum L., ~17 Gb) requires high-resolution genome maps saturated with ordered markers to assist in anchoring and orienting BAC contigs/ sequence scaffolds for whole genome sequence assembly. Radiation hybrid (RH) mapping has proven to be an e...

  11. Has the incidence of radiation-induced bowel damage following treatment of uterine carcinoma changed in the last 20 years

    Energy Technology Data Exchange (ETDEWEB)

    Allen-Mersh, T.C.; Wilson, E.J.; Hope-Stone, H.F.; Mann, C.V.

    1986-07-01

    Radiation-induced bowel damage occurred in 4.3% of patients treated primarily by irradiation for uterine carcinoma during the period 1962-1982. There has been a progressive rise in the incidence of radiation damage and radiation-induced rectovaginal fistula during this 20-year period. Radiation from intracavitary sources was a contributory factor in 92% of injured cases. The rising incidence of bowel damage in our patients may be due to an increase in the number of patients receiving a high rectal dose from the intracavitary source. There was a significantly (P<0.01) higher incidence of radiation injury in cases of cervical carcinoma compared to endometrical carcinoma. This was because cervical carcinoma tended to present at a more advanced stage than endometrial carcinoma and was more frequently treated with combined external and intracavitary irradiation. There was no significant increase in the incidence of complications among patients undergoing hysterectomy.

  12. DNA Damage in Melania Snail (Semisulcospira libertine) Irradiated with Gamma Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Tae Ho; Kim, Jin Kyu [Korea Atomic Energy Research Institute, Advanced Radiation Technology Institute, Jeongeup (Korea, Republic of); An, Kwang Guk [Chungnam National University, Daejeon (Korea, Republic of); Nili, Mohammad [Dawnesh Radiation Research Institute, Barcelona (Spain)

    2010-10-15

    Generally radiological protection has focused on human. But International Commission on Radiological Protection (ICRP) requires the effect data of ionizing radiation on nonhuman biota for the radiological protection of the environment. The choice of a melania snail as a model for environmental biomonitoring of radiation genotoxicity took into account that invertebrates represent one of aquatic species. The comet assay or single cell gel electrophoresis (SCGE) assay, first introduced by Ostling and Johanson, was used to detect DNA single strand breaks and to investigate the application of this technique as a tool for aquatic biomonitoring. Comet assay offers considerable advantages over some other assays used in DNA damage detection, such as chromosomal aberrations, sister chromatid Exchange and the micronucleus test, since there is no need for cells to be in a dividing state. Other advantages are its rapidity, relatively low coast, and wide applicability to virtually any nucleated cell type. In this study, we evaluated DNA damage in cells of Semisulcospira libertina after irradiation with {sup 60}Co gamma radiation by using the comet assay

  13. Radiation damage caused by cold neutrons in boron doped CMOS active pixel sensors

    Science.gov (United States)

    Linnik, B.; Bus, T.; Deveaux, M.; Doering, D.; Kudejova, P.; Wagner, F. M.; Yazgili, A.; Stroth, J.

    2017-05-01

    CMOS Monolithic Active Pixel Sensors (MAPS) are considered as an emerging technology in the field of charged particle tracking. They will be used in the vertex detectors of experiments like STAR, CBM and ALICE and are considered for the ILC and the tracker of ATLAS. In those applications, the sensors are exposed to sizeable radiation doses. While the tolerance of MAPS to ionizing radiation and fast hadrons is well known, the damage caused by low energy neutrons was not studied so far. Those slow neutrons may initiate nuclear fission of 10B dopants found in the B-doped silicon active medium of MAPS. This effect was expected to create an unknown amount of radiation damage beyond the predictions of the NIEL (Non Ionizing Energy Loss) model for pure silicon. We estimate the impact of this effect by calculating the additional NIEL created by this fission. Moreover, we show first measured data for CMOS sensors which were irradiated with cold neutrons. The empirical results contradict the prediction of the updated NIEL model both, qualitatively and quantitatively: the sensors irradiated with slow neutrons show an unexpected and strong acceptor removal, which is not observed in sensors irradiated with MeV neutrons.

  14. On thermal and radiation damage to silicon crystals in the LHC proton beam

    Energy Technology Data Exchange (ETDEWEB)

    Smirnov, G., E-mail: george.smirnov@cern.ch [JINR, 141980 Dubna (Russian Federation); CERN, CH-1211 Geneva 23 (Switzerland); Lechner, A., E-mail: Anton.Lechner@cern.ch [CERN, CH-1211 Geneva 23 (Switzerland); Perillo Marcone, A., E-mail: antonio.perillo-marcone@cern.ch [CERN, CH-1211 Geneva 23 (Switzerland); Schoofs, P., E-mail: philippe.schoofs@cern.ch [CERN, CH-1211 Geneva 23 (Switzerland); EPFL, CH-1015 Lausanne (Switzerland)

    2013-08-15

    We investigate thermal and radiation effects in silicon crystals which can be used for extracting beam halo particles in high energy accelerators. Application of bent crystals for removing halo is considered as a promising technique to enhance the beam collimation efficiency. Feasibility studies of a crystal-based cleaning system at the LHC have been recently approved in the framework of the UA9 experiment at CERN. In view of these studies and considering the enormous energy density stored in LHC beams, one requires a reliable knowledge of potential crystal damage due to thermal and radiation effects. In this article, we present damage estimates for a silicon strip crystal based on FLUKA simulations and subsequent thermal analysis using ANSYS Workbench. Heating of the crystal is investigated for hypothetical beam impact scenarios. The degradation of deflection efficiency due to radiation effects is estimated for amorphous crystal orientation and is then extrapolated down to channeling mode by evaluating the fraction of incoherent recoils of silicon atoms.

  15. On thermal and radiation damage to silicon crystals in the LHC proton beam

    Science.gov (United States)

    Smirnov, G.; Lechner, A.; Perillo Marcone, A.; Schoofs, P.

    2013-08-01

    We investigate thermal and radiation effects in silicon crystals which can be used for extracting beam halo particles in high energy accelerators. Application of bent crystals for removing halo is considered as a promising technique to enhance the beam collimation efficiency. Feasibility studies of a crystal-based cleaning system at the LHC have been recently approved in the framework of the UA9 experiment at CERN. In view of these studies and considering the enormous energy density stored in LHC beams, one requires a reliable knowledge of potential crystal damage due to thermal and radiation effects. In this article, we present damage estimates for a silicon strip crystal based on FLUKA simulations and subsequent thermal analysis using ANSYS Workbench. Heating of the crystal is investigated for hypothetical beam impact scenarios. The degradation of deflection efficiency due to radiation effects is estimated for amorphous crystal orientation and is then extrapolated down to channeling mode by evaluating the fraction of incoherent recoils of silicon atoms.

  16. A Review on Radiation Damage in Concrete for Nuclear Facilities: From Experiments to Modeling

    Directory of Open Access Journals (Sweden)

    Beatrice Pomaro

    2016-01-01

    Full Text Available Concrete is a relatively cheap material and easy to be cast into variously shaped structures. Its good shielding properties against neutrons and gamma-rays, due to its intrinsic water content and relatively high-density, respectively, make it the most widely used material for radiation shielding also. Concrete is so chosen as biological barrier in nuclear reactors and other nuclear facilities where neutron sources are hosted. Theoretical formulas are available in nuclear engineering manuals for the optimum thickness of shielding for radioprotection purposes; however they are restricted to one-dimensional problems; besides the basic empirical constants do not consider radiation damage effects, while its long-term performance is crucial for the safe operation of such facilities. To understand the behaviour of concrete properties, it is necessary to examine concrete strength and stiffness, water behavior, volume change of cement paste, and aggregate under irradiated conditions. Radiation damage process is not well understood yet and there is not a unified approach to the practical and predictive assessment of irradiated concrete, which combines both physics and structural mechanics issues. This paper provides a collection of the most distinguished contributions on this topic in the past 50 years. At present a remarkable renewed interest in the subject is shown.

  17. Inter- and intra-specific pan-genomes of Borrelia burgdorferi sensu lato: genome stability and adaptive radiation

    Science.gov (United States)

    2013-01-01

    Background Lyme disease is caused by spirochete bacteria from the Borrelia burgdorferi sensu lato (B. burgdorferi s.l.) species complex. To reconstruct the evolution of B. burgdorferi s.l. and identify the genomic basis of its human virulence, we compared the genomes of 23 B. burgdorferi s.l. isolates from Europe and the United States, including B. burgdorferi sensu stricto (B. burgdorferi s.s., 14 isolates), B. afzelii (2), B. garinii (2), B. “bavariensis” (1), B. spielmanii (1), B. valaisiana (1), B. bissettii (1), and B. “finlandensis” (1). Results Robust B. burgdorferi s.s. and B. burgdorferi s.l. phylogenies were obtained using genome-wide single-nucleotide polymorphisms, despite recombination. Phylogeny-based pan-genome analysis showed that the rate of gene acquisition was higher between species than within species, suggesting adaptive speciation. Strong positive natural selection drives the sequence evolution of lipoproteins, including chromosomally-encoded genes 0102 and 0404, cp26-encoded ospC and b08, and lp54-encoded dbpA, a07, a22, a33, a53, a65. Computer simulations predicted rapid adaptive radiation of genomic groups as population size increases. Conclusions Intra- and inter-specific pan-genome sizes of B. burgdorferi s.l. expand linearly with phylogenetic diversity. Yet gene-acquisition rates in B. burgdorferi s.l. are among the lowest in bacterial pathogens, resulting in high genome stability and few lineage-specific genes. Genome adaptation of B. burgdorferi s.l. is driven predominantly by copy-number and sequence variations of lipoprotein genes. New genomic groups are likely to emerge if the current trend of B. burgdorferi s.l. population expansion continues. PMID:24112474

  18. Melatonin Role in Ameliorating Radiation-induced Skin Damage: From Theory to Practice (A Review of Literature

    Directory of Open Access Journals (Sweden)

    Abbaszadeh A.

    2017-06-01

    Full Text Available Normal skin is composed of epidermis and dermis. Skin is susceptible to radiation damage because it is a continuously renewing organ containing rapidly proliferating mature cells. Radiation burn is a damage to the skin or other biological tissues caused by exposure to radiofrequency energy or ionizing radiation. Acute skin reaction is the most frequently occurring side effect of radiation therapy. Generally, any chemical/ biological agent given before or at the time of irradiation to prevent or ameliorate damage to normal tissues is called a radioprotector. Melatonin is a highly lipophilic substance that easily penetrates organic membranes and therefore is able to protect important intracellular structures including mitochondria and DNA against oxidative damage directly at the sites where such a kind of damage would occur. Melatonin leads to an increase in the molecular level of some important antioxidative enzymes such as superoxide, dismotase and glutation-peroxidase, and also a reduction in synthetic activity of nitric oxide. There is a large body of evidence which proves the efficacy of Melatonin in ameliorating UV and X ray-induced skin damage. We propose that, in the future, Melatonin would improve the therapeutic ratio in radiation oncology and ameliorate skin damage more effectively when administered in optimal and non-toxic doses

  19. Detection of DNA Damage by Space Radiation in Human Fibroblasts Flown on the International Space Station

    Science.gov (United States)

    Lu, Tao; Zhang, Ye; Wong, Michael; Feiveson, Alan; Gaza, Ramona; Stoffle, Nicholas; Wang, Huichen; Wilson, Bobby; Rohde, Larry; Stodieck, Louis; hide

    2017-01-01

    Space radiation consists of energetic charged particles of varying charges and energies. Exposure of astronauts to space radiation on future long duration missions to Mars, or missions back to the Moon, is expected to result in deleterious consequences such as cancer and comprised central nervous system (CNS) functions. Space radiation can also cause mutation in microorganisms, and potentially influence the evolution of life in space. Measurement of the space radiation environment has been conducted since the very beginning of the space program. Compared to the quantification of the space radiation environment using physical detectors, reports on the direct measurement of biological consequences of space radiation exposure have been limited, due primarily to the low dose and low dose rate nature of the environment. Most of the biological assays fail to detect the radiation effects at acute doses that are lower than 5 centiSieverts. In a recent study, we flew cultured confluent human fibroblasts in mostly G1 phase of the cell cycle to the International Space Station (ISS). The cells were fixed in space after arriving on the ISS for 3 and 14 days, respectively. The fixed cells were later returned to the ground and subsequently stained with the gamma-H2AX (Histone family, member X) antibody that are commonly used as a marker for DNA damage, particularly DNA double strand breaks, induced by both low-and high-linear energy transfer radiation. In our present study, the gamma-H2AX (Histone family, member X) foci were captured with a laser confocal microscope. To confirm that some large track-like foci were from space radiation exposure, we also exposed, on the ground, the same type of cells to both low-and high-linear energy transfer protons, and high-linear energy transfer Fe ions. In addition, we exposed the cells to low dose rate gamma rays, in order to rule out the possibility that the large track-like foci can be induced by chronic low-linear energy transfer

  20. Investigation on the use of Americium Oxide for Space Power Sources: Radiation Damage Studies

    Directory of Open Access Journals (Sweden)

    Wiss T.

    2017-01-01

    Several candidate Americium compounds will be investigated for chemical stability at high temperature and for self-irradiation damage. New thermo-electric converter materials containing actinides will be assessed, and a robust encapsulation designed. Safety analyses will be performed including launch explosion and re-entry accidents. The research will conclude in a conceptual design of a prototype power source. In the first part of this study, americium dioxide will be considered from the point of view of its chemical durability and of its behavior against radiation damage and helium formation, two aspects to be carefully investigated due to the high alpha-activity of the americium. Transmission electron Microscopy (TEM and helium thermal desorption spectrometry (TDS experiments will be described and results on aged (more than 30 years AmO2 reported. Some comparison with 238PuO2 based RTG’s will be discussed.

  1. Analytical studies into radiation-induced starch damage in black and white peppers

    Science.gov (United States)

    Sharif, M. M.; Farkas, J.

    1993-07-01

    Temperature dependency of the apparent viscosity of heat-gelatinized suspensions of untreated and irradiated pepper samples has been investigated. There was a close linear correlation between the logaritm of "fluidity" /reciprocal of the apparent viscosity) and the reciprocal absolute temperature of the measurement. The slope of the regression line(the temperature dependence of fluidity) increased with the radiation dose. Gelatinization thermograms of aqueous suspensions of ground pepper samples were obtained by differential scanning calorimetry. Temperature characteristics of heat-gelatinization endotherms showed no significant differences between untreated and irradiated samples. A colorimetric method for damaged starch, the estimation of reducing power, and the alcohol-induced turbidity of aqueous extracts showed statistically significant increases of starch damage at doses higher than 4 kGy. These indices of starch-depolymerization have been changed less dramatically by irradiation than the apparent viscosity of the heat-gelatinized suspensions.

  2. DNA Base Damage by Reactive Oxygen Species, Oxidizing Agents, and UV Radiation

    Science.gov (United States)

    Cadet, Jean; Wagner, J. Richard

    2013-01-01

    Emphasis has been placed in this article dedicated to DNA damage on recent aspects of the formation and measurement of oxidatively generated damage in cellular DNA in order to provide a comprehensive and updated survey. This includes single pyrimidine and purine base lesions, intrastrand cross-links, purine 5′,8-cyclonucleosides, DNA–protein adducts and interstrand cross-links formed by the reactions of either the nucleobases or the 2-deoxyribose moiety with the hydroxyl radical, one-electron oxidants, singlet oxygen, and hypochlorous acid. In addition, recent information concerning the mechanisms of formation, individual measurement, and repair-rate assessment of bipyrimidine photoproducts in isolated cells and human skin upon exposure to UVB radiation, UVA photons, or solar simulated light is critically reviewed. PMID:23378590

  3. Fast heavy-ion radiation damage of glycine in aqueous solution

    Energy Technology Data Exchange (ETDEWEB)

    Nomura, Shinji [Department of Nuclear Engineering, Kyoto University, Kyoto 615-8530 (Japan); Tsuchida, Hidetsugu, E-mail: tsuchida@nucleng.kyoto-u.ac.jp [Department of Nuclear Engineering, Kyoto University, Kyoto 615-8530 (Japan); Quantum Science and Engineering Center, Kyoto University, Uji 611-0011 (Japan); Furuya, Ryosuke [Department of Nuclear Engineering, Kyoto University, Kyoto 615-8530 (Japan); Majima, Takuya; Itoh, Akio [Department of Nuclear Engineering, Kyoto University, Kyoto 615-8530 (Japan); Quantum Science and Engineering Center, Kyoto University, Uji 611-0011 (Japan)

    2016-12-15

    Fast heavy-ion radiolysis of biomolecules in aqueous solution is investigated for an atomistic understanding of radiation damage to normal cells during heavy-particle beam therapy. The smallest amino acid glycine was used as a model biomaterial. Microjets of aqueous glycine solutions under vacuum were irradiated with 4.0-MeV carbon ions corresponding to energies in the Bragg peak region. To understand the effects of the water environment on molecular damage, the yield of glycine dissociation was measured by secondary ion mass spectroscopy. The yield was significantly reduced relative to gas-phase glycine targets. This implies that the numerous water molecules surrounding a single glycine molecule act as a buffer that suppresses dissociation. This is an environmental effect similar to that observed for other biomolecular cluster targets.

  4. Modelling single shot damage thresholds of multilayer optics for high-intensity short-wavelength radiation sources

    NARCIS (Netherlands)

    Loch, R.A.; Sobierajski, R.; Louis, Eric; Bosgra, J.; Bosgra, J.; Bijkerk, Frederik

    2012-01-01

    The single shot damage thresholds of multilayer optics for highintensity short-wavelength radiation sources are theoretically investigated, using a model developed on the basis of experimental data obtained at the FLASH and LCLS free electron lasers. We compare the radiation hardness of commonly

  5. DETECTION OF LOW DOSE RADIATION-AND CHEMICALLY-INDUCED DNA DAMAGE USING TEMPERATURE DIFFERENTIAL FLUORESCENCE ASSAYS

    Science.gov (United States)

    Rapid, sensitive and simple assays for radiation- and chemically-induced DNA damage can be of significant benefit to a number of fields including radiation biology, clinical research, and environmental monitoring. Although temperature-induced DNA strand separation has been use...

  6. New Perspectives on Oxidized Genome Damage and Repair Inhibition by Pro-Oxidant Metals in Neurological Diseases

    Directory of Open Access Journals (Sweden)

    Joy Mitra

    2014-07-01

    Full Text Available The primary cause(s of neuronal death in most cases of neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease, are still unknown. However, the association of certain etiological factors, e.g., oxidative stress, protein misfolding/aggregation, redox metal accumulation and various types of damage to the genome, to pathological changes in the affected brain region(s have been consistently observed. While redox metal toxicity received major attention in the last decade, its potential as a therapeutic target is still at a cross-roads, mostly because of the lack of mechanistic understanding of metal dyshomeostasis in affected neurons. Furthermore, previous studies have established the role of metals in causing genome damage, both directly and via the generation of reactive oxygen species (ROS, but little was known about their impact on genome repair. Our recent studies demonstrated that excess levels of iron and copper observed in neurodegenerative disease-affected brain neurons could not only induce genome damage in neurons, but also affect their repair by oxidatively inhibiting NEIL DNA glycosylases, which initiate the repair of oxidized DNA bases. The inhibitory effect was reversed by a combination of metal chelators and reducing agents, which underscore the need for elucidating the molecular basis for the neuronal toxicity of metals in order to develop effective therapeutic approaches. In this review, we have focused on the oxidative genome damage repair pathway as a potential target for reducing pro-oxidant metal toxicity in neurological diseases.

  7. New Perspectives on Oxidized Genome Damage and Repair Inhibition by Pro-Oxidant Metals in Neurological Diseases

    Science.gov (United States)

    Mitra, Joy; Guerrero, Erika N.; Hegde, Pavana M.; Wang, Haibo; Boldogh, Istvan; Rao, Kosagi Sharaf; Mitra, Sankar; Hegde, Muralidhar L.

    2014-01-01

    The primary cause(s) of neuronal death in most cases of neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease, are still unknown. However, the association of certain etiological factors, e.g., oxidative stress, protein misfolding/aggregation, redox metal accumulation and various types of damage to the genome, to pathological changes in the affected brain region(s) have been consistently observed. While redox metal toxicity received major attention in the last decade, its potential as a therapeutic target is still at a cross-roads, mostly because of the lack of mechanistic understanding of metal dyshomeostasis in affected neurons. Furthermore, previous studies have established the role of metals in causing genome damage, both directly and via the generation of reactive oxygen species (ROS), but little was known about their impact on genome repair. Our recent studies demonstrated that excess levels of iron and copper observed in neurodegenerative disease-affected brain neurons could not only induce genome damage in neurons, but also affect their repair by oxidatively inhibiting NEIL DNA glycosylases, which initiate the repair of oxidized DNA bases. The inhibitory effect was reversed by a combination of metal chelators and reducing agents, which underscore the need for elucidating the molecular basis for the neuronal toxicity of metals in order to develop effective therapeutic approaches. In this review, we have focused on the oxidative genome damage repair pathway as a potential target for reducing pro-oxidant metal toxicity in neurological diseases. PMID:25036887

  8. Performance, radiation damage effects and upgrade of the LHCB vertex locator

    Energy Technology Data Exchange (ETDEWEB)

    Capua, Stefano de, E-mail: stefano.decapua@hep.manchester.co.uk

    2013-12-21

    LHCb is a dedicated experiment to study new physics in the decays of heavy hadrons at the Large Hadron Collider (LHC) at CERN. Heavy hadrons are identified through their flight distance in the Vertex Locator (VELO), the retractable silicon-strip vertex detector surrounding the LHCb interaction point at only 8 mm from the beam during normal LHC operation. The VELO consists of a series of silicon micro-strip detectors and operates in an extreme and highly non-uniform radiation environment. The performance of the LHCb VELO during the first three years of LHC physics running and the primary results from radiation damage studies are presented. Plans for an upgraded detector by 2018 with a 40 MHz readout are also presented.

  9. Modeling Radiation Damage Effects in 3D Pixel Digitization for the ATLAS Detector

    CERN Document Server

    Giugliarelli, Gilberto; The ATLAS collaboration

    2018-01-01

    Silicon Pixel detectors are at the core of the current and planned upgrade of the ATLAS experiment. They constitute the part of ATLAS closest to the interaction point and for this reason they will be exposed – over their lifetime – to a significant amount of radiation: prior to the HL-LHC, the innermost layers will receive a fluence of 10^15 neq/cm2 and their HL–LHC upgrades will have to cope with an order of magnitude higher fluence integrated over their lifetimes. This poster presents the details of a new digitization model that includes radiation damage effects to the 3D Pixel sensors for the ATLAS Detector.

  10. Using LEDs to stimulate the recovery of radiation damage to plastic scintillators

    Energy Technology Data Exchange (ETDEWEB)

    Wetzel, J., E-mail: james-wetzel@uiowa.edu [The University of Iowa, Iowa City, IA (United States); Tiras, E. [The University of Iowa, Iowa City, IA (United States); Bilki, B. [The University of Iowa, Iowa City, IA (United States); Beykent University, Istanbul (Turkey); Onel, Y. [The University of Iowa, Iowa City, IA (United States); Winn, D. [Fairfield University, Fairfield, CT (United States)

    2017-03-15

    In this study, we consider using LEDs to stimulate the recovery of scintillators damaged from radiation in high radiation environments. We irradiated scintillating tiles of polyethylene naphthalate (PEN), Eljen brand EJ-260 (EJN), an overdoped EJ-260 (EJ2P), and a lab-produced elastomer scintillator (ES) composed of p-terphenyl (ptp) in epoxy. Two different high-dose irradiations took place, with PEN dosed to 100 kGy, and the others to 78 kGy. We found that the ‘blue’ scintillators (PEN and ES) recovered faster and maximally higher with LEDs than without. Conversely exposing the ‘green’ scintillators (EJ-260) to LED light had a nearly negligible effect on the recovery. We hypothesize that the ‘green’ scintillators require wavelengths that match their absorption and emission spectra for LED stimulated recovery.

  11. Ultraviolet radiation effects on the infrared damage rate of a thermal control coating

    Science.gov (United States)

    Bass, J. A.

    1972-01-01

    The effects of ultraviolet radiation on the infrared reflectance of ZnO silicone white thermal coatings were investigated. Narrow band ultraviolet radiation for wavelengths in the 2200A to 3500A range by a monochromator and a high pressure, 150-W Eimac xenon lamp. The sample was irradiated while in a vacuum of at least 0.000001 torr, and infrared reflectance was measured in situ with a spectroreflectometer at 19,500A. Reflectance degradation was studied as a function of wavelength, time, intensity, and dose. Damage was wavelength dependent at constant exposure, but no maximum was evident above the shortest wavelength investigated here. The degradation rate at constant intensity was an exponential function of time and varies with intensity.

  12. Radiation damage and annealing of lithium-doped silicon solar cells

    Science.gov (United States)

    Statler, R. L.

    1971-01-01

    Evidence has been presented that a lithium-diffused crucible-grown silicon solar cell can be made with better efficiency than the flight-quality n p 10 ohms-cm solar cell. When this lithium cell is exposed to a continuous radiation evironment at 60 C (electron spectrum from gamma rays) it has a higher power output than the N/P cell after a fluence equivalent to 1 MeV. A comparison of annealing of proton- and electron-damage in this lithium cell reveals a decidedly faster rate of recovery and higher level of recoverable power from the proton effects. Therefore, the lithium cell shows a good potential for many space missions where the proton flux is a significant fraction of the radiation field to be encountered.

  13. Infrared response measurements on radiation-damaged Si/Li/ detectors.

    Science.gov (United States)

    Sher, A. H.; Liu, Y. M.; Keery, W. J.

    1972-01-01

    The improved infrared response (IRR) technique has been used to qualitatively compare radiation effects on Si(Li) detectors with energy levels reported for silicon in the literature. Measurements have been made on five commercial silicon detectors and one fabricated in-house, both before and after irradiation with fast neutrons, 1.9-MeV protons, and 1.6-MeV electrons. Effects dependent upon the extent of radiation damage have been observed. It seems likely that the photo-EMF, or photo-voltage, effect is the basic mechanism for the observation of IRR in p-i-n diodes with a wide i-region. Experimental characteristics of the IRR measurement are in agreement with those of the photovoltage effect.

  14. Sensitivity coefficients for the stochastic estimation of the radiation damage to the reactor pressure vessel

    Energy Technology Data Exchange (ETDEWEB)

    Alvarez, C.M.; Hernandez Valle, S. [Centro de Investigaciones Tecnologicas, Nucleares y Ambientales, La Habana (Cuba). E-mail: calvarez@ctn.isctn.edu.cu; svalle@ctn.isctn.edu.cu

    2000-07-01

    The construction of the sensitivity matrix in the case of the vessel radiation damage estimation by Monte Carlo techniques poses new problems related to the uncertainties of the obtained responses. In the case of deterministic calculations, the sensitivity coefficient obtention is a straightforward procedure based on the perturbation formalism through the calculation of the adjoint fluxes. In the paper an alternative procedure implementation based on the differential operator method is described with the modifications needed to the used HEXANN-EVALU code for the response estimations in the VVER-440 pressure vessel. (author)

  15. The effect of solvation on the radiation damage rate constants for adenine

    DEFF Research Database (Denmark)

    Milhøj, Birgitte Olai; Sauer, Stephan P. A.

    2016-01-01

    It is a well known fact, that water plays an important part in almost all biological systems and that inclusion of solvation effects might therefore be of utmost importance in studies of radiation damage to DNA. In the present investigation we have studied the effect of different solvation models...... in calculations of Gibbs free energies and reaction rates for the reaction between the OH radical and the DNA nucleobase adenine using Density Functional Theory at the ωB97X-D/6-311++G(2df,2pd) level with the Eckart tunneling correction. The solvent, water, has been included through either the implicit...

  16. Ultraviolet radiation, sun damage and preventing; Ultrafiolett straaling, solskader og forebygging

    Energy Technology Data Exchange (ETDEWEB)

    Johnsen, B.; Christensen, T.; Nilsen, L.T.; Hannevik, M.

    2013-03-01

    The report focuses on the large impact of health damages due to excessive UV exposure from natural sun. The first part of the report gives background information on factors significantly affecting the intensity of UV radiation. The second part gives an overview of health effects related to UV exposure, with recommendations on how to avoid excessive UV exposure and still enjoy the positive sides of outdoor activity. The report is intended to contribute to informational activities about sun exposure as recommended by the World Health Organisation and the World Meteorology Organisation. (Author)

  17. Annealing of natural metamict zircons: II high degree of radiation damage

    CERN Document Server

    Colombo, M

    1998-01-01

    In situ time-dependent high-temperature X-ray powder diffraction was used to study the amorphous to crystalline transition in natural zircons which are characterized by a high degree of radiation damage. It was possible to distinguish two stages of the annealing process: (i) the recovery of the heavily disturbed but still crystalline domains and (ii) the recrystallization of the amorphous regions. The first stage is very fast under the chosen experimental conditions and, at least apparently, is not thermally activated. The second stage is a diffusion-controlled process, whose products (zircon or zircon and zirconia phases) are strongly correlated to the annealing temperature.

  18. Hydrogen-rich PBS protects cultured human cells from ionizing radiation-induced cellular damage

    Directory of Open Access Journals (Sweden)

    Qian Liren

    2010-01-01

    Full Text Available Hydroxyl radicals play an important role in ionizing radiation-induced cellular damage, while hydrogen can selectively reduce hydroxyl radicals in vitro. This study was designed to test the hypothesis that hydrogen-rich PBS may be an effective radioprotective agent in vitro. Compared to cells pretreated without hydrogen, we demonstrated that treating cells with hydrogen-rich PBS before irradiation could significantly inhibit IR-induced apoptosis, increase viability of human intestinal crypt cells, significantly increase endogenous antioxidant, and decrease malondialdehyde and 8-hydroxydeoxyguanosine concentrations of human lymphocyte AHH-1 cells. It is concluded that hydrogen has a potential as an effective and safe radioprotective agent.

  19. Measuring radiation damage dynamics by pulsed ion beam irradiation: 2016 project annual report

    Energy Technology Data Exchange (ETDEWEB)

    Kucheyev, Sergei O. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2017-01-04

    The major goal of this project is to develop and demonstrate a novel experimental approach to access the dynamic regime of radiation damage formation in nuclear materials. In particular, the project exploits a pulsed-ion-beam method in order to gain insight into defect interaction dynamics by measuring effective defect interaction time constants and defect diffusion lengths. For Year 3, this project had the following two major milestones: (i) the demonstration of the measurement of thermally activated defect-interaction processes by pulsed ion beam techniques and (ii) the demonstration of alternative characterization techniques to study defect dynamics. As we describe below, both of these milestones have been met.

  20. A Leakage Current-based Measurement of the Radiation Damage in the ATLAS Pixel Detector

    CERN Document Server

    Gorelov, Igor; The ATLAS collaboration

    2015-01-01

    A measurement has been made of the radiation damage incurred by the ATLAS Pixel Detector barrel silicon modules from the beginning of operations through the end of 2012. This translates to hadronic fluence received over the full period of operation at energies up to and including 8 TeV. The measurement is based on a per-module measurement of the silicon sensor leakage current. The results are presented as a function of integrated luminosity and compared to predictions by the Hamburg Model. This information can be used to predict limits on the lifetime of the Pixel Detector due to current, for various operating scenarios.

  1. Operational Experience and Performance with the ATLAS Pixel detector with emphasis on radiation damage

    CERN Document Server

    Garcia Pascual, Juan Antonio; The ATLAS collaboration

    2017-01-01

    The tracking performance of the ATLAS detector relies critically on its 4-layer Pixel Detector, that has undergone significant hardware and software upgrades to meet the challenges imposed by the higher collision energy, pileup and luminosity that are being delivered by the Large Hadron Collider, with record breaking instantaneous luminosities of 1.3 x 10$^{34}$ cm$^{-2}$ s$^{-1}$ recently surpassed. The key status and performance metrics of the ATLAS Pixel Detector are summarised, and the operational experience and requirements to ensure optimum data quality and data taking efficiency are described, with special emphasis to radiation damage experience.

  2. Operational Experience and Performance with the ATLAS Pixel detector with emphasis on radiation damage

    CERN Document Server

    Butti, Pierfrancesco; The ATLAS collaboration

    2017-01-01

    The tracking performance of the ATLAS detector relies critically on its 4-layer Pixel Detector, that has undergone significant hardware and software upgrades to meet the challenges imposed by the higher collision energy, pileup and luminosity that are being delivered by the Large Hadron Collider, with record breaking instantaneous luminosities of 1.3 x 10^34 cm-2 s-1 recently surpassed. The key status and performance metrics of the ATLAS Pixel Detector are summarised, and the operational experience and requirements to ensure optimum data quality and data taking efficiency are described, with special emphasis to radiation damage experience.

  3. Characterisation of radiation damage in silicon photomultipliers with a Monte Carlo model

    CERN Document Server

    Majos, S Sanchez; Pochodzalla, J

    2008-01-01

    Measured response functions and low photon yield spectra of silicon photomultipliers (SiPM) were compared to multi-photoelectron pulse-height distributions generated by a Monte Carlo model. Characteristic parameters for SiPM were derived. The devices were irradiated with 14 MeV electrons at the Mainz microtron MAMI. It is shown that the first noticeable damage consists of an increase in the rate of dark pulses and the loss of uniformity in the pixel gains. Higher radiation doses reduced also the photon detection efficiency. The results are especially relevant for applications of SiPM in fibre detectors at high luminosity experiments.

  4. Use of the comet-FISH assay to compare DNA damage and repair in p53 and hTERT genes following ionizing radiation.

    Directory of Open Access Journals (Sweden)

    Declan J McKenna

    Full Text Available The alkaline single cell gel electrophoresis (comet assay can be combined with fluorescent in situ hybridisation (FISH methodology in order to investigate the localisation of specific gene domains within an individual cell. The number and position of the fluorescent signal(s provides information about the relative damage and subsequent repair that is occurring in the targeted gene domain(s. In this study, we have optimised the comet-FISH assay to detect and compare DNA damage and repair in the p53 and hTERT gene regions of bladder cancer cell-lines RT4 and RT112, normal fibroblasts and Cockayne Syndrome (CS fibroblasts following γ-radiation. Cells were exposed to 5Gy γ-radiation and repair followed for up to 60 minutes. At each repair time-point, the number and location of p53 and hTERT hybridisation spots was recorded in addition to standard comet measurements. In bladder cancer cell-lines and normal fibroblasts, the p53 gene region was found to be rapidly repaired relative to the hTERT gene region and the overall genome, a phenomenon that appeared to be independent of hTERT transcriptional activity. However, in the CS fibroblasts, which are defective in transcription coupled repair (TCR, this rapid repair of the p53 gene region was not observed when compared to both the hTERT gene region and the overall genome, proving the assay can detect variations in DNA repair in the same gene. In conclusion, we propose that the comet-FISH assay is a sensitive and rapid method for detecting differences in DNA damage and repair between different gene regions in individual cells in response to radiation. We suggest this increases its potential for measuring radiosensitivity in cells and may therefore have value in a clinical setting.

  5. Use of the Comet-FISH Assay to Compare DNA Damage and Repair in p53 and hTERT Genes following Ionizing Radiation

    Science.gov (United States)

    McKenna, Declan J.; Doherty, Bernadette A.; Downes, C. Stephen; McKeown, Stephanie R.; McKelvey-Martin, Valerie J.

    2012-01-01

    The alkaline single cell gel electrophoresis (comet) assay can be combined with fluorescent in situ hybridisation (FISH) methodology in order to investigate the localisation of specific gene domains within an individual cell. The number and position of the fluorescent signal(s) provides information about the relative damage and subsequent repair that is occurring in the targeted gene domain(s). In this study, we have optimised the comet-FISH assay to detect and compare DNA damage and repair in the p53 and hTERT gene regions of bladder cancer cell-lines RT4 and RT112, normal fibroblasts and Cockayne Syndrome (CS) fibroblasts following γ-radiation. Cells were exposed to 5Gy γ-radiation and repair followed for up to 60 minutes. At each repair time-point, the number and location of p53 and hTERT hybridisation spots was recorded in addition to standard comet measurements. In bladder cancer cell-lines and normal fibroblasts, the p53 gene region was found to be rapidly repaired relative to the hTERT gene region and the overall genome, a phenomenon that appeared to be independent of hTERT transcriptional activity. However, in the CS fibroblasts, which are defective in transcription coupled repair (TCR), this rapid repair of the p53 gene region was not observed when compared to both the hTERT gene region and the overall genome, proving the assay can detect variations in DNA repair in the same gene. In conclusion, we propose that the comet-FISH assay is a sensitive and rapid method for detecting differences in DNA damage and repair between different gene regions in individual cells in response to radiation. We suggest this increases its potential for measuring radiosensitivity in cells and may therefore have value in a clinical setting. PMID:23145163

  6. Space Radiation Effects on Human Cells: Modeling DNA Breakage, DNA Damage Foci Distribution, Chromosomal Aberrations and Tissue Effects

    Science.gov (United States)

    Ponomarev, A. L.; Huff, J. L.; Cucinotta, F. A.

    2011-01-01

    Future long-tem space travel will face challenges from radiation concerns as the space environment poses health risk to humans in space from radiations with high biological efficiency and adverse post-flight long-term effects. Solar particles events may dramatically affect the crew performance, while Galactic Cosmic Rays will induce a chronic exposure to high-linear-energy-transfer (LET) particles. These types of radiation, not present on the ground level, can increase the probability of a fatal cancer later in astronaut life. No feasible shielding is possible from radiation in space, especially for the heavy ion component, as suggested solutions will require a dramatic increase in the mass of the mission. Our research group focuses on fundamental research and strategic analysis leading to better shielding design and to better understanding of the biological mechanisms of radiation damage. We present our recent effort to model DNA damage and tissue damage using computational models based on the physics of heavy ion radiation, DNA structure and DNA damage and repair in human cells. Our particular area of expertise include the clustered DNA damage from high-LET radiation, the visualization of DSBs (DNA double strand breaks) via DNA damage foci, image analysis and the statistics of the foci for different experimental situations, chromosomal aberration formation through DSB misrepair, the kinetics of DSB repair leading to a model-derived spectrum of chromosomal aberrations, and, finally, the simulation of human tissue and the pattern of apoptotic cell damage. This compendium of theoretical and experimental data sheds light on the complex nature of radiation interacting with human DNA, cells and tissues, which can lead to mutagenesis and carcinogenesis later in human life after the space mission.

  7. Pudendal Nerve and Internal Pudendal Artery Damage May Contribute to Radiation-Induced Erectile Dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Nolan, Michael W., E-mail: mwnolan@ncsu.edu [Department of Clinical Sciences, and Center for Comparative Medicine and Translational Research, North Carolina State University, Raleigh, North Carolina (United States); Department of Environmental and Radiologic Health Sciences, Colorado State University, Fort Collins, Colorado (United States); Marolf, Angela J. [Department of Environmental and Radiologic Health Sciences, Colorado State University, Fort Collins, Colorado (United States); Ehrhart, E.J. [Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado (United States); Rao, Sangeeta [Department of Clinical Sciences, Colorado State University, Fort Collins, Colorado (United States); Kraft, Susan L. [Department of Environmental and Radiologic Health Sciences, Colorado State University, Fort Collins, Colorado (United States); Engel, Stephanie [Department of Clinical Sciences, Colorado State University, Fort Collins, Colorado (United States); Yoshikawa, Hiroto; Golden, Anne E. [Department of Environmental and Radiologic Health Sciences, Colorado State University, Fort Collins, Colorado (United States); Wasserman, Todd H. [Department of Radiation Oncology, Washington University, St. Louis, Missouri (United States); LaRue, Susan M. [Department of Environmental and Radiologic Health Sciences, Colorado State University, Fort Collins, Colorado (United States)

    2015-03-15

    Purpose/Objectives: Erectile dysfunction is common after radiation therapy for prostate cancer; yet, the etiopathology of radiation-induced erectile dysfunction (RI-ED) remains poorly understood. A novel animal model was developed to study RI-ED, wherein stereotactic body radiation therapy (SBRT) was used to irradiate the prostate, neurovascular bundles (NVB), and penile bulb (PB) of dogs. The purpose was to describe vascular and neurogenic injuries after the irradiation of only the NVB or the PB, and after irradiation of all 3 sites (prostate, NVB, and PB) with varying doses of radiation. Methods and Materials: Dogs were treated with 50, 40, or 30 Gy to the prostate, NVB, and PB, or 50 Gy to either the NVB or the PB, by 5-fraction SBRT. Electrophysiologic studies of the pudendal nerve and bulbospongiosus muscles and ultrasound studies of pelvic perfusion were performed before and after SBRT. The results of these bioassays were correlated with histopathologic changes. Results: SBRT caused slowing of the systolic rise time, which corresponded to decreased arterial patency. Alterations in the response of the internal pudendal artery to vasoactive drugs were observed, wherein SBRT caused a paradoxical response to papaverine, slowing the systolic rise time after 40 and 50 Gy; these changes appeared to have some dose dependency. The neurofilament content of penile nerves was also decreased at high doses and was more profound when the PB was irradiated than when the NVB was irradiated. These findings are coincident with slowing of motor nerve conduction velocities in the pudendal nerve after SBRT. Conclusions: This is the first report in which prostatic irradiation was shown to cause morphologic arterial damage that was coincident with altered internal pudendal arterial tone, and in which decreased motor function in the pudendal nerve was attributed to axonal degeneration and loss. Further investigation of the role played by damage to these structures in RI-ED is

  8. Protective Effect of Pyruvate Against Radiation-Induced Damage in Collagenized Tissues

    Science.gov (United States)

    Griko, Y. V.; Yan, Xiaoli

    2016-01-01

    Exposure to high doses of ionizing radiation produces both acute and late effects on the collagenized tissues and have profound effects on wound healing. Because of the crucial practical importance for new radioprotective agents, our study has been focused on evaluation of the efficacy of non-toxic naturally occurring compounds to protect tissue integrity against high-dose gamma radiation. Here, we demonstrate that molecular integrity of collagen may serve as a sensitive biological marker for quantitative evaluation of molecular damage to collagenized tissue and efficacy of radioprotective agents. Increasing doses of gamma radiation (0-50kGy) result in progressive destruction of the native collagen fibrils, which provide a structural framework, strength, and proper milieu for the regenerating tissue. The strategy used in this study involved the thermodynamic specification of all structural changes in collagenized matrix of skin, aortic heart valve, and bone tissue induced by different doses and conditions of g-irradiation. This study describes a simple biophysical approach utilizing the Differential Scanning Calorimetry (DSC) to characterize the structural resistance of the aortic valve matrix exposed to different doses of g-irradiation. It allows us to identify the specific response of each constituent as well as to determine the influence of the different treatments on the characteristic parameters of protein structure. We found that pyruvate, a substance that naturally occurs in the body, provide significant protection (up to 80%) from biochemical and biomechanical damage to the collagenized tissue through the effective targeting of reactive oxygen species. The recently discovered role of pyruvate in the cell antioxidant defense to O2 oxidation, and its essential constituency in the daily human diet, indicate that the administration of pyruvate-based radioprotective formulations may provide safe and effective protection from deleterious effects of ionizing

  9. Debris and radiation-induced damage effects on EUV nanolithography source collector mirror optics performance.

    Energy Technology Data Exchange (ETDEWEB)

    Allain, J. P.; Nieto, M.; Hendricks, M.; Harilal, S. S.; Hassanein, A.; Mathematics and Computer Science

    2007-01-01

    Exposure of collector mirrors facing the hot, dense pinch plasma in plasma-based EUV light sources to debris (fast ions, neutrals, off-band radiation, droplets) remains one of the highest critical issues of source component lifetime and commercial feasibility of nanolithography at 13.5-nm. Typical radiators used at 13.5-nm include Xe and Sn. Fast particles emerging from the pinch region of the lamp are known to induce serious damage to nearby collector mirrors. Candidate collector configurations include either multi-layer mirrors (MLM) or single-layer mirrors (SLM) used at grazing incidence. Studies at Argonne have focused on understanding the underlying mechanisms that hinder collector mirror performance at 13.5-nm under fast Sn or Xe exposure. This is possible by a new state-of-the-art in-situ EUV reflectometry system that measures real time relative EUV reflectivity (15-degree incidence and 13.5-nm) variation during fast particle exposure. Intense EUV light and off-band radiation is also known to contribute to mirror damage. For example offband radiation can couple to the mirror and induce heating affecting the mirror's surface properties. In addition, intense EUV light can partially photo-ionize background gas (e.g., Ar or He) used for mitigation in the source device. This can lead to local weakly ionized plasma creating a sheath and accelerating charged gas particles to the mirror surface and inducing sputtering. In this paper we study several aspects of debris and radiation-induced damage to candidate EUVL source collector optics materials. The first study concerns the use of IMD simulations to study the effect of surface roughness on EUV reflectivity. The second studies the effect of fast particles on MLM reflectivity at 13.5-nm. And lastly the third studies the effect of multiple energetic sources with thermal Sn on 13.5-nm reflectivity. These studies focus on conditions that simulate the EUVL source environment in a controlled way.

  10. Debris- and radiation-induced damage effects on EUV nanolithography source collector mirror optics performance

    Science.gov (United States)

    Allain, J. P.; Nieto, M.; Hendricks, M.; Harilal, S. S.; Hassanein, A.

    2007-05-01

    Exposure of collector mirrors facing the hot, dense pinch plasma in plasma-based EUV light sources to debris (fast ions, neutrals, off-band radiation, droplets) remains one of the highest critical issues of source component lifetime and commercial feasibility of nanolithography at 13.5-nm. Typical radiators used at 13.5-nm include Xe and Sn. Fast particles emerging from the pinch region of the lamp are known to induce serious damage to nearby collector mirrors. Candidate collector configurations include either multi-layer mirrors (MLM) or single-layer mirrors (SLM) used at grazing incidence. Studies at Argonne have focused on understanding the underlying mechanisms that hinder collector mirror performance at 13.5-nm under fast Sn or Xe exposure. This is possible by a new state-of-the-art in-situ EUV reflectometry system that measures real time relative EUV reflectivity (15-degree incidence and 13.5-nm) variation during fast particle exposure. Intense EUV light and off-band radiation is also known to contribute to mirror damage. For example offband radiation can couple to the mirror and induce heating affecting the mirror's surface properties. In addition, intense EUV light can partially photo-ionize background gas (e.g., Ar or He) used for mitigation in the source device. This can lead to local weakly ionized plasma creating a sheath and accelerating charged gas particles to the mirror surface and inducing sputtering. In this paper we study several aspects of debris and radiation-induced damage to candidate EUVL source collector optics materials. The first study concerns the use of IMD simulations to study the effect of surface roughness on EUV reflectivity. The second studies the effect of fast particles on MLM reflectivity at 13.5-nm. And lastly the third studies the effect of multiple energetic sources with thermal Sn on 13.5-nm reflectivity. These studies focus on conditions that simulate the EUVL source environment in a controlled way.

  11. Genomic variation at the tips of the adaptive radiation of Darwin's finches.

    Science.gov (United States)

    Chaves, Jaime A; Cooper, Elizabeth A; Hendry, Andrew P; Podos, Jeffrey; De León, Luis F; Raeymaekers, Joost A M; MacMillan, W Owen; Uy, J Albert C

    2016-11-01

    Adaptive radiation unfolds as selection acts on the genetic variation underlying functional traits. The nature of this variation can be revealed by studying the tips of an ongoing adaptive radiation. We studied genomic variation at the tips of the Darwin's finch radiation; specifically focusing on polymorphism within, and variation among, three sympatric species of the genus Geospiza. Using restriction site-associated DNA (RAD-seq), we characterized 32 569 single-nucleotide polymorphisms (SNPs), from which 11 outlier SNPs for beak and body size were uncovered by a genomewide association study (GWAS). Principal component analysis revealed that these 11 SNPs formed four statistically linked groups. Stepwise regression then revealed that the first PC score, which included 6 of the 11 top SNPs, explained over 80% of the variation in beak size, suggesting that selection on these traits influences multiple correlated loci. The two SNPs most strongly associated with beak size were near genes associated with beak morphology across deeper branches of the radiation: delta-like 1 homologue (DLK1) and high-mobility group AT-hook 2 (HMGA2). Our results suggest that (i) key adaptive traits are associated with a small fraction of the genome (11 of 32 569 SNPs), (ii) SNPs linked to the candidate genes are dispersed throughout the genome (on several chromosomes), and (iii) micro- and macro-evolutionary variation (roots and tips of the radiation) involve some shared and some unique genomic regions. © 2016 John Wiley & Sons Ltd.

  12. Evaluation of γ-radiation-induced DNA damage in two species of bivalves and their relative sensitivity using comet assay.

    Science.gov (United States)

    Praveen Kumar, M K; Shyama, S K; Sonaye, B S; Naik, U Roshini; Kadam, S B; Bipin, P D; D'costa, A; Chaubey, R C

    2014-05-01

    Ionizing radiation is known to induce genetic damage in diverse groups of organisms. Under accidental situations, large quantities of radioactive elements get released into the environment and radiation emitted from these radionuclides may adversely affect both the man and the non-human biota. The present study is aimed (a) to know the genotoxic effect of gamma radiation on aquatic fauna employing two species of selected bivalves, (b) to evaluate the possible use of 'Comet assay' for detecting genetic damage in haemocytes of bivalves as a biomarker for environmental biomonitoring and also (c) to compare the relative sensitivity of two species of bivalves viz. Paphia malabarica and Meretrix casta to gamma radiation. The comet assays was optimized and validated using different concentrations (18, 32 and 56 mg/L) of ethyl methanesulfonate (EMS), a direct-acting reference genotoxic agent, to which the bivalves were exposed for various times (24, 48 and 72 h). Bivalves were irradiated (single acute exposure) with 5 different doses (viz. 2, 4, 6, 8 and 10 Gy) of gamma radiation and their genotoxic effects on the haemocytes were studied using the comet assay. Haemolymph was collected from the adductor muscle at 24, 48 and 72 h of both EMS-exposed and irradiated bivalves and comet assay was carried out using standard protocol. A significant increase in DNA damage was observed as indicated by an increase in % tail DNA damage at different concentrations of EMS and all the doses of gamma radiation as compared to controls in both bivalve species. This showed a dose-dependent increase of genetic damage induced in bivalves by EMS as well as gamma radiation. Further, the highest DNA damage was observed at 24h. The damage gradually decreased with time, i.e. was smaller at 48 and 72 h than at 24h post irradiation in both species of bivalves. This may indicate repair of the damaged DNA and/or loss of heavily damaged cells as the post irradiation time advanced. The present study

  13. Induction of DNA–protein cross-links by ionizing radiation and their elimination from the genome

    Energy Technology Data Exchange (ETDEWEB)

    Nakano, Toshiaki; Mitsusada, Yusuke [Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Higashi-Hiroshima 739-8526 (Japan); Salem, Amir M.H. [Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Higashi-Hiroshima 739-8526 (Japan); Department of Pathology, Medical Research Division, National Research Centre, El-Bohouth St., Dokki, Giza 12311 (Egypt); Shoulkamy, Mahmoud I. [Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Higashi-Hiroshima 739-8526 (Japan); Department of Zoology, Biological Science Building, Faculty of Science, Minia University, Minia 61519 (Egypt); Sugimoto, Tatsuya [Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Higashi-Hiroshima 739-8526 (Japan); Hirayama, Ryoichi; Uzawa, Akiko [Research Center for Charged Particle Therapy, National Institute of Radiological Sciences (NIRS), Chiba 263-8555 (Japan); Furusawa, Yoshiya [Development and Support Center, National Institute of Radiological Sciences (NIRS), Chiba 263-8555 (Japan); Ide, Hiroshi, E-mail: ideh@hiroshima-u.ac.jp [Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Higashi-Hiroshima 739-8526 (Japan)

    2015-01-15

    Highlights: • Normoxic and hypoxic mouse tumors were irradiated with X-rays and C-ion beams. • DNA–protein cross-links (DPCs) and DNA double-strand breaks (DSBs) were analyzed. • C-ion beams produced more DPCs than did X-rays in normoxic and hypoxic tumor cells. • DPCs were eliminated from the genome much more slowly than DSBs. • Persisting DPCs may have deleterious effects on cells in conjunction with DSBs. - Abstract: Ionizing radiation produces various types of DNA lesions, such as base damage, single-strand breaks, double-strand breaks (DSBs), and DNA–protein cross-links (DPCs). Of these, DSBs are the most critical lesions underlying the lethal effects of ionizing radiation. With DPCs, proteins covalently trapped in DNA constitute strong roadblocks to replication and transcription machineries, and hence can be lethal to cells. The formation of DPCs by ionizing radiation is promoted in the absence of oxygen, whereas that of DSBs is retarded. Accordingly, the contribution of DPCs to the lethal events in irradiated cells may not be negligible for hypoxic cells, such as those present in tumors. However, the role of DPCs in the lethal effects of ionizing radiation remains largely equivocal. In the present study, normoxic and hypoxic mouse tumors were irradiated with X-rays [low linear energy transfer (LET) radiation] and carbon (C)-ion beams (high LET radiation), and the resulting induction of DPCs and DSBs and their removal from the genome were analyzed. X-rays and C-ion beams produced more DPCs in hypoxic tumors than in normoxic tumors. Interestingly, the yield of DPCs was slightly but statistically significantly greater (1.3- to 1.5-fold) for C-ion beams than for X-rays. Both X-rays and C-ion beams generated two types of DPC that differed according to their rate of removal from the genome. This was also the case for DSBs. The half-lives of the rapidly removed components of DPCs and DSBs were similar (<1 h), but those of the slowly removed components

  14. Molecular Mechanisms of Ultraviolet Radiation-Induced DNA Damage and Repair

    Directory of Open Access Journals (Sweden)

    Rajesh P. Rastogi

    2010-01-01

    Full Text Available DNA is one of the prime molecules, and its stability is of utmost importance for proper functioning and existence of all living systems. Genotoxic chemicals and radiations exert adverse effects on genome stability. Ultraviolet radiation (UVR (mainly UV-B: 280–315 nm is one of the powerful agents that can alter the normal state of life by inducing a variety of mutagenic and cytotoxic DNA lesions such as cyclobutane-pyrimidine dimers (CPDs, 6-4 photoproducts (6-4PPs, and their Dewar valence isomers as well as DNA strand breaks by interfering the genome integrity. To counteract these lesions, organisms have developed a number of highly conserved repair mechanisms such as photoreactivation, base excision repair (BER, nucleotide excision repair (NER, and mismatch repair (MMR. Additionally, double-strand break repair (by homologous recombination and nonhomologous end joining, SOS response, cell-cycle checkpoints, and programmed cell death (apoptosis are also operative in various organisms with the expense of specific gene products. This review deals with UV-induced alterations in DNA and its maintenance by various repair mechanisms.

  15. Synthetic Secoisolariciresinol Diglucoside (LGM2605 Protects Human Lung in an Ex Vivo Model of Proton Radiation Damage

    Directory of Open Access Journals (Sweden)

    Anastasia Velalopoulou

    2017-11-01

    Full Text Available Radiation therapy for the treatment of thoracic malignancies has improved significantly by directing of the proton beam in higher doses on the targeted tumor while normal tissues around the tumor receive much lower doses. Nevertheless, exposure of normal tissues to protons is known to pose a substantial risk in long-term survivors, as confirmed by our work in space-relevant exposures of murine lungs to proton radiation. Thus, radioprotective strategies are being sought. We established that LGM2605 is a potent protector from radiation-induced lung toxicity and aimed in the current study to extend the initial findings of space-relevant, proton radiation-associated late lung damage in mice by looking at acute changes in human lung. We used an ex vivo model of organ culture where tissue slices of donor living human lung were kept in culture and exposed to proton radiation. We exposed donor human lung precision-cut lung sections (huPCLS, pretreated with LGM2605, to 4 Gy proton radiation and evaluated them 30 min and 24 h later for gene expression changes relevant to inflammation, oxidative stress, and cell cycle arrest, and determined radiation-induced senescence, inflammation, and oxidative tissue damage. We identified an LGM2605-mediated reduction of proton radiation-induced cellular senescence and associated cell cycle changes, an associated proinflammatory phenotype, and associated oxidative tissue damage. This is a first report on the effects of proton radiation and of the radioprotective properties of LGM2605 on human lung.

  16. Combined small angle X-ray solution scattering with atomic force microscopy for characterizing radiation damage on biological macromolecules.

    Science.gov (United States)

    Costa, Luca; Andriatis, Alexander; Brennich, Martha; Teulon, Jean-Marie; Chen, Shu-Wen W; Pellequer, Jean-Luc; Round, Adam

    2016-10-27

    Synchrotron radiation facilities are pillars of modern structural biology. Small-Angle X-ray scattering performed at synchrotron sources is often used to characterize the shape of biological macromolecules. A major challenge with high-energy X-ray beam on such macromolecules is the perturbation of sample due to radiation damage. By employing atomic force microscopy, another common technique to determine the shape of biological macromolecules when deposited on flat substrates, we present a protocol to evaluate and characterize consequences of radiation damage. It requires the acquisition of images of irradiated samples at the single molecule level in a timely manner while using minimal amounts of protein. The protocol has been tested on two different molecular systems: a large globular tetremeric enzyme (β-Amylase) and a rod-shape plant virus (tobacco mosaic virus). Radiation damage on the globular enzyme leads to an apparent increase in molecular sizes whereas the effect on the long virus is a breakage into smaller pieces resulting in a decrease of the average long-axis radius. These results show that radiation damage can appear in different forms and strongly support the need to check the effect of radiation damage at synchrotron sources using the presented protocol.

  17. Novel connections between DNA replication, telomere homeostasis, and the DNA damage response revealed by a genome-wide screen for TEL1/ATM interactions in Saccharomyces cerevisiae.

    Science.gov (United States)

    Piening, Brian D; Huang, Dongqing; Paulovich, Amanda G

    2013-04-01

    Tel1 is the budding yeast ortholog of the mammalian tumor suppressor and DNA damage response (DDR) kinase ATM. However, tel1-Δ cells, unlike ATM-deficient cells, do not exhibit sensitivity to DNA-damaging agents, but do display shortened (but stably maintained) telomere lengths. Neither the extent to which Tel1p functions in the DDR nor the mechanism by which Tel1 contributes to telomere metabolism is well understood. To address the first question, we present the results from a comprehensive genome-wide screen for genetic interactions with tel1-Δ that cause sensitivity to methyl methanesulfonate (MMS) and/or ionizing radiation, along with follow-up characterizations of the 13 interactions yielded by this screen. Surprisingly, many of the tel1-Δ interactions that confer DNA damage sensitivity also exacerbate the short telomere phenotype, suggesting a connection between these two phenomena. Restoration of normal telomere length in the tel1-Δ xxx-Δ mutants results in only minor suppression of the DNA damage sensitivity, demonstrating that the sensitivity of these mutants must also involve mechanisms independent of telomere length. In support of a model for increased replication stress in the tel1-Δ xxx-Δ mutants, we show that depletion of dNTP pools through pretreatment with hydroxyurea renders tel1-Δ cells (but not wild type) MMS-sensitive, demonstrating that, under certain conditions, Tel1p does indeed play a critical role in the DDR.

  18. New Paradigms in the Repair of Oxidative Damage in Human Genome

    Science.gov (United States)

    Dutta, Arijit; Yang, Chunying; Sengupta, Shiladitya; Mitra, Sankar; Hegde, Muralidhar L.

    2015-01-01

    Oxidized bases in the mammalian genome, which are invariably mutagenic due to their mis-pairing property, are continuously induced by endogenous reactive oxygen species (ROS) and more abundantly after oxidative stress. Unlike bulky base adducts induced by UV and other environmental mutagens in the genome that block replicative DNA polymerases, oxidatively damaged bases such as 5-hydoxyuracil (5-OHU), produced by oxidative deamination of cytosine in the template strand, do not block replicative polymerases and thus need to be repaired prior to replication in order to prevent mutation. Following up our earlier studies, which showed that the Nei endonuclease VIII like 1 (NEIL1) DNA glycosylase, one of five base excision repair (BER)-initiating enzymes in mammalian cells, has enhanced expression during the S-phase and higher affinity for replication fork-mimicking single-stranded (ss) DNA substrates, we recently provided direct experimental evidence for NEIL1’s role in replicating template-strand repair. The key requirement for this event, which we named as the ‘cow-catcher’ mechanism of pre-replicative BER, is NEIL1’s non-productive binding (substrate binding without product formation) to the lesion base in ss DNA template to stall DNA synthesis, causing fork regression. Repair of the lesion in re-annealed duplex is then carried out by NEIL1 in association with the DNA replication proteins. NEIL1 (and other BER-initiating enzymes) also interact with several accessory and non-canonical proteins including the heterogeneous nuclear ribonucleoprotein U (hnRNP-U) and Y-box-binding protein 1 (YB-1) as well as high mobility group box 1 protein (HMGB1), whose precise roles in BER are still obscure. In this review, we have discussed the recent advances in our understanding of oxidative genome damage repair pathways with particular focus on the pre-replicative template strand repair and the role of scaffold factors like X-ray repair cross-complementing protein 1 (XRCC1

  19. Modelling electron distributions within ESA's Gaia satellite CCD pixels to mitigate radiation damage

    Science.gov (United States)

    Seabroke, G. M.; Holland, A. D.; Burt, D.; Robbins, M. S.

    2009-08-01

    The Gaia satellite is a high-precision astrometry, photometry and spectroscopic ESA cornerstone mission, currently scheduled for launch in 2012. Its primary science drivers are the composition, formation and evolution of the Galaxy. Gaia will achieve its unprecedented positional accuracy requirements with detailed calibration and correction for radiation damage. At L2, protons cause displacement damage in the silicon of CCDs. The resulting traps capture and emit electrons from passing charge packets in the CCD pixel, distorting the image PSF and biasing its centroid. Microscopic models of Gaia's CCDs are being developed to simulate this effect. The key to calculating the probability of an electron being captured by a trap is the 3D electron density within each CCD pixel. However, this has not been physically modelled for the Gaia CCD pixels. In Seabroke, Holland & Cropper (2008), the first paper of this series, we motivated the need for such specialised 3D device modelling and outlined how its future results will fit into Gaia's overall radiation calibration strategy. In this paper, the second of the series, we present our first results using Silvaco's physics-based, engineering software: the ATLAS device simulation framework. Inputting a doping profile, pixel geometry and materials into ATLAS and comparing the results to other simulations reveals that ATLAS has a free parameter, fixed oxide charge, that needs to be calibrated. ATLAS is successfully benchmarked against other simulations and measurements of a test device, identifying how to use it to model Gaia pixels and highlighting the affect of different doping approximations.

  20. Ultraviolet Radiation, Aging and the Skin: Prevention of Damage by Topical cAMP Manipulation

    Directory of Open Access Journals (Sweden)

    Alexandra Amaro-Ortiz

    2014-05-01

    Full Text Available Being the largest and most visible organ of the body and heavily influenced by environmental factors, skin is ideal to study the long-term effects of aging. Throughout our lifetime, we accumulate damage generated by UV radiation. UV causes inflammation, immune changes, physical changes, impaired wound healing and DNA damage that promotes cellular senescence and carcinogenesis. Melanoma is the deadliest form of skin cancer and among the malignancies of highest increasing incidence over the last several decades. Melanoma incidence is directly related to age, with highest rates in individuals over the age of 55 years, making it a clear age-related disease. In this review, we will focus on UV-induced carcinogenesis and photo aging along with natural protective mechanisms that reduce amount of “realized” solar radiation dose and UV-induced injury. We will focus on the theoretical use of forskolin, a plant-derived pharmacologically active compound to protect the skin against UV injury and prevent aging symptoms by up-regulating melanin production. We will discuss its use as a topically-applied root-derived formulation of the Plectranthus barbatus (Coleus forskolii plant that grows naturally in Asia and that has long been used in various Aryuvedic teas and therapeutic preparations.

  1. The behaviour of copper in view of radiation damage in the LHC luminosity upgrade

    CERN Document Server

    Flukiger, R.

    2013-01-01

    In view of the safe operation of the quadrupoles in the luminosity upgrade of the LHC accelerator, the response of the copper stabilizer at low temperatures to the various high energy radiation sources is of primary importance. The present study takes into account the expected high energy spectrum of the simultaneous radiation by neutrons, protons, pions, electrons and photons, calculated using the FLUKA code by F. Cerutti (CERN) as well as on literature values. It was found that proton irradiation causes a considerably higher damage than neutron irradiation: in spite of a 3.8% proton fraction, the measured damage is of the order of 20%, which fits with the calculations of N. Mokhov (Fermilab) on the contribution of protons to the dpa. The same calculations indicate that the total effect of protons, pions and electrons is at least as high as that of neutrons. Since recent neutron experiments of Nakamoto et al. show that the RRR of Cu is reduced from 200 to 50-120 for a fluence of 10^{21} n/cm^{2}, it follows ...

  2. Comparison of a fast analytical model of radiation damage effects in CCDs with experimental tests

    Science.gov (United States)

    Prod'homme, Thibaut; Weiler, Michael; Brown, Scott W.; Short, Alexander D. T.; Brown, Anthony G. A.

    2010-07-01

    ESA's Gaia mission aims to create a complete and highly accurate stereoscopic map of the Milky Way. The stellar parallaxes will be determined at the micro-arcsecond level, as a consequence the measurement of the stellar image location on the CCD must be highly accurate. The solar wind protons will create charge traps in the CCDs of Gaia, which will induce large charge loss and distort the stellar images causing a degradation of the location measurement accuracy. Accurate modelling of the stellar image distortion induced by radiation is required to mitigate these effects. We assess the capability of a fast physical analytical model of radiation damage effects called the charge distortion model (CDM) to reproduce experimental data. To realize this assessment we developed a rigorous procedure that compares at the sub-pixel level the model outcomes to damaged images extracted from the experimental tests. We show that CDM can reproduce accurately up to a certain level the test data acquired on a highly irradiated device operated in time delay integration mode for different signal levels and different illumination histories. We discuss the potential internal and external factors that contributed to limit the agreement between the data and the charge distortion model. To investigate these limiting factors further, we plan to apply our comparison procedure on a synthetic dataset generated through detailed Monte-Carlo simulations at the CCD electrode level.

  3. Survival, DNA Integrity, and Ultrastructural Damage in Antarctic Cryptoendolithic Eukaryotic Microorganisms Exposed to Ionizing Radiation.

    Science.gov (United States)

    Pacelli, Claudia; Selbmann, Laura; Zucconi, Laura; Raguse, Marina; Moeller, Ralf; Shuryak, Igor; Onofri, Silvano

    2017-02-01

    Life dispersal between planets, planetary protection, and the search for biosignatures are main topics in astrobiology. Under the umbrella of the STARLIFE project, three Antarctic endolithic microorganisms, the melanized fungus Cryomyces antarcticus CCFEE 515, a hyaline strain of Umbilicaria sp. (CCFEE 6113, lichenized fungus), and a Stichococcus sp. strain (C45A, green alga), were exposed to high doses of space-relevant gamma radiation (60Co), up to 117.07 kGy. After irradiation survival, DNA integrity and ultrastructural damage were tested. The first was assessed by clonogenic test; viability and dose responses were reasonably described by the linear-quadratic formalism. DNA integrity was evaluated by PCR, and ultrastructural damage was observed by transmission electron microscopy. The most resistant among the tested organisms was C. antarcticus both in terms of colony formation and DNA preservation. Besides, results clearly demonstrate that DNA was well detectable in all the tested organisms even when microorganisms were dead. This high resistance provides support for the use of DNA as a possible biosignature during the next exploration campaigns. Implication in planetary protection and contamination during long-term space travel are put forward. Key Words: Biosignatures-Ionizing radiation-DNA integrity-Eukaryotic microorganisms-Fingerprinting-Mars exploration. Astrobiology 17, 126-135.

  4. Lightweight Damage Tolerant, High-Temperature Radiators for Nuclear Power and Propulsion

    Science.gov (United States)

    Craven, Paul D.; SanSoucie, Michael P.

    2015-01-01

    NASA is increasingly emphasizing exploration to bodies beyond near-Earth orbit. New propulsion systems and new spacecraft are being built for these missions. As the target bodies get further out from Earth, high energy density systems, e.g., nuclear fusion, for propulsion and power will be advantageous. The mass and size of these systems, including supporting systems such as the heat exchange system, including thermal radiators, will need to be as small as possible. Conventional heat exchange systems are a significant portion of the total thermal management mass and size. Nuclear electric propulsion (NEP) is a promising option for high-speed, in-space travel due to the high energy density of nuclear fission power sources and efficient electric thrusters. Heat from the reactor is converted to power for use in propulsion or for system power. The heat not used in the power conversion is then radiated to space as shown in figure 1. Advanced power conversion technologies will require high operating temperatures and would benefit from lightweight radiator materials. Radiator performance dictates power output for nuclear electric propulsion systems. Pitch-based carbon fiber materials have the potential to offer significant improvements in operating temperature, thermal conductivity, and mass. These properties combine to allow significant decreases in the total mass of the radiators and significant increases in the operating temperature of the fins. A Center-funded project at NASA Marshall Space Flight Center has shown that high thermal conductivity, woven carbon fiber fins with no matrix material, can be used to dissipate waste heat from NEP systems and because of high specific power (kW/kg), will require less mass and possibly less total area than standard metal and composite radiator fins for radiating the same amount of heat. This project uses an innovative approach to reduce the mass and size required for the thermal radiators to the point that in-space NEP and power

  5. When genome integrity and cell cycle decisions collide: roles of polo kinases in cellular adaptation to DNA damage.

    Science.gov (United States)

    Serrano, Diego; D'Amours, Damien

    2014-09-01

    The drive to proliferate and the need to maintain genome integrity are two of the most powerful forces acting on biological systems. When these forces enter in conflict, such as in the case of cells experiencing DNA damage, feedback mechanisms are activated to ensure that cellular proliferation is stopped and no further damage is introduced while cells repair their chromosomal lesions. In this circumstance, the DNA damage response dominates over the biological drive to proliferate, and may even result in programmed cell death if the damage cannot be repaired efficiently. Interestingly, the drive to proliferate can under specific conditions overcome the DNA damage response and lead to a reactivation of the proliferative program in checkpoint-arrested cells. This phenomenon is known as adaptation to DNA damage and is observed in all eukaryotic species where the process has been studied, including normal and cancer cells in humans. Polo-like kinases (PLKs) are critical regulators of the adaptation response to DNA damage and they play key roles at the interface of cell cycle and checkpoint-related decisions in cells. Here, we review recent progress in defining the specific roles of PLKs in the adaptation process and how this conserved family of eukaryotic kinases can integrate the fundamental need to preserve genomic integrity with effective cellular proliferation.

  6. Effect of adiponectin deficiency on intestinal damage and hematopoietic responses of mice exposed to gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Ponemone, Venkatesh; Fayad, Raja; Gove, Melissa E.; Pini, Maria [Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL 60612 (United States); Fantuzzi, Giamila, E-mail: giamila@uic.edu [Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL 60612 (United States)

    2010-08-07

    Adiponectin (APN) is an adipose tissue-derived cytokine that regulates insulin sensitivity and inflammation. It is also involved in modulation of cell proliferation by binding to various growth factors. Based on its known effects in modulating cell proliferation and oxidative stress, APN may potentially be involved in regulating tissue damage and repair following irradiation. Adiponectin KO mice and their WT littermates were exposed to a single whole-body dose of 3 or 6 Gy gamma radiation. Radiation-induced alterations were studied in jejunum, blood, bone marrow and thymus at days 1 and 5 post-irradiation and compared with sham-irradiated groups. In WT mice, irradiation did not significantly alter serum APN levels while inducing a significant decrease in serum leptin. Irradiation caused a significant reduction in thymocyte cellularity, with concomitant decrease in CD4{sup +}, CD8{sup +} and CD4{sup +}CD8{sup +} T cell populations, with no significant differences between WT and APN KO mice. Irradiation resulted in a significantly higher increase in the frequency of micronucleated reticulocytes in the blood of APN KO compared with WT mice, whereas frequency of micronucleated normochromatic erythrocytes in the bone marrow at day 5 was significantly higher in WT compared with APN KO mice. Finally, irradiation induced similar alterations in villus height and crypt cell proliferation in the jejunum of WT and APN KO mice. Jejunum explants from sham-irradiated APN KO mice produced higher levels of IL-6 compared with tissue from WT animals, but the difference was no longer apparent following irradiation. Our data indicate that APN deficiency does not play a significant role in modulating radiation-induced gastrointestinal injury in mice, while it may participate in regulation of damage to the hematopoietic system.

  7. Mobile phone radiation induces reactive oxygen species production and DNA damage in human spermatozoa in vitro.

    Science.gov (United States)

    De Iuliis, Geoffry N; Newey, Rhiannon J; King, Bruce V; Aitken, R John

    2009-07-31

    In recent times there has been some controversy over the impact of electromagnetic radiation on human health. The significance of mobile phone radiation on male reproduction is a key element of this debate since several studies have suggested a relationship between mobile phone use and semen quality. The potential mechanisms involved have not been established, however, human spermatozoa are known to be particularly vulnerable to oxidative stress by virtue of the abundant availability of substrates for free radical attack and the lack of cytoplasmic space to accommodate antioxidant enzymes. Moreover, the induction of oxidative stress in these cells not only perturbs their capacity for fertilization but also contributes to sperm DNA damage. The latter has, in turn, been linked with poor fertility, an increased incidence of miscarriage and morbidity in the offspring, including childhood cancer. In light of these associations, we have analyzed the influence of RF-EMR on the cell biology of human spermatozoa in vitro. Purified human spermatozoa were exposed to radio-frequency electromagnetic radiation (RF-EMR) tuned to 1.8 GHz and covering a range of specific absorption rates (SAR) from 0.4 W/kg to 27.5 W/kg. In step with increasing SAR, motility and vitality were significantly reduced after RF-EMR exposure, while the mitochondrial generation of reactive oxygen species and DNA fragmentation were significantly elevated (PDNA damage bio-marker, 8-OH-dG, and DNA fragmentation after RF-EMR exposure. RF-EMR in both the power density and frequency range of mobile phones enhances mitochondrial reactive oxygen species generation by human spermatozoa, decreasing the motility and vitality of these cells while stimulating DNA base adduct formation and, ultimately DNA fragmentation. These findings have clear implications for the safety of extensive mobile phone use by males of reproductive age, potentially affecting both their fertility and the health and wellbeing of their

  8. MRI findings of radiation-induced myocardial damage in patients with oesophageal cancer.

    Science.gov (United States)

    Umezawa, R; Ota, H; Takanami, K; Ichinose, A; Matsushita, H; Saito, H; Takase, K; Jingu, K

    2014-12-01

    To evaluate radiation-induced myocardial damage after mediastinal radiotherapy using MRI. Between May 2010 and April 2011, delayed contrast-enhanced MRI was performed for patients who had maintained a complete response to curative radiotherapy for oesophageal cancer for more than 6 months. The patients received radiotherapy with a median total dose of 66 Gy (60-70 Gy) for the primary tumour and metastatic lymph nodes. Images of MRI were analysed by a 17-segment method recommended by the American Heart Association. A segment included mainly in the 40 Gy dose line was defined as Segment 40 Gy, a segment included mainly in the 60 Gy dose line as Segment 60 Gy, and a segment out of the radiation fields as Segment OUT. The percentage of late gadolinium enhancement (LGE) was examined in those categories. The layer in which LGE was predominantly distributed was evaluated for each patient. Four hundred and eight segments in 24 patients were analysed. The median interval from completion of radiotherapy to MRI was 23.5 months (range 6-88 months). LGE was detected in 12 of the 24 patients. LGE was detected in 15.38% of Segment 40 Gy cases, 21.21% of Segment 60 Gy cases, and 0% of Segment OUT cases. LGE in mid-myocardial and subendocardial layers was detected in 11 patients and one patient, respectively. LGE suggesting radiation induced myocardial fibrosis was observed by performing delayed contrast-enhanced MRI. Care should be taken when planning radiotherapy to avoid late cardiac damage. Copyright © 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  9. Genome-wide maps of alkylation damage, repair, and mutagenesis in yeast reveal mechanisms of mutational heterogeneity.

    Science.gov (United States)

    Mao, Peng; Brown, Alexander J; Malc, Ewa P; Mieczkowski, Piotr A; Smerdon, Michael J; Roberts, Steven A; Wyrick, John J

    2017-10-01

    DNA base damage is an important contributor to genome instability, but how the formation and repair of these lesions is affected by the genomic landscape and contributes to mutagenesis is unknown. Here, we describe genome-wide maps of DNA base damage, repair, and mutagenesis at single nucleotide resolution in yeast treated with the alkylating agent methyl methanesulfonate (MMS). Analysis of these maps revealed that base excision repair (BER) of alkylation damage is significantly modulated by chromatin, with faster repair in nucleosome-depleted regions, and slower repair and higher mutation density within strongly positioned nucleosomes. Both the translational and rotational settings of lesions within nucleosomes significantly influence BER efficiency; moreover, this effect is asymmetric relative to the nucleosome dyad axis and is regulated by histone modifications. Our data also indicate that MMS-induced mutations at adenine nucleotides are significantly enriched on the nontranscribed strand (NTS) of yeast genes, particularly in BER-deficient strains, due to higher damage formation on the NTS and transcription-coupled repair of the transcribed strand (TS). These findings reveal the influence of chromatin on repair and mutagenesis of base lesions on a genome-wide scale and suggest a novel mechanism for transcription-associated mutation asymmetry, which is frequently observed in human cancers. © 2017 Mao et al.; Published by Cold Spring Harbor Laboratory Press.

  10. Radiation damage studies on STAR250 CMOS sensor at 300 keV for electron microscopy

    Science.gov (United States)

    Faruqi, A. R.; Henderson, R.; Holmes, J.

    2006-09-01

    There is a pressing need for better electronic detectors to replace film for recording high-resolution images using electron cryomicroscopy. Our previous work has shown that direct electron detection in CMOS sensors is promising in terms of resolution and efficiency at 120 keV [A.R. Faruqi, R. Henderson, M. Prydderch, R. Turchetta, P. Allport, A. Evans, Nucl. Instr. and Meth. 546 (2005) 170], but in addition, the detectors must not be damaged by the electron irradiation. We now present new measurements on the radiation tolerance of a 25 μm pitch CMOS active-pixel sensor, the STAR250, which was designed by FillFactory using radiation-hard technology for space applications. Our tests on the STAR250 aimed to establish the imaging performance at 300 keV following irradiation. The residual contrast, measured on shadow images of a 300 mesh grid, was >80% after corrections for increased dark current, following irradiation with up to 5×10 7 electrons/pixel (equivalent to 80,000 electron/μm 2). A CMOS sensor with this degree of radiation tolerance would survive a year of normal usage for low-dose electron cryomicroscopy, which is a very useful advance.

  11. Radiation damage studies on STAR250 CMOS sensor at 300 keV for electron microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Faruqi, A.R. [MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH (United Kingdom)]. E-mail: arf@mrc-lmb.cam.ac.uk; Henderson, R. [MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH (United Kingdom); Holmes, J. [Sira Technology Ltd., South Hill, Chislehurst, Kent BR7 5EH (United Kingdom)

    2006-09-01

    There is a pressing need for better electronic detectors to replace film for recording high-resolution images using electron cryomicroscopy. Our previous work has shown that direct electron detection in CMOS sensors is promising in terms of resolution and efficiency at 120 keV [A.R. Faruqi, R. Henderson, M. Prydderch, R. Turchetta, P. Allport, A. Evans, Nucl. Instr. and Meth. 546 (2005) 170], but in addition, the detectors must not be damaged by the electron irradiation. We now present new measurements on the radiation tolerance of a 25 {mu}m pitch CMOS active-pixel sensor, the STAR250, which was designed by FillFactory using radiation-hard technology for space applications. Our tests on the STAR250 aimed to establish the imaging performance at 300 keV following irradiation. The residual contrast, measured on shadow images of a 300 mesh grid, was >80% after corrections for increased dark current, following irradiation with up to 5x10{sup 7} electrons/pixel (equivalent to 80,000 electron/{mu}m{sup 2}). A CMOS sensor with this degree of radiation tolerance would survive a year of normal usage for low-dose electron cryomicroscopy, which is a very useful advance.

  12. Proton radiation damage assessment of a CCD for use in a Ultraviolet and Visible Spectrometer

    Science.gov (United States)

    Gow, J. P. D.; Mason, J.; Leese, M.; Hathi, B.; Patel, M.

    2017-01-01

    This paper describes the radiation environment and radiation damage analysis performed for the Nadir and Occultation for MArs Discovery (NOMAD) Ultraviolet and Visible Spectrometer (UVIS) channel launched onboard the ExoMars Trace Gas Orbiter (TGO) in 2016. The aim of the instrument is to map the temporal and spatial variation of trace gases such as ozone and dust/cloud aerosols in the atmosphere of Mars. The instrument consists of a set of two miniature telescope viewing optics which allow for selective input onto the optical bench, where an e2v technologies CCD30-11 will be used as the detector. A Geometry Description Markup Language model of the spacecraft and instrument box was created and through the use of ESA's SPace ENVironment Information System (SPENVIS) an estimate of the 10 MeV equivalent proton fluence was made at a number of radiation sensitive regions within NOMAD, including that of the CCD30-11 which is the focus of this paper. The end of life 10 MeV equivalent proton fluence at the charge coupled device was estimated to be 4.7 × 109 protons.cm-2 three devices were irradiated at different levels up a 10 MeV equivalent fluence of 9.4 × 109 protons.cm-2. The dark current, charge transfer inefficiency, charge storage, and cosmetic quality of the devices was investigated pre- and post-irradiation, determining that the devices will continue to provide excellent science throughout the mission.

  13. Mechanism of Radiation Damage Reduction in Equiatomic Multicomponent Single Phase Alloys

    Science.gov (United States)

    Granberg, F.; Nordlund, K.; Ullah, Mohammad W.; Jin, K.; Lu, C.; Bei, H.; Wang, L. M.; Djurabekova, F.; Weber, W. J.; Zhang, Y.

    2016-04-01

    Recently a new class of metal alloys, of single-phase multicomponent composition at roughly equal atomic concentrations ("equiatomic"), have been shown to exhibit promising mechanical, magnetic, and corrosion resistance properties, in particular, at high temperatures. These features make them potential candidates for components of next-generation nuclear reactors and other high-radiation environments that will involve high temperatures combined with corrosive environments and extreme radiation exposure. In spite of a wide range of recent studies of many important properties of these alloys, their radiation tolerance at high doses remains unexplored. In this work, a combination of experimental and modeling efforts reveals a substantial reduction of damage accumulation under prolonged irradiation in single-phase NiFe and NiCoCr alloys compared to elemental Ni. This effect is explained by reduced dislocation mobility, which leads to slower growth of large dislocation structures. Moreover, there is no observable phase separation, ordering, or amorphization, pointing to a high phase stability of this class of alloys.

  14. Accelerated aging tests of radiation damaged lasers and photodiodes for the CMS tracker optical links

    CERN Document Server

    Gill, K; Batten, J; Cervelli, G; Grabit, R; Jensen, F; Troska, Jan K; Vasey, F

    1999-01-01

    The combined effects of radiation damage and accelerated ageing in COTS lasers and p-i-n photodiodes are presented. Large numbers of these devices are employed in future High Energy Physics experiments and it is vital that these devices are confirmed to be sufficiently robust in terms of both radiation resistance and reliability. Forty 1310 nm InGaAsP edge-emitting lasers (20 irradiated) and 30 InGaAs p- i-n photodiodes (19 irradiated) were aged for 4000 hours at 80 degrees C with periodic measurements made of laser threshold and efficiency, in addition to p-i-n leakage current and photocurrent. There were no sudden failures and there was very little wearout- related degradation in either unirradiated or irradiated sample groups. The results suggest that the tested devices have a sufficiently long lifetime to operate for at least 10 years inside the Compact Muon Solenoid experiment despite being exposed to a harsh radiation environment. (13 refs).

  15. Fundamental Processes of Coupled Radiation Damage and Mechanical Behavior in Nuclear Fuel Materials for High Temperature Reactors

    Energy Technology Data Exchange (ETDEWEB)

    Phillpot, Simon; Tulenko, James

    2011-09-08

    The objective of this work has been to elucidate the relationship among microstructure, radiation damage and mechanical properties for nuclear fuel materials. As representative nuclear materials, we have taken an hcp metal (Mg as a generic metal, and Ti alloys for fast reactors) and UO2 (representing fuel). The degradation of the thermo-mechanical behavior of nuclear fuels under irradiation, both the fissionable material itself and its cladding, is a longstanding issue of critical importance to the nuclear industry. There are experimental indications that nanocrystalline metals and ceramics may be more resistant to radiation damage than their coarse-grained counterparts. The objective of this project look at the effect of microstructure on radiation damage and mechanical behavior in these materials. The approach to be taken was state-of-the-art, large-scale atomic-level simulation. This systematic simulation program of the effects of irradiation on the structure and mechanical properties of polycrystalline Ti and UO2 identified radiation damage mechanisms. Moreover, it will provided important insights into behavior that can be expected in nanocrystalline microstructures and, by extension, nanocomposites. The fundamental insights from this work can be expected to help in the design microstructures that are less susceptible to radiation damage and thermomechanical degradation.

  16. Evaluation of DNA damage induced by gamma radiation in gill and muscle tissues of Cyprinus carpio and their relative sensitivity.

    Science.gov (United States)

    M K, Praveen Kumar; Shyama, Soorambail K; D'Costa, Avelyno; Kadam, Samit B; Sonaye, Bhagatsingh Harisingh; Chaubey, Ramesh Chandra

    2017-10-01

    The effect of radiation on the aquatic environment is of major concern in recent years. Limited data is available on the genotoxicity of gamma radiation on different tissues of aquatic organisms. Hence, the present investigation was carried out to study the DNA damage induced by gamma radiation in the gill and muscle tissues and their relative sensitivity using the comet assay in the freshwater teleost fish, common carp (Cyprinus carpio). The comet assay was optimized and validated in common carp using cyclophosphamide (CP), a reference genotoxic agent. The fish were exposed (acute) to various doses of gamma radiation (2, 4, 6, 8 and 10Gy) and samplings (gill and muscle tissue) were done at regular intervals (24, 48 and 72h) to assess the DNA damage. A significant increase in DNA damage was observed as indicated by an increase in % tail DNA for all doses of gamma radiation in both tissues. We also observed a dose-related increase and a time-dependent decrease of DNA damage. In comparison, DNA damage showed different sensitivity among the tissues at different doses. This shows that a particular dose may have different effects on different tissues which could be due to physiological factors of the particular tissue. Our study also suggests that the gills and muscle of fish are sensitive and reliable tissues for evaluating the genotoxic effects of reference and environmental agents, using the comet assay. Copyright © 2017. Published by Elsevier Inc.

  17. Genetic compensation of high dose radiation-induced damage in an anhydrobiotic insect

    Science.gov (United States)

    Gusev, Oleg; Nakahara, Yuichi; Sakashita, Tetsuya; Kikawada, Takahiro; Okuda, Takashi

    Anhydrobiotic larvae of African chironomid Polypedilum vanderplanki are known to show an extremely high tolerance against a range of stresses. The tolerance against various extreme environments exhibited by that insect might be due to being almost completely desiccated replacing water with trehalose, a state where little or no chemical reactions occur. From 2005 dried larvae of this insect are being used in a number of space experiments, both inside and outside of ISS as a model organism for estimation the limits of higher organisms' resistance to space environment stresses and long-term storage of the alive anhydrobiotic organisms during continues spaceflight. We have shown previously that both hydrated and dried larvae of Polypedilum vanderplanki have very higher tolerance against both highand low-linear energy transfer (LET), surviving after 7000Gy irradiation. It was suggested that the larvae would have effective DNA-reparation system in addition to artificial protection provided by glass-stage without water. In the present study we conducted analysis of stress-related gene expression in the larvae after 70-2000 Gy irradiations. Both DNA damage level and activity of DNA-reparation, anti-apoptotic and protein-damage related genes were analyzed. Direct visualization of DNA damage in the larvae fat body cells using Comet Assay showed that fragmented by radiation DNA is re-arranged within 76-98 hours after exposure. We found that massive overexpression of hsp and anti-oxidant genes occur in larvae entering anhydrobiosis , and provides refolding of proteins after rehydration. In the irradiated larvae overexpression of DNA-reparation enzymes anti-apoptotic genes was confirmed, suggesting that survival after high-dose irradiation is a result of combination of highly effective blocking of entering the apoptosis after severe DNA damage and DNA reparation.

  18. A helium-based model for the effects of radiation damage annealing on helium diffusion kinetics in apatite

    Science.gov (United States)

    Willett, Chelsea D.; Fox, Matthew; Shuster, David L.

    2017-11-01

    Widely used to study surface processes and the development of topography through geologic time, (U-Th)/He thermochronometry in apatite depends on a quantitative description of the kinetics of 4He diffusion across a range of temperatures, timescales, and geologic scenarios. Empirical observations demonstrate that He diffusivity in apatite is not solely a function of temperature, but also depends on damage to the crystal structure from radioactive decay processes. Commonly-used models accounting for the influence of thermal annealing of radiation damage on He diffusivity assume the net effects evolve in proportion to the rate of fission track annealing, although the majority of radiation damage results from α-recoil. While existing models adequately quantify the net effects of damage annealing in many geologic scenarios, experimental work suggests different annealing rates for the two damage types. Here, we introduce an alpha-damage annealing model (ADAM) that is independent of fission track annealing kinetics, and directly quantifies the influence of thermal annealing on He diffusivity in apatite. We present an empirical fit to diffusion kinetics data and incorporate this fit into a model that tracks the competing effects of radiation damage accumulation and annealing on He diffusivity in apatite through geologic time. Using time-temperature paths to illustrate differences between models, we highlight the influence of damage annealing on data interpretation. In certain, but not all, geologic scenarios, the interpretation of low-temperature thermochronometric data can be strongly influenced by which model of radiation damage annealing is assumed. In particular, geologic scenarios involving 1-2 km of sedimentary burial are especially sensitive to the assumed rate of annealing and its influence on He diffusivity. In cases such as basement rocks in Grand Canyon and the Canadian Shield, (U-Th)/He ages predicted from the ADAM can differ by hundreds of Ma from those

  19. Evaluation of γ-radiation-induced DNA damage in two species of bivalves and their relative sensitivity using comet assay

    Energy Technology Data Exchange (ETDEWEB)

    Praveen Kumar, M.K., E-mail: here.praveen@gmail.com [Department of Zoology, Goa University, Goa 403206 (India); Shyama, S.K., E-mail: skshyama@gmail.com [Department of Zoology, Goa University, Goa 403206 (India); Sonaye, B.S. [Department of Radiation Oncology, Goa Medical College, Goa (India); Naik, U Roshini; Kadam, S.B.; Bipin, P.D.; D’costa, A. [Department of Zoology, Goa University, Goa 403206 (India); Chaubey, R.C. [Radiation Biology and Health Science Division, Bhabha Atomic Research Centre, Mumbai (India)

    2014-05-01

    Highlights: • Possible genotoxic effect of accidental exposure of aquatic fauna to γ radiation. • Relative sensitivity of bivalves to γ radiation is also analyzed using comet assay. • γ radiation induced significant genetic damage in both the species of bivalves. • P. malabarica and M. casta exhibited a similar level of sensitivity to γ radiation. • Comet assay may be used as a biomarker for the environmental biomonitoring. - Abstract: Ionizing radiation is known to induce genetic damage in diverse groups of organisms. Under accidental situations, large quantities of radioactive elements get released into the environment and radiation emitted from these radionuclides may adversely affect both the man and the non-human biota. The present study is aimed (a) to know the genotoxic effect of gamma radiation on aquatic fauna employing two species of selected bivalves, (b) to evaluate the possible use of ‘Comet assay’ for detecting genetic damage in haemocytes of bivalves as a biomarker for environmental biomonitoring and also (c) to compare the relative sensitivity of two species of bivalves viz. Paphia malabarica and Meretrix casta to gamma radiation. The comet assays was optimized and validated using different concentrations (18, 32 and 56 mg/L) of ethyl methanesulfonate (EMS), a direct-acting reference genotoxic agent, to which the bivalves were exposed for various times (24, 48 and 72 h). Bivalves were irradiated (single acute exposure) with 5 different doses (viz. 2, 4, 6, 8 and 10 Gy) of gamma radiation and their genotoxic effects on the haemocytes were studied using the comet assay. Haemolymph was collected from the adductor muscle at 24, 48 and 72 h of both EMS-exposed and irradiated bivalves and comet assay was carried out using standard protocol. A significant increase in DNA damage was observed as indicated by an increase in % tail DNA damage at different concentrations of EMS and all the doses of gamma radiation as compared to controls in

  20. Characterization of radiation damage induced by swift heavy ions in graphite

    Energy Technology Data Exchange (ETDEWEB)

    Hubert, Christian

    2016-05-15

    Graphite is a classical material in neutron radiation environments, being widely used in nuclear reactors and power plants as a moderator. For high energy particle accelerators, graphite provides ideal material properties because of the low Z of carbon and its corresponding low stopping power, thus when ion projectiles interact with graphite is the energy deposition rather low. This work aims to improve the understanding of how the irradiation with swift heavy ions (SHI) of kinetic energies in the range of MeV to GeV affects the structure of graphite and other carbon-based materials. Special focus of this project is given to beam induced changes of thermo-mechanical properties. For this purpose the Highly oriented pyrolytic graphite (HOPG) and glassy carbon (GC) (both serving as model materials), isotropic high density polycrystalline graphite (PG) and other carbon based materials like carbon fiber carbon composites (CFC), chemically expanded graphite (FG) and molybdenum carbide enhanced graphite composites (MoC) were exposed to different ions ranging from {sup 131}Xe to {sup 238}U provided by the UNILAC accelerator at GSI in Darmstadt, Germany. To investigate structural changes, various in-situ and off-line measurements were performed including Raman spectroscopy, x-ray diffraction and x-ray photo-electron spectroscopy. Thermo-mechanical properties were investigated using the laser-flash-analysis method, differential scanning calorimetry, micro/nano-indentation and 4-point electrical resistivity measurements. Beam induced stresses were investigated using profilometry. Obtained results provided clear evidence that ion beam-induced radiation damage leads to structural changes and degradation of thermal, mechanical and electrical properties of graphite. PG transforms towards a disordered sp2 structure, comparable to GC at high fluences. Irradiation-induced embrittlement is strongly reducing the lifetime of most high-dose exposed accelerator components. For

  1. Cell to Cell Variability of Radiation-Induced Foci: Relation between Observed Damage and Energy Deposition.

    Directory of Open Access Journals (Sweden)

    Gaëtan Gruel

    Full Text Available Most studies that aim to understand the interactions between different types of photon radiation and cellular DNA assume homogeneous cell irradiation, with all cells receiving the same amount of energy. The level of DNA damage is therefore generally determined by averaging it over the entire population of exposed cells. However, evaluating the molecular consequences of a stochastic phenomenon such as energy deposition of ionizing radiation by measuring only an average effect may not be sufficient for understanding some aspects of the cellular response to this radiation. The variance among the cells associated with this average effect may also be important for the behaviour of irradiated tissue. In this study, we accurately estimated the distribution of the number of radiation-induced γH2AX foci (RIF per cell nucleus in a large population of endothelial cells exposed to 3 macroscopic doses of gamma rays from 60Co. The number of RIF varied significantly and reproducibly from cell to cell, with its relative standard deviation ranging from 36% to 18% depending on the macroscopic dose delivered. Interestingly, this relative cell-to-cell variability increased as the dose decreased, contrary to the mean RIF count per cell. This result shows that the dose effect, in terms of the number of DNA lesions indicated by RIF is not as simple as a purely proportional relation in which relative SD is constant with dose. To analyse the origins of this observed variability, we calculated the spread of the specific energy distribution for the different target volumes and subvolumes in which RIF can be generated. Variances, standard deviations and relative standard deviations all changed similarly from dose to dose for biological and calculated microdosimetric values. This similarity is an important argument that supports the hypothesis of the conservation of the association between the number of RIF per nucleus and the specific energy per DNA molecule. This

  2. Comparison of Interfacial Strengthening in Creep Deformation and Radiation Damage Processes of Advanced Structural Materials for Nuclear Applications

    Science.gov (United States)

    Zhu, Hanliang

    2018-02-01

    The mechanisms for microstructural strengthening in creep deformation and radiation damage processes of advanced structural materials for nuclear applications are compared. During creep and irradiation, various defects are generated and move in the microstructure. Any microstructural features that can retard such defect movement may improve both creep and radiation damage resistance. Interfaces in the microstructure are important barriers for preventing defect motion. To achieve ultrahigh strength and enhanced radiation damage resistance, an extremely high density of interfaces has been designed in recently developed nanostructured materials. However, interface-mediated processes may govern the deformation of these materials, decreasing their creep properties. Methods for improving the creep resistance of nanostructured materials are reviewed and discussed.

  3. Non-targeted and delayed effects of exposure to ionizing radiation: I. Radiation-induced genomic instability and bystander effects in vitro

    Science.gov (United States)

    Morgan, William F.

    2003-01-01

    A long-standing dogma in the radiation sciences is that energy from radiation must be deposited in the cell nucleus to elicit a biological effect. A number of non-targeted, delayed effects of ionizing radiation have been described that challenge this dogma and pose new challenges to evaluating potential hazards associated with radiation exposure. These effects include induced genomic instability and non-targeted bystander effects. The in vitro evidence for non-targeted effects in radiation biology will be reviewed, but the question as to how one extrapolates from these in vitro observations to the risk of radiation-induced adverse health effects such as cancer remains open.

  4. Radiation damage production in massive cascades initiated by fusion neutrons in tungsten

    Energy Technology Data Exchange (ETDEWEB)

    Sand, A.E., E-mail: andrea.sand@helsinki.fi [Department of Physics, P.O. Box 43, FI-00014 University of Helsinki (Finland); Nordlund, K. [Department of Physics, P.O. Box 43, FI-00014 University of Helsinki (Finland); Dudarev, S.L. [CCFE, Culham Science Centre, Oxfordshire OX14 3DB (United Kingdom)

    2014-12-15

    Neutrons in fusion reactors produce primary radiation damage from displacement cascades in tungsten (W) at an average PKA energy of 150 keV. We find, using molecular dynamics simulations, that cascades at this energy do not break up into subcascades. The massive amount of energy concentrated in the liquid-like heat spike facilitates a fairly high rate of formation of large dislocation loops and other defect structures, of sizes readily visible in today’s electron microscopes. We investigate the structures and distribution of the cascade debris in W predicted by different interatomic potentials. In particular, our simulations show the formation of 〈100〉-type dislocation loops, in agreement with recent experiments and in contradiction to the earlier held view that only 1/2〈111〉-type loops occur in W.

  5. Radiation Damage in Nuclear Fuel for Advanced Burner Reactors: Modeling and Experimental Validation

    Energy Technology Data Exchange (ETDEWEB)

    Jensen, Niels Gronbech; Asta, Mark; Ozolins, Nigel Browning' Vidvuds; de Walle, Axel van; Wolverton, Christopher

    2011-12-29

    The consortium has completed its existence and we are here highlighting work and accomplishments. As outlined in the proposal, the objective of the work was to advance the theoretical understanding of advanced nuclear fuel materials (oxides) toward a comprehensive modeling strategy that incorporates the different relevant scales involved in radiation damage in oxide fuels. Approaching this we set out to investigate and develop a set of directions: 1) Fission fragment and ion trajectory studies through advanced molecular dynamics methods that allow for statistical multi-scale simulations. This work also includes an investigation of appropriate interatomic force fields useful for the energetic multi-scale phenomena of high energy collisions; 2) Studies of defect and gas bubble formation through electronic structure and Monte Carlo simulations; and 3) an experimental component for the characterization of materials such that comparisons can be obtained between theory and experiment.

  6. An Analysis of the Radiation Damage to the ATLAS Semiconductor Tracker End-Caps

    CERN Document Server

    Millar, Declan; Moretti, Stefano

    The motivation, theoretical principles and analytical procedure for an assessment of the radiation damage to the ATLAS SCT end-caps is presented. An analysis of the leakage current across end-cap modules is performed for 2011 and 2012 data. A comparison between the observed and expected leakage current is made, with measurements favouring the shape of the theoretical evolution. Measured data is found to be systematically lower than predicted for a large subset of end-cap modules, while the remainder show surface current effects which interfere with bulk current observation. Uniform differences for modules at different radial distances suggest a radial temperature distribution in the end-caps, with absolute silicon sensor temperature to be established in further analysis.

  7. Sirtuin 7 promotes cellular survival following genomic stress by attenuation of DNA damage, SAPK activation and p53 response

    Energy Technology Data Exchange (ETDEWEB)

    Kiran, Shashi; Oddi, Vineesha [Laboratory of Cancer Biology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, Telangana, 500001 (India); Ramakrishna, Gayatri, E-mail: gayatrirama1@gmail.com [Laboratory of Cancer Biology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, Telangana, 500001 (India); Laboratory of Cancer Cell Biology, Department of Research, Institute of Liver and Biliary Sciences, Delhi 110070 (India)

    2015-02-01

    Maintaining the genomic integrity is a constant challenge in proliferating cells. Amongst various proteins involved in this process, Sirtuins play a key role in DNA damage repair mechanisms in yeast as well as mammals. In the present work we report the role of one of the least explored Sirtuin viz., SIRT7, under conditions of genomic stress when treated with doxorubicin. Knockdown of SIRT7 sensitized osteosarcoma (U2OS) cells to DNA damage induced cell death by doxorubicin. SIRT7 overexpression in NIH3T3 delayed cell cycle progression by causing delay in G1 to S transition. SIRT7 overexpressing cells when treated with low dose of doxorubicin (0.25 µM) showed delayed onset of senescence, lesser accumulation of DNA damage marker γH2AX and lowered levels of growth arrest markers viz., p53 and p21 when compared to doxorubicin treated control GFP expressing cells. Resistance to DNA damage following SIRT7 overexpression was also evident by EdU incorporation studies where cellular growth arrest was significantly delayed. When treated with higher dose of doxorubicin (>1 µM), SIRT7 conferred resistance to apoptosis by attenuating stress activated kinases (SAPK viz., p38 and JNK) and p53 response thereby shifting the cellular fate towards senescence. Interestingly, relocalization of SIRT7 from nucleolus to nucleoplasm together with its co-localization with SAPK was an important feature associated with DNA damage. SIRT7 mediated resistance to doxorubicin induced apoptosis and senescence was lost when p53 level was restored by nutlin treatment. Overall, we propose SIRT7 attenuates DNA damage, SAPK activation and p53 response thereby promoting cellular survival under conditions of genomic stress. - Highlights: • Knockdown of SIRT7 sensitized cells to DNA damage induced apoptosis. • SIRT7 delayed onset of premature senescence by attenuating DNA damage response. • Overexpression of SIRT7 delayed cell cycle progression by delaying G1/S transition. • Upon DNA damage SIRT

  8. Protection of radiation induced DNA and membrane damages by total triterpenes isolated from Ganoderma lucidum (Fr.) P. Karst.

    Science.gov (United States)

    Smina, T P; Maurya, D K; Devasagayam, T P A; Janardhanan, K K

    2015-05-25

    The total triterpenes isolated from the fruiting bodies of Ganoderma lucidum was examined for its potential to prevent γ-radiation induced membrane damage in rat liver mitochondria and microsomes. The effects of total triterpenes on γ-radiation-induced DNA strand breaks in pBR 322 plasmid DNA in vitro and human peripheral blood lymphocytes ex vivo were evaluated. The protective effect of total triterpenes against γ-radiation-induced micronuclei formations in mice bone marrow cells in vivo were also evaluated. The results indicated the significant effectiveness of Ganoderma triterpenes in protecting the DNA and membrane damages consequent to the hazardous effects of radiation. The findings suggest the potential use of Ganoderma triterpenes in radio therapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. Report on the Study of Radiation Damage in Calcium Fluoride and Magnesium Fluoride Crystals for use in Excimer Laser Applications

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    1999-10-04

    A study was performed to investigate the effects of radiation damage in calcium fluoride and magnesium fluoride crystals caused by gamma rays and UV photons from excimer lasers. The purpose was to study and correlate the damage caused by these two different mechanisms in various types of material used for fabricating optical elements in high power excimer lasers and lens systems of lithography tools. These optical systems are easily damaged by the laser itself, and it is necessary to use only the most radiation resistant materials for certain key elements. It was found that a clear correlation exists between the, radiation induced damage caused by high energy gamma rays and that produced by UV photons from the excimer laser. This correlation allows a simple procedure to be developed to select the most radiation resistant material at the ingot level, which would be later used to fabricate various components of the optical system. This avoids incurring the additional cost of fabricating actual optical elements with material that would later be damaged under prolonged use. The result of this screening procedure can result in a considerable savings in the overall cost of the lens and laser system.

  10. Differential Processing of Low and High LET Radiation Induced DNA Damage: Investigation of Switch from ATM to ATR Signaling

    Science.gov (United States)

    Saha, Janapriya; Wang, Minli; Hada, Megumi; Cucinotta, Francis A.

    2011-01-01

    The members of the phosphatidylinositol kinase-like kinase family of proteins namely ataxia-telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR) are directly responsible for the maintenance of genomic integrity by mounting DDR through signaling and facilitating the recruitment of repair factors at the sites of DNA damage along with coordinating the deployment of cell cycle checkpoints to permit repair by phosphorylating Checkpoint kinase Chk1, Chk2 and p53. High LET radiation from GCR (Galactic Cosmic Rays) consisting mainly of protons and high energy and charged (HZE) particles from SPE (Solar Particle Event) pose a major health risk for astronauts on their space flight missions. The determination of these risks and the design of potential safeguards require sound knowledge of the biological consequences of lesion induction and the capability of the cells to counter them. We here strive to determine the coordination of ATM and ATR kinases at the break sites directly affecting checkpoint signaling and DNA repair and whether differential processing of breaks induced by low and high LET radiation leads to possible augmentation of swap of these damage sensors at the sites of DNA damage. Exposure of cells to IR triggers rapid autophosphorylation of serine-1981 that causes dimer dissociation and initiates monomer formation of ATM. ATM kinase activity depends on the disruption of the dimer, which allows access and phosphorylation of downstream ATM substrates like Chk2. Evidence suggests that ATM is activated by the alterations in higher-order chromatin structure although direct binding of ATM to DSB ends may be a crucial step in its activation. On the other hand, in case of ATR, RPA (replication protein A)-coated ssDNA (single-stranded DNA) generated as a result of stalled DNA replication or during processing of chromosomal lesions is crucial for the localization of ATR to sites of DNA damage in association with ATR-interacting protein (ATRIP). Although the

  11. Radiation damage in a micron-sized protein crystal studied via reciprocal space mapping and Bragg coherent diffractive imaging

    Directory of Open Access Journals (Sweden)

    H. D. Coughlan

    2015-07-01

    Full Text Available For laboratory and synchrotron based X-ray sources, radiation damage has posed a significant barrier to obtaining high-resolution structural data from biological macromolecules. The problem is particularly acute for micron-sized crystals where the weaker signal often necessitates the use of higher intensity beams to obtain the relevant data. Here, we employ a combination of techniques, including Bragg coherent diffractive imaging to characterise the radiation induced damage in a micron-sized protein crystal over time. The approach we adopt here could help screen for potential protein crystal candidates for measurement at X-ray free election laser sources.

  12. Measurement of Radiation Damage of Water-based Liquid Scintillator and Liquid Scintillator

    CERN Document Server

    Bignell, Lindsey J; Hans, Sunej; Jaffe, David E; Rosero, Richard; Vigdor, Steven; Viren, Brett; Worcester, Elizabeth; Yeh, Minfang; Zhang, Chao

    2015-01-01

    Liquid scintillating phantoms have been proposed as a means to perform real-time 3D dosimetry for proton therapy treatment plan verification. We have studied what effect radiation damage to the scintillator will have upon this application. We have performed measurements of the degradation of the light yield and optical attenuation length of liquid scintillator and water-based liquid scintillator after irradiation by 201 MeV proton beams that deposited doses of approximately 52 Gy, 300 Gy, and 800 Gy in the scintillator. Liquid scintillator and water-based liquid scintillator (composed of $5\\%$ scintillating phase) exhibit light yield reductions of $1.74 \\pm 0.55 \\%$ and $1.31 \\pm 0.59 \\%$ after $\\approx$ 800 Gy of proton dose, respectively. Whilst some increased optical attenuation was observed in the irradiated samples, the measured reduction to the light yield is also due to damage to the scintillation light production. Based on our results and conservative estimates of the expected dose in a clinical conte...

  13. Effects of radiation on levels of DNA damage in normal non-adjacent mucosa from colorectal cancer cases.

    LENUS (Irish Health Repository)

    Sheridan, Juliette

    2013-03-01

    Defects in DNA repair pathways have been linked with colorectal cancer (CRC). Adjuvant radiotherapy has become commonplace in the treatment of rectal cancer however it is associated with a higher rate of second cancer formation. It is known that radiation results in DNA damage directly or indirectly by radiation-induced bystander effect (RIBE) by causing double-strand breaks (DSBs). The majority of work in RIBE has been performed in cell lines and limited studies have been in or ex vivo.

  14. Late skin damage in rabbits and monkeys after exposure to particulate radiations

    Science.gov (United States)

    Bergtold, D. S.; Cox, A. B.; Lett, J. T.; Su, C. M.

    Skin biopsies were taken from the central regions of the ears of New Zealand white rabbits following localized exposure of one ear of each rabbit to 530 MeV/amu Ar or 365 MeV/amu Ne ions. The unirradiated ears served as controls. Biopsies were taken also from the chests and inner thighs of rhesus monkeys after whole-body exposure to 32 MeV protons and from unirradiated control animals. The linear energy transfers (LET∞'s) for the radiations were 90 +/- 5, 35 +/- 3, and ~1.2 keV/μm, respectively. In the rabbit studies, explants were removed with a 2 mm diameter dermal punch at post-irradiation times up to five years after exposure. Similar volumes of monkey tissue were taken from skin samples excised surgically 16-18 years following proton irradiation. Fibroblast cultures were initiated from the explants and were propagated in vitro until terminal senescence (cessation of cell division) occurred. Cultures from irradiated tissue exhibited decreases in doubling potential that were dependent on radiation dose and LET∞ and seemed to reflect damage to stem cell populations. The implications of these results for astronauts exposed to heavy ions and/or protons in space include possible manifestations of residual effects in the skin many years after exposure (e.g. unsatisfactory responses to trauma or surgery).

  15. Recovery From Radiation-induced Bone Marrow Damage by HSP25 Through Tie2 Signaling

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hae-June [Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kwon, Hee-Chung [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Chung, Hee-Yong [College of Medicine, Hanyang University, Seoul (Korea, Republic of); Lee, Yoon-Jin [Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Lee, Yun-Sil, E-mail: yslee0425@ewha.ac.kr [College of Pharmacy and Division of Life and Pharmaceutical Sciences, Ewha Woman' s University, Seoul (Korea, Republic of)

    2012-09-01

    Purpose: Whole-body radiation therapy can cause severe injury to the hematopoietic system, and therefore it is necessary to identify a novel strategy for overcoming this injury. Methods and Materials: Mice were irradiated with 4.5 Gy after heat shock protein 25 (HSP25) gene transfer using an adenoviral vector. Then, peripheral blood cell counts, histopathological analysis, and Western blotting on bone marrow (BM) cells were performed. The interaction of HSP25 with Tie2 was investigated with mouse OP9 and human BM-derived mesenchymal stem cells to determine the mechanism of HSP25 in the hematopoietic system. Results: HSP25 transfer increased BM regeneration and reduced apoptosis following whole-body exposure to ionizing radiation (IR). The decrease in Tie2 protein expression that followed irradiation of the BM was blocked by HSP25 transfer, and Tie2-positive cells were more abundant among the BM cells of HSP25-transferred mice, even after IR exposure. Following systemic RNA interference of Tie2 before IR, HSP25-mediated radioprotective effects were partially blocked in both mice and cell line systems. Stability of Tie2 was increased by HSP25, a response mediated by the interaction of HSP25 with Tie2. IR-induced tyrosine phosphorylation of Tie2 was augmented by HSP25 overexpression; downstream events in the Tie2 signaling pathway, including phosphorylation of AKT and EKR1/2, were also activated. Conclusions: HSP25 protects against radiation-induced BM damage by interacting with and stabilizing Tie2. This may be a novel strategy for HSP25-mediated radioprotection in BM.

  16. Radiation damage to the uterus -- review of the effects of treatment of childhood cancer.

    Science.gov (United States)

    Critchley, Hilary O D; Bath, Louise E; Wallace, W Hamish B

    2002-05-01

    At the present time approximately 1 in 1000 young people aged between 16 and 35 years will have been cured of cancer in childhood and some of the treatment regimens used will have predictable effects on their future fertility prospects. In young women who have been exposed to radiotherapy below the diaphragm, the reproductive problems include the risk of ovarian failure and significantly impaired development of the uterus. The magnitude of the risk is related to the radiation field, total dose and fractionation schedule. Premature labour and low birth weight infants have been reported after flank abdominal radiotherapy. Female long-term survivors treated with total body irradiation and marrow transplantation are also at risk of ovarian follicular depletion and impaired uterine growth and blood flow, and of early pregnancy loss and premature labour if pregnancy is achieved. Despite standard oestrogen replacement, the uterus of these young girls is often reduced to 40% of normal adult size. Uterine volume correlates with the age at which radiation was received. Regrettably, it is likely that radiation damage to the uterine musculature and vasculature adversely affects prospects for pregnancy in these women. It has been demonstrated that, in women treated with total body irradiation, sex steroid replacement in physiological doses significantly increases uterine volume and endometrial thickness, as well as re-establishing uterine blood flow. However, it is not known whether standard regimens of oestrogen replacement therapy are sufficient to facilitate uterine growth in adolescent women treated with total body irradiation in childhood. Even if the uterus is able to respond to exogenous sex steroid stimulation, and appropriate assisted reproductive technologies are available, a successful pregnancy outcome is by no means ensured. The uterine factor remains a concern and women who are survivors of childhood cancer and their carers must recognize that these pregnancies

  17. Mobile phone radiation induces reactive oxygen species production and DNA damage in human spermatozoa in vitro.

    Directory of Open Access Journals (Sweden)

    Geoffry N De Iuliis

    Full Text Available BACKGROUND: In recent times there has been some controversy over the impact of electromagnetic radiation on human health. The significance of mobile phone radiation on male reproduction is a key element of this debate since several studies have suggested a relationship between mobile phone use and semen quality. The potential mechanisms involved have not been established, however, human spermatozoa are known to be particularly vulnerable to oxidative stress by virtue of the abundant availability of substrates for free radical attack and the lack of cytoplasmic space to accommodate antioxidant enzymes. Moreover, the induction of oxidative stress in these cells not only perturbs their capacity for fertilization but also contributes to sperm DNA damage. The latter has, in turn, been linked with poor fertility, an increased incidence of miscarriage and morbidity in the offspring, including childhood cancer. In light of these associations, we have analyzed the influence of RF-EMR on the cell biology of human spermatozoa in vitro. PRINCIPAL FINDINGS: Purified human spermatozoa were exposed to radio-frequency electromagnetic radiation (RF-EMR tuned to 1.8 GHz and covering a range of specific absorption rates (SAR from 0.4 W/kg to 27.5 W/kg. In step with increasing SAR, motility and vitality were significantly reduced after RF-EMR exposure, while the mitochondrial generation of reactive oxygen species and DNA fragmentation were significantly elevated (P<0.001. Furthermore, we also observed highly significant relationships between SAR, the oxidative DNA damage bio-marker, 8-OH-dG, and DNA fragmentation after RF-EMR exposure. CONCLUSIONS: RF-EMR in both the power density and frequency range of mobile phones enhances mitochondrial reactive oxygen species generation by human spermatozoa, decreasing the motility and vitality of these cells while stimulating DNA base adduct formation and, ultimately DNA fragmentation. These findings have clear implications

  18. High radiation and desiccation tolerance of nitrogen-fixing cultures of the cyanobacterium Anabaena sp. strain PCC 7120 emanates from genome/proteome repair capabilities.

    Science.gov (United States)

    Singh, Harinder; Anurag, Kirti; Apte, Shree Kumar

    2013-10-12

    The filamentous nitrogen-fixing cyanobacterium, Anabaena sp. strain PCC 7120 was found to tolerate very high doses of 60Co-gamma radiation or prolonged desiccation. Post-stress, cells remained intact and revived all the vital functions. A remarkable capacity to repair highly disintegrated genome and recycle the damaged proteome appeared to underlie such high radioresistance and desiccation tolerance. The close similarity observed between the cellular response to irradiation or desiccation stress lends strong support to the notion that tolerance to these stresses may involve similar mechanisms.

  19. Radiation-induced genomic instability: Are epigenetic mechanisms the missing link?

    Energy Technology Data Exchange (ETDEWEB)

    Aypar, Umut; Morgan, William F.; Baulch, Janet E.

    2011-02-01

    Purpose: This review examines the evidence for the hypothesis that epigenetics are involved in the initiation and perpetuation of radiation-induced genomic instability (RIGI). Conclusion: In addition to the extensively studied targeted effects of radiation, it is now apparent that non-targeted delayed effects such as RIGI are also important post-irradiation outcomes. In RIGI, unirradiated progeny cells display phenotypic changes at delayed times after radiation of the parental cell. RIGI is thought to be important in the process of carcinogenesis, however, the mechanism by which this occurs remains to be elucidated. In the genomically unstable clones developed by Morgan and colleagues, radiation-induced mutations, double-strand breaks, or changes in mRNA levels alone could not account for the initiation or perpetuation of RIGI. Since changes in the DNA sequence could not fully explain the mechanism of RIGI, inherited epigenetic changes may be involved. Epigenetics are known to play an important role in many cellular processes and epigenetic aberrations can lead to carcinogenesis. Recent studies in the field of radiation biology suggest that the changes in methylation patterns may be involved in RIGI. Together these clues have led us to hypothesize that epigenetics may be the missing link in understanding the mechanism behind RIGI.

  20. Scaffold attachment factor A (SAF-A) and Ku temporally regulate repair of radiation-induced clustered genome lesions

    Science.gov (United States)

    Mantha, Anil K.; Hegde, Pavana M.; Pandey, Arvind; Sengupta, Shiladitya; Yu, Yaping; Calsou, Patrick; Chen, David; Lees-Miller, Susan P.; Mitra, Sankar

    2016-01-01

    Ionizing radiation (IR) induces highly cytotoxic double-strand breaks (DSBs) and also clustered oxidized bases in mammalian genomes. Base excision repair (BER) of bi-stranded oxidized bases could generate additional DSBs as repair intermediates in the vicinity of direct DSBs, leading to loss of DNA fragments. This could be avoided if DSB repair via DNA-PK-mediated nonhomologous end joining (NHEJ) precedes BER initiated by NEIL1 and other DNA glycosylases (DGs). Here we show that DNA-PK subunit Ku inhibits DGs via direct interaction. The scaffold attachment factor (SAF)-A, (also called hnRNP-U), phosphorylated at Ser59 by DNA-PK early after IR treatment, is linked to transient release of chromatin-bound NEIL1, thus preventing BER. SAF-A is subsequently dephosphorylated. Ku inhibition of DGs in vitro is relieved by unphosphorylated SAF-A, but not by the phosphomimetic Asp59 mutant. We thus propose that SAF-A, in concert with Ku, temporally regulates base damage repair in irradiated cell genome. PMID:27303920

  1. Radiation-induced cardiac damage in early left breast cancer patients: risk factors, biological mechanisms, radiobiology, and dosimetric constraints.

    Science.gov (United States)

    Sardaro, Angela; Petruzzelli, Maria Fonte; D'Errico, Maria Patrizia; Grimaldi, Luca; Pili, Giorgio; Portaluri, Maurizio

    2012-05-01

    Today there is general awareness of the potential damage to the heart in left-sided (more than in right-sided) breast cancer radiotherapy (RT). Historical changes in tumor and heart doses are presented here along with the impact of different RT techniques and volumes. Individual and pharmacological risk factors are also examined with respect to radiation damage. The biological mechanisms of harm are only partially understood, such as the radiobiology of heart damage due to the presence of various radiosensitive structures and their topographic heterogeneity. Furthermore, individual variability may expose patients to higher or lower risks of late cardiac damage or death. Damage mechanisms and radiobiological characteristics in heart irradiation are presented in relation to dosimetric and biological parameters. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  2. A molecular dynamics simulation of DNA damage induction by ionizing radiation

    Science.gov (United States)

    Abolfath, Ramin M.; Carlson, David J.; Chen, Zhe J.; Nath, Ravinder

    2013-10-01

    We present a multi-scale simulation of the early stage of DNA damages by the indirect action of hydroxyl (•OH) free radicals generated by electrons and protons. The computational method comprises of interfacing the Geant4-DNA Monte Carlo with ReaxFF molecular dynamics software. A clustering method was employed to map the coordinates of •OH-radicals extracted from the ionization-track-structures onto nano-meter simulation voxels filled with DNA and water molecules. The molecular dynamics simulation provides the time-evolution and chemical reactions in individual simulation voxels as well as the energy-landscape accounted for the DNA-•OH chemical reaction that is essential for the first-principle enumeration of hydrogen abstractions, chemical bond breaks, and DNA-lesions induced by collection of ions in clusters less than the critical dimension which is approximately 2-3 Å. We show that the formation of broken bonds leads to DNA-base and backbone damages that collectively propagate to DNA single and double-strand breaks. For illustration of the methodology, we focused on particles with an initial energy of 1 MeV. Our studies reveal a qualitative difference in DNA damage induced by low energy electrons and protons. Electrons mainly generate small pockets of •OH-radicals, randomly dispersed in the cell volume. In contrast, protons generate larger clusters along a straight-line parallel to the direction of the particle. The ratio of the total DNA double-strand breaks induced by a single proton and electron track is determined to be ≈4 in the linear scaling limit. In summary, we have developed a multi-scale computational model based on first-principles to study the interaction of ionizing radiation with DNA molecules. The main advantage of our hybrid Monte Carlo approach using Geant4-DNA and ReaxFF is the multi-scale simulation of the cascade of both physical and chemical events which result in the formation of biological damage. The tool developed in this

  3. Genome damage in peripheral blood lymphocytes of diabetic and non-diabetic individuals after intervention with vegetables and plant oil.

    Science.gov (United States)

    Müllner, Elisabeth; Brath, Helmut; Toferer, Daniela; Adrigan, Sonja; Bulla, Marie-Therese; Stieglmayer, Roswitha; Wallner, Marlies; Marek, Reinhard; Wagner, Karl-Heinz

    2013-03-01

    Recent studies suggest increased cancer risk in patients with type 2 diabetes mellitus (T2DM) compared with healthy individuals. The present study aims to assess whether T2DM is associated with increased genome instability and whether a healthy diet with natural foods can improve genome stability in peripheral blood lymphocytes (PBLs). Seventy-six diabetic and 21 non-diabetic individuals were randomly assigned to either an 'intervention' or an 'information only' group. All participants received information about the beneficial effects of a healthy diet, while subjects of the intervention group received additionally 300g of vegetables and 25ml of plant oil rich in polyunsaturated fatty acids per day for 8 weeks. Chromosomal damage was assessed using the cytokinesis-block micronucleus (MN) cytome assay. Levels of chromosomal damage did not differ between diabetic and non-diabetic individuals. However, diabetic individuals with MN frequency above the high 50th percentile had significantly higher levels of fasting plasma glucose, glycosylated haemoglobin and were at higher risk for cardiovascular disease (CVD), assessed by the Framingham general cardiovascular risk score. Non-diabetic individuals with MN frequency above the 50th percentile had significantly lower vitamin B12 levels. The intervention with vegetables and plant oil led to significant increases in folate, γ-tocopherol, α- and β-carotene while vitamin B12 was significantly reduced. Levels of chromosomal damage were not altered, only apoptosis was slightly increased. The results suggest interactions between glycaemic control, CVD risk and genome stability in individuals with T2DM. However, a healthy diet does not improve genome damage in PBLs.

  4. Functional Genomic Investigation of the Molecular Biological Impact of Electron Beam Radiation in Lymphoma Cells.

    Science.gov (United States)

    Gopal, Ramani; Rani, Usha; Murugesan, Ram; Kumar, Kirushna; Sanjeev, Ganesh; Ganesan, Kumaresan

    2016-05-01

    The biological response of electron beam radiation (EBR) in tumors remains underexplored. This study describes the molecular biological and genomic impact of EBR on tumor cells. A mouse model bearing Dalton's lymphoma ascites cells was exposed to an 8-MeV pulsed electron beam, at a dose rate of 2 Gy/min using a microtron, a linear accelerator. The radiation-induced changes were assessed by histopathology, fluorescence-activated cell sorting, signaling pathway-focused reporter assays, and gene expression by microarray analysis. EBR was found to increase apoptosis and G2-M cell cycle arrest with concomitant tumor regression in vivo. The microarray data revealed that EBR induced tumor regression, apoptosis, and cell cycle arrest mediated by p53, PPAR, and SMAD2/3/4 signaling pathways. Activation of interferon regulatory factor and NFkB signaling were also found upon EBR. Chemo-genomics exploration revealed the possibility of drugs that can be effectively used in combination with EBR. For the first time, an 8-MeV pulse EBR induced genomic changes, and their consequence in molecular and biological processes were identified in lymphoma cells. The comprehensive investigation of radiation-mediated responses in cancer cells also revealed the potential therapeutic features of EBR. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Combined Bulk and Surface Radiation Damage Effects at Very High Fluences in Silicon Detectors: Measurements and TCAD Simulations

    CERN Document Server

    Moscatelli, F; Morozzi, A; Mendicino, R; Dalla Betta, G F; Bilei, G M

    2016-01-01

    In this work we propose a new combined TCAD radiation damage modelling scheme, featuring both bulk and surface radiation damage effects, for the analysis of silicon detectors aimed at the High Luminosity LHC. In particular, a surface damage model has been developed by introducing the relevant parameters (NOX, NIT) extracted from experimental measurements carried out on p-type substrate test structures after gamma irradiations at doses in the range 10-500 Mrad(Si). An extended bulk model, by considering impact ionization and deep-level cross-sections variation, was included as well. The model has been validated through the comparison of the simulation findings with experimental measurements carried out at very high fluences (2×1016 1 MeV equivalent n/cm2) thus fostering the application of this TCAD approach for the design and optimization of the new generation of silicon detectors to be used in future HEP experiments.

  6. The effect of radiation damage on optical and scintillation properties of BGO crystals grown by the LTG Cz technique

    CERN Document Server

    Gusev, V A; Kupriyanov, I N; Kuznecov, G N; Shlegel, V N; Antsygin, V D; Vasiliev, Y V

    2002-01-01

    BGO crystals grown by the low-thermal-gradient Czochralski technique (LTG Cz) exhibit two distinct types of behavior upon radiation damage and recovery. The crystals termed as of L-type remain colorless after gamma-radiation doses as high as 10 Mrad. As the irradiation dose increases the scintillation light output shows a weak monotonous degradation to 15-25%, saturating at around several hundreds krad doses. The crystals termed as of N-type attain yellow coloration after irradiation. The light output drops abruptly for 35-50% as early as after 1 krad and does not change further on. The present work is devoted to the study of radiation damage effects, self-recovery, optically stimulated recovery and thermo-stimulated current in the L- and N-type BGO crystals produced by LTG Cz.

  7. Atomic structure from large-area, low-dose exposures of materials: A new route to circumvent radiation damage

    Energy Technology Data Exchange (ETDEWEB)

    Meyer, J.C., E-mail: jannik.meyer@univie.ac.at; Kotakoski, J.; Mangler, C.

    2014-10-15

    Beam-induced structural modifications are a major nuisance in the study of materials by high-resolution electron microscopy. Here, we introduce a new approach to circumvent the radiation damage problem by a statistical treatment of large, noisy, low-dose data sets of non-periodic configurations (e.g. defects) in the material. We distribute the dose over a mixture of different defect structures at random positions and with random orientations, and recover representative model images via a maximum likelihood search. We demonstrate reconstructions from simulated images at such low doses that the location of individual entities is not possible. The approach may open a route to study currently inaccessible beam-sensitive configurations. - Highlights: • A new approach to circumvent radiation damage. • Statistical treatment of large noisy data sets. • Analysis of radiation sensitive material defects.

  8. X-ray-excited optical luminescence of protein crystals: a new tool for studying radiation damage during diffraction data collection.

    Science.gov (United States)

    Owen, Robin L; Yorke, Briony A; Pearson, Arwen R

    2012-05-01

    During X-ray irradiation protein crystals radiate energy in the form of small amounts of visible light. This is known as X-ray-excited optical luminescence (XEOL). The XEOL of several proteins and their constituent amino acids has been characterized using the microspectrophotometers at the Swiss Light Source and Diamond Light Source. XEOL arises primarily from aromatic amino acids, but the effects of local environment and quenching within a crystal mean that the XEOL spectrum of a crystal is not the simple sum of the spectra of its constituent parts. Upon repeated exposure to X-rays XEOL spectra decay non-uniformly, suggesting that XEOL is sensitive to site-specific radiation damage. However, rates of XEOL decay were found not to correlate to decays in diffracting power, making XEOL of limited use as a metric for radiation damage to protein crystals. © 2012 International Union of Crystallography

  9. Biology of Extreme Radiation Resistance: The Way of Deinococcus radiodurans

    Science.gov (United States)

    Krisko, Anita; Radman, Miroslav

    2013-01-01

    The bacterium Deinococcus radiodurans is a champion of extreme radiation resistance that is accounted for by a highly efficient protection against proteome, but not genome, damage. A well-protected functional proteome ensures cell recovery from extensive radiation damage to other cellular constituents by molecular repair and turnover processes, including an efficient repair of disintegrated DNA. Therefore, cell death correlates with radiation-induced protein damage, rather than DNA damage, in both robust and standard species. From the reviewed biology of resistance to radiation and other sources of oxidative damage, we conclude that the impact of protein damage on the maintenance of life has been largely underestimated in biology and medicine. PMID:23818498

  10. Phenolic compounds isolated from Pilea microphylla prevent radiation-induced cellular DNA damage

    Directory of Open Access Journals (Sweden)

    Punit Bansal

    2011-12-01

    Full Text Available Six phenolic compounds namely, quercetin-3-O-rutinoside (1, 3-O-caffeoylquinic acid (2, luteolin-7-O-glucoside (3, apigenin-7-O-rutinoside (4, apigenin-7-O-β-d-glucopyranoside (5 and quercetin (6 were isolated from the whole plant of Pilea microphylla using conventional open-silica gel column chromatography and preparative HPLC. Further, these compounds were characterized by 1D, 2D NMR techniques and high-resolution LC–MS. Compounds 1–3 and 6 exhibited significant antioxidant potential in scavenging free radicals such as DPPH, ABTS and SOD with IC50 of 3.3–20.4 μmol/L. The same compounds also prevented lipid peroxidation with IC50 of 10.4–32.2 μmol/L. The compounds also significantly prevented the Fenton reagent-induced calf thymus DNA damage. Pre-treatment with compounds 1–3 and 6 in V79 cells attenuated radiation-induced formation of reactive oxygen species, lipid peroxidation, cytotoxicity and DNA damage, correlating the antioxidant activity of polyphenols with their radioprotective effects. Compounds 1, 3 and 6 significantly inhibited lipid peroxidation, presumably due to 3′,4′-catechol ortho-dihydroxy moiety in the B-ring, which has a strong affinity for phospholipid membranes. Oxidation of flavonoids, with catechol structure on B-ring, yields a fairly stable ortho-semiquinone radical by facilitating electron delocalization, which is involved in antioxidant mechanism. Hence, the flavonoid structure, number and location of hydroxyl groups together determine the antioxidant and radioprotection mechanism.

  11. Ion-beam cancer therapy: news about a multiscale approach to radiation damage.

    Science.gov (United States)

    Surdutovich, Eugene; Scifoni, Emanuele; Solov'yov, Andrey V

    2010-01-01

    We report the present stage of development of our multiscale approach to the physics related to radiation damage caused by irradiation of a tissue with energetic ions. This approach is designed to quantify the most important physical, chemical, and biological phenomena taking place during and following such an irradiation in order to understand the scenario of the events leading to cell death and provide a better means for clinically necessary calculations with an adequate accuracy. On this stage, we overview the latest progress in calculating energy spectra of secondary electrons in liquid water and the results of an application of the inelastic thermal spike model to liquid water in order to calculate the heat transfer in the vicinity of the incident-ion track. The dependence of energy distributions of secondary electrons, resulting from ionization of the liquid water, on the energy of primary ions is studied in two regimes. For slow ions, a new parameterization of energy spectra in liquid water is suggested. For fast ions, different dispersion schemes on the basis of a dielectric response function approach are used and compared. Thermal spike calculations indicate a very large temperature increase in the vicinity of ion tracks near the Bragg peak during the time interval from 10(-15) to 10(-9)s after the ion's passage. An increase of pressure, as large as tens of MPa, can also be induced during that time. These effects suggest a possibility of thermo-mechanical pathways to disruption of irradiated DNA. A combination of a temperature spike and electron/hole interactions may be a dominant pathway of DNA damage. 2010 Elsevier B.V. All rights reserved.

  12. In-situ spectroscopy of radiation damage of PTFE irradiated with high-energy heavy ions

    Energy Technology Data Exchange (ETDEWEB)

    Delgado, A.O.; Rizzutto, M.A. [Universidade de Sao Paulo (IF/USP), SP (Brazil). Inst. de Fisica; Severin, D.; Seidl, T.; Neumann, R.; Trautmann, C. [GSI Helmholtz Centre for Heavy Ion Research, Darmstadt (Germany)

    2010-07-01

    Full text: Polytetrafluoroethylene (PTFE) shows an outstanding combination of chemical and physical properties such as excellent resistance to chemical reagents, thermal stability in a wide temperature range, high electric resistance, and low friction coefficient. However, PTFE is known to be extremely sensitive to high energy radiation undergoing scission of the main chain. Depending on the irradiation parameters, temperature, and atmosphere, cross-linking mechanisms can be also observed. Sometimes these mechanisms have a very short lifetime, therefore it is necessary to measure the radiation damages during the irradiation process. PTFE films (50 {mu}m thick, Enflo Canada Ltd.) were irradiated with U and Au ions up to energies of 1.3 GeV and fluences of 1 x 10{sup 13} ions/cm{sup 2} at the accelerator UNILAC at the GSI in Darmstadt, Germany. The irradiations were performed at cryo (T 23K) and room temperature in the new setup at the M3-beam line of the materials research M-Branch. This setup allows in-situ investigations of ion irradiation induced material changes with infrared spectroscopy (FTIR) and residual gas analysis (RGA). Mass spectra recorded during room temperature ion irradiation show outgassing of several fragments, with CF and CF{sub 3} being the most dominant species. Almost no fragments are observed during the cryo-irradiation. However, subsequent sample heating to room temperature leads to outgassing of the fragments starting above 150 K. This result indicates that at low irradiation temperatures small fragments are frozen in and accumulated in the sample. The online FTIR analysis of the irradiated samples shows a decrease in the absorption intensity of the bands assigned to the CF{sub 2} bonds, evidencing scission of the main polymer chain. The CF{sub 2} degradation is accompanied by the formation of the CF{sub 3} group indicated by two new bands, one at 738 cm{sup -1} (terminal - CF{sub 3} group) and another at 985 cm{sup -1} (-CF{sub 3} side

  13. Gene Mutation as Biomarker of Radiation Induced Cell Injury and Genomic Instability

    Directory of Open Access Journals (Sweden)

    M Syaifudin

    2006-07-01

    Full Text Available Gene expression profiling and its mutation has become one of the most widely used approaches to identify genes and their functions in the context of identify and categorize genes to be used as radiation effect markers including cell and tissue sensitivities. Ionizing radiation produces genetic damage and changes in gene expression that may lead to cancer due to specific protein that controlling cell proliferation altered the function, its expression or both. P53 protein encoded by p53 gene plays an important role in protecting cell by inducing growth arrest and or cell suicide (apoptosis after deoxyribonucleic acid (DNA damage induced by mutagen such as ionizing radiation. The mutant and thereby dysfunctional of this gene was found in more than 50% of various human cancers, but it is as yet unclear how p53 mutations lead to neoplastic development. Wild-type p53 has been postulated to play a role in DNA repair, suggesting that expression of mutant forms of p53 might alter cellular resistance to the DNA damage caused by radiation. Moreover, p53 is thought to function as a cell cycle checkpoint after irradiation, also suggesting that mutant p53 might change the cellular proliferative response to radiation. p53 mutations affect the cellular response to DNA damage, either by increasing DNA repair processes or, possibly, by increasing cellular tolerance to DNA damage. The association of p53 mutations with increased radioresistance suggests that alterations in the p53 gene might lead to oncogenic transformation. Current attractive model of carcinogenesis also showed that p53 gene is the major target of radiation. The majority of p53 mutations found so far is single base pairchanges (point mutations, which result in amino acid substitutionsor truncated forms of the P53 protein, and are widely distributedthroughout the evolutionarily conserved regions of the gene. Examination of p53 mutations in human cancer also shows an association between particular

  14. Damage Simulation and Ultrasonic Detection of Asphalt Mixture under the Coupling Effects of Water-Temperature-Radiation

    Directory of Open Access Journals (Sweden)

    Yong-chun Cheng

    2013-01-01

    Full Text Available In order to accurately simulate the performance changes of asphalt pavement in the hot rainy days, laboratory water-temperature-radiation cycle test is designed and carried out for the damage simulation of asphalt mixture under the environmental effect of rain, high temperatures, and sunshine. Ultrasonic detection method is used to determine the ultrasonic velocity of asphalt mixture specimen under different temperatures and water contents in the process of water-temperature-radiation cycles. Thus, we get the preliminary damage assessment. Splitting strength attenuation is defined as the damage parameter. In addition, the regression prediction models of the ultrasonic velocity and damage coefficient of asphalt mixture are constructed using the grey theory, neural network method, and support vector machine theory, respectively. We compare the prediction results of the three different models. It can be concluded that the model derived from the support vector machine possesses higher accuracy and stability, which can more satisfactorily reflect the relationship between ultrasonic velocity and damage coefficient. Therefore, the damage degree of the asphalt mixture can be obtained.

  15. Detection of some irradiated spices on the basis of radiation induced damage of starch

    Science.gov (United States)

    Farkas, J.; Sharif, M. M.; Koncz, Á.

    Untreated and irradiated samples of spices were suspended in water, alkalized, and after heat-gelatinization, the apparent viscosity was determined by a rotational viscometer. Several spices, i.e. white pepper, black pepper, nutmeg and ginger showed considerable loss of viscosity as a function of γ-radiation dose in the dose range required for microbial decontamination of natural spices. Less promising results were obtained with spices such as allspice, garlic powder, and onion powder forming low-viscosity heat-treated suspensions even when unirradiated viscometric studies were also performed with a number of pepper samples of various origin to estimate the "natural" variation of rheological properties. Irradiation and storage studies were performed with ground black pepper samples of moisture contents in equilibrium with air of 25%, 50% and 75% R.H., respectively, either untreated or irradiated with 4, 8, 16 or 32 kGy, to study the effect of equilibrium relative humidity and storage time on detectability of radiation treatment. During the entire storage period of 100 days, statistically significant differences of the apparent viscosities of heat-gelatinized suspensions remained detectable between untreated samples and those irradiated with 8 kGy or higher doses. The apparent viscosity of high-moisture (75% E.R.H.) untreated samples was decreasing during long-term storage. Differences between viscosities of untreated and irradiated samples were enlarged when measured at elevated temperatures such as 50°C in the rotational viscometer, or in the boiling-water bath of a falling number apparatus. Other analytical indices such as onset and peak temperatures of gelatinization endotherms by DSC (damaged starch content), by colorimetry, reducing sugar content, alcohol-induced turbidity of hot water extracts of pepper samples, have been changed less dramatically by irradiation than the apparent viscosity of the gelatinized suspensions

  16. Investigation of new sensor concepts and development of an effective model for the simulation of radiation damage hochbestrahlter silicon particle detectors

    CERN Document Server

    Eber, Robert

    Silicon sensors in the Tracker of the CMS experiment at CERN will suffer from sever radiation damage after the upgrade of the LHC beyond 2023. A new sensor design is presented and a two-defect radiation damage model for the simulation is developed for the prediction of the performance of future silicon sensors.

  17. Amifostine, a radioprotectant agent, protects rat brain tissue lipids against ionizing radiation induced damage: An FTIR microspectroscopic imaging study

    Energy Technology Data Exchange (ETDEWEB)

    Cakmak G.; Miller L.; Zorlu, F.; Severcan, F.

    2012-03-03

    Amifostine is the only approved radioprotective agent by FDA for reducing the damaging effects of radiation on healthy tissues. In this study, the protective effect of amifostine against the damaging effects of ionizing radiation on the white matter (WM) and grey matter (GM) regions of the rat brain were investigated at molecular level. Sprague-Dawley rats, which were administered amifostine or not, were whole-body irradiated at a single dose of 800 cGy, decapitated after 24 h and the brain tissues of these rats were analyzed using Fourier transform infrared microspectroscopy (FTIRM). The results revealed that the total lipid content and CH{sub 2} groups of lipids decreased significantly and the carbonyl esters, olefinic=CH and CH{sub 3} groups of lipids increased significantly in the WM and GM after exposure to ionizing radiation, which could be interpreted as a result of lipid peroxidation. These changes were more prominent in the WM of the brain. The administration of amifostine before ionizing radiation inhibited the radiation-induced lipid peroxidation in the brain. In addition, this study indicated that FTIRM provides a novel approach for monitoring ionizing radiation induced-lipid peroxidation and obtaining different molecular ratio images can be used as biomarkers to detect lipid peroxidation in biological systems.

  18. Amifostine, a radioprotectant agent, protects rat brain tissue lipids against ionizing radiation induced damage: an FTIR microspectroscopic imaging study.

    Science.gov (United States)

    Cakmak, Gulgun; Miller, Lisa M; Zorlu, Faruk; Severcan, Feride

    2012-04-15

    Amifostine is the only approved radioprotective agent by FDA for reducing the damaging effects of radiation on healthy tissues. In this study, the protective effect of amifostine against the damaging effects of ionizing radiation on the white matter (WM) and grey matter (GM) regions of the rat brain were investigated at molecular level. Sprague-Dawley rats, which were administered amifostine or not, were whole-body irradiated at a single dose of 800 cGy, decapitated after 24 h and the brain tissues of these rats were analyzed using Fourier transform infrared microspectroscopy (FTIRM). The results revealed that the total lipid content and CH(2) groups of lipids decreased significantly and the carbonyl esters, olefinic=CH and CH(3) groups of lipids increased significantly in the WM and GM after exposure to ionizing radiation, which could be interpreted as a result of lipid peroxidation. These changes were more prominent in the WM of the brain. The administration of amifostine before ionizing radiation inhibited the radiation-induced lipid peroxidation in the brain. In addition, this study indicated that FTIRM provides a novel approach for monitoring ionizing radiation induced-lipid peroxidation and obtaining different molecular ratio images can be used as biomarkers to detect lipid peroxidation in biological systems. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. The Beneficial Radioprotective Effect of Tomato Seed Oil Against Gamma Radiation-Induced Damage in Male Rats.

    Science.gov (United States)

    Ezz, Magda K; Ibrahim, Nashwa K; Said, Mahmoud M; Farrag, Mostafa A

    2018-01-16

    Radiation protection research receives intense focus due to its significant impact on human health. The present study was undertaken to investigate the protective effect of pretreatment with tomato seed oil (TSO) against gamma radiation-induced damage in rats. Male Wistar rats were divided into four groups: (1) untreated control; (2) TSO-supplemented; (3) gamma-irradiated; (4) TSO-pretreated and gamma-irradiated. Acute exposure of animals to a single gamma radiation dose (6 Gy) induced oxidative stress in major body organs, altered serum lipid homeostasis, significantly increased serum testosterone and sorbitol dehydrogenase levels, and elicited a systemic inflammation as manifested by the induction of serum vascular cell adhesion molecule-1. Oral pretreatment with TSO (1 ml/kg; 3 times/week for 8 weeks) before exposure to gamma radiation protected rats against ionizing radiation-induced oxidative stress, restored lipid homeostasis, and suppressed systemic inflammation. Histological findings of target tissues verified biochemical data. The radioprotective ability of TSO was attributed to its content of phytosterols, policosanol, and antioxidants, including lycopene, β-carotene, lutein, and tocopherols. TSO is considered a promising radioprotective agent that can be effectively used to protect the body from the damaging effects of harmful radiation.

  20. Development of radiation-induced mutation techniques and functional genomics studies

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Sub; Kang, Si Yong; Kim, Jin Baek [KAERI, Daejeon (Korea, Republic of); and others

    2012-01-15

    This project has been performed to develop plant genetic resources using radiation (gamma-rays, ion-beam, space environments), to conduct functional genomics studies with mutant resources, and to develop new radiation plant breeding techniques using various radiation sources during 3 years. In the first section, we developed flower genetic resources, functional crop resources, and bio-industrial plant resources. In the second section, we cloned several mutated genes and studied mechanisms of gene expression and genetic diversity of mutations induced by gamma-rays. In the third section, we developed new plant breeding techniques using gamma-phytotron, heavy ion-beam, and space environments. Based on these results, a total of 8 cultivars containing Chrysanthemum, Hibiscus, kenaf, rice, and soybean were applied for plant variety protection (PVP) and a total of 4 cultivars were registered for PVP. Also, license agreement for the dwarf type Hibiscus mutant 'Ggoma' was conducted with Supro co. and the manufacturing technology for natural antioxidant pear-grape vinegar was transferred into Enzenic co. Also, 8 gene sequences, such as F3'H and LDOX genes associated with flower color in Chrysanthemum and EPSPS gene from Korean lawn grass, were registered in the database of National Center for Biotechnology Information (NCBI). In the future study, we will develop new radiation mutation breeding techniques through the mutation spectrum induced by various radiation sources, the studies for mechanism of the cellular response to radiation, and the comparative{center_dot}structural{center_dot}functional genomics studies for useful traits.

  1. Constructive and critical approach of the radiation damage simulation; Approche constructive et critique de la simulation du dommage d'irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Becquart, Ch

    2002-11-15

    This work deals with the problem of radiation damage in materials for applications in development of fission and nuclear fusion technologies. It is organised in 3 sections. In section 1 are presented the mechanisms of formation and the evolution kinetics of the primary damage. Section 2 is devoted to the study of the sensitivity of the radiation damage at different approximations. Section 3 discusses the contribution of the ab initio calculations to the study of radiation damage and more particularly the point defects in a dilute Fe-Cu ferritic alloy. This work is illustrated by several publications added in each section. (O.M.)

  2. [Blocking 1800 MHz mobile phone radiation-induced reactive oxygen species production and DNA damage in lens epithelial cells by noise magnetic fields].

    Science.gov (United States)

    Wu, Wei; Yao, Ke; Wang, Kai-jun; Lu, De-qiang; He, Ji-liang; Xu, Li-hong; Sun, Wen-jun

    2008-01-01

    To investigate whether the exposure to the electromagnetic noise can block reactive oxygen species (ROS) production and DNA damage of lens epithelial cells induced by 1800 MHz mobile phone radiation. The DCFH-DA method and comet assay were used respectively to detect the intracellular ROS and DNA damage of cultured human lens epithelial cells induced by 4 W/kg 1800 MHz mobile phone radiation or/and 2 muT electromagnetic noise for 24 h intermittently. 1800 MHz mobile phone radiation at 4 W/kg for 24 h increased intracellular ROS and DNA damage significantly (PDNA damage of mobile phone radiation plus noise group were not significant enhanced (P>0.05) as compared to sham exposure group. Electromagnetic noise can block intracellular ROS production and DNA damage of human lens epithelial cells induced by 1800 MHz mobile phone radiation.

  3. An edge-TCT setup for the investigation of radiation damaged silicon sensors

    Energy Technology Data Exchange (ETDEWEB)

    Feindt, Finn; Scharf, Christian; Garutti, Erika; Klanner, Robert [Institute for Experimental Physics, Hamburg University, Luruper Chaussee 149, D-22761 Hamburg (Germany)

    2016-07-01

    The aim of this work is to measure the electric field, drift velocity and charge collection of electrons and holes in radiation-damaged silicon strip sensors. For this purpose the edge Transient Current Technique (TCT) is employed. In contrast to conventional TCT, this method requires light from a sub-ns pulsed, infrared laser to be focused to a μm-size spot and scanned across the polished edge of a strip sensor. Thus electron-hole pairs are generated at a known depth in the sensor. Electrons and holes drift in the electric field and induce transient currents on the sensor electrodes. The current wave forms are analyzed as a function of the applied voltage and the position of the laser focus in order to determine the electric field, the drift velocities and the charge collection. In this talk the setup and the procedure for polishing the sensor edge are described, and first results, regarding the measurement of the laser light focus are presented.

  4. Damage to the optic radiation in multiple sclerosis is associated with retinal injury and visual disability.

    Science.gov (United States)

    Reich, Daniel S; Smith, Seth A; Gordon-Lipkin, Eliza M; Ozturk, Arzu; Caffo, Brian S; Balcer, Laura J; Calabresi, Peter A

    2009-08-01

    To determine whether damage to the optic radiation (OR) in multiple sclerosis (MS) is associated with optic nerve injury and visual dysfunction. Case-control study. Referral center. Ninety referred patients with MS and 29 healthy volunteers. Magnetic resonance imaging indices along the OR were reconstructed with diffusion tensor tractography. Retinal nerve fiber layer thickness and visual acuity at high and low contrast were measured in a subset of the MS group (n = 36). All tested magnetic resonance imaging indices (fractional anisotropy [FA]; mean, parallel, and perpendicular [lambda( perpendicular)] diffusivity; T2 relaxation time; and magnetization transfer ratio) were significantly abnormal in patients with MS. Mean retinal nerve fiber layer thickness was significantly correlated with FA (r = 0.55; P 80 mum), letter acuity scores at 2.5% contrast were correlated with OR-specific FA (r = 0.55; P = .004), lambda( perpendicular) (r = -0.40; P = .04), and magnetization transfer ratio (r = 0.54; P = .01), as well as the fraction of OR volume made up of lesions (r = -0.69; P visual disability.

  5. Incident particle range dependence of radiation damage in a power bipolar junction transistor

    Science.gov (United States)

    Liu, Chao-Ming; Li, Xing-Ji; Geng, Hong-Bin; Rui, Er-Ming; Guo, Li-Xin; Yang, Jian-Qun

    2012-10-01

    The characteristic degradations in silicon NPN bipolar junction transistors (BJTs) of type 3DD155 are examined under the irradiations of 25-MeV carbon (C), 40-MeV silicon (Si), and 40-MeV chlorine (Cl) ions respectively. Different electrical parameters are measured in-situ during the exposure of heavy ions. The experimental data shows that the changes in the reciprocal of the gain variation (Δ(1/β)) of 3DD155 transistors irradiated respectively by 25-MeV C, 40-MeV Si, and 40-MeV Cl ions each present a nonlinear behaviour at a low fluence and a linear response at a high fluence. The Δ(1/β) of 3DD155 BJT irradiated by 25-MeV C ions is greatest at a given fluence, a little smaller when the device is irradiated by 40-MeV Si ions, and smallest in the case of the 40-MeV Cl ions irradiation. The measured and calculated results clearly show that the range of heavy ions in the base region of BJT affects the level of radiation damage.

  6. Radiation-induced lung damage promotes breast cancer lung-metastasis through CXCR4 signaling.

    Science.gov (United States)

    Feys, Lynn; Descamps, Benedicte; Vanhove, Christian; Vral, Anne; Veldeman, Liv; Vermeulen, Stefan; De Wagter, Carlos; Bracke, Marc; De Wever, Olivier

    2015-09-29

    Radiotherapy is a mainstay in the postoperative treatment of breast cancer as it reduces the risks of local recurrence and mortality after both conservative surgery and mastectomy. Despite recent efforts to decrease irradiation volumes through accelerated partial irradiation techniques, late cardiac and pulmonary toxicity still occurs after breast irradiation. The importance of this pulmonary injury towards lung metastasis is unclear. Preirradiation of lung epithelial cells induces DNA damage, p53 activation and a secretome enriched in the chemokines SDF-1/CXCL12 and MIF. Irradiated lung epithelial cells stimulate adhesion, spreading, growth, and (transendothelial) migration of human MDA-MB-231 and murine 4T1 breast cancer cells. These metastasis-associated cellular activities were largely mimicked by recombinant CXCL12 and MIF. Moreover, an allosteric inhibitor of the CXCR4 receptor prevented the metastasis-associated cellular activities stimulated by the secretome of irradiated lung epithelial cells. Furthermore, partial (10%) irradiation of the right lung significantly stimulated breast cancer lung-specific metastasis in the syngeneic, orthotopic 4T1 breast cancer model.Our results warrant further investigation of the potential pro-metastatic effects of radiation and indicate the need to develop efficient drugs that will be successful in combination with radiotherapy to prevent therapy-induced spread of cancer cells.

  7. Structural and Optical Investigations of Radiation Damage in Transparent PET Polymer Films

    Directory of Open Access Journals (Sweden)

    Shiv Govind Prasad

    2011-01-01

    Full Text Available Effects of gamma irradiation at different doses up to 135 kGy on polyethylene terephthalate (PET polymer films have been investigated by X-ray diffraction (XRD, Fourier transform infrared (FTIR spectroscopy, and ultraviolet-visible (UV-VIS spectroscopy. From XRD analysis, it was found that even at a high dose of gamma irradiation of 135 kGy, crystallinity of the PET samples remain unchanged. However, the FTIR peak at 871 cm−1 (depicting C–H bending mode of out-of-plane vibration and another at 1303 cm−1 (representing C–H bending mode of in-plane vibration disappear for gamma-irradiated PET. In this study, it has also been found that γ-irradiation in air enhances the optical absorption in the wavelength region 320–370 nm. This has been attributed to free radicals being produced in the polymer by the γ-radiation. Further, the free radicals react with oxygen of air to form carbonyl group and hydroxyls. With increasing γ-dose, there is a red shift of the UV—near visible cutoff for PET. XRD and FTIR observations on γ-damage have been correlated.

  8. Cross-generational trans fat intake exacerbates UV radiation-induced damage in rat skin.

    Science.gov (United States)

    Barcelos, R C S; Vey, L T; Segat, H J; Roversi, K; Roversi, Kr; Dias, V T; Trevizol, F; Kuhn, F T; Dolci, G S; Pase, C S; Piccolo, J; Veit, J C; Emanuelli, T; Luz, S C A; Bürger, M E

    2014-07-01

    We evaluated the influence of dietary fats on ultraviolet radiation (UVR)-induced oxidative damage in skin of rats. Animals from two consecutive generations born of dams supplemented with fats during pregnancy and breastfeeding were maintained in the same supplementation: soybean-oil (SO, rich in n-6 FA, control group), fish-oil (FO, rich in n-3 FA) or hydrogenated-vegetable-fat (HVF, rich in TFA). At 90 days of age, half the animals from the 2nd generation were exposed to UVR (0.25 J/cm(2)) 3×/week for 12 weeks. The FO group presented higher incorporation of n-3 FA in dorsal skin, while the HVF group incorporated TFA. Biochemical changes per se were observed in skin of the HVF group: greater generation of reactive oxygen species (ROS), lower mitochondrial integrity and increased Na(+)K(+)-ATPase activity. UVR exposure increased skin wrinkles scores and ROS generation and decreased mitochondrial integrity and reduced-glutathione levels in the HVF group. In FO, UVR exposure was associated with smaller skin thickness and reduced levels of protein-carbonyl, together with increased catalase activity and preserved Na(+)K(+)-ATPase function. In conclusion, while FO may be protective, trans fat may be harmful to skin health by making it more vulnerable to UVR injury and thus more prone to develop photoaging and skin cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Wavelength dependence of ultraviolet radiation-induced DNA damage as determined by laser irradiation suggests that cyclobutane pyrimidine dimers are the principal DNA lesions produced by terrestrial sunlight

    Science.gov (United States)

    Besaratinia, Ahmad; Yoon, Jae-in; Schroeder, Christi; Bradforth, Stephen E.; Cockburn, Myles; Pfeifer, Gerd P.

    2011-01-01

    To elucidate the involvement of specific ultraviolet (UV) wavelengths in solar mutagenesis, we used a laser system to investigate the induction of DNA damage, both in the overall genome and at the nucleotide resolution level, in the genomic DNA of transgenic Big Blue mouse fibroblasts irradiated with a series of UV wavelengths, inclusive of UVC (λ320 nm). Subsequently, we sought correlation between the locations of UV-induced DNA lesions in the cII transgene of irradiated DNA samples and the frequency distribution and codon position of the induced cII mutations in counterpart mouse cells irradiated with simulated sunlight. Using a combination of enzymatic digestion assays coupled with gel electrophoresis, immunodot blot assays, and DNA footprinting assays, we demonstrated a unique wavelength-dependent formation of photodimeric lesions, i.e., cyclobutane pyrimidine dimers (CPDs) and (6–4) photoproducts [(6–4)PPs], based on direct UV absorption of DNA, in irradiated mouse genomic DNA, which could partially explain the induction of mutations in mouse cells irradiated with simulated sunlight. Most notably, there was a divergence of CPD and (6–4)PP formation at an irradiation wavelength of 296 nm in mouse genomic DNA. Whereas substantial formation of (6–4)PPs was detectable in samples irradiated at this wavelength, which intensified as the irradiation wavelength decreased, only small quantities of these lesions were found in samples irradiated at wavelengths of 300–305 nm, with no detectable level of (6–4)PPs in samples irradiated with longer wavelengths. Although CPD formation followed the same pattern of increase with decreasing wavelengths of irradiation, there were substantial levels of CPDs in samples irradiated with UVB wavelengths borderlined with UVA, and small but detectable levels of these lesions in samples irradiated with longer wavelengths. Because the terrestrial sunlight spectrum rolls off sharply at wavelengths ∼300 nm, our findings

  10. Radiation-Induced Upregulation of Gene Expression From Adenoviral Vectors Mediated by DNA Damage Repair and Regulation

    Energy Technology Data Exchange (ETDEWEB)

    Nokisalmi, Petri; Rajecki, Maria; Pesonen, Sari; Escutenaire, Sophie [Cancer Gene Therapy Group, Molecular Cancer Biology Program, Transplantation Laboratory, Haartman Institute, and Finnish Institute for Molecular Medicine, University of Helsinki, Helsinki (Finland); Helsinki and Uusimaa Hospital District Laboratory, Helsinki University Central Hospital, Helsinki (Finland); Soliymani, Rabah [Protein Chemistry Unit, Department of Anatomy, Institute of Biomedicine, Biomedicum Helsinki (Finland); Tenhunen, Mikko [Department of Radiation and Oncology, Helsinki University Central Hospital, Helsinki (Finland); Ahtiainen, Laura [Cancer Gene Therapy Group, Molecular Cancer Biology Program, Transplantation Laboratory, Haartman Institute, and Finnish Institute for Molecular Medicine, University of Helsinki, Helsinki (Finland); Helsinki and Uusimaa Hospital District Laboratory, Helsinki University Central Hospital, Helsinki (Finland); Hemminki, Akseli, E-mail: akseli.hemminki@helsinki.fi [Cancer Gene Therapy Group, Molecular Cancer Biology Program, Transplantation Laboratory, Haartman Institute, and Finnish Institute for Molecular Medicine, University of Helsinki, Helsinki (Finland); Helsinki and Uusimaa Hospital District Laboratory, Helsinki University Central Hospital, Helsinki (Finland)

    2012-05-01

    Purpose: In the present study, we evaluated the combination of replication-deficient adenoviruses and radiotherapy in vitro. The purpose of the present study was to analyze the mechanism of radiation-mediated upregulation of adenoviral transgene expression. Methods and Materials: Adenoviral transgene expression (luciferase or green fluorescent protein) was studied with and without radiation in three cell lines: breast cancer M4A4-LM3, prostate cancer PC-3MM2, and lung cancer LNM35/enhanced green fluorescent protein. The effect of the radiation dose, modification of the viral capsid, and five different transgene promoters were studied. The cellular responses were studied using mass spectrometry and immunofluorescence analysis. Double strand break repair was modulated by inhibitors of heat shock protein 90, topoisomerase-I, and DNA protein kinase, and transgene expression was measured. Results: We found that a wide range of radiation doses increased adenoviral transgene expression regardless of the cell line, transgene, promoter, or viral capsid modification. Treatment with adenovirus, radiation, and double strand break repair inhibitors resulted in persistence of double strand breaks and subsequent increases in adenovirus transgene expression. Conclusions: Radiation-induced enhancement of adenoviral transgene expression is linked to DNA damage recognition and repair. Radiation induces a global cellular response that results in increased production of RNA and proteins, including adenoviral transgene products. This study provides a mechanistic rationale for combining radiation with adenoviral gene delivery.

  11. RITRACKS: A Software for Simulation of Stochastic Radiation Track Structure, Micro and Nanodosimetry, Radiation Chemistry and DNA Damage for Heavy Ions

    Science.gov (United States)

    Plante, I; Wu, H

    2014-01-01

    The code RITRACKS (Relativistic Ion Tracks) has been developed over the last few years at the NASA Johnson Space Center to simulate the effects of ionizing radiations at the microscopic scale, to understand the effects of space radiation at the biological level. The fundamental part of this code is the stochastic simulation of radiation track structure of heavy ions, an important component of space radiations. The code can calculate many relevant quantities such as the radial dose, voxel dose, and may also be used to calculate the dose in spherical and cylindrical targets of various sizes. Recently, we have incorporated DNA structure and damage simulations at the molecular scale in RITRACKS. The direct effect of radiations is simulated by introducing a slight modification of the existing particle transport algorithms, using the Binary-Encounter-Bethe model of ionization cross sections for each molecular orbitals of DNA. The simulation of radiation chemistry is done by a step-by-step diffusion-reaction program based on the Green's functions of the diffusion equation]. This approach is also used to simulate the indirect effect of ionizing radiation on DNA. The software can be installed independently on PC and tablets using the Windows operating system and does not require any coding from the user. It includes a Graphic User Interface (GUI) and a 3D OpenGL visualization interface. The calculations are executed simultaneously (in parallel) on multiple CPUs. The main features of the software will be presented.

  12. Pharmacological doses of daily ascorbate protect tumours from radiation damage after a single dose of radiation in an intracranial mouse glioma model

    Directory of Open Access Journals (Sweden)

    Carole eGrasso

    2014-12-01

    Full Text Available Pharmacological ascorbate is currently used as an anti-cancer treatment, potentially in combination with radiation therapy, by integrative medicine practitioners. In the acidic, metal-rich tumour environment, ascorbate acts as a pro-oxidant, with a mode of action similar to that of ionising radiation; both treatments kill cells predominantly by free radical-mediated DNA damage. The brain tumour, glioblastoma multiforme (GBM, is very resistant to radiation; radiosensitising GBM cells will improve survival of GBM patients. Here we demonstrate that a single fraction (6 Gy of radiation combined with a one hour exposure to ascorbate (5 mM sensitised murine glioma GL261cells to radiation in survival and colony-forming assays in vitro. In addition, we report the effect of a single fraction (4.5 Gy of whole brain radiation combined with daily intra-peritoneal injections of ascorbate (1 mg/kg in an intra-cranial GL261 glioma mouse model. Tumour-bearing C57BL/6 mice were divided into four groups: one group received a single dose of 4.5 Gy to the brain eight days after tumour implantation, a second group received daily intra-peritoneal injections of ascorbate (day 8-45 after implantation, a third group received both treatments and a fourth control group received no treatment. While radiation delayed tumour progression, intra-peritoneal ascorbate alone had no effect on tumour progression. Tumour progression was faster in tumour-bearing mice treated with radiation and daily ascorbate than those treated with radiation alone. Histological analysis showed less necrosis in tumours treated with both radiation and ascorbate, consistent with a radio-protective effect of ascorbate in vivo. Discrepancies between our in vitro and in vivo results may be explained by differences in the tumour micro-environment which determines whether ascorbate remains outside the cell, acting as a pro-oxidant or whether it enters the cells and acts as an anti-oxidant.

  13. Space Radiation Induced Cytogenetic Damage in the Blood Lymphocytes of Astronauts: Persistence of Damage After Flight and the Effects of Repeat Long Duration Missions

    Science.gov (United States)

    George, Kerry; Rhone, Jordan; Chappell, L. J.; Cucinotta, F. A.

    2010-01-01

    Cytogenetic damage was assessed in blood lymphocytes from astronauts before and after they participated in long-duration space missions of three months or more. The frequency of chromosome damage was measured by fluorescence in situ hybridization (FISH) chromosome painting before flight and at various intervals from a few days to many months after return from the mission. For all individuals, the frequency of chromosome exchanges measured within a month of return from space was higher than their prefight yield. However, some individuals showed a temporal decline in chromosome damage with time after flight. Statistical analysis using combined data for all astronauts indicated a significant overall decreasing trend in total chromosome exchanges with time after flight, although this trend was not seen for all astronauts and the yield of chromosome damage in some individuals actually increased with time after flight. The decreasing trend in total exchanges was slightly more significant when statistical analysis was restricted to data collected more than 220 days after return from flight. In addition, limited data on multiple flights show a lack of correlation between time in space and translocation yields. Data from three crewmembers who has participated in two separate long-duration space missions provide limited information on the effect of repeat flights and show a possible adaptive response to space radiation exposure.

  14. Neutron induced radiation damage of plastic scintillators for the upgrade of the Tile Calorimeter of the ATLAS detector.

    Science.gov (United States)

    Mdhluli, J. E.; Jivan, H.; Erasmus, R.; Davydov, Yu I.; Baranov, V.; Mthembu, S.; Mellado, B.; Sideras-Haddad, E.; Solovyanov, O.; Sandrock, C.; Peter, G.; Tlou, S.; Khanye, N.; Tjale, B.

    2017-07-01

    With the prediction that the plastic scintillators in the gap region of the Tile Calorimeter will sustain a significantly large amount of radiation damage during the HL-LHC run time, the current plastic scintillators will need to be replaced during the phase 2 upgrade in 2018. The scintillators in the gap region were exposed to a radiation environment of up to 10 kGy/year during the first run of data taking and with the luminosity being increased by a factor of 10, the radiation environment will be extremely harsh. We report on the radiation damage to the optical properties of plastic scintillators following irradiation using a neutron beam of the IBR-2 pulsed reactor in Joint Institute for Nuclear Research (JINR), Dubna. A comparison is drawn between polyvinyl toluene based commercial scintillators EJ200, EJ208 and EJ260 as well as polystyrene based scintillator from Kharkov. The samples were subjected to irradiation with high energy neutrons and a flux density range of 1 × 106-7.7 × 106. Light transmission, Raman spectroscopy, fluorescence spectroscopy and light yield testing was performed to characterize the damage induced in the samples. Preliminary results from the tests done indicate a minute change in the optical properties of the scintillators with further studies underway to gain a better understanding of the interaction between neutrons with plastic scintillators.

  15. Limiting radiation damage for high-brilliance biological solution scattering: practical experience at the EMBL P12 beamline PETRAIII.

    Science.gov (United States)

    Jeffries, Cy M; Graewert, Melissa A; Svergun, Dmitri I; Blanchet, Clément E

    2015-03-01

    Radiation damage is the general curse of structural biologists who use synchrotron small-angle X-ray scattering (SAXS) to investigate biological macromolecules in solution. The EMBL-P12 biological SAXS beamline located at the PETRAIII storage ring (DESY, Hamburg, Germany) caters to an extensive user community who integrate SAXS into their diverse structural biology programs. The high brilliance of the beamline [5.1 × 10(12) photons s(-1), 10 keV, 500 (H) µm × 250 (V) µm beam size at the sample position], combined with automated sample handling and data acquisition protocols, enable the high-throughput structural characterization of macromolecules in solution. However, considering the often-significant resources users invest to prepare samples, it is crucial that simple and effective protocols are in place to limit the effects of radiation damage once it has been detected. Here various practical approaches are evaluated that users can implement to limit radiation damage at the P12 beamline to maximize the chances of collecting quality data from radiation sensitive samples.

  16. High background radiation areas of Ramsar in Iran: evaluation of DNA damage by alkaline single cell gel electrophoresis (SCGE).

    Science.gov (United States)

    Masoomi, J R; Mohammadi, Sh; Amini, M; Ghiassi-Nejad, M

    2006-01-01

    The hot springs in special areas in Ramsar, a northern coastal town in Iran, contain (226)Ra and (222)Rn. The natural radiation effects, radiosensitivity or adaptive responses, on the inhabitants of high natural radiation in Ramsar were studied. The single cell gel electrophoresis was used to monitor DNA damages. Three groups of volunteers were selected, one from high natural background radiation areas as the case group and two from normal background radiation areas as controls (control 1 and control 2). The latter one had the similar living situation to case group while the other (control 2) had different living situation from the other groups. Peripheral blood mononuclear cells (PMNCs) were separated and irradiated by (60)Co source at five different gamma doses. It was found that the spontaneous level of DNA damage and the induced DNA damage in all challenging doses in case group was considerably higher than control groups (p < 0.05). On the other hand, the repair rate in those volunteers, who received less than 10.2 mSv/y was significantly more than the control groups. In the contrary, individuals who live in homes with more than 10.2 mSv/y had incomplete repair. Additionally the plasma and urinary levels of vitamin C were measured spectrophotometrically. Although the concentration of vitamin C of plasma was equal in case and control 1 groups, the urinary level of vitamin C was found to be lower in the case group.

  17. TU-CD-BRB-05: Radiation Damage Signature of White Matter Fiber Bundles Using Diffusion Tensor Imaging (DTI)

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, T; Chapman, C; Lawrence, T; Cao, Y [University of Michigan, Ann Arbor, MI (United States); Tsien, C [Washington University at St. Louis, St. Louis, MO (United States)

    2015-06-15

    Purpose: To develop an automated and scalable approach and identify temporal, spatial and dosimetric patterns of radiation damage of white matter (WM) fibers following partial brain irradiation. Methods: An automated and scalable approach was developed to extract DTI features of 22 major WM fibers from 33 patients with low-grade/benign tumors treated by radiation therapy (RT). DTI scans of the patients were performed pre-RT, 3- and 6-week during RT, and 1, 6 and 18 months after RT. The automated tractography analysis was applied to 198 datasets as: (1) intra-subject registration of longitudinal DTI, (2) spatial normalization of individual-patient DTI to the Johns Hopkins WM Atlas, (3) automatic fiber tracking regulated by the WM Atlas, and (4) segmentation of WM into 22 major tract profiles. Longitudinal percentage changes in fractional anisotropy (FA), and mean, axial and radial diffusivity (MD/AD/RD) of each tract from pre-RT were quantified and correlated to 95%, 90% and 80% percentiles of doses and mean doses received by the tract. Heatmaps were used to identify clusters of significant correlation and reveal temporal, spatial and dosimetric signatures of WM damage. A multivariate linear regression was further carried out to determine influence of clinical factors. Results: Of 22 tracts, AD/MD changes in 12 tracts had significant correlation with doses, especially at 6 and 18 months post-RT, indicating progressive radiation damage after RT. Most interestingly, the DTI-index changes in the elongated tracts were associated with received maximum doses, suggesting a serial-structure behavior; while short association fibers were affected by mean doses, indicating a parallel-structure response. Conclusion: Using an automated DTI-tractography analysis of whole brain WM fibers, we reveal complex radiation damage patterns of WM fibers. Damage in WM fibers that play an important role in the neural network could be associated with late neurocognitive function declines

  18. Identification of novel genes involved in DNA damage response by screening a genome-wide Schizosaccharomyces pombe deletion library

    Directory of Open Access Journals (Sweden)

    Pan Xian

    2012-11-01

    Full Text Available Abstract Background DNA damage response (DDR plays pivotal roles in maintaining genome integrity and stability. An effective DDR requires the involvement of hundreds of genes that compose a complicated network. Because DDR is highly conserved in evolution, studies in lower eukaryotes can provide valuable information to elucidate the mechanism in higher organisms. Fission yeast (Schizosaccharomyces pombe has emerged as an excellent model for DDR research in recent years. To identify novel genes involved in DDR, we screened a genome-wide S. pombe haploid deletion library against six different DNA damage reagents. The library covered 90.5% of the nonessential genes of S. pombe. Results We have identified 52 genes that were actively involved in DDR. Among the 52 genes, 20 genes were linked to DDR for the first time. Flow cytometry analysis of the repair defective mutants revealed that most of them exhibited a defect in cell cycle progression, and some caused genome instability. Microarray analysis and genetic complementation assays were carried out to characterize 6 of the novel DDR genes in more detail. Data suggested that SPBC2A9.02 and SPAC27D7.08c were required for efficient DNA replication initiation because they interacted genetically with DNA replication initiation proteins Abp1 and Abp2. In addition, deletion of sgf73+, meu29+, sec65+ or pab1+ caused improper cytokinesis and DNA re-replication, which contributed to the diploidization in the mutants. Conclusions A genome-wide screen of genes involved in DDR emphasized the key role of cell cycle control in the DDR network. Characterization of novel genes identified in the screen helps to elucidate the mechanism of the DDR network and provides valuable clues for understanding genome stability in higher eukaryotes.

  19. Participation of gap junction communication in potentially lethal damage repair and DNA damage in human fibroblasts exposed to low- or high-LET radiation

    Science.gov (United States)

    Autsavapromporn, Narongchai; Suzuki, Masao; Plante, Ianik; Liu, Cuihua; Uchihori, Yukio; Hei, Tom K.; Azzam, Edouard I.; Murakami, Takeshi

    2014-01-01

    Existing research has not fully explained how different types of ionizing radiation (IR) modulate the responses of cell populations or tissues. In our previous work, we showed that gap junction intercellular communication (GJIC) mediates the propagation of stressful effects among irradiated cells exposed to high linear energy transfer (LET) radiations, in which almost every cells is traversed by an IR track. In the present study, we conducted an in-depth study of the role of GJIC in modulating the repair of potentially lethal damage (PLDR) and micronuclei formation in cells exposed to low- or high-LET IR. Confluent human fibroblasts were exposed in the presence or absence of a gap junction inhibitor to 200 kV X rays (LET ∼ 1.7 keV/µm), carbon ions (LET ∼ 76 keV/µm), silicon ions (LET ∼ 113 keV/µm) or iron ions (LET ∼ 400 keV/µm) that resulted in isosurvival levels. The fibroblasts were incubated for various times at 37 °C. As expected, high-LET IR were more effective than were low-LET X rays at killing cells and damaging DNA shortly after irradiation. However, when cells were held in a confluent state for several hours, PLDR associated with a reduction in DNA damage, occurred only in cells exposed to X rays. Interestingly, inhibition of GJIC eliminated the enhancement of toxic effects, which resulted in an increase of cell survival and reduction in the level of micronucleus formation in cells exposed to high, but not in those exposed to low-LET IR. The experiment shows that gap-junction communication plays an important role in the propagation of stressful effects among irradiated cells exposed to high-LET IR while GJIC has only a minimal effect on PLDR and DNA damage following low-LET irradiation. Together, our results show that PLDR and induction of DNA damage clearly depend on gap-junction communication and radiation quality. PMID:23867854

  20. Micro-CT for anatomic referencing in PET and SPECT: radiation dose, biologic damage, and image quality.

    Science.gov (United States)

    Kersemans, Veerle; Thompson, James; Cornelissen, Bart; Woodcock, Michael; Allen, Philip D; Buls, Nico; Muschel, Ruth J; Hill, Mark A; Smart, Sean C

    2011-11-01

    CT is widely used for anatomic referencing of PET and SPECT images of small animals but requires sufficiently high radiation doses capable of causing significant DNA damage. Therefore, we described the relationship between radiation dose, biologic damage, and image quality to determine whether CT can be used without significantly compromising radiotherapy and tumor development studies. The CT dose index generated by the nanoSPECT/CT system was compared with measurements using EBT2 gafchromic film. The effects of micro-CT were evaluated in 2 mouse strains that differ in sensitivity to radiation. γH2AX foci analysis to determine leukocyte, liver, and jejunum DNA damage and hematoxylin and eosin staining to investigate macroscopic jejunum damage were performed. Signal-to-noise ratio, contrast-to-noise ratio, and scanner linearity were determined to assess image quality. For the standard settings, that is, as set by the manufacturers, EBT2 gafchromic film dosimetry showed that the nanoSPECT/CT system underestimated the absorbed dose. Moreover, significant doses were obtained, resulting in a significant increase in γH2AX formation in leukocytes, liver, and jejunum 40 min after CT, using preset parameters when compared with nonimaged controls. The jejenum response was more pronounced for the more radiosensitive strain. In contrast to leukocytes, the liver and jejunum still showed evidence of DNA damage 3 d after CT. Contrast-to-noise ratio, signal-to-noise ratio, and scanner linearity were sufficient to allow for anatomic referencing for both imaging protocols tested. Anatomic reference images can be produced with no observable DNA damage or compromising image quality using low radiographic voltage, flux, and duration.

  1. Novel Double-Hit Model of Radiation and Hyperoxia-Induced Oxidative Cell Damage Relevant to Space Travel

    Directory of Open Access Journals (Sweden)

    Ralph A. Pietrofesa

    2016-06-01

    Full Text Available Spaceflight occasionally requires multiple extravehicular activities (EVA that potentially subject astronauts to repeated changes in ambient oxygen superimposed on those of space radiation exposure. We thus developed a novel in vitro model system to test lung cell damage following repeated exposure to radiation and hyperoxia. Non-tumorigenic murine alveolar type II epithelial cells (C10 were exposed to >95% O2 for 8 h only (O2, 0.25 Gy ionizing γ-radiation (IR only, or a double-hit combination of both challenges (O2 + IR followed by 16 h of normoxia (ambient air containing 21% O2 and 5% CO2 (1 cycle = 24 h, 2 cycles = 48 h. Cell survival, DNA damage, apoptosis, and indicators of oxidative stress were evaluated after 1 and 2 cycles of exposure. We observed a significant (p < 0.05 decrease in cell survival across all challenge conditions along with an increase in DNA damage, determined by Comet analysis and H2AX phosphorylation, and apoptosis, determined by Annexin-V staining, relative to cells unexposed to hyperoxia or radiation. DNA damage (GADD45α and cleaved-PARP, apoptotic (cleaved caspase-3 and BAX, and antioxidant (HO-1 and Nqo1 proteins were increased following radiation and hyperoxia exposure after 1 and 2 cycles of exposure. Importantly, exposure to combination challenge O2 + IR exacerbated cell death and DNA damage compared to individual exposures O2 or IR alone. Additionally levels of cell cycle proteins phospho-p53 and p21 were significantly increased, while levels of CDK1 and Cyclin B1 were decreased at both time points for all exposure groups. Similarly, proteins involved in cell cycle arrest was more profoundly changed with the combination challenges as compared to each stressor alone. These results correlate with a significant 4- to 6-fold increase in the ratio of cells in G2/G1 after 2 cycles of exposure to hyperoxic conditions. We have characterized a novel in vitro model of double-hit, low-level radiation and hyperoxia

  2. Novel Double-Hit Model of Radiation and Hyperoxia-Induced Oxidative Cell Damage Relevant to Space Travel.

    Science.gov (United States)

    Pietrofesa, Ralph A; Velalopoulou, Anastasia; Lehman, Stacey L; Arguiri, Evguenia; Solomides, Pantelis; Koch, Cameron J; Mishra, Om P; Koumenis, Constantinos; Goodwin, Thomas J; Christofidou-Solomidou, Melpo

    2016-06-16

    Spaceflight occasionally requires multiple extravehicular activities (EVA) that potentially subject astronauts to repeated changes in ambient oxygen superimposed on those of space radiation exposure. We thus developed a novel in vitro model system to test lung cell damage following repeated exposure to radiation and hyperoxia. Non-tumorigenic murine alveolar type II epithelial cells (C10) were exposed to >95% O₂ for 8 h only (O₂), 0.25 Gy ionizing γ-radiation (IR) only, or a double-hit combination of both challenges (O₂ + IR) followed by 16 h of normoxia (ambient air containing 21% O₂ and 5% CO₂) (1 cycle = 24 h, 2 cycles = 48 h). Cell survival, DNA damage, apoptosis, and indicators of oxidative stress were evaluated after 1 and 2 cycles of exposure. We observed a significant (p < 0.05) decrease in cell survival across all challenge conditions along with an increase in DNA damage, determined by Comet analysis and H2AX phosphorylation, and apoptosis, determined by Annexin-V staining, relative to cells unexposed to hyperoxia or radiation. DNA damage (GADD45α and cleaved-PARP), apoptotic (cleaved caspase-3 and BAX), and antioxidant (HO-1 and Nqo1) proteins were increased following radiation and hyperoxia exposure after 1 and 2 cycles of exposure. Importantly, exposure to combination challenge O₂ + IR exacerbated cell death and DNA damage compared to individual exposures O₂ or IR alone. Additionally levels of cell cycle proteins phospho-p53 and p21 were significantly increased, while levels of CDK1 and Cyclin B1 were decreased at both time points for all exposure groups. Similarly, proteins involved in cell cycle arrest was more profoundly changed with the combination challenges as compared to each stressor alone. These results correlate with a significant 4- to 6-fold increase in the ratio of cells in G2/G1 after 2 cycles of exposure to hyperoxic conditions. We have characterized a novel in vitro model of double-hit, low-level radiation and hyperoxia

  3. SERIES: Genomic instability in cancer Balancing repair and tolerance of DNA damage caused by alkylating agents

    Science.gov (United States)

    Fu, Dragony; Calvo, Jennifer A.; Samson, Leona D

    2013-01-01

    Alkylating agents comprise a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER), and mismatch repair (MMR) respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial for an organism's favorable response to alkylating agents. Furthermore, an individual's response to alkylating agents can vary considerably from tissue to tissue and from person to person, pointing to genetic and epigenetic mechanisms that modulate alkylating agent toxicity. PMID:22237395

  4. Cleavage factor I links transcription termination to DNA damage response and genome integrity maintenance in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Hélène Gaillard

    2014-03-01

    Full Text Available During transcription, the nascent pre-mRNA undergoes a series of processing steps before being exported to the cytoplasm. The 3'-end processing machinery involves different proteins, this function being crucial to cell growth and viability in eukaryotes. Here, we found that the rna14-1, rna15-1, and hrp1-5 alleles of the cleavage factor I (CFI cause sensitivity to UV-light in the absence of global genome repair in Saccharomyces cerevisiae. Unexpectedly, CFI mutants were proficient in UV-lesion repair in a transcribed gene. DNA damage checkpoint activation and RNA polymerase II (RNAPII degradation in response to UV were delayed in CFI-deficient cells, indicating that CFI participates in the DNA damage response (DDR. This is further sustained by the synthetic growth defects observed between rna14-1 and mutants of different repair pathways. Additionally, we found that rna14-1 suffers severe replication progression defects and that a functional G1/S checkpoint becomes essential in avoiding genetic instability in those cells. Thus, CFI function is required to maintain genome integrity and to prevent replication hindrance. These findings reveal a new function for CFI in the DDR and underscore the importance of coordinating transcription termination with replication in the maintenance of genomic stability.

  5. Repair of DNA damaged by ionizing radiation and other oxidative agents in yeast and human

    Energy Technology Data Exchange (ETDEWEB)

    Louisek Prakash

    2000-01-15

    OAK B202 Treatment of cells with oxidative DNA damaging agents such as ionizing radiation and hydrogen peroxide produces .OH radicals which attack DNA, producing single strand breaks and double strand breaks that have a 3'-blocked terminus with a phosphoglycolate or a phosphate group attached to the 3'-terminus. While DNA strand breaks with 3'-blocked termini are the hallmark of oxidative DNA damage, the mechanisms by which such blocked 3'-termini are removed in eukaryotes remain poorly understood. The goals of this project were to identify the various genes that function in cleaning the blocked 3'ends from DNA strand breaks generated by treatments with ionizing radiation and hydrogen peroxide, to purify the proteins encoded by these genes and to characterize their biochemical activities, and to determine the biological consequences when such damage is not repaired. Because of the high degree of conservation of DNA repair proteins between yeast and humans, and because of the ease of genetic manipulations, initial studies were to be carried out in Saccharomyces cerevisiae. The homologous genes and proteins would then be studied in humans. One aspect of our proposed research was to purify the Apn2 protein from yeast cells and to examine its AP endonuclease and 3'-phosphodiesterase activities. Apn2-like proteins have been identified in eukaryotes other than yeast, including humans, and these proteins form a distinct subfamily within the ExoIII/Ape1/Apn2 family of proteins. We purified the Apn2 protein from yeast and showed that it is a class II AP endonuclease. (Class II AP endonucleases cleave the phosphodiester backbone on the 5'-side of the AP site and produce a 3'-OH group and a 5'-baseless deoxyribose 5'-phosphate residue). Yeast Apn2 and its orthologs in higher eukaryotes differ from E. coli ExoIII and human Ape1 in possessing a C terminus that is absent from the ExoIII/Ape1 subfamily. We found that deletion of

  6. Repair of DNA damaged by ionizing radiation and other oxidative agents in yeast and human

    Energy Technology Data Exchange (ETDEWEB)

    Louise Prakash

    2000-01-15

    Treatment of cells with oxidative DNA damaging agents such as ionizing radiation and hydrogen peroxide produces .OH radicals which attack DNA, producing single strand breaks and double strand breaks that have a 3'-blocked terminus with a phosphoglycolate or a phosphate group attached to the 3'-terminus. While DNA strand breaks with 3'-blocked termini are the hallmark of oxidative DNA damage, the mechanisms by which such blocked 3'-termini are removed in eukaryotes remain poorly understood. The goals of this project were to identify the various genes that function in cleaning the blocked 3'-ends from DNA strand breaks generated by treatments with ionizing radiation and hydrogen peroxide, to purify the proteins encoded by these genes and to characterize their biochemical activities, and to determine the biological consequences when such damage is not repaired. Because of the high degree of conservation of DNA repair proteins between yeast and humans, and because of the ease of genetic manipulations, initial studies were to be carried out in Saccharomyces cerevisiae. The homologous genes and proteins would then be studied in humans. One aspect of our proposed research was to purify the Apn2 protein from yeast cells and to examine its AP endonuclease and 3'-phosphodiesterase activities. Apn2-like proteins have been identified in eukaryotes other than yeast, including humans, and these proteins form a distinct subfamily within the ExoIII/Ape1/Apn2 family of proteins. We purified the Apn2 protein from yeast and showed that it is a class II AP endonuclease. (Class II AP endonucleases cleave the phosphodiester backbone on the 5'-side of the AP site and produce a 3'-OH group and a 5'-baseless deoxyribose 5'-phosphate residue). Yeast Apn2 and its orthologs in higher eukaryotes differ from E. coli ExoIII and human Ape1 in possessing a C terminus that is absent from the ExoIII/Ape1 subfamily. We found that deletion of the

  7. Dynamic Behavior of the RNA Polymerase II and the Ubiquitin Proteasome System During the Neuronal DNA Damage Response to Ionizing Radiation.

    Science.gov (United States)

    Casafont, Iñigo; Palanca, Ana; Lafarga, Vanesa; Mata-Garrido, Jorge; Berciano, Maria T; Lafarga, Miguel

    2016-12-01

    Neurons are highly vulnerable to genotoxic agents. To restore genome integrity upon DNA lesions, neurons trigger a DNA damage response (DDR) that requires chromatin modifications and transcriptional silencing at DNA damage sites. To study the reorganization of the active RNA polymerase II (Pol II), which transcribes all mRNA-encoding genes, and the participation of the ubiquitin-proteasome system (UPS) in the neuronal DDR, we have used rat sensory ganglion neurons exposed to X-rays (4 Gy) ionizing radiation (IR). In control neurons, Pol II appears concentrated in numerous chromatin microfoci identified as transcription factories by the incorporation of 5'-fluorouridine into nascent RNA. Upon IR treatment, numerous IR-induced foci (IRIF), which were immunoreactive for γH2AX and 53BP1, were observed as early as 30 min post-IR; their number progressively reduced at 3 h, 1 day, and 3 days post-IR. The formation of IRIF was associated with a decrease in Pol II levels by both immunofluorescence and Western blotting. Treatment with the proteasome inhibitor bortezomib strongly increased Pol II levels in both control and irradiated neurons, suggesting that proteasome plays a proteolytic role by clearing stalled Pol II complexes at DNA damage sites, as a prelude to DNA repair. Neuronal IRIF recruited ubiquitylated proteins, including ubiquitylated histone H2A (Ub-H2A), and the catalytic proteasome 20S. Ub-H2A has been associated with transcriptional silencing at DNA damage sites. On the other hand, the participation of UPS in neuronal DDR may be essential for the ubiquitylation of Pol II and other proteasome substrates of the DNA repair machinery and their subsequent proteasome-mediated degradation.

  8. A study on the radiation damage and recovery of neutron irradiated vessel steel using magnetic Barkhausen noise

    Science.gov (United States)

    Park, Duck-Gun; Jeong, Hee-Tae; Hong, Jun-Hwa

    1999-04-01

    The radiation damage and thermal recovery characteristic of neutron irradiated SA508-3 reactor pressure vessel steel specimens have been investigated. Two recovery stages were identified from the results of hardness measurements during isochronal annealing and the mechanism responsible for the two stages was explained by using the results of Barkhausen noise measurement on the basis of the interaction between radiation induced defects and the magnetic domain wall. The coercivity was not changed by neutron irradiation, whereas the maximum magnetic induction increased. Barkhausen noise parameters associated with the domain wall motion were decreased by neutron irradiation and recovered with subsequent heat treatments.

  9. Genomic and Phenotypic Characterization of Yeast Biosensor for Deep-space Radiation

    Science.gov (United States)

    Marina, Diana B.; Santa Maria, Sergio; Bhattacharya, Sharmila

    2016-01-01

    The BioSentinel mission was selected to launch as a secondary payload onboard NASA Exploration Mission 1 (EM-1) in 2018. In BioSentinel, the budding yeast Saccharomyces cerevisiae will be used as a biosensor to measure the long-term impact of deep-space radiation to living organisms. In the 4U-payload, desiccated yeast cells from different strains will be stored inside microfluidic cards equipped with 3-color LED optical detection system to monitor cell growth and metabolic activity. At different times throughout the 12-month mission, these cards will be filled with liquid yeast growth media to rehydrate and grow the desiccated cells. The growth and metabolic rates of wild-type and radiation-sensitive strains in deep-space radiation environment will be compared to the rates measured in the ground- and microgravity-control units. These rates will also be correlated with measurements obtained from onboard physical dosimeters. In our preliminary long-term desiccation study, we found that air-drying yeast cells in 10% trehalose is the best method of cell preservation in order to survive the entire 18-month mission duration (6-month pre-launch plus 12-month full-mission periods). However, our study also revealed that desiccated yeast cells have decreasing viability over time when stored in payload-like environment. This suggests that the yeast biosensor will have different population of cells at different time points during the long-term mission. In this study, we are characterizing genomic and phenotypic changes in our yeast biosensor due to long-term storage and desiccation. For each yeast strain that will be part of the biosensor, several clones were reisolated after long-term storage by desiccation. These clones were compared to their respective original isolate in terms of genomic composition, desiccation tolerance and radiation sensitivity. Interestingly, clones from a radiation-sensitive mutant have better desiccation tolerance compared to their original isolate

  10. Hypersensitivity to DNA damage in antephase as a safeguard for genome stability

    NARCIS (Netherlands)

    Feringa, Femke M.; Krenning, Lenno; Koch, André; Van Den Berg, Jeroen; Van Den Broek, Bram; Jalink, Kees; Medema, René H.

    2016-01-01

    Activation of the DNA-damage response can lead to the induction of an arrest at various stages in the cell cycle. These arrests are reversible in nature, unless the damage is too excessive. Here we find that checkpoint reversibility is lost in cells that are in very late G2, but not yet fully

  11. Hypersensitivity to DNA damage in antephase as a safeguard for genome stability.

    Science.gov (United States)

    Feringa, Femke M; Krenning, Lenno; Koch, André; van den Berg, Jeroen; van den Broek, Bram; Jalink, Kees; Medema, René H

    2016-08-26

    Activation of the DNA-damage response can lead to the induction of an arrest at various stages in the cell cycle. These arrests are reversible in nature, unless the damage is too excessive. Here we find that checkpoint reversibility is lost in cells that are in very late G2, but not yet fully committed to enter mitosis (antephase). We show that antephase cells exit the cell cycle and enter senescence at levels of DNA damage that induce a reversible arrest in early G2. We show that checkpoint reversibility critically depends on the presence of the APC/C inhibitor Emi1, which is degraded just before mitosis. Importantly, ablation of the cell cycle withdrawal mechanism in antephase promotes cell division in the presence of broken chromosomes. Thus, our data uncover a novel, but irreversible, DNA-damage response in antephase that is required to prevent the propagation of DNA damage during cell division.

  12. A 2-Stage Genome-Wide Association Study to Identify Single Nucleotide Polymorphisms Associated With Development of Erectile Dysfunction Following Radiation Therapy for Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kerns, Sarah L. [Department of Radiation Oncology, Mount Sinai School of Medicine, New York, New York (United States); Departments of Pathology and Genetics, Albert Einstein College of Medicine, Bronx, New York (United States); Stock, Richard [Department of Radiation Oncology, Mount Sinai School of Medicine, New York, New York (United States); Stone, Nelson [Department of Radiation Oncology, Mount Sinai School of Medicine, New York, New York (United States); Department of Urology, Mount Sinai School of Medicine, New York, New York (United States); Buckstein, Michael [Department of Radiation Oncology, Mount Sinai School of Medicine, New York, New York (United States); Shao, Yongzhao [Division of Biostatistics, New York University School of Medicine, New York, New York (United States); Campbell, Christopher [Departments of Pathology and Genetics, Albert Einstein College of Medicine, Bronx, New York (United States); Rath, Lynda [Department of Radiation Oncology, Mount Sinai School of Medicine, New York, New York (United States); De Ruysscher, Dirk; Lammering, Guido [Department of Radiation Oncology, Maastricht University Medical Center, Maastricht (Netherlands); Hixson, Rosetta; Cesaretti, Jamie; Terk, Mitchell [Florida Radiation Oncology Group, Jacksonville, Florida (United States); Ostrer, Harry [Departments of Pathology and Genetics, Albert Einstein College of Medicine, Bronx, New York (United States); Rosenstein, Barry S., E-mail: barry.rosenstein@mssm.edu [Department of Radiation Oncology, Mount Sinai School of Medicine, New York, New York (United States); Department of Radiation Oncology, New York University School of Medicine, New York, New York (United States); Departments of Dermatology and Preventive Medicine, Mount Sinai School of Medicine, New York, New York (United States)

    2013-01-01

    Purpose: To identify single nucleotide polymorphisms (SNPs) associated with development of erectile dysfunction (ED) among prostate cancer patients treated with radiation therapy. Methods and Materials: A 2-stage genome-wide association study was performed. Patients were split randomly into a stage I discovery cohort (132 cases, 103 controls) and a stage II replication cohort (128 cases, 102 controls). The discovery cohort was genotyped using Affymetrix 6.0 genome-wide arrays. The 940 top ranking SNPs selected from the discovery cohort were genotyped in the replication cohort using Illumina iSelect custom SNP arrays. Results: Twelve SNPs identified in the discovery cohort and validated in the replication cohort were associated with development of ED following radiation therapy (Fisher combined P values 2.1 Multiplication-Sign 10{sup -5} to 6.2 Multiplication-Sign 10{sup -4}). Notably, these 12 SNPs lie in or near genes involved in erectile function or other normal cellular functions (adhesion and signaling) rather than DNA damage repair. In a multivariable model including nongenetic risk factors, the odds ratios for these SNPs ranged from 1.6 to 5.6 in the pooled cohort. There was a striking relationship between the cumulative number of SNP risk alleles an individual possessed and ED status (Sommers' D P value = 1.7 Multiplication-Sign 10{sup -29}). A 1-allele increase in cumulative SNP score increased the odds for developing ED by a factor of 2.2 (P value = 2.1 Multiplication-Sign 10{sup -19}). The cumulative SNP score model had a sensitivity of 84% and specificity of 75% for prediction of developing ED at the radiation therapy planning stage. Conclusions: This genome-wide association study identified a set of SNPs that are associated with development of ED following radiation therapy. These candidate genetic predictors warrant more definitive validation in an independent cohort.

  13. Amifostine use in radiation-induced kidney damage. Preclinical evaluation with scintigraphic and histopathologic parameters

    Energy Technology Data Exchange (ETDEWEB)

    Kaldir, M. [The Ministry of Health, Numune Hospital, Erzurum (Turkey); Cosar-Alas, R.; Yurut-Caloglu, V.; Saynak, M.; Caloglu, M.; Kocak, Z.; Tokatli, F.; Uzal, C. [Dept. of Radiation Oncology, Faculty of Medicine, Trakya Univ., Edirne (Turkey); Cermik, T.F. [Dept. of Nuclear Medicine, Faculty of Medicine, Trakya Univ., Edirne (Turkey); Altaner, S. [Dept. of Pathology, Faculty of Medicine, Trakya Univ., Edirne (Turkey); Tuere, M. [Dept. of Biostatistics, Faculty of Medicine, Trakya Univ., Edirne (Turkey); Parlar, S. [Dept. of Medical Radiophysics, Faculty of Medicine, Trakya Univ., Edirne (Turkey)

    2008-07-15

    Purpose: to assess the degree of protective effects of amifostine on kidney functions via semiquantitative static renal scintigraphy and histopathologic analysis. Material and methods: 30 female albino rats were divided into three equal groups as control (CL), radiotherapy alone (RT), and radiotherapy + amifostine (RT+AMI). The animals in the CL and RT groups were given phosphate-buffered saline, whereas the animals in the RT+AMI group received amifostine (200 mg/kg) by intraperitoneal injection 30 min before irradiation. RT and RT+AMI groups were irradiated with a single dose of 6 Gy using a {sup 60}Co unit at a source-skin distance of 80 cm to the whole right kidney. They were followed up for 6 months. CL, RT, and RT+AMI groups underwent static kidney scintigraphy at the beginning of the experiment and, again, on the day before sacrificing. Histopathologically, tubular atrophy and fibrosis of the kidney damage were evaluated. Results: after irradiation, the median value of right kidney function was 48% (44-49%) and 50.5% (49%-52%) in RT and RT+AMI groups, respectively (p = 0.0002). Grade 1 kidney fibrosis was observed to be 60% in the RT group, while it was only 30% in the RT+AMI group. Grade 2 kidney fibrosis was 30% and 0% in the RT and RT+AMI group, respectively. Grade 1 tubular atrophy was 70% and 50% in the RT and RT+AMI group, respectively. Grade 2 tubular atrophy effect was the same in both groups (10%). Conclusion: static kidney scintigraphy represents an objective and reproducible method to noninvasively investigate kidney function following irradiation. Amifostine produced a significant reduction in radiation-induced loss of renal function. (orig.)

  14. Binary-Encounter-Bethe ionisation cross sections for simulation of DNA damage by the direct effect of ionising radiation.

    Science.gov (United States)

    Plante, I; Cucinotta, F A

    2015-09-01

    DNA damage is of crucial importance in the understanding of the effects of ionising radiation. To refine existing DNA damage models, an approach using the Binary-Encounter-Bethe (BEB) cross sections was developed. The differential cross sections for ionisation of the molecular orbitals of the DNA bases, sugars and phosphates are calculated using the electron binding energy, the mean kinetic energy and the occupancy number of each orbital as parameters. The resulting cross section has an analytic form which is quite convenient to use for Monte-Carlo codes that randomly sample the energy loss occurring during an ionisation event. We also describe an algorithm to simulate the interactions of electrons with DNA in the radiation transport code RITRACKS using the integrated BEB cross section for the bases, sugar and phosphates. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. Effect of the Space Environment on the Induction of DNA-repair Related Proteins and Recovery from Radiation Damage

    Science.gov (United States)

    Kobayashi, Y.; Watanabe, H.; Kikuchi, M.; Narumi, I.

    Recovery of bacterial cells from radiation damage and the effects of microgravity were examined in an STS-79 Shuttle/Mir Mission-4 experiment using the extremely radioresistant bacterium Deinococcus radiodurans. The cells were irradiated with gamma rays before the space flight and incubated on board the Space-Shuttle. The survival of the wild type cells incubated in space increased compared with the ground controls, suggesting that the recovery of this bacterium from radiation damage was enhanced under microgravity. No difference was observed for the survival of radiosensitive mutant rec30 cells whether incubated in space or on the ground. The amount of DNA-repair related RecA protein induced under microgravity was similar to those of ground controls, however, induction of PprA protein, the product of a newly found gene related to the DNA repair mechanism of D. radiodurans, was enhanced under microgravity compared with ground controls

  16. Synchrotron radiation circular dichroism spectroscopy of proteins and applications in structural and functional genomics.

    Science.gov (United States)

    Miles, Andrew J; Wallace, B A

    2006-01-01

    The technique of Synchrotron Radiation Circular Dichroism (SRCD) spectroscopy and its advantages over conventional circular dichroism spectroscopy are described in this tutorial review, as well as recent applications of the technique in structural and functional genomics. Circular dichroism (CD) spectroscopy is a well-established method in biological chemistry and structural biology, but its utility can be limited by the low flux of the light source in the far ultraviolet and vacuum ultraviolet wavelength regions in conventional CD instruments. The development of synchrotron radiation circular dichroism (SRCD), using the intense light of a synchrotron beam, has greatly expanded the utility of the method, especially as a tool for both structural and functional genomics. These applications take advantage of the enhanced features of SRCD relative to conventional CD: the ability to measure lower wavelength data containing more electronic transitions and hence more structural information, the higher signal-to-noise hence requiring smaller samples, the higher intensity enabling measurements in absorbing buffers and in the presence of lipids and detergents, and the ability to do faster measurements enabling high throughput and time-resolved spectroscopy.This article discusses recent developments in SRCD instrumentation, software, sample preparation and methods of analyses, with particular emphasis on their applications to the study of proteins. These advances have led to new applications in structural genomics (SG), including the potential for fold recognition as a means of target selection and the examination of membrane proteins, a class of proteins usually excluded from SG programmes. Other SG uses include detection of macromolecular interactions as a screen for complex formation, and examination of glycoproteins and sugar components. In functional genomics (FG) new applications include screening for ligand binding as a means of identifying function, and examination of

  17. Study on the bias-dependent effects of proton-induced damage in CdZnTe radiation detectors using ion beam induced charge microscopy.

    Science.gov (United States)

    Gu, Yaxu; Jie, Wanqi; Rong, Caicai; Xu, Lingyan; Xu, Yadong; Lv, Haoyan; Shen, Hao; Du, Guanghua; Guo, Na; Guo, Rongrong; Zha, Gangqiang; Wang, Tao; Xi, Shouzhi

    2016-09-01

    The influence of damage induced by 2MeV protons on CdZnTe radiation detectors is investigated using ion beam induced charge (IBIC) microscopy. Charge collection efficiency (CCE) in irradiated region is found to be degraded above a fluence of 3.3×10(11)p/cm(2) and the energy spectrum is severely deteriorated with increasing fluence. Moreover, CCE maps obtained under the applied biases from 50V to 400V suggests that local radiation damage results in significant degradation of CCE uniformity, especially under low bias, i. e., 50V and 100V. The CCE nonuniformity induced by local radiation damage, however, can be greatly improved by increasing the detector applied bias. This bias-dependent effect of 2MeV proton-induced radiation damage in CdZnTe detectors is attributed to the interaction of electron cloud and radiation-induced displacement defects. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Protective effect of propolis on radiation-induced chromosomal damage on Chinese hamster ovary cells (CHO-K1)

    Energy Technology Data Exchange (ETDEWEB)

    Spigoti, Geyza; Bartolini, Paolo; Okazaki, Kayo [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)], e-mail: kokazaki@ipen.br; Tsutsumi, Shiguetoshi [Amazon Food Ltd., Tokyo (Japan)], e-mail: fwip5138@mb.infoweb.ne.jp

    2009-07-01

    In the last years, particular interest has been given to investigations concerning natural, effective and nontoxic compounds with radioprotective capacity in concert with increasing utilization of different types of ionizing radiation for various applications. Among them, propolis, a resinous mixture of substances collected by honey bees (Apis mellifera) has been considered promising since it presents several advantageous characteristics, i.e., antiinflammatory, anticarcinogenic, antimicrobial and free radical scavenging action. It is, therefore, a direct antioxidant that protects cells and organisms from the adverse effects of ionizing radiation. These relevant biological activities are mainly mediated by the flavonoids, present at relatively high concentrations in the propolis. Considering that the chemical composition and, consequently, the biological activity of propolis is variable according to the environmental plant ecology, the present study was conducted in order to evaluate the radioprotective capacity of Brazilian propolis, collected in the State of Rio Grande do Sul, against genotoxic damages induced by {sup 60}Co {gamma}-radiation in Chinese hamster ovary cells (CHO-K1). for this purpose, micronucleus induction was analyzed concerning irreparable damage, specifically related to DNA double-strand breaks, that are potentially carcinogenic. CHO-K1 cells were submitted to different concentrations of propolis (3 - 33 {mu}g/ml), 1 h before irradiation, with 1 Gy of {gamma} radiation (0.722 Gy/min). The data obtained showed a decreasing tendency in the quantity of radioinduced damage on cells previously treated with propolis. The radioprotective effect was more prominent at higher propolis concentration. The treatment with propolis alone did not induce genotoxic effects on CHO-K1 cells. Beside that, the treatment with propolis, associated or not with radiation, did not influence the kinetics of cellular proliferation. (author)

  19. The Flaxseed-Derived Lignan Phenolic Secoisolariciresinol Diglucoside (SDG Protects Non-Malignant Lung Cells from Radiation Damage

    Directory of Open Access Journals (Sweden)

    Anastasia Velalopoulou

    2015-12-01

    Full Text Available Plant phenolic compounds are common dietary antioxidants that possess antioxidant and anti-inflammatory properties. Flaxseed (FS has been reported to be radioprotective in murine models of oxidative lung damage. Flaxseed’s protective properties are attributed to its main biphenolic lignan, secoisolariciresinol diglucoside (SDG. SDG is a free radical scavenger, shown in cell free systems to protect DNA from radiation-induced damage. The objective of this study was to investigate the in vitro radioprotective efficacy of SDG in murine lung cells. Protection against irradiation (IR-induced DNA double and single strand breaks was assessed by γ-H2AX labeling and alkaline comet assay, respectively. The role of SDG in modulating the levels of cytoprotective enzymes was evaluated by qPCR and confirmed by Western blotting. Additionally, effects of SDG on clonogenic survival of irradiated cells were evaluated. SDG protected cells from IR-induced death and ameliorated DNA damage by reducing mean comet tail length and percentage of γ-H2AX positive cells. Importantly, SDG significantly increased gene and protein levels of antioxidant HO-1, GSTM1 and NQO1. Our results identify the potent radioprotective properties of the synthetic biphenolic SDG, preventing DNA damage and enhancing the antioxidant capacity of normal lung cells; thus, rendering SDG a potential radioprotector against radiation exposure.

  20. Nested radiations and the pulse of angiosperm diversification: increased diversification rates often follow whole genome duplications.

    Science.gov (United States)

    Tank, David C; Eastman, Jonathan M; Pennell, Matthew W; Soltis, Pamela S; Soltis, Douglas E; Hinchliff, Cody E; Brown, Joseph W; Sessa, Emily B; Harmon, Luke J

    2015-07-01

    Our growing understanding of the plant tree of life provides a novel opportunity to uncover the major drivers of angiosperm diversity. Using a time-calibrated phylogeny, we characterized hot and cold spots of lineage diversification across the angiosperm tree of life by modeling evolutionary diversification using stepwise AIC (MEDUSA). We also tested the whole-genome duplication (WGD) radiation lag-time model, which postulates that increases in diversification tend to lag behind established WGD events. Diversification rates have been incredibly heterogeneous throughout the evolutionary history of angiosperms and reveal a pattern of 'nested radiations' - increases in net diversification nested within other radiations. This pattern in turn generates a negative relationship between clade age and diversity across both families and orders. We suggest that stochastically changing diversification rates across the phylogeny explain these patterns. Finally, we demonstrate significant statistical support for the WGD radiation lag-time model. Across angiosperms, nested shifts in diversification led to an overall increasing rate of net diversification and declining relative extinction rates through time. These diversification shifts are only rarely perfectly associated with WGD events, but commonly follow them after a lag period. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  1. Modulation of Radiation-Induced Genetic Damage by HCMV in Peripheral Blood Lymphocytes from a Brain Tumor Case-Control Study

    Energy Technology Data Exchange (ETDEWEB)

    Rourke, Elizabeth A.; Lopez, Mirtha S.; Monroy, Claudia M. [Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030 (United States); Scheurer, Michael E. [Department of Pediatrics and Dan L. Duncan Cancer Center, The Baylor College of Medicine, Houston, TX 77030 (United States); Etzel, Carol J. [Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030 (United States); Albrecht, Thomas [Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, TX 77555 (United States); Bondy, Melissa L.; El-Zein, Randa A., E-mail: relzein@mdanderson.org [Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030 (United States)

    2010-04-12

    Human cytomegalovirus (HCMV) infection occurs early in life and viral persistence remains through life. An association between HCMV infection and malignant gliomas has been reported, suggesting that HCMV may play a role in glioma pathogenesis and could facilitate an accrual of genotoxic damage in the presence of γ-radiation; an established risk factor for gliomas. We tested the hypothesis that HCMV infection modifies the sensitivity of cells to γ-radiation-induced genetic damage. We used peripheral blood lymphocytes (PBLs) from 110 glioma patients and 100 controls to measure the level of chromosome damage and cell death. We evaluated baseline, HCMV-, γ-radiation and HCMV + γ-radiation induced genetic instability with the comprehensive Cytokinesis-Blocked Micronucleus Cytome (CBMN-CYT). HCMV, similar to radiation, induced a significant increase in aberration frequency among cases and controls. PBLs infected with HCMV prior to challenge with γ-radiation led to a significant increase in aberrations as compared to baseline, γ-radiation and HCMV alone. With regards to apoptosis, glioma cases showed a lower percentage of induction following in vitro exposure to γ-radiation and HCMV infection as compared to controls. This strongly suggests that, HCMV infection enhances the sensitivity of PBLs to γ-radiation-induced genetic damage possibly through an increase in chromosome damage and decrease in apoptosis.

  2. Caryocar brasiliense camb protects against genomic and oxidative damage in urethane-induced lung carcinogenesis

    Science.gov (United States)

    Colombo, N.B.R.; Rangel, M.P.; Martins, V.; Hage, M.; Gelain, D.P.; Barbeiro, D.F.; Grisolia, C.K.; Parra, E.R.; Capelozzi, V.L.

    2015-01-01

    The antioxidant effects of Caryocar brasiliense Camb, commonly known as the pequi fruit, have not been evaluated to determine their protective effects against oxidative damage in lung carcinogenesis. In the present study, we evaluated the role of pequi fruit against urethane-induced DNA damage and oxidative stress in forty 8-12 week old male BALB/C mice. An in vivo comet assay was performed to assess DNA damage in lung tissues and changes in lipid peroxidation and redox cycle antioxidants were monitored for oxidative stress. Prior supplementation with pequi oil or its extract (15 µL, 60 days) significantly reduced urethane-induced oxidative stress. A protective effect against DNA damage was associated with the modulation of lipid peroxidation and low protein and gene expression of nitric oxide synthase. These findings suggest that the intake of pequi fruit might protect against in vivo genotoxicity and oxidative stress. PMID:26200231

  3. Silencing of poly(ADP-ribose) glycohydrolase sensitizes lung cancer cells to radiation through the abrogation of DNA damage checkpoint

    Energy Technology Data Exchange (ETDEWEB)

    Nakadate, Yusuke [Shien-Lab, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Department of Bioengineering, Graduate School of Engineering, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585 (Japan); Kodera, Yasuo; Kitamura, Yuka [Shien-Lab, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Tachibana, Taro [Department of Bioengineering, Graduate School of Engineering, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585 (Japan); Tamura, Tomohide [Division of Thoracic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Koizumi, Fumiaki, E-mail: fkoizumi@ncc.go.jp [Division of Thoracic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan)

    2013-11-29

    Highlights: •Radiosensitization by PARG silencing was observed in multiple lung cancer cells. •PAR accumulation was enhanced by PARG silencing after DNA damage. •Radiation-induced G2/M arrest and checkpoint activation were impaired by PARG siRNA. -- Abstract: Poly(ADP-ribose) glycohydrolase (PARG) is a major enzyme that plays a role in the degradation of poly(ADP-ribose) (PAR). PARG deficiency reportedly sensitizes cells to the effects of radiation. In lung cancer, however, it has not been fully elucidated. Here, we investigated whether PARG siRNA contributes to an increased radiosensitivity using 8 lung cancer cell lines. Among them, the silencing of PARG induced a radiosensitizing effect in 5 cell lines. Radiation-induced G2/M arrest was largely suppressed by PARG siRNA in PC-14 and A427 cells, which exhibited significantly enhanced radiosensitivity in response to PARG knockdown. On the other hand, a similar effect was not observed in H520 cells, which did not exhibit a radiosensitizing effect. Consistent with a cell cycle analysis, radiation-induced checkpoint signals were not well activated in the PC-14 and A427 cells when treated with PARG siRNA. These results suggest that the increased sensitivity to radiation induced by PARG knockdown occurs through the abrogation of radiation-induced G2/M arrest and checkpoint activation in lung cancer cells. Our findings indicate that PARG could be a potential target for lung cancer treatments when used in combination with radiotherapy.

  4. Comparing simulations and test data of a radiation damaged charge-coupled device for the Euclid mission

    Science.gov (United States)

    Skottfelt, Jesper; Hall, David J.; Gow, Jason P. D.; Murray, Neil J.; Holland, Andrew D.; Prod'homme, Thibaut

    2017-04-01

    The visible imager instrument on board the Euclid mission is a weak-lensing experiment that depends on very precise shape measurements of distant galaxies obtained by a large charge-coupled device (CCD) array. Due to the harsh radiative environment outside the Earth's atmosphere, it is anticipated that the CCDs over the mission lifetime will be degraded to an extent that these measurements will be possible only through the correction of radiation damage effects. We have therefore created a Monte Carlo model that simulates the physical processes taking place when transferring signals through a radiation-damaged CCD. The software is based on Shockley-Read-Hall theory and is made to mimic the physical properties in the CCD as closely as possible. The code runs on a single electrode level and takes the three-dimensional trap position, potential structure of the pixel, and multilevel clocking into account. A key element of the model is that it also takes device specific simulations of electron density as a direct input, thereby avoiding making any analytical assumptions about the size and density of the charge cloud. This paper illustrates how test data and simulated data can be compared in order to further our understanding of the positions and properties of the individual radiation-induced traps.

  5. Endoscopic findings of rectal mucosal damage after pelvic radiotherapy for cervical carcinoma: correlation of rectal mucosal damage with radiation dose and clinical symptoms

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Tae Gyu; Huh, Seung Jae; Park, Won [Dept. of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2013-06-15

    To describe chronic rectal mucosal damage after pelvic radiotherapy (RT) for cervical cancer and correlate these findings with clinical symptoms and radiation dose. Thirty-two patients who underwent pelvic RT were diagnosed with radiation-induced proctitis based on endoscopy findings. The median follow-up period was 35 months after external beam radiotherapy (EBRT) and intracavitary radiotherapy (ICR). The Vienna Rectoscopy Score (VRS) was used to describe the endoscopic findings and compared to the European Organization for Research and Treatment of Cancer (EORTC)/Radiation Therapy Oncology Group (RTOG) morbidity score and the dosimetric parameters of RT (the ratio of rectal dose calculated at the rectal point [RP] to the prescribed dose, biologically effective dose [BED] at the RP in the ICR and EBRT plans, {alpha}/{beta} = 3). Rectal symptoms were noted in 28 patients (rectal bleeding in 21 patients, bowel habit changes in 6, mucosal stools in 1), and 4 patients had no symptoms. Endoscopic findings included telangiectasia in 18 patients, congested mucosa in 20, ulceration in 5, and stricture in 1. The RP ratio, BEDICR, BEDICR+EBRT was significantly associated with the VRS (RP ratio, median 76.5%; BEDICR, median 37.1 Gy3; BEDICR+EBRT, median 102.5 Gy3; p < 0.001). The VRS was significantly associated with the EORTC/RTOG score (p = 0.038). The most prevalent endoscopic findings of RT-induced proctitis were telangiectasia and congested mucosa. The VRS was significantly associated with the EORTC/RTOG score and RP radiation dose.

  6. An update on the mechanisms and pathophysiological consequences of genomic instability with a focus on ionizing radiation

    OpenAIRE

    Streffer C

    2015-01-01

    Christian Streffer Institute for Medical Radiobiology, University Clinics Essen, Essen, Germany Abstract: The genome of eukaryotic cells is generally instable. DNA damage occurs by endogenous processes and exogenous toxic agents. The efficient DNA repair pathways conserve the genetic information to a large extent throughout the life. However, exposure to genotoxic agents can increase the genomic instability. This phenomenon develops in a delayed manner after approximately 20 and more cell ge...

  7. Ultraviolet Radiation-Induced Cytogenetic Damage in White, Hispanic and Black Skin Melanocytes: A Risk for Cutaneous Melanoma

    Directory of Open Access Journals (Sweden)

    Amrita Dasgupta

    2015-08-01

    Full Text Available Cutaneous Melanoma (CM is a leading cause of cancer deaths, with reports indicating a rising trend in the incidence rate of melanoma among Hispanics in certain U.S. states. The level of melanin pigmentation in the skin is suggested to render photoprotection from the DNA-damaging effects of Ultraviolet Radiation (UVR. UVR-induced DNA damage leads to cytogenetic defects visualized as the formation of micronuclei, multinuclei and polymorphic nuclei in cells, and a hallmark of cancer risk. The causative relationship between Sun exposure and CM is controversial, especially in Hispanics and needs further evaluation. This study was initiated with melanocytes from White, Hispanic and Black neonatal foreskins which were exposed to UVR to assess their susceptibility to UVR-induced modulation of cellular growth, cytogenetic damage, intracellular and released melanin. Our results show that White and Hispanic skin melanocytes with similar levels of constitutive melanin are susceptible to UVR-induced cytogenetic damage, whereas Black skin melanocytes are not. Our data suggest that the risk of developing UVR-induced CM in a skin type is correlated with the level of cutaneous pigmentation and its ethnic background. This study provides a benchmark for further investigation on the damaging effects of UVR as risk for CM in Hispanics.

  8. Ultraviolet Radiation-Induced Cytogenetic Damage in White, Hispanic and Black Skin Melanocytes: A Risk for Cutaneous Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Dasgupta, Amrita [Hampton University Skin of Color Research Institute, Hampton, VA 23668 (United States); Katdare, Meena, E-mail: mkatdare@gmail.com [Hampton University Skin of Color Research Institute, Hampton, VA 23668 (United States); Department of Dermatology, Eastern Virginia Medical School, Norfolk, VA 23507 (United States)

    2015-08-14

    Cutaneous Melanoma (CM) is a leading cause of cancer deaths, with reports indicating a rising trend in the incidence rate of melanoma among Hispanics in certain U.S. states. The level of melanin pigmentation in the skin is suggested to render photoprotection from the DNA-damaging effects of Ultraviolet Radiation (UVR). UVR-induced DNA damage leads to cytogenetic defects visualized as the formation of micronuclei, multinuclei and polymorphic nuclei in cells, and a hallmark of cancer risk. The causative relationship between Sun exposure and CM is controversial, especially in Hispanics and needs further evaluation. This study was initiated with melanocytes from White, Hispanic and Black neonatal foreskins which were exposed to UVR to assess their susceptibility to UVR-induced modulation of cellular growth, cytogenetic damage, intracellular and released melanin. Our results show that White and Hispanic skin melanocytes with similar levels of constitutive melanin are susceptible to UVR-induced cytogenetic damage, whereas Black skin melanocytes are not. Our data suggest that the risk of developing UVR-induced CM in a skin type is correlated with the level of cutaneous pigmentation and its ethnic background. This study provides a benchmark for further investigation on the damaging effects of UVR as risk for CM in Hispanics.

  9. Genomic instability in rat: Breakpoints induced by ionising radiation and interstitial telomeric-like sequences

    Energy Technology Data Exchange (ETDEWEB)

    Camats, Nuria [Institut de Biotecnologia i Biomedicina (IBB), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Departament de Biologia Cel.lular, Fisiologia i Immunologia Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Ruiz-Herrera, Aurora [Departament de Biologia Cel.lular, Fisiologia i Immunologia Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Parrilla, Juan Jose [Servicio de Ginecologia y Obstetricia, Hospital Universitario Virgen de la Arrixaca, Ctra, Madrid-Cartagena, s/n, El Palmar, 30120 Murcia (Spain); Acien, Maribel [Servicio de Ginecologia y Obstetricia, Hospital Universitario Virgen de la Arrixaca, Ctra, Madrid-Cartagena, s/n, El Palmar, 30120 Murcia (Spain); Paya, Pilar [Servicio de Ginecologia y Obstetricia, Hospital Universitario Virgen de la Arrixaca, Ctra, Madrid-Cartagena, s/n, El Palmar, 30120 Murcia (Spain); Giulotto, Elena [Dipartimento di Genetica e Microbiologia Adriano Buzzati Traverso, Universita degli Studi di Pavia, 27100 Pavia (Italy); Egozcue, Josep [Departament de Biologia Cel.lular, Fisiologia i Immunologia Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Garcia, Francisca [Institut de Biotecnologia i Biomedicina (IBB), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Garcia, Montserrat [Institut de Biotecnologia i Biomedicina (IBB), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain) and Departament de Biologia Cellular, Fisiologia i Immunologia Universitat Autonoma de Barcelona, 08193 Barcelona (Spain)]. E-mail: Montserrat.Garcia.Caldes@uab.es

    2006-03-20

    The Norwegian rat (Rattus norvegicus) is the most widely studied experimental species in biomedical research although little is known about its chromosomal structure. The characterisation of possible unstable regions of the karyotype of this species would contribute to the better understanding of its genomic architecture. The cytogenetic effects of ionising radiation have been widely used for the study of genomic instability, and the importance of interstitial telomeric-like sequences (ITSs) in instability of the genome has also been reported in previous studies in vertebrates. In order to describe the unstable chromosomal regions of R. norvegicus, the distribution of breakpoints induced by X-irradiation and ITSs in its karyotype were analysed in this work. For the X-irradiation analysis, 52 foetuses (from 14 irradiated rats) were studied, 4803 metaphases were analysed, and a total of 456 breakpoints induced by X-rays were detected, located in 114 chromosomal bands, with 25 of them significantly affected by X-irradiation (hot spots). For the analysis of ITSs, three foetuses (from three rats) were studied, 305 metaphases were analysed and 121 ITSs were detected, widely distributed in the karyotype of this species. Seventy-six percent of all hot spots analysed in this study were co-localised with ITSs.

  10. Purine and its analogues and radiation damage in Bacillus megaterium spores

    Energy Technology Data Exchange (ETDEWEB)

    Powers, E.L.

    1986-12-01

    As an extension of results obtained from radiation studies on caffeine both in other laboratories and more recently in this laboratory using the bacterial spore as the test system, six compounds with chemical structures closely resembling that of caffeine were tested as radiation modifiers. Of these compounds, purine, adenine and hypoxanthine resembled caffeine in sensitizing spores to radiation, while theobromine, xanthine and theophylline did not. These responses are discussed in relation to the electron sequestration hypothesis of cellular sensitization to high-energy radiation.

  11. Comparison of space flight and heavy ion radiation induced genomic/epigenomic mutations in rice (Oryza sativa)

    Science.gov (United States)

    Shi, Jinming; Lu, Weihong; Sun, Yeqing

    2014-04-01

    Rice seeds, after space flight and low dose heavy ion radiation treatment were cultured on ground. Leaves of the mature plants were obtained for examination of genomic/epigenomic mutations by using amplified fragment length polymorphism (AFLP) and methylation sensitive amplification polymorphism (MSAP) method, respectively. The mutation sites were identified by fragment recovery and sequencing. The heritability of the mutations was detected in the next generation. Results showed that both space flight and low dose heavy ion radiation can induce significant alterations on rice genome and epigenome (P < 0.05). For both genetic and epigenetic assays, while there was no significant difference in mutation rates and their ability to be inherited to the next generation, the site of mutations differed between the space flight and radiation treated groups. More than 50% of the mutation sites were shared by two radiation treated groups, radiated with different LET value and dose, while only about 20% of the mutation sites were shared by space flight group and radiation treated group. Moreover, in space flight group, we found that DNA methylation changes were more prone to occur on CNG sequence than CG sequence. Sequencing results proved that both space flight and heavy ion radiation induced mutations were widely spread on rice genome including coding region and repeated region. Our study described and compared the characters of space flight and low dose heavy ion radiation induced genomic/epigenomic mutations. Our data revealed the mechanisms of application of space environment for mutagenesis and crop breeding. Furthermore, this work implicated that the nature of mutations induced under space flight conditions may involve factors beyond ion radiation.

  12. Final report- Links between persistent DNA damage, genome instability, and aging

    Energy Technology Data Exchange (ETDEWEB)

    Dynan, William S. [Emory Univ., Atlanta, GA (United States)

    2016-11-30

    The goal of the project was to determine whether high linear energy transfer (LET) space radiation produces the same or different effects as low doses of terrestrial (low-LET) radiation. The work used the Japanese medaka fish (Oryzias latipes) as a vertebrate model organism that can be maintained in large numbers at low cost for lifetime studies. To determine whether simulated space radiation produced the same or different effects as low doses of low-LET radiation, medaka embryos were irradiated at doses ranging from 0.1 to 9 Gray (Gy) of high-LET charged particle radiation (1000 MeV/nucleon 56-Fe ions) or 0.1 Gy to 27 Gy of low-LET gamma-rays. To examine the effect of irradiation on potential biomarkers, the population was sampled at intervals from 8 to 28 months post-irradiation and liver tissue was subjected to histological and molecular analysis. Charged particle radiation and aging contributed synergistically to accumulation of lipid oxidation products, which are a marker of chronic oxidative stress. This was mirrored by a decline in mRNA encoding the transcriptional activator PPARGC1A, which is required for mitochondrial maintenance and for defense against oxidative stress. Additionally, mitochondria had an elongated and enlarged ultrastructure. Depending on the endpoint, effects of gamma-rays in the same dose range were either lesser or not detected. Together, results indicate that a single exposure to high-LET, but not low-LET radiation, early in life, leads to increased oxidative stress throughout the normal lifespan of the individual.

  13. Genomic instability and radiation risk in molecular pathways to colon cancer.

    Directory of Open Access Journals (Sweden)

    Jan Christian Kaiser

    Full Text Available Colon cancer is caused by multiple genomic alterations which lead to genomic instability (GI. GI appears in molecular pathways of microsatellite instability (MSI and chromosomal instability (CIN with clinically observed case shares of about 15-20% and 80-85%. Radiation enhances the colon cancer risk by inducing GI, but little is known about different outcomes for MSI and CIN. Computer-based modelling can facilitate the understanding of the phenomena named above. Comprehensive biological models, which combine the two main molecular pathways to colon cancer, are fitted to incidence data of Japanese a-bomb survivors. The preferred model is selected according to statistical criteria and biological plausibility. Imprints of cell-based processes in the succession from adenoma to carcinoma are identified by the model from age dependences and secular trends of the incidence data. Model parameters show remarkable compliance with mutation rates and growth rates for adenoma, which has been reported over the last fifteen years. Model results suggest that CIN begins during fission of intestinal crypts. Chromosomal aberrations are generated at a markedly elevated rate which favors the accelerated growth of premalignant adenoma. Possibly driven by a trend of Westernization in the Japanese diet, incidence rates for the CIN pathway increased notably in subsequent birth cohorts, whereas rates pertaining to MSI remained constant. An imbalance between number of CIN and MSI cases began to emerge in the 1980s, whereas in previous decades the number of cases was almost equal. The CIN pathway exhibits a strong radio-sensitivity, probably more intensive in men. Among young birth cohorts of both sexes the excess absolute radiation risk related to CIN is larger by an order of magnitude compared to the MSI-related risk. Observance of pathway-specific risks improves the determination of the probability of causation for radiation-induced colon cancer in individual patients

  14. Image-based quantitative determination of DNA damage signal reveals a threshold for G2 checkpoint activation in response to ionizing radiation

    National Research Council Canada - National Science Library

    Ishikawa, Aya; Yamauchi, Motohiro; Suzuki, Keiji; Yamashita, Shunichi

    2010-01-01

    ...). As growth of ionizing radiation (IR)-induced foci amplifies the ATM-dependent DNA damage signal, the formation of discrete foci plays a crucial role in cell cycle checkpoint activation, especially in cells exposed to lower doses of IR...

  15. Collateral DNA damage produced by genome-editing drones: exception or rule?

    Science.gov (United States)

    Canela, Andres; Stanlie, Andre; Nussenzweig, André

    2015-05-21

    In the recent issue of Nature Biotechnology, Frock et al. (2015) developed an elegant technique to capture translocation partners that can be utilized to determine off-target regions of genome-editing endonucleases as well as endogenous mutators at nucleotide resolution. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Gross genomic damage measured by DNA image cytometry independently predicts gastric cancer patient survival

    NARCIS (Netherlands)

    Belien, J.A.M.; Buffart, T.E.; Gill, A.; Broeckaert, M.A.M.; Quirke, P.; Meijer, G.A.; Grabsch, H.

    2009-01-01

    BACKGROUND: DNA aneuploidy reflects gross genomic changes. It can be measured by flow cytometry (FCM-DNA) or image cytometry (ICM-DNA). In gastric cancer, the prevalence of DNA aneuploidy has been reported to range from 27 to 100%, with conflicting associations with clinicopathological variables.

  17. The prevention of radiation-induced DNA damage and apoptosis in human intestinal epithelial cells by salvianic acid A

    Directory of Open Access Journals (Sweden)

    Yanjun Zhang

    2014-07-01

    Full Text Available The topic of radiation always provokes public debate, and the uses of radiation for therapeutic and other purposes have always been associated with some anxiety. Salvia miltiorrhiza Bunge has been widely used for the treatment of various diseases including cerebrovascular diseases, coronary artery diseases, and myocardial infarction. Salvianolic acid A (SAA d (+-(3,4-dihydroxyphenyl lactic acid is the principal effective, watersoluble constituent of Salvia miltiorrhiza Bunge. In our present study, radiation-induced DNA damage and apoptosis in human intestinal epithelial cells (HIEC in the presence and absence of SAA were examined. We investigated the effects of SAA on ROS formation and the activity of enzymatic antioxidants (SOD, the lipid peroxidative index and the levels of non-enzymatic antioxidant (GSH. Finally, we investigated whether the reduction of radiation-induced cell death caused by SAA might be related to mitochondria-dependent apoptosis. Present findings indicate that SAA is a promising radioprotective agent with a strong antioxidant activity. SAA exerted its protective action on the proliferative activity of HIEC cells as evidenced by decreased cytotoxicity after exposure to γ-radiation. It is possible that SAA achieved its radioprotective action, at least in part, by enhancing DNA repair and the activity of antioxidant enzymes, by scavenging ROS and by inhibiting the mitochondria-dependent apoptotic pathway.

  18. Organisms posses enzymes that function in the repair of DNA damaged by radiations, chemicals and metabolic events

    Energy Technology Data Exchange (ETDEWEB)

    Mizuma, Nagayo [Kyoto Univ., Kumatori, Osaka (Japan). Research Reactor Inst.

    1998-01-01

    This report briefly describes the studies on the mechanism of in vivo DNA repairing by the author in Research Reactor Institute, Kyoto Univ. for the past 30 years. First, the ability of UV radiation to induce transformation was investigated with viral DNA. The formation of thymine-thymine dimer was found harmful to organisms and such dimers were removable by UV-radiation at a low frequency. The mutability was determined in three different E.coli strains with mutator gene, mutT, mutS or mutL. The ability to excise 8-oxoguanin developed in primer DNA was deficient in mutT and miss-pairing left after DNA replication could not be recovered in mutL and mutS strains. Further, DNA repairing mechanism was investigated in other microorganisms; single-strand cleavage caused by exposure to BNCB radiation (boron-neutron-captured beam) could not be repaired in E. coli. Whereas for Deinococcus radiodurans, of which survival rate was not decreased by {gamma}-ray radiation at 5 kGy or less, it was found that its single-strand DNA was damaged by {gamma}-radiation to smaller molecules, but it was mended to the similar size to that in the non-irradiated cells during incubation. In addition, the transformation frequency was also recovered in the actinomycetes. Thus, it was demonstrated that de novo protein synthesis is necessary for the repairing system of recombination. (M.N.)

  19. Site specific X-ray induced changes in organic and metal organic compounds and their influence on global radiation damage

    Energy Technology Data Exchange (ETDEWEB)

    Heintz, Desiree Ellen

    2012-07-15

    The aim of this work was to systematically investigate the effects of specific and global X-ray radiation damage to biological samples and obtain a conclusive model to describe the underlying principles. Based on the systematic studies performed in this work, it was possible to propose two conclusive mechanisms to describe X-ray induced photoreduction and global radiation damage. The influence of chemical composition, temperature and solvent on X-ray induced photoreduction was investigated by X-ray Absorption Near Edge Spectroscopy and single crystal X-ray diffraction of two B12 cofactors - cyano- and methylcobalamin - as well as iron(II) and iron(III) complexes. The obtained results revealed that X-ray induced photoreduction is a ligand dependent process, with a redox reaction taking place within the complex. It could further be shown that selective hydrogen abstraction plays an important role in the process of X-ray induced photoreduction. Based on the experimental results of this work, a model to describe X-ray induced photoreduction of metal organic complexes could be proposed. The process of X-ray induced hydrogen abstraction was further investigated in a combined X-ray and neutron diffraction study on the amino acids L-serine and L-alanine, which were used as model compounds for proteins, and the nucleoside deoxythymidine (thymidine) as a model for DNA. A damage mechanism for L-serine could be found. It involves the abstraction of two hydrogen atoms, one from the hydroxyl group and one from the adjacent methylene group. Such a hydrogen abstraction results in the formation of a carbonyl group. X-ray diffraction measurements on cyano- and methylcobalamin as well as on three metal amino acid complexes, containing nickel(II) and copper(II), respectively, were conducted to investigate the contribution of X-ray induced photoreduction to global radiation damage. Results from these measurements combined with the results from L-serine, L-alanine and thymidine allowed

  20. Oxidative Genome Damage and Its Repair in Neurodegenerative Diseases: Function of Transition Metals as a Double-Edged Sword

    Science.gov (United States)

    Hegde, Muralidhar L.; Hegde, Pavana M.; Rao, K.S.J.; Mitra, Sankar

    2013-01-01

    The neurons in the central nervous system (CNS) with high O2 consumption and prolonged life span are chronically exposed to high levels of reactive oxygen species (ROS). Accumulation of ROS-induced genome damage in the form of oxidized bases and single-strand breaks (SSBs) as well as their defective or reduced repair in the brain has been implicated in the etiology of various neurological disorders including Alzheimer’s/Parkinson’s diseases (AD/PD). Although inactivating mutations in some DNA repair genes have been linked to hereditary neurodegenerative diseases, the underlying mechanisms of repair deficiencies for the sporadic diseases is not understood. The ROS-induced DNA damages are predominantly repaired via highly conserved and regulated base excision/SSB repair (BER/SSBR) pathway. We recently made an interesting discovery that transition metals iron (Fe) and copper (Cu) which accumulate excessively in the brains of AD, PD and other neurodegenerative diseases, act as a ‘double-edged sword’ by inducing genotoxic ROS and inhibiting DNA damage repair at the same time. These metals inhibit the base excision activity of NEIL family DNA glycosylases by oxidizing them, changing their structure, and inhibiting their binding to downstream repair proteins. Metal chelators and reducing agents partially reverse the inhibition, while curcumin with both chelating and reducing activities reverses the inhibition nearly completely. In this review, we have discussed the possible etiological linkage of BER/SSBR defects to neurodegenerative diseases and therapeutic potential of metal chelators in restoring DNA repair capacity. PMID:21441656

  1. Study of radiation damage restoration and antimony ions redistribution in Si(1 0 0) and Si(1 1 1) crystals

    Science.gov (United States)

    Labbani, R.; Halimi, R.; Chafi, Z.

    2002-03-01

    In this work, we study the radiation damage restoration and antimony ions redistribution into and oriented silicon substrates. The samples are implanted with antimony to a dose of 5×10 14 Sb + cm -2 at 60 keV energy, then annealed under oxygen atmosphere at 900°C, 30 min. The thin layer of SiO 2 (which is formed on Si surface by dry oxidation and expected to prevent any loss of Sb + dopant during Si recovery) is removed by a 10% HF solution. The specimens are analyzed by H + Rutherford Backscattering Spectrometry (RBS) operating at 0.3 MeV energy in both random and channelling modes. The values of the projected range, Rp, the standard deviation, Δ Rp, and the dose of antimony ions, which are estimated with a simple program, are in agreement with tabulated ones. It is also shown that the surface damage restoration is better for Si(1 0 0) samples than for Si(1 1 1) ones, in other words, the radiation damage is more significant in Si(1 1 1) substrates. Moreover, for both Si(1 0 0) and Si(1 1 1), it has been noticed that an important quantity of implanted antimony is localized in substitutional silicon sites. This fact is more pronounced in Si(1 0 0). On the other hand, it has been found, for Si(1 0 0) substrates only, that antimony ions are redistributed into the silicon lattice following a Gaussian law.

  2. Mechanism of cluster DNA damage repair in response to high-atomic number and energy particles radiation

    Energy Technology Data Exchange (ETDEWEB)

    Asaithamby, Aroumougame, E-mail: Aroumougame.Asaithamy@UTsouthwestern.edu [Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390 (United States); Chen, David J., E-mail: David.Chen@UTsouthwestern.edu [Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390 (United States)

    2011-06-03

    Low-linear energy transfer (LET) radiation (i.e., {gamma}- and X-rays) induces DNA double-strand breaks (DSBs) that are rapidly repaired (rejoined). In contrast, DNA damage induced by the dense ionizing track of high-atomic number and energy (HZE) particles is slowly repaired or is irreparable. These unrepaired and/or misrepaired DNA lesions may contribute to the observed higher relative biological effectiveness for cell killing, chromosomal aberrations, mutagenesis, and carcinogenesis in HZE particle irradiated cells compared to those tre