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Sample records for repair radiation damage

  1. UV Radiation Damage and Bacterial DNA Repair Systems

    Science.gov (United States)

    Zion, Michal; Guy, Daniel; Yarom, Ruth; Slesak, Michaela

    2006-01-01

    This paper reports on a simple hands-on laboratory procedure for high school students in studying both radiation damage and DNA repair systems in bacteria. The sensitivity to ultra-violet (UV) radiation of both "Escherichia coli" and "Serratia marcescens" is tested by radiating them for varying time periods. Two growth temperatures are used in…

  2. Extra lethal damage due to residual incompletely repaired sublethal damage in hyperfractionated and continuous radiation treatment

    Energy Technology Data Exchange (ETDEWEB)

    Chen, J.; van de Geijn, J.; Goffman, T. (ROB, DCT, NCI, NIH, Bethesda, Maryland 20892 (US))

    1991-05-01

    In the conventional linear--quadratic model of single-dose response, the {alpha} and {beta} terms reflect lethal damage created {ital during} the delivery of a dose, from two different presumed molecular processes, one linear with dose, the other quadratic. With the conventional one-fraction-per-day (or less) regimens, the sublethal damage (SLD), presumably repairing exponentially over time, is essentially completely fixed by the time of the next dose of radiation. If this assumption is true, the effects of subsequent fractions of radiation should be independent, that is, there should be little, if any, reversible damage left from previous fractions, at the time of the next dose. For multiple daily fractions, or for the limiting case, continuous radiation, this simplification may overlook damaged cells that have had insufficient time for repair. A generalized method is presented for accounting for extra lethal damage (ELD) arising from such residual SLD for hyperfractionation and continuous irradiation schemes. It may help to predict differences in toxicity and tumor control, if any, obtained with unconventional'' treatment regimens. A key element in the present model is the finite size and the dynamic character of the pool of sublethal damage. Besides creating the usual linear and quadratic components of lethal damage, each new fraction converts a certain fraction of the existing SLD into ELD, and creates some new SLD.

  3. DNA repair pathways in radiation induced cellular damage: a molecular approach

    NARCIS (Netherlands)

    L.R. van Veelen (Lieneke)

    2005-01-01

    markdownabstract__Abstract__ DNA damage, especially double-strand breaks, can be induced by endogenous or exogenous darnaging agents, such as ionizing radiation. Repair of DNA damage is very important in maintaining genomic stability. Incorrect repair may lead to chromosomal aberrations,

  4. DNA repair pathways in radiation induced cellular damage: a molecular approach

    NARCIS (Netherlands)

    L.R. van Veelen (Lieneke)

    2005-01-01

    markdownabstract__Abstract__ DNA damage, especially double-strand breaks, can be induced by endogenous or exogenous darnaging agents, such as ionizing radiation. Repair of DNA damage is very important in maintaining genomic stability. Incorrect repair may lead to chromosomal aberrations, translocat

  5. Perspectives in radiation biophysics: From radiation track structure simulation to mechanistic models of DNA damage and repair

    Science.gov (United States)

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

    2016-11-01

    In radiation targeted therapy and genetic risk estimation of low dose radiation protection there is a crucial need for full description of DNA damage response and repair (DDR) leading to cell death and cell mutation. We propose such a description can be arrived through realistic track-structure simulations together with mechanistic mathematical formulation of DDR and the availability of experimental data for testing the proof of principle. In this paper we review briefly first the state of the art in DNA damage and repair, and then the recent advances in the physics of track structure which represents an essential tool in radiation biophysics.

  6. Non-DBS DNA Repair Genes Regulate Radiation-induced Cytogenetic Damage Repair and Cell Cycle Progression

    Science.gov (United States)

    Zhang, Ye; Rohde, Larry H.; Emami, Kamal; Casey, Rachael; Wu, Honglu

    2008-01-01

    Changes of gene expression profile are one of the most important biological responses in living cells after ionizing radiation (IR) exposure. Although some studies have shown that genes up-regulated by IR may play important roles in DNA damage repair, the relationship between the regulation of gene expression by IR, particularly genes not known for their roles in DSB repair, and its impact on cytogenetic responses has not been systematically studied. In the present study, the expression of 25 genes selected on the basis of their transcriptional changes in response to IR was individually knocked down by transfection with small interfering RNA in human fibroblast cells. The purpose of this study is to identify new roles of these selected genes on regulating DSB repair and cell cycle progression , as measured in the micronuclei formation and chromosome aberration. In response to IR, the formation of MN was significantly increased by suppressed expression of 5 genes: Ku70 in the DSB repair pathway, XPA in the NER pathway, RPA1 in the MMR pathway, and RAD17 and RBBP8 in cell cycle control. Knocked-down expression of 4 genes (MRE11A, RAD51 in the DSB pathway, SESN1, and SUMO1) significantly inhibited cell cycle progression, possibly because of severe impairment of DNA damage repair. Furthermore, loss of XPA, P21, or MLH1 expression resulted in both significantly enhanced cell cycle progression and increased yields of chromosome aberrations, indicating that these gene products modulate both cell cycle control and DNA damage repair. Most of the 11 genes that affected cytogenetic responses are not known to have clear roles influencing DBS repair. Nine of these 11 genes were up-regulated in cells exposed to gamma radiation, suggesting that genes transcriptionally modulated by IR were critical to regulate the biological consequences after IR.

  7. Non-DBS DNA Repair Genes Regulate Radiation-induced Cytogenetic Damage Repair and Cell Cycle Progression

    Science.gov (United States)

    Zhang, Ye; Rohde, Larry H.; Emami, Kamal; Casey, Rachael; Wu, Honglu

    2008-01-01

    Changes of gene expression profile are one of the most important biological responses in living cells after ionizing radiation (IR) exposure. Although some studies have shown that genes up-regulated by IR may play important roles in DNA damage repair, the relationship between the regulation of gene expression by IR, particularly genes not known for their roles in DSB repair, and its impact on cytogenetic responses has not been systematically studied. In the present study, the expression of 25 genes selected on the basis of their transcriptional changes in response to IR was individually knocked down by transfection with small interfering RNA in human fibroblast cells. The purpose of this study is to identify new roles of these selected genes on regulating DSB repair and cell cycle progression , as measured in the micronuclei formation and chromosome aberration. In response to IR, the formation of MN was significantly increased by suppressed expression of 5 genes: Ku70 in the DSB repair pathway, XPA in the NER pathway, RPA1 in the MMR pathway, and RAD17 and RBBP8 in cell cycle control. Knocked-down expression of 4 genes (MRE11A, RAD51 in the DSB pathway, SESN1, and SUMO1) significantly inhibited cell cycle progression, possibly because of severe impairment of DNA damage repair. Furthermore, loss of XPA, P21, or MLH1 expression resulted in both significantly enhanced cell cycle progression and increased yields of chromosome aberrations, indicating that these gene products modulate both cell cycle control and DNA damage repair. Most of the 11 genes that affected cytogenetic responses are not known to have clear roles influencing DBS repair. Nine of these 11 genes were up-regulated in cells exposed to gamma radiation, suggesting that genes transcriptionally modulated by IR were critical to regulate the biological consequences after IR.

  8. DNA damage and repair in plants under ultraviolet and ionizing radiations.

    Science.gov (United States)

    Gill, Sarvajeet S; Anjum, Naser A; Gill, Ritu; Jha, Manoranjan; Tuteja, Narendra

    2015-01-01

    Being sessile, plants are continuously exposed to DNA-damaging agents present in the environment such as ultraviolet (UV) and ionizing radiations (IR). Sunlight acts as an energy source for photosynthetic plants; hence, avoidance of UV radiations (namely, UV-A, 315-400 nm; UV-B, 280-315 nm; and UV-C, exposure, plants make use of several DNA repair mechanisms. In the light of recent breakthrough, the current minireview (a) introduces UV/IR and overviews UV/IR-mediated DNA damage products and (b) critically discusses the biochemistry and genetics of major pathways responsible for the repair of UV/IR-accrued DNA damage. The outcome of the discussion may be helpful in devising future research in the current context.

  9. Delayed repair of radiation induced clustered DNA damage: Friend or foe?

    Energy Technology Data Exchange (ETDEWEB)

    Eccles, Laura J., E-mail: laura.eccles@rob.ox.ac.uk [DNA Damage Group, Gray Institute for Radiation Oncology and Biology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ (United Kingdom); O' Neill, Peter, E-mail: peter.oneill@rob.ox.ac.uk [DNA Damage Group, Gray Institute for Radiation Oncology and Biology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ (United Kingdom); Lomax, Martine E., E-mail: martine.lomax@rob.ox.ac.uk [DNA Damage Group, Gray Institute for Radiation Oncology and Biology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ (United Kingdom)

    2011-06-03

    A signature of ionizing radiation exposure is the induction of DNA clustered damaged sites, defined as two or more lesions within one to two helical turns of DNA by passage of a single radiation track. Clustered damage is made up of double strand breaks (DSB) with associated base lesions or abasic (AP) sites, and non-DSB clusters comprised of base lesions, AP sites and single strand breaks. This review will concentrate on the experimental findings of the processing of non-DSB clustered damaged sites. It has been shown that non-DSB clustered damaged sites compromise the base excision repair pathway leading to the lifetime extension of the lesions within the cluster, compared to isolated lesions, thus the likelihood that the lesions persist to replication and induce mutation is increased. In addition certain non-DSB clustered damaged sites are processed within the cell to form additional DSB. The use of E. coli to demonstrate that clustering of DNA lesions is the major cause of the detrimental consequences of ionizing radiation is also discussed. The delayed repair of non-DSB clustered damaged sites in humans can be seen as a 'friend', leading to cell killing in tumour cells or as a 'foe', resulting in the formation of mutations and genetic instability in normal tissue.

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

    Science.gov (United States)

    Sterpone, Silvia; Cozzi, Renata

    2010-01-01

    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. PMID:20798883

  11. 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.

  12. DNA Damage and Repair in Plants under Ultraviolet and Ionizing Radiations

    Directory of Open Access Journals (Sweden)

    Sarvajeet S. Gill

    2015-01-01

    Full Text Available Being sessile, plants are continuously exposed to DNA-damaging agents present in the environment such as ultraviolet (UV and ionizing radiations (IR. Sunlight acts as an energy source for photosynthetic plants; hence, avoidance of UV radiations (namely, UV-A, 315–400 nm; UV-B, 280–315 nm; and UV-C, <280 nm is unpreventable. DNA in particular strongly absorbs UV-B; therefore, it is the most important target for UV-B induced damage. On the other hand, IR causes water radiolysis, which generates highly reactive hydroxyl radicals (OH• and causes radiogenic damage to important cellular components. However, to maintain genomic integrity under UV/IR exposure, plants make use of several DNA repair mechanisms. In the light of recent breakthrough, the current minireview (a introduces UV/IR and overviews UV/IR-mediated DNA damage products and (b critically discusses the biochemistry and genetics of major pathways responsible for the repair of UV/IR-accrued DNA damage. The outcome of the discussion may be helpful in devising future research in the current context.

  13. Excision repair of UV radiation-induced DNA damage in Caenorhabditis elegans

    Energy Technology Data Exchange (ETDEWEB)

    Hartman, P.S.; Hevelone, J.; Dwarakanath, V.; Mitchell, D.L. (Texas Christian Univ., Fort Worth (USA))

    1989-06-01

    Radioimmunoassays were used to monitor the removal of antibody-binding sites associated with the two major UV radiation-induced DNA photoproducts (cyclobutane dimers and (6-4) photoproducts). Unlike with cultured human cells, where (6-4) photoproducts are removed more rapidly than cyclobutane dimers, the kinetics of repair were similar for both lesions. Repair capacity in wild type diminished throughout development. The radioimmunoassays were also employed to confirm the absence of photoreactivation in C. elegans. In addition, three radiation-sensitive mutants (rad-1, rad-2, rad-7) displayed normal repair capacities. An excision defect was much more pronounced in larvae than embryos in the fourth mutant tested (rad-3). This correlates with the hypersensitivity pattern of this mutant and suggests that DNA repair may be developmentally regulated in C. elegans. The mechanism of DNA repair in C. elegans as well as the relationship between the repair of specific photoproducts and UV radiation sensitivity during development are discussed.

  14. Nicotinamide enhances repair of ultraviolet radiation-induced DNA damage in primary melanocytes.

    Science.gov (United States)

    Thompson, Benjamin C; Surjana, Devita; Halliday, Gary M; Damian, Diona L

    2014-07-01

    Cutaneous melanoma is a significant cause of morbidity and mortality. Nicotinamide is a safe, widely available vitamin that reduces the immune suppressive effects of UV, enhances DNA repair in keratinocytes and has shown promise in the chemoprevention of non-melanoma skin cancer. Here, we report the effect of nicotinamide on DNA damage and repair in primary human melanocytes. Nicotinamide significantly enhanced the repair of oxidative DNA damage (8-oxo-7,8-dihydro-2'-deoxyguanosine) and cyclobutane pyrimidine dimers induced by UV exposure. It also enhanced the repair of 8-oxo-7,8-dihydro-2'-deoxyguanosine induced by the culture conditions in unirradiated melanocytes. A significant increase in the percentage of melanocytes undergoing unscheduled but not scheduled DNA synthesis was observed, confirming that nicotinamide enhances DNA repair in human melanocytes. In summary, nicotinamide, by enhancing DNA repair in melanocytes, is a potential agent for the chemoprevention of cutaneous melanoma.

  15. 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.

  16. Nrf2 facilitates repair of radiation induced DNA damage through homologous recombination repair pathway in a ROS independent manner in cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Jayakumar, Sundarraj; Pal, Debojyoti; Sandur, Santosh K., E-mail: sskumar@barc.gov.in

    2015-09-15

    Highlights: • Nrf2 inhibition in A549 cells led to attenuated DNA repair and radiosensitization. • Influence of Nrf2 on DNA repair is not linked to its antioxidant function. • Nrf2 influences DNA repair through homologous recombination (HR) repair pathway. • Many genes involved in HR pathway show ARE sequences in their upstream region. - Abstract: Nrf2 is a redox sensitive transcription factor that is involved in the co-ordinated transcription of genes involved in redox homeostasis. But the role of Nrf2 in DNA repair is not investigated in detail. We have employed A549 and MCF7 cells to study the role of Nrf2 on DNA repair by inhibiting Nrf2 using all-trans retinoic acid (ATRA) or by knock down approach prior to radiation exposure (4 Gy). DNA damage and repair analysis was studied by γH2AX foci formation and comet assay. Results suggested that the inhibition of Nrf2 in A549 or MCF7 cells led to significant slowdown in DNA repair as compared to respective radiation controls. The persistence of residual DNA damage even in the presence of free radical scavenger N-acetyl cysteine, suggested that the influence of Nrf2 on DNA repair was not linked to its antioxidant functions. Further, its influence on non-homologous end joining repair pathway was studied by inhibiting both Nrf2 and DNA-PK together. This led to synergistic reduction of survival fraction, indicating that Nrf2 may not be influencing the NHEJ pathway. To investigate the role of homologous recombination repair (HR) pathway, RAD51 foci formation was monitored. There was a significant reduction in the foci formation in cells treated with ATRA or shRNA against Nrf2 as compared to their respective radiation controls. Further, Nrf2 inhibition led to significant reduction in mRNA levels of RAD51. BLAST analysis was also performed on upstream regions of DNA repair genes to identify antioxidant response element and found that many repair genes that are involved in HR pathway may be regulated by Nrf2

  17. 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...

  18. 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.

  19. Nicotinamide enhances repair of ultraviolet radiation-induced DNA damage in human keratinocytes and ex vivo skin.

    Science.gov (United States)

    Surjana, Devita; Halliday, Gary M; Damian, Diona L

    2013-05-01

    Nicotinamide (vitamin B3) protects from ultraviolet (UV) radiation-induced carcinogenesis in mice and from UV-induced immunosuppression in mice and humans. Recent double-blinded randomized controlled Phase 2 studies in heavily sun-damaged individuals have shown that oral nicotinamide significantly reduces premalignant actinic keratoses, and may reduce new non-melanoma skin cancers. Nicotinamide is a precursor of nicotinamide adenine dinucleotide (NAD(+)), an essential coenzyme in adenosine triphosphate (ATP) production. Previously, we showed that nicotinamide prevents UV-induced ATP decline in HaCaT keratinocytes. Energy-dependent DNA repair is a key determinant of cellular survival after exposure to DNA-damaging agents such as UV radiation. Hence, in this study we investigated whether nicotinamide protection from cellular energy loss influences DNA repair. We treated HaCaT keratinocytes with nicotinamide and exposed them to low-dose solar-simulated UV (ssUV). Excision repair was quantified using an assay of unscheduled DNA synthesis. Nicotinamide increased both the proportion of cells undergoing excision repair and the repair rate in each cell. We then investigated ssUV-induced cyclobutane pyrimidine dimers (CPDs) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8oxoG) formation and repair by comet assay in keratinocytes and with immunohistochemistry in human skin. Nicotinamide reduced CPDs and 8oxoG in both models and the reduction appeared to be due to enhancement of DNA repair. These results show that nicotinamide enhances two different pathways for repair of UV-induced photolesions, supporting nicotinamide's potential as an inexpensive, convenient and non-toxic agent for skin cancer chemoprevention.

  20. Mechanistic Modelling of DNA Repair and Cellular Survival Following Radiation-Induced DNA Damage

    Science.gov (United States)

    McMahon, Stephen J.; Schuemann, Jan; Paganetti, Harald; Prise, Kevin M.

    2016-09-01

    Characterising and predicting the effects of ionising radiation on cells remains challenging, with the lack of robust models of the underlying mechanism of radiation responses providing a significant limitation to the development of personalised radiotherapy. In this paper we present a mechanistic model of cellular response to radiation that incorporates the kinetics of different DNA repair processes, the spatial distribution of double strand breaks and the resulting probability and severity of misrepair. This model enables predictions to be made of a range of key biological endpoints (DNA repair kinetics, chromosome aberration and mutation formation, survival) across a range of cell types based on a set of 11 mechanistic fitting parameters that are common across all cells. Applying this model to cellular survival showed its capacity to stratify the radiosensitivity of cells based on aspects of their phenotype and experimental conditions such as cell cycle phase and plating delay (correlation between modelled and observed Mean Inactivation Doses R2 > 0.9). By explicitly incorporating underlying mechanistic factors, this model can integrate knowledge from a wide range of biological studies to provide robust predictions and may act as a foundation for future calculations of individualised radiosensitivity.

  1. Radiosensitivity and capacity for radiation-induced sublethal damage repair of canine transitional cell carcinoma (TCC) cell lines.

    Science.gov (United States)

    Parfitt, S L; Milner, R J; Salute, M E; Hintenlang, D E; Farese, J P; Bacon, N J; Bova, F J; Rajon, D A; Lurie, D M

    2011-09-01

    Understanding the inherent radiosensitivity and repair capacity of canine transitional cell carcinoma (TCC) can aid in optimizing radiation protocols to treat this disease. The objective of this study was to evaluate the parameters surviving fraction at 2 Gy (SF(2) ), α/β ratio and capacity for sublethal damage repair (SLDR) in response to radiation. Dose-response and split-dose studies were performed using the clonogenic assay. The mean SF(2) for three established TCC cell lines was high at 0.61. All the three cell lines exhibited a low to moderate α/β ratio, with the mean being 3.27. Two cell lines exhibited statistically increased survival at 4 and 24 h in the dose-response assay. Overall, our results indicate that the cell lines are moderately radioresistant, have a high repair capacity and behave similarly to a late-responding normal tissue. These findings indicate that the radiation protocols utilizing higher doses with less fractionation may be more effective for treating TCC.

  2. DSB repair model for mammalian cells in early S and G1 phases of the cell cycle: application to damage induced by ionizing radiation of different quality.

    Science.gov (United States)

    Taleei, Reza; Girard, Peter M; Nikjoo, Hooshang

    2015-02-01

    The purpose of this work is to test the hypothesis that kinetics of double strand breaks (DSB) repair is governed by complexity of DSB. To test the hypothesis we used our recent published mechanistic mathematical model of DSB repair for DSB induced by selected protons, deuterons, and helium ions of different energies representing radiations of different qualities. In light of recent advances in experimental and computational techniques, the most appropriate method to study cellular responses in radiation therapy, and exposures to low doses of ionizing radiations is using mechanistic approaches. To this end, we proposed a 'bottom-up' approach to study cellular response that starts with the DNA damage. Monte Carlo track structure method was employed to simulate initial damage induced in the genomic DNA by direct and indirect effects. Among the different types of DNA damage, DSB are known to be induced in simple and complex forms. The DSB repair model in G1 and early S phases of the cell cycle was employed to calculate the repair kinetics. The model considers the repair of simple and complex DSB, and the DSB produced in the heterochromatin. The inverse sampling method was used to calculate the repair kinetics for each individual DSB. The overall repair kinetics for 500 DSB induced by single tracks of the radiation under test were compared with experimental results. The results show that the model is capable of predicting the repair kinetics for the DSB induced by radiations of different qualities within an accepted range of uncertainty.

  3. Recent advances in the study of ionizing radiation damage and repair.

    Science.gov (United States)

    Arrand, J E; Michael, B D

    1992-06-01

    This workshop, organized under the auspices of the EC Concerted Action Programme on DNA Repair and Cancer, was held at the CRC Gray Laboratory, Northwood, Middlesex, UK, 23-25 October 1991. The 42 participants were drawn mainly from laboratories participating in the EC Concerted Action, with a few visitors from elsewhere. The discussions centred on the increasing convergence of classical radiobiology and biophysics with molecular biology and mammalian cell genetics to study mechanisms of DNA strand break accumulation and repair following exposure to ionizing radiation. There was a strong emphasis on the application of this research both to cancer radiotherapy and to detection of individuals at risk from cancer due to exposure to ionizing radiation. The first two days were organized as six workshop sessions; on the third day we joined forces with Julie Denekamp and dedicated a session to the memory of our late friend and colleague, Nic McNally. The rest of this day was devoted to reviews by his colleagues and collaborators of the fields of research to which he contributed so much. An evening of music and readings, organized by Joanna and Rachel McNally, completed the memorial. Here we review the first seven sessions of the workshop, emphasizing the more recent approaches and the new information they have given us.

  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. Nicotinamide Enhances Repair of Arsenic and Ultraviolet Radiation-Induced DNA Damage in HaCaT Keratinocytes and Ex Vivo Human Skin

    OpenAIRE

    Thompson, Benjamin C.; Halliday, Gary M.; Damian, Diona L

    2015-01-01

    Arsenic-induced skin cancer is a significant global health burden. In areas with arsenic contamination of water sources, such as China, Pakistan, Myanmar, Cambodia and especially Bangladesh and West Bengal, large populations are at risk of arsenic-induced skin cancer. Arsenic acts as a co-carcinogen with ultraviolet (UV) radiation and affects DNA damage and repair. Nicotinamide (vitamin B3) reduces premalignant keratoses in sun-damaged skin, likely by prevention of UV-induced cellular energy ...

  6. Nicotinamide Enhances Repair of Arsenic and Ultraviolet Radiation-Induced DNA Damage in HaCaT Keratinocytes and Ex Vivo Human Skin

    OpenAIRE

    Thompson, Benjamin C.; Halliday, Gary M.; Damian, Diona L.

    2015-01-01

    Arsenic-induced skin cancer is a significant global health burden. In areas with arsenic contamination of water sources, such as China, Pakistan, Myanmar, Cambodia and especially Bangladesh and West Bengal, large populations are at risk of arsenic-induced skin cancer. Arsenic acts as a co-carcinogen with ultraviolet (UV) radiation and affects DNA damage and repair. Nicotinamide (vitamin B3) reduces premalignant keratoses in sun-damaged skin, likely by prevention of UV-induced cellular energy ...

  7. Effects of UV-B radiation on tetraspores of Chondrus ocellatus Holm (Rhodophyta), and effects of red and blue light on repair of UV-B-induced damage

    Science.gov (United States)

    Ju, Qing; Xiao, Hui; Wang, You; Tang, Xuexi

    2015-05-01

    We evaluated the effects of red and blue light on the repair of UV-B radiation-induced damage in tetraspores of Chondrus ocellatus Holm. Tetraspores of C. ocellatus were treated with different UV-B radiation levels (0, 36, 72, 108, 144 and 180 J/m2), and thereafter subjected to PAR, darkness, or red or blue light during a 2-h repair stage, each day for 48 days. The diameters and cellular contents of cyclobutane pyrimidine dimmers (CPDs), chlorophyll a (Chl a), phycoerythrin, and UV-B-absorbing mycosporinelike amino acids (MAAs) contents of the tetraspores were determined. Our results show that low doses of UV-B radiation (36 and 72 J/m2) promoted the growth of C. ocellatus; however, increased UV-B radiation gradually reduced the C. ocellatus growth (greater than 72 J/m2). The MAAs (palythine and asterina-330) in C. ocellatus were detected and analyzed by LC/MS. Our results suggest that moderate red light could induce the growth of this alga in aquaculture. In addition, photorepair was inhibited by red light, so there may be some other DNA repair mechanism activated by red light. Blue light promoted the activity of DNA photolyase, greatly improving remediation efficiency. Red and blue lights were found to reduce the capacity of C. ocellatus to form MAAs. Therefore, PAR, red light, and blue light play different roles during the repair processes for damage induced by UV-B radiation.

  8. 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

  9. DOE contractors' workshop: Cellular and molecular aspects of radiation induced DNA damage and repair

    Energy Technology Data Exchange (ETDEWEB)

    1987-01-01

    For four decades the US Department of Energy and its predecessors have been the lead federal agency in supporting radiation biology research. Over the years emphasis in this program has gradually shifted from dose-effect studies on animals to research on the effects of radiations of various qualities on cells and molecules. Mechanistic studies on the action of radiation at the subcellular level are few in number and there is a need for more research in this area if we are to gain a better understanding of how radiation affects living cells. The intent of this workshop was to bring together DOE contractors and grantees who are investigating the effects of radiation at the cellular and molecular levels. The aims were to foster the exchange of information on research projects and experimental results, promote collaborative research efforts, and obtain an overview of research currently supported by the Health Effects Research Division of the Office of Health and Environmental Research. The latter is needed by the Office for program planning purposes. This report on the workshop which took place in Albuquerque, New Mexico on March 10-11, 1987, includes an overview with future research recommendations, extended abstracts of the plenary presentations, shorter abstracts of each poster presentation, a workshop agenda and the names and addresses of the attendees.

  10. Damage Avoidance and Repair Mechanisms of Extreme Halophiles to Ionizing Radiation

    Science.gov (United States)

    2013-07-01

    tolerance   to   desiccation  that...abilities.   Early   work   on   the   desiccation   resistance   of   extremely   radiation-­‐resistant   bacteria   revealed...imparts  IR  resistance  to  these  organisms.  The  distribution  of  extremely   IR  and   desiccation

  11. BioSentinel: Mission Development of a Radiation Biosensor to Gauge DNA Damage and Repair Beyond Low Earth Orbit on a 6U Nanosatellite

    Science.gov (United States)

    Sanchez, Hugo; Lewis, Brian; Hanel, Robert

    2015-01-01

    We are designing and developing a 6U (10 x 22 x 34 cm; 14 kg) nanosatellite as a secondary payload to fly aboard NASAs Space Launch System (SLS) Exploration Mission (EM) 1, scheduled for launch in late 2017. For the first time in over forty years, direct experimental data from biological studies beyond low Earth orbit (LEO) will be obtained during BioSentinels 12- to 18-month mission. BioSentinel will measure the damage and repair of DNA in a biological organism and allow us to compare that to information from onboard physical radiation sensors. In order to understand the relative contributions of the space environments two dominant biological perturbations, reduced gravity and ionizing radiation, results from deep space will be directly compared to data obtained in LEO (on ISS) and on Earth. These data points will be available for validation of existing biological radiation damage and repair models, and for extrapolation to humans, to assist in mitigating risks during future long-term exploration missions beyond LEO. The BioSentinel Payload occupies 4U of the spacecraft and will utilize the monocellular eukaryotic organism Saccharomyces cerevisiae (yeast) to report DNA double-strand-break (DSB) events that result from ambient space radiation. DSB repair exhibits striking conservation of repair proteins from yeast to humans. Yeast was selected because of 1) its similarity to cells in higher organisms, 2) the well-established history of strains engineered to measure DSB repair, 3) its spaceflight heritage, and 4) the wealth of available ground and flight reference data. The S. cerevisiae flight strain will include engineered genetic defects to prevent growth and division until a radiation-induced DSB activates the yeasts DNA repair mechanisms. The triggered culture growth and metabolic activity directly indicate a DSB and its successful repair. The yeast will be carried in the dry state within the 1-atm PL container in 18 separate fluidics cards with each card

  12. Impaired Cytogenetic Damage Repair and Cell Cycle Regulation in Response to Ionizing Radiation in Human Fibroblast Cells with Individual Knock-down of 25 Genes

    Science.gov (United States)

    Zhang, Ye; Rohde, Larry; Emami, Kamal; Hammond, Dianne; Casey, Rachael; Mehta, Satish; Jeevarajan, Antony; Pierson, Duane; Wu, Honglu

    2008-01-01

    Changes of gene expression profile are one of the most important biological responses in living cells after ionizing radiation (IR) exposure. Although some studies have demonstrated that genes with upregulated expression induced by IR may play important roles in DNA damage sensing, cell cycle checkpoint and chromosomal repair, the relationship between the regulation of gene expression by IR and its impact on cytogenetic responses to ionizing radiation has not been systematically studied. In our present study, the expression of 25 genes selected based on their transcriptional changes in response to IR or from their known DNA repair roles were individually knocked down by siRNA transfection in human fibroblast cells. Chromosome aberrations (CA) and micronuclei (MN) formation were measured as the cytogenetic endpoints. Our results showed that the yield of MN and/or CA formation were significantly increased by suppressed expression of 5 genes that included Ku70 in the DSB repair pathway; XPA in the NER pathway; RPA1 in the MMR pathway; RAD17 and RBBP8 in cell cycle control. Knocked-down expression of 4 genes including MRE11A, RAD51 in the DSB pathway, and SESN1 and SUMO1 showed significant inhibition of cell cycle progression, possibly because of severe impairment of DNA damage repair. Furthermore, loss of XPA, p21 and MLH1 expression resulted in both enhanced cell cycle progression and significantly higher yield of cytogenetic damage, indicating the involvement of these gene products in both cell cycle control and DNA damage repair. Of these 11 genes that affected the cytogenetic response, 9 were up-regulated in the cells exposed to gamma radiation, suggesting that genes transcriptionally modulated by IR were critical to regulating the biological consequences after IR. Failure to express these IR-responsive genes, such as by gene mutation, could seriously change the outcome of the post IR scenario and lead to carcinogenesis.

  13. Ionizing radiation-induced DNA damage and its repair in human cells. Final performance report, July 1992--June 1995

    Energy Technology Data Exchange (ETDEWEB)

    Dizdaroglu, M.

    1995-12-31

    The studies of DNA damage in living cells in vitro and in vivo were continued. A variety of systems including cultured mammalian cells, animals, and human tissues were used to conduct these studies. In addition, enzymatic repair of DNA base damage was studied using several DNA glycosylases. To this end, substrate specificities of these enzymes were examined in terms of a large number of base lesions in DNA. In the first phase of the studies, the author sought to introduce improvements to his methodologies for measurement of DNA damage using the technique of gas chromatography/mass spectrometry (GC/MS). In particular, the quantitative measurement of DNA base damage and DNA-protein crosslinks was improved by incorporation of isotope-dilution mass spectrometry into the methodologies. This is one of the most accurate techniques for quantification of organic compounds. Having improved the measurement technique, studies of DNA damage in living cells and DNA repair by repair enzymes were pursued. This report provides a summary of these studies with references to the original work.

  14. [Studies of the repair of radiation-induced genetic damage in Drosophila]. Annual progress report, October 1, 1988--June 1, 1989

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1989-12-31

    The primary goal of this study is to achieve a more thorough understanding of the mechanisms employed by higher organisms to repair DNA damage induced by both ionizing and nonionizing radiation. These studies are also contributing to an improved understanding of the processes of mutagenesis and carcinogenesis in higher eukaryotes. The studies employ Drosophila as a model organism for investigating repair functions that are common to all higher eukaryotes. Drosophila was chosen in the early phases of this study primarily because of the ease with which one can isolate and characterize repair-deficient mutants in a metazoan organism. The laboratory has gone on to investigate the metabolic defects of such mutants while others have performed complementary genetic and cytogenetic studies which relate DNA repair processes to mutagenesis and chromosome stability. The repair studies have exploited the capacity to introduce mutant Drosophila cells into tissue culture and thereby compare repair defects directly with those of homologous human disorders. Researchers are currently employing recombinant DNA technology to investigate the mechanisms of the DNA repair pathways defined by those mutants.

  15. Nicotinamide enhances repair of arsenic and ultraviolet radiation-induced DNA damage in HaCaT keratinocytes and ex vivo human skin.

    Directory of Open Access Journals (Sweden)

    Benjamin C Thompson

    Full Text Available Arsenic-induced skin cancer is a significant global health burden. In areas with arsenic contamination of water sources, such as China, Pakistan, Myanmar, Cambodia and especially Bangladesh and West Bengal, large populations are at risk of arsenic-induced skin cancer. Arsenic acts as a co-carcinogen with ultraviolet (UV radiation and affects DNA damage and repair. Nicotinamide (vitamin B3 reduces premalignant keratoses in sun-damaged skin, likely by prevention of UV-induced cellular energy depletion and enhancement of DNA repair. We investigated whether nicotinamide modifies DNA repair following exposure to UV radiation and sodium arsenite. HaCaT keratinocytes and ex vivo human skin were exposed to 2μM sodium arsenite and low dose (2J/cm2 solar-simulated UV, with and without nicotinamide supplementation. DNA photolesions in the form of 8-oxo-7,8-dihydro-2'-deoxyguanosine and cyclobutane pyrimidine dimers were detected by immunofluorescence. Arsenic exposure significantly increased levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine in irradiated cells. Nicotinamide reduced both types of photolesions in HaCaT keratinocytes and in ex vivo human skin, likely by enhancing DNA repair. These results demonstrate a reduction of two different photolesions over time in two different models in UV and arsenic exposed cells. Nicotinamide is a nontoxic, inexpensive agent with potential for chemoprevention of arsenic induced skin cancer.

  16. Nicotinamide enhances repair of arsenic and ultraviolet radiation-induced DNA damage in HaCaT keratinocytes and ex vivo human skin.

    Science.gov (United States)

    Thompson, Benjamin C; Halliday, Gary M; Damian, Diona L

    2015-01-01

    Arsenic-induced skin cancer is a significant global health burden. In areas with arsenic contamination of water sources, such as China, Pakistan, Myanmar, Cambodia and especially Bangladesh and West Bengal, large populations are at risk of arsenic-induced skin cancer. Arsenic acts as a co-carcinogen with ultraviolet (UV) radiation and affects DNA damage and repair. Nicotinamide (vitamin B3) reduces premalignant keratoses in sun-damaged skin, likely by prevention of UV-induced cellular energy depletion and enhancement of DNA repair. We investigated whether nicotinamide modifies DNA repair following exposure to UV radiation and sodium arsenite. HaCaT keratinocytes and ex vivo human skin were exposed to 2μM sodium arsenite and low dose (2J/cm2) solar-simulated UV, with and without nicotinamide supplementation. DNA photolesions in the form of 8-oxo-7,8-dihydro-2'-deoxyguanosine and cyclobutane pyrimidine dimers were detected by immunofluorescence. Arsenic exposure significantly increased levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine in irradiated cells. Nicotinamide reduced both types of photolesions in HaCaT keratinocytes and in ex vivo human skin, likely by enhancing DNA repair. These results demonstrate a reduction of two different photolesions over time in two different models in UV and arsenic exposed cells. Nicotinamide is a nontoxic, inexpensive agent with potential for chemoprevention of arsenic induced skin cancer.

  17. Influence of 1.8-GHz (GSM) radiofrequency radiation (RFR) on DNA damage and repair induced by X-rays in human leukocytes in vitro.

    Science.gov (United States)

    Zhijian, Chen; Xiaoxue, Li; Yezhen, Lu; Deqiang, Lu; Shijie, Chen; Lifen, Jin; Jianlin, Lou; Jiliang, He

    2009-01-01

    In the present study, the in vitro comet assay was used to determine whether 1.8-GHz radiofrequency radiation (RFR) can influence DNA repair in human leukocytes exposed to X-rays. The specific energy absorption rate (SAR) of 2 W/kg (the current European safety limit) was applied. The leukocytes from four young healthy donors were intermittently exposed to RFR for 24 h (fields on for 5 min, fields off for 10 min), and then irradiated with X-rays at doses of 0.25, 0.5, 1.0 and 2.0 Gy. DNA damage to human leukocytes was detected using the comet assay at 0, 15, 45, 90, 150 and 240 min after exposure to X-rays. Using the comet assay, the percent of DNA in the tail (% tail DNA) served as the indicator of DNA damage; the DNA repair percentage (DRP) served as the indicator of the DNA repair speed. The results demonstrated that (1) the DNA repair speeds of human leukocytes after X-ray exposure exhibited individual differences among the four donors; (2) the intermittent exposures of 1.8-GHz RFR at the SAR of 2 W/kg for 24 h did not directly induce DNA damage or exhibit synergistic effects with X-rays on human leukocytes.

  18. Effect of chronic low dose natural radiation in human peripheral blood mononuclear cells: Evaluation of DNA damage and repair using the alkaline comet assay

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, P.R. Vivek, E-mail: prvkumar06@gmail.com [Low Level Radiation Research Laboratory, Radiation Biology and Health Sciences Division, Bio-Science Group, Bhabha Atomic Research Centre, IRE Campus, Beach Road, Kollam 691 001, Kerala (India); Seshadri, M. [Low Level Radiation Research Section, Radiation Biology and Health Sciences Division, Bio-Science Group, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085 (India); Jaikrishan, G. [Low Level Radiation Research Laboratory, Radiation Biology and Health Sciences Division, Bio-Science Group, Bhabha Atomic Research Centre, IRE Campus, Beach Road, Kollam 691 001, Kerala (India); Das, Birajalaxmi [Low Level Radiation Research Section, Radiation Biology and Health Sciences Division, Bio-Science Group, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085 (India)

    2015-05-15

    Highlights: • Effect of chronic low dose natural radiation in radio adaptive response studied. • PBMCs of subjects from NLNRA and HLNRA were challenged with gamma radiation. • DNA damage and repair in PBMCs was compared using the alkaline comet assay. • Significant reduction in DNA damage in subjects of high dose group from HLNRA noted. • Probable induction of an in vivo radio adaptive response in subjects from HLNRA. - Abstract: This study investigates whether peripheral blood mononuclear cells (PBMCs) from inhabitants of Kerala in southwest India, exposed to chronic low dose natural radiation in vivo (>1 mSv year{sup −1}), respond with a radioadaptive response to a challenging dose of gamma radiation. Toward this goal, PBMCs isolated from 77 subjects from high-level natural radiation areas (HLNRA) and 37 subjects from a nearby normal level natural radiation area (NLNRA) were challenged with 2 Gy and 4 Gy gamma radiation. Subjects from HLNRA were classified based on the mean annual effective dose received, into low dose group (LDG) and high dose group (HDG) with mean annual effective doses of 2.69 mSv (N = 43, range 1.07 mSv year{sup −1} to 5.55 mSv year{sup −1}) and 9.62 mSv (N = 34, range 6.07 mSv year{sup −1} to17.41 mSv year{sup −1}), respectively. DNA strand breaks and repair kinetics (at 7 min, 15 min and 30 min after 4 Gy) were evaluated using the alkaline single cell gel electrophoresis (comet) assay. Initial levels of DNA strand breaks observed after either a 2 Gy or a 4 Gy challenging dose were significantly lower in subjects of the HDG from HLNRA compared to subjects of NLNRA (2 Gy, P = 0.01; 4 Gy, P = 0.02) and LDG (2 Gy P = 0.01; 4 Gy, P = 0.05). Subjects of HDG from HLNRA showed enhanced rejoining of DNA strand breaks (HDG/NLNRA, P = 0.06) during the early stage of repair (within 7 min). However at later times a similar rate of rejoining of strand breaks was observed across the groups (HDG, LDG and NLNRA). Preliminary results from

  19. BioSentinel: Mission Development of a Radiation Biosensor to Gauge DNA Damage and Repair Beyond Low Earth Orbit on a 6U Nanosatellite.

    Science.gov (United States)

    Lewis, Brian; Hanel, Robert; Bhattacharya, Sharmila; Ricco, Antonion J.; Agasid, Elwood; Reiss-Bubenheim, Debra; Straume, Tore; Parra, Macerena; Boone, Travis; Santa Maria, Sergio; hide

    2015-01-01

    We are designing and developing a "6U" (10 x 22 x 34 cm; 14 kg) nanosatellite as a secondary payload to fly aboard NASA's Space Launch System (SLS) Exploration Mission (EM) 1, scheduled for launch in late 2017. For the first time in over forty years, direct experimental data from biological studies beyond low Earth orbit (LEO) will be obtained during BioSentinel's 12- to 18- month mission. BioSentinel will measure the damage and repair of DNA in a biological organism and allow us to compare that to information from onboard physical radiation sensors. In order to understand the relative contributions of the space environment's two dominant biological perturbations, reduced gravity and ionizing radiation, results from deep space will be directly compared to data obtained in LEO (on ISS) and on Earth. These data points will be available for validation of existing biological radiation damage and repair models, and for extrapolation to humans, to assist in mitigating risks during future long-term exploration missions beyond LEO. The BioSentinel Payload occupies 4U of the spacecraft and will utilize the monocellular eukaryotic organism Saccharomyces cerevisiae (yeast) to report DNA double-strand-break (DSB) events that result from ambient space radiation. DSB repair exhibits striking conservation of repair proteins from yeast to humans. Yeast was selected because of 1) its similarity to cells in higher organisms, 2) the well-established history of strains engineered to measure DSB repair, 3) its spaceflight heritage, and 4) the wealth of available ground and flight reference data. The S. cerevisiae flight strain will include engineered genetic defects to prevent growth and division until a radiation-induced DSB activates the yeast's DNA repair mechanisms. The triggered culture growth and metabolic activity directly indicate a DSB and its successful repair. The yeast will be carried in the dry state within the 1-atm P/L container in 18 separate fluidics cards with each

  20. Normal repair of ultraviolet radiation-induced DNA damage in familial melanoma without CDKN2A or CDK4 gene mutation.

    Science.gov (United States)

    Shannon, J A; Matias, C; Luxford, C; Kefford, R F; Mann, G J

    1999-04-01

    Excessive sun exposure and family history are strong risk factors for the development of cutaneous melanoma. Inherited susceptibility to this type of skin cancer could therefore result from constitutively impaired capacity to repair ultraviolet (UV)-induced DNA lesions. While a proportion of familial melanoma kindreds exhibit germline mutations in the cell cycle regulatory gene CDKN2A (p16INK4a) or its protein target, cyclin-dependent kinase 4 (CDK4), the biochemical basis of most familial melanoma is unknown. We have examined lymphoblastoid cell lines from melanoma-affected and unaffected individuals from large hereditary melanoma kindreds which are not attributable to CDKN2A or CDK4 gene mutation. These lines were tested for sensitivity of clonogenic growth to UV radiation and for their ability to repair transfected UV-damaged plasmid templates (host cell reactivation). Two of seven affected-unaffected pairs differed in colony survival after exposure to UVB radiation; however, no significant differences were observed in the host-cell reactivation assays. These results indicate that melanoma susceptibility genes other than CDKN2A and CDK4 do not impair net capacity to repair UV-induced DNA damage.

  1. Endonuclease IV Is the Main Base Excision Repair Enzyme Involved in DNA Damage Induced by UVA Radiation and Stannous Chloride

    Directory of Open Access Journals (Sweden)

    Ellen S. Motta

    2010-01-01

    Full Text Available Stannous chloride (SnCl2 and UVA induce DNA lesions through ROS. The aim of this work was to study the toxicity induced by UVA preillumination, followed by SnCl2 treatment. E. coli BER mutants were used to identify genes which could play a role in DNA lesion repair generated by these agents. The survival assays showed (i The nfo mutant was the most sensitive to SnCl2; (ii lethal synergistic effect was observed after UVA pre-illumination, plus SnCl2 incubation, the nfo mutant being the most sensitive; (iii wild type and nfo mutants, transformed with pBW21 plasmid (nfo+ had their survival increased following treatments. The alkaline agarose gel electrophoresis assays pointed that (i UVA induced DNA breaks and fpg mutant was the most sensitive; (ii SnCl2-induced DNA strand breaks were higher than those from UVA and nfo mutant had the slowest repair kinetics; (iii UVA+SnCl2 promoted an increase in DNA breaks than SnCl2 and, again, nfo mutant displayed the slowest repair kinetics. In summary, Nfo protects E. coli cells against damage induced by SnCl2 and UVA+ SnCl2.

  2. DNA damage induction and/or repair as mammalian cell biomarker for the prediction of cellular radiation response

    Science.gov (United States)

    Baumstark-Khan, C.

    DNA damage and its repair processes are key factors in cancer induction and also in the treatment of malignancies. Cancer prevention during extended space missions becomes a topic of great importance for space radiobiology. The knowledge of individual responsiveness would allow the protection strategy to be tailored optimally in each case. Radiobiological analysis of cultured cells derived from tissue explants from individuals has shown that measurement of the surviving fraction after 2 Gy (SF2) may be used to predict the individual responsiveness. However, clonogenic assays are timeconsuming, thus alternative assays for the determination of radiore-sponse are being sought. For that reason CHO cell strains having different repair capacities were used for examining whether DNA strand break repair is a suitable experimental design to allow predictive statements. Cellular survival (CFA assay) and DNA strand breaks (total DNA strand breaks: FADU technique; DSBs: non-denaturing elution) were determined in parallel immediately after irradiation as well as after a 24 hour recovery period according to dose. There were no correlations between the dose-response curves of the initial level of DNA strand breaks and parameters that describe clonogenic survival curves (SF2). A good correlation exists between intrinsic cellular radioresistance and the extent of residual DNA strand breaks.

  3. Dietary proanthocyanidins prevent ultraviolet radiation-induced non-melanoma skin cancer through enhanced repair of damaged DNA-dependent activation of immune sensitivity.

    Science.gov (United States)

    Katiyar, Santosh K; Pal, Harish C; Prasad, Ram

    2017-04-12

    Numerous plant products have been used to prevent and manage a wide variety of diseases for centuries. These products are now considered as promising options for the development of more effective and less toxic alternatives to the systems of medicine developed primarily in developed countries in the modern era. Grape seed proanthocyanidins (GSPs) are of great interest due to their anti-carcinogenic effects that have been demonstrated using various tumor models including ultraviolet (UV) radiation-induced non-melanoma skin cancer. In a pre-clinical mouse model supplementation of a control diet (AIN76A) with GSPs at concentrations of 0.2% and 0.5% (w/w) significantly inhibits the growth and multiplicity of UVB radiation-induced skin tumors. In this review, we summarize the evidence that this inhibition of UVB-induced skin tumor development by dietary GSPs is mediated by a multiplicity of coordinated effects including: (i) Promotion of the repair of damaged DNA by nuclear excision repair mechanisms, and (ii) DNA repair-dependent stimulation of the immune system following the functional activation of dendritic cells and effector T cells. Dietary GSPs hold promise for the development of an effective alternative strategy for the prevention of excessive solar UVB radiation exposure-induced skin diseases including the risk of non-melanoma skin cancer in humans. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Interactive effects of ultraviolet-B radiation and pesticide exposure on DNA photo-adduct accumulation and expression of DNA damage and repair genes in Xenopus laevis embryos.

    Science.gov (United States)

    Yu, Shuangying; Tang, Song; Mayer, Gregory D; Cobb, George P; Maul, Jonathan D

    2015-02-01

    Pesticide use and ultraviolet-B (UVB) radiation have both been suggested to adversely affect amphibians; however, little is known about their interactive effects. One potential adverse interaction could involve pesticide-induced dysregulation of DNA repair pathways, resulting in greater numbers of DNA photo-adducts from UVB exposure. In the present study, we investigated the interactive effects of UVB radiation and two common pesticides (endosulfan and α-cypermethrin) on induction of DNA photo-adducts and expression of DNA damage and repair related genes in African clawed frog (Xenopus laevis) embryos. We examined 13 genes that are, collectively, involved in stress defense, cell cycle arrest, nucleotide excision repair (NER), base excision repair, mismatch repair, DNA repair regulation, and apoptosis. We exposed X. laevis embryos to 0, 25, and 50 μg/L endosulfan or 0, 2.5, and 5.0 μg/L α-cypermethrin for 96 h, with environmentally relevant exposures of UVB radiation during the last 7 h of the 96 h exposure. We measured the amount of cyclobutane pyrimidine dimers (CPDs) and mRNA abundance of the 13 genes among treatments including control, pesticide only, UVB only, and UVB and pesticide co-exposures. Each of the co-exposure scenarios resulted in elevated CPD levels compared to UVB exposure alone, suggesting an inhibitory effect of endosulfan and α-cypermethrin on CPD repair. This is attributed to results indicating that α-cypermethrin and endosulfan reduced mRNA abundance of XPA and HR23B, respectively, to levels that may affect the initial recognition of DNA lesions. In contrast, both pesticides increased transcript abundance of CSA and MUTL. In addition, mRNA abundance of HSP70 and GADD45α were increased by endosulfan and mRNA abundance of XPG was increased by α-cypermethrin. XPC, HR23B, XPG, and GADD45α exhibited elevated mRNA concentrations whereas there was a reduction in MUTL transcript concentrations in UVB-alone treatments. It appeared that even

  5. Impact of 1.8-GHz radiofrequency radiation (RFR) on DNA damage and repair induced by doxorubicin in human B-cell lymphoblastoid cells.

    Science.gov (United States)

    Zhijian, Chen; Xiaoxue, Li; Yezhen, Lu; Shijie, Chen; Lifen, Jin; Jianlin, Lou; Deqiang, Lu; Jiliang, He

    2010-01-01

    In the present in vitro study, a comet assay was used to determine whether 1.8-GHz radiofrequency radiation (RFR, SAR of 2W/kg) can influence DNA repair in human B-cell lymphoblastoid cells exposed to doxorubicin (DOX) at the doses of 0microg/ml, 0.05microg/ml, 0.075microg/ml, 0.10microg/ml, 0.15microg/ml and 0.20microg/ml. The combinative exposures to RFR with DOX were divided into five categories. DNA damage was detected at 0h, 6h, 12h, 18h and 24h after exposure to DOX via the comet assay, and the percent of DNA in the tail (% tail DNA) served as the indicator of DNA damage. The results demonstrated that (1) RFR could not directly induce DNA damage of human B-cell lymphoblastoid cells; (2) DOX could significantly induce DNA damage of human B-cell lymphoblastoid cells with the dose-effect relationship, and there were special repair characteristics of DNA damage induced by DOX; (3) E-E-E type (exposure to RFR for 2h, then simultaneous exposure to RFR and DOX, and exposure to RFR for 6h, 12h, 18h and 24h after exposure to DOX) combinative exposure could obviously influence DNA repair at 6h and 12h after exposure to DOX for four DOX doses (0.075microg/ml, 0.10microg/ml, 0.15microg/ml and 0.20microg/ml) in human B-cell lymphoblastoid cells. Copyright 2009 Elsevier B.V. All rights reserved.

  6. Interactive effects of ultraviolet-B radiation and pesticide exposure on DNA photo-adduct accumulation and expression of DNA damage and repair genes in Xenopus laevis embryos

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Shuangying, E-mail: shuangying.yu@ttu.edu [Department of Environmental Toxicology, The Institute of Environmental and Human Health, Texas Tech University, 1207 S. Gilbert Dr., Lubbock, TX 79416 (United States); Tang, Song, E-mail: song.tang@usask.ca [Department of Environmental Toxicology, The Institute of Environmental and Human Health, Texas Tech University, 1207 S. Gilbert Dr., Lubbock, TX 79416 (United States); Mayer, Gregory D., E-mail: greg.mayer@ttu.edu [Department of Environmental Toxicology, The Institute of Environmental and Human Health, Texas Tech University, 1207 S. Gilbert Dr., Lubbock, TX 79416 (United States); Cobb, George P., E-mail: george_cobb@baylor.edu [Department of Environmental Science, Baylor University, One Bear Place #97266, Waco, TX 76798 (United States); Maul, Jonathan D., E-mail: jonathan.maul@ttu.edu [Department of Environmental Toxicology, The Institute of Environmental and Human Health, Texas Tech University, 1207 S. Gilbert Dr., Lubbock, TX 79416 (United States)

    2015-02-15

    Highlights: • Interactive effects of UVB radiation-pesticide co-exposures were examined in frogs. • Responses included induction of DNA photo-adducts and DNA damage and repair genes. • Elevated DNA adduct levels occurred for co-exposures compared to UVB alone. • One mechanism is that pesticides may alter nuclear excision repair gene expression. - Abstract: Pesticide use and ultraviolet-B (UVB) radiation have both been suggested to adversely affect amphibians; however, little is known about their interactive effects. One potential adverse interaction could involve pesticide-induced dysregulation of DNA repair pathways, resulting in greater numbers of DNA photo-adducts from UVB exposure. In the present study, we investigated the interactive effects of UVB radiation and two common pesticides (endosulfan and α-cypermethrin) on induction of DNA photo-adducts and expression of DNA damage and repair related genes in African clawed frog (Xenopus laevis) embryos. We examined 13 genes that are, collectively, involved in stress defense, cell cycle arrest, nucleotide excision repair (NER), base excision repair, mismatch repair, DNA repair regulation, and apoptosis. We exposed X. laevis embryos to 0, 25, and 50 μg/L endosulfan or 0, 2.5, and 5.0 μg/L α-cypermethrin for 96 h, with environmentally relevant exposures of UVB radiation during the last 7 h of the 96 h exposure. We measured the amount of cyclobutane pyrimidine dimers (CPDs) and mRNA abundance of the 13 genes among treatments including control, pesticide only, UVB only, and UVB and pesticide co-exposures. Each of the co-exposure scenarios resulted in elevated CPD levels compared to UVB exposure alone, suggesting an inhibitory effect of endosulfan and α-cypermethrin on CPD repair. This is attributed to results indicating that α-cypermethrin and endosulfan reduced mRNA abundance of XPA and HR23B, respectively, to levels that may affect the initial recognition of DNA lesions. In contrast, both pesticides

  7. DNA repair. [UV radiation

    Energy Technology Data Exchange (ETDEWEB)

    Setlow, R.

    1978-01-01

    Some topics discussed are as follows: difficulty in extrapolating data from E. coli to mammalian systems; mutations caused by UV-induced changes in DNA; mutants deficient in excision repair; other postreplication mechanisms; kinds of excision repair systems; detection of repair by biochemical or biophysical means; human mutants deficient in repair; mutagenic effects of UV on XP cells; and detection of UV-repair defects among XP individuals. (HLW)

  8. Interactive Effects of Temperature and UV Radiation on Photosynthesis of Chlorella Strains from Polar, Temperate and Tropical Environments: Differential Impacts on Damage and Repair.

    Science.gov (United States)

    Wong, Chiew-Yen; Teoh, Ming-Li; Phang, Siew-Moi; Lim, Phaik-Eem; Beardall, John

    2015-01-01

    Global warming and ozone depletion, and the resulting increase of ultraviolet radiation (UVR), have far-reaching impacts on biota, especially affecting the algae that form the basis of the food webs in aquatic ecosystems. The aim of the present study was to investigate the interactive effects of temperature and UVR by comparing the photosynthetic responses of similar taxa of Chlorella from Antarctic (Chlorella UMACC 237), temperate (Chlorella vulgaris UMACC 248) and tropical (Chlorella vulgaris UMACC 001) environments. The cultures were exposed to three different treatments: photosynthetically active radiation (PAR; 400-700 nm), PAR plus ultraviolet-A (320-400 nm) radiation (PAR + UV-A) and PAR plus UV-A and ultraviolet-B (280-320 nm) radiation (PAR + UV-A + UV-B) for one hour in incubators set at different temperatures. The Antarctic Chlorella was exposed to 4, 14 and 20°C. The temperate Chlorella was exposed to 11, 18 and 25°C while the tropical Chlorella was exposed to 24, 28 and 30°C. A pulse-amplitude modulated (PAM) fluorometer was used to assess the photosynthetic response of microalgae. Parameters such as the photoadaptive index (Ek) and light harvesting efficiency (α) were determined from rapid light curves. The damage (k) and repair (r) rates were calculated from the decrease in ΦPSIIeff over time during exposure response curves where cells were exposed to the various combinations of PAR and UVR, and fitting the data to the Kok model. The results showed that UV-A caused much lower inhibition than UV-B in photosynthesis in all Chlorella isolates. The three isolates of Chlorella from different regions showed different trends in their photosynthesis responses under the combined effects of UVR (PAR + UV-A + UV-B) and temperature. In accordance with the noted strain-specific characteristics, we can conclude that the repair (r) mechanisms at higher temperatures were not sufficient to overcome damage caused by UVR in the Antarctic Chlorella strain

  9. ZRBA1, a Mixed EGFR/DNA Targeting Molecule, Potentiates Radiation Response Through Delayed DNA Damage Repair Process in a Triple Negative Breast Cancer Model

    Energy Technology Data Exchange (ETDEWEB)

    Heravi, Mitra [Department of Human Genetics, McGill University, Montreal (Canada); Department of Radiation Oncology, McGill University, Montreal (Canada); Segal Cancer Center, Jewish General Hospital, Montreal (Canada); Kumala, Slawomir [Department of Radiation Oncology, McGill University, Montreal (Canada); Segal Cancer Center, Jewish General Hospital, Montreal (Canada); Rachid, Zakaria; Jean-Claude, Bertrand J. [Cancer Drug Research Laboratory, McGill University Health Center, Montreal (Canada); Radzioch, Danuta [Department of Human Genetics, McGill University, Montreal (Canada); Muanza, Thierry M., E-mail: tmuanza@yahoo.com [Department of Radiation Oncology, McGill University, Montreal (Canada); Segal Cancer Center, Jewish General Hospital, Montreal (Canada)

    2015-06-01

    Purpose: ZRBA1 is a combi-molecule designed to induce DNA alkylating lesions and to block epidermal growth factor receptor (EGFR) TK domain. Inasmuch as ZRBA1 downregulates the EGFR TK-mediated antisurvival signaling and induces DNA damage, we postulated that it might be a radiosensitizer. The aim of this study was to further investigate the potentiating effect of ZRBA1 in combination with radiation and to elucidate the possible mechanisms of interaction between these 2 treatment modalities. Methods and Materials: The triple negative human breast MDA-MB-468 cancer cell line and mouse mammary cancer 4T1 cell line were used in this study. Clonogenic assay, Western blot analysis, and DNA damage analysis were performed at multiple time points after treatment. To confirm our in vitro findings, in vivo tumor growth delay assay was performed. Results: Our results show that a combination of ZRBA1 and radiation increases the radiation sensitivity of both cell lines significantly with a dose enhancement factor of 1.56, induces significant numbers of DNA strand breaks, prolongs higher DNA damage up to 24 hours after treatment, and significantly increases tumor growth delay in a syngeneic mouse model. Conclusions: Our data suggest that the higher efficacy of this combination could be partially due to increased DNA damage and delayed DNA repair process and to the inhibition of EGFR. The encouraging results of this combination demonstrated a significant improvement in treatment efficiency and therefore could be applicable in early clinical trial settings.

  10. Nimotuzumab enhances radiation sensitivity of NSCLC H292 cells in vitro by blocking epidermal growth factor receptor nuclear translocation and inhibiting radiation-induced DNA damage repair

    Directory of Open Access Journals (Sweden)

    Teng K

    2015-04-01

    Full Text Available Kai Teng,1,2,* Yong Zhang,1,* Xiaoyan Hu,1 Yihui Ding,1 Rui Gong,1 Li Liu1,* 1Department of Thoracic Oncology, Cancer Center of Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2Department of Radiation Oncology, Hainan Cancer Hospital, Haikou, Hainan, People’s Republic of China *These authors contributed equally to this work Background: The epidermal growth factor receptor (EGFR signaling pathway plays a significant role in radiation resistance. There is evidence that EGFR nuclear translocation is associated with DNA double-strand breaks (DSB repair. Nimotuzumab has shown the effect of radiosensitization in various cancer cells, but little is known about the relationship between nimotuzumab and EGFR nuclear translocation in non-small cell lung cancer (NSCLC cell lines. In this study, we selected two NSCLC cell lines, namely, H292 (with high EGFR expression and H1975 (with low EGFR expression and explored the mechanisms underlying radiation sensitivity.Methods: MTT assay, clonogenic survival assay, and flow cytometry were performed separately to test cell viability, radiation sensitivity, cell cycle distribution, and apoptosis. Protein γ-H2AX, DNA-PK/p-DNA-PK, and EGFR/p-EGFR expression were further compared both in the cytoplasm and the nucleus with the western blot.Results: Nimotuzumab reduced the viability of H292 cells and sensitized H292 cells to ionizing radiation. The radiation sensitivity enhancement ratio (SER was 1.304 and 1.092 for H292 and H1975 cells, respectively. H292 cells after nimotuzumab administration were arrested at the G0/G1 phase in response to radiation. Apoptosis was without statistical significance in both cell lines. γ-H2AX formation in the combination group (nimotuzumab and radiation increased both in the cytoplasm and the nucleus along with the decreased expression of nuclear EGFR/p-EGFR and p-DNA-PK in H292 cells (P<0.05 that

  11. Chromatin structure and DNA damage repair

    Directory of Open Access Journals (Sweden)

    Dinant Christoffel

    2008-11-01

    Full Text Available Abstract The integrity of the genome is continuously challenged by both endogenous and exogenous DNA damaging agents. These damaging agents can induce a wide variety of lesions in the DNA, such as double strand breaks, single strand breaks, oxidative lesions and pyrimidine dimers. The cell has evolved intricate DNA damage response mechanisms to counteract the genotoxic effects of these lesions. The two main features of the DNA damage response mechanisms are cell-cycle checkpoint activation and, at the heart of the response, DNA repair. For both damage signalling and repair, chromatin remodelling is most likely a prerequisite. Here, we discuss current knowledge on chromatin remodelling with respect to the cellular response to DNA damage, with emphasis on the response to lesions resolved by nucleotide excision repair. We will discuss the role of histone modifications as well as their displacement or exchange in nucleotide excision repair and make a comparison with their requirement in transcription and double strand break repair.

  12. Genetic polymorphisms in XRCC1, OGG1, APE1 and XRCC3 DNA repair genes, ionizing radiation exposure and chromosomal DNA damage in interventional cardiologists

    Energy Technology Data Exchange (ETDEWEB)

    Andreassi, Maria Grazia, E-mail: andreas@ifc.cnr.it [CNR Institute of Clinical Physiology, National Research Council, Pisa (Italy); Foffa, Ilenia [CNR Institute of Clinical Physiology, National Research Council, Pisa (Italy); Sant' Anna School of Advanced Studies, Pisa (Italy); Manfredi, Samantha; Botto, Nicoletta [CNR Institute of Clinical Physiology, National Research Council, Pisa (Italy); Cioppa, Angelo [Clinica Cardiologica ' Montevergine' , Mercogliano (Italy); Picano, Eugenio [CNR Institute of Clinical Physiology, National Research Council, Pisa (Italy); Clinica Cardiologica ' Montevergine' , Mercogliano (Italy)

    2009-06-18

    Interventional cardiologists working in high-volume cardiac catheterization laboratory are exposed to significant occupational radiation risks. Common single-nucleotide polymorphisms (SNPs) in DNA repair genes are thought to modify the effects of low-dose radiation exposure on DNA damage, the main initiating event in the development of cancer and hereditary disease. The aim of this study was to determine the relationship between XRCC1 (Arg194Trp and Arg399Gln), OGG1 (Ser326Cys), APE1 (Asp148Glu) and XRCC3 (Thr241Met) SNPs and chromosomal DNA damage. We enrolled 77 subjects: 40 interventional cardiologists (27 male, 41.3 {+-} 9.4 years and 13 female, 37.8 {+-} 8.4 years) and 37 clinical cardiologists (26 male, 39.4 {+-} 9.5 years and 11 female, 35.0 {+-} 9.8 years) without radiation exposure as the control group. Micronucleus (MN) assay was performed as biomarker of chromosomal DNA damage and an early predictor of cancer. MN frequency was significantly higher in interventional cardiologists than in clinical physicians (19.7 {+-} 7.8 per mille vs. 13.5 {+-} 6.3 per mille , p = 0.0003). Within the exposed group, individuals carrying a XRCC3 Met241 allele had higher frequency than homozygous XRCC3 Thr241 (21.2 {+-} 7.8 per mille vs. 16.6 {+-} 7.1 per mille , p = 0.03). Individuals with two or more risk alleles showed a higher MN frequency when compared to subjects with one or no risk allele (18.4 {+-} 6.6 per mille vs. 14.4 {+-} 6.1 per mille , p = 0.02). An interactive effect was found between smoking, exposure >10 years and the presence of the two or more risk alleles on the MN frequency (F = 6.3, p = 0.02). XRCC3 241Met alleles, particularly in combination with multiple risk alleles of DNA repair genes, contribute to chromosomal DNA damage levels in interventional cardiologists.

  13. 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.

  14. REC-2006—A Fractionated Extract of Podophyllum hexandrum Protects Cellular DNA from Radiation-Induced Damage by Reducing the Initial Damage and Enhancing Its Repair In Vivo

    Directory of Open Access Journals (Sweden)

    Pankaj Chaudhary

    2011-01-01

    Full Text Available Podophyllum hexandrum, a perennial herb commonly known as the Himalayan May Apple, is well known in Indian and Chinese traditional systems of medicine. P. hexandrum has been widely used for the treatment of venereal warts, skin infections, bacterial and viral infections, and different cancers of the brain, lung and bladder. This study aimed at elucidating the effect of REC-2006, a bioactive fractionated extract from the rhizome of P. hexandrum, on the kinetics of induction and repair of radiation-induced DNA damage in murine thymocytes in vivo. We evaluated its effect on non-specific radiation-induced DNA damage by the alkaline halo assay in terms of relative nuclear spreading factor (RNSF and gene-specific radiation-induced DNA damage via semi-quantitative polymerase chain reaction. Whole body exposure of animals with gamma rays (10 Gy caused a significant amount of DNA damage in thymocytes (RNSF values 17.7 ± 0.47, 12.96 ± 1.64 and 3.3 ± 0.014 and a reduction in the amplification of β-globin gene to 0, 28 and 43% at 0, 15 and 60 min, respectively. Administrating REC-2006 at a radioprotective concentration (15 mg kg−1 body weight 1 h before irradiation resulted in time-dependent reduction of DNA damage evident as a decrease in RNSF values 6.156 ± 0.576, 1.647 ± 0.534 and 0.496 ± 0.012, and an increase in β-globin gene amplification 36, 95 and 99%, at 0, 15 and 60 min, respectively. REC-2006 scavenged radiation-induced hydroxyl radicals in a dose-dependent manner stabilized DPPH free radicals and also inhibited superoxide anions. Various polyphenols and flavonoides present in REC-2006 might contribute to scavenging of radiation-induced free radicals, thereby preventing DNA damage and stimulating its repair.

  15. Simulated microgravity influenced the expression of DNA damage repair genes

    Science.gov (United States)

    Zhang, Meng; Sun, Yeqing; Jiawei, Liu; Wang, Ting

    2016-07-01

    Ionizing radiation and microgravity were considered to be the most important stress factors of space environmental the respective study of the biological effects of the radiation and microgravity carried out earlier, but the interaction of the effects of radiation with microgravity started later, and due to difference of the materials and methods the result of this experiment were not consistent. To further investigate the influence of microgravity on the expression of the radiation damage repair genes, the seed of Arabidopsis (Col) and its gravity-insensitive mutant (PIN2) were exposed to 0.1Gy of the dose of energetic carbon-ion beam radiation (LET = 30KeV / μm), and the germinated seed were than fixed in the 3D random positioning apparatus immediately for a 10-day simulated microgravity. By measuring the deflection angle of root tip and the changes of the expression of Ku70 and RAD51 protein, we investigated the impact of microgravity effect on radiation damage repair systems. The results shown that radiation, microgravity and microgravity with radiation could increase the angle of the root of the Col significantly, but no obvious effect on PIN2 type. The radiation could increase the expression of Ku70 significantly in both Col and PIN2, microgravity does not affect the expression, but the microgravity with radiation could decrease the expression of Ku70. This result shown that the microgravity could influence the radiation damage repair systems in molecular level. Moreover, our findings were important to understand the molecular mechanism of the impact of microgravity effect on radiation damage repair systems in vivo.

  16. DNA repair and radiation sensitivity in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Chen, D.J.C.; Stackhouse, M. [Los Alamos National Lab., NM (United States); Chen, D.S. [Rochester Univ., NY (United States). Dept. of Radiation Oncology

    1993-02-01

    Ionizing radiation induces various types of damage in mammalian cells including DNA single-strand breaks, DNA double-strand breaks (DSB), DNA-protein cross links, and altered DNA bases. Although human cells can repair many of these lesions there is little detailed knowledge of the nature of the genes and the encoded enzymes that control these repair processes. We report here on the cellular and genetic analyses of DNA double-strand break repair deficient mammalian cells. It has been well established that the DNA double-strand break is one of the major lesions induced by ionizing radiation. Utilizing rodent repair-deficient mutant, we have shown that the genes responsible for DNA double-strand break repair are also responsible for the cellular expression of radiation sensitivity. The molecular genetic analysis of DSB repair in rodent/human hybrid cells indicate that at least 6 different genes in mammalian cells are responsible for the repair of radiation-induced DNA double-strand breaks. Mapping and the prospect of cloning of human radiation repair genes are reviewed. Understanding the molecular and genetic basis of radiation sensitivity and DNA repair in man will provide a rational foundation to predict the individual risk associated with radiation exposure and to prevent radiation-induced genetic damage in the human population.

  17. DNA repair and radiation sensitivity in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Chen, D.J.C.; Stackhouse, M. (Los Alamos National Lab., NM (United States)); Chen, D.S. (Rochester Univ., NY (United States). Dept. of Radiation Oncology)

    1993-01-01

    Ionizing radiation induces various types of damage in mammalian cells including DNA single-strand breaks, DNA double-strand breaks (DSB), DNA-protein cross links, and altered DNA bases. Although human cells can repair many of these lesions there is little detailed knowledge of the nature of the genes and the encoded enzymes that control these repair processes. We report here on the cellular and genetic analyses of DNA double-strand break repair deficient mammalian cells. It has been well established that the DNA double-strand break is one of the major lesions induced by ionizing radiation. Utilizing rodent repair-deficient mutant, we have shown that the genes responsible for DNA double-strand break repair are also responsible for the cellular expression of radiation sensitivity. The molecular genetic analysis of DSB repair in rodent/human hybrid cells indicate that at least 6 different genes in mammalian cells are responsible for the repair of radiation-induced DNA double-strand breaks. Mapping and the prospect of cloning of human radiation repair genes are reviewed. Understanding the molecular and genetic basis of radiation sensitivity and DNA repair in man will provide a rational foundation to predict the individual risk associated with radiation exposure and to prevent radiation-induced genetic damage in the human population.

  18. Inducible repair of oxidative DNA damage in Escherichia coli.

    Science.gov (United States)

    Demple, B; Halbrook, J

    Hydrogen peroxide is lethal to many cell types, including the bacterium Escherichia coli. Peroxides yield transient radical species that can damage DNA and cause mutations. Such partially reduced oxygen species are occasionally released during cellular respiration and are generated by lethal and mutagenic ionizing radiation. Because cells live in an environment where the threat of oxidative DNA damage is continual, cellular mechanisms may have evolved to avoid and repair this damage. Enzymes are known which evidently perform these functions. We report here that resistance to hydrogen peroxide toxicity can be induced in E. coli, that this novel induction is specific and occurs, in part, at the level of DNA repair.

  19. Repairable-conditionally repairable damage model based on dual Poisson processes.

    Science.gov (United States)

    Lind, B K; Persson, L M; Edgren, M R; Hedlöf, I; Brahme, A

    2003-09-01

    The advent of intensity-modulated radiation therapy makes it increasingly important to model the response accurately when large volumes of normal tissues are irradiated by controlled graded dose distributions aimed at maximizing tumor cure and minimizing normal tissue toxicity. The cell survival model proposed here is very useful and flexible for accurate description of the response of healthy tissues as well as tumors in classical and truly radiobiologically optimized radiation therapy. The repairable-conditionally repairable (RCR) model distinguishes between two different types of damage, namely the potentially repairable, which may also be lethal, i.e. if unrepaired or misrepaired, and the conditionally repairable, which may be repaired or may lead to apoptosis if it has not been repaired correctly. When potentially repairable damage is being repaired, for example by nonhomologous end joining, conditionally repairable damage may require in addition a high-fidelity correction by homologous repair. The induction of both types of damage is assumed to be described by Poisson statistics. The resultant cell survival expression has the unique ability to fit most experimental data well at low doses (the initial hypersensitive range), intermediate doses (on the shoulder of the survival curve), and high doses (on the quasi-exponential region of the survival curve). The complete Poisson expression can be approximated well by a simple bi-exponential cell survival expression, S(D) = e(-aD) + bDe(-cD), where the first term describes the survival of undamaged cells and the last term represents survival after complete repair of sublethal damage. The bi-exponential expression makes it easy to derive D(0), D(q), n and alpha, beta values to facilitate comparison with classical cell survival models.

  20. Radiation damage tolerant nanomaterials

    Directory of Open Access Journals (Sweden)

    I.J. Beyerlein

    2013-11-01

    Full Text Available Designing a material from the atomic level to achieve a tailored response in extreme conditions is a grand challenge in materials research. Nanostructured metals and composites provide a path to this goal because they contain interfaces that attract, absorb and annihilate point and line defects. These interfaces recover and control defects produced in materials subjected to extremes of displacement damage, impurity implantation, stress and temperature. Controlling radiation-induced-defects via interfaces is shown to be the key factor in reducing the damage and imparting stability in certain nanomaterials under conditions where bulk materials exhibit void swelling and/or embrittlement. We review the recovery of radiation-induced point defects at free surfaces and grain boundaries and stabilization of helium bubbles at interphase boundaries and present an approach for processing bulk nanocomposites containing interfaces that are stable under irradiation.

  1. Radiation damage in graphite

    CERN Document Server

    Simmons, John Harry Walrond

    1965-01-01

    Nuclear Energy, Volume 102: Radiation Damage in Graphite provides a general account of the effects of irradiation on graphite. This book presents valuable work on the structure of the defects produced in graphite crystals by irradiation. Organized into eight chapters, this volume begins with an overview of the description of the methods of manufacturing graphite and of its physical properties. This text then presents details of the method of setting up a scale of irradiation dose. Other chapters consider the effect of irradiation at a given temperature on a physical property of graphite. This

  2. YNK1, the yeast homolog of human metastasis suppressor NM23, is required for repair of UV radiation- and etoposide-induced DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Yang Mengmeng; Jarrett, Stuart G.; Craven, Rolf [Department of Molecular and Biomedical Pharmacology, College of Medicine, University of Kentucky, Lexington, KY 40536-0298 (United States); Kaetzel, David M. [Department of Molecular and Biomedical Pharmacology, College of Medicine, University of Kentucky, Lexington, KY 40536-0298 (United States)], E-mail: dmkaetz@uky.edu

    2009-01-15

    In humans, NM23-H1 is a metastasis suppressor whose expression is reduced in metastatic melanoma and breast carcinoma cells, and which possesses the ability to inhibit metastatic growth without significant impact on the transformed phenotype. NM23-H1 exhibits three enzymatic activities in vitro, each with potential to maintain genomic stability, a 3'-5' exonuclease and two kinases, nucleoside diphosphate kinase (NDPK), and protein histidine kinase. Herein we have investigated the potential contributions of NM23 proteins to DNA repair in the yeast, Saccharomyces cerevisiae, which contains a single NM23 homolog, YNK1. Ablation of YNK1 delayed repair of UV- and etoposide-induced nuclear DNA damage by 3-6 h. However, YNK1 had no impact upon the kinetics of MMS-induced DNA repair. Furthermore, YNK1 was not required for repair of mitochondrial DNA damage. To determine whether the nuclear DNA repair deficit manifested as an increase in mutation frequency, the CAN1 forward assay was employed. An YNK1 deletion was associated with increased mutation rates following treatment with either UV (2.6x) or MMS (1.6x). Mutation spectral analysis further revealed significantly increased rates of base substitution and frameshift mutations following UV treatment in the ynk1{delta} strain. This study indicates a novel role for YNK1 in DNA repair in yeast, and suggests an anti-mutator function that may contribute to the metastasis suppressor function of NM23-H1 in humans.

  3. Effect of ionizing radiation in sensory ganglion neurons: organization and dynamics of nuclear compartments of DNA damage/repair and their relationship with transcription and cell cycle.

    Science.gov (United States)

    Casafont, Iñigo; Palanca, Ana; Lafarga, Vanesa; Berciano, Maria T; Lafarga, Miguel

    2011-10-01

    Neurons are very sensitive to DNA damage induced by endogenous and exogenous genotoxic agents, as defective DNA repair can lead to neurodevelopmental disorders, brain tumors and neurodegenerative diseases with severe clinical manifestations. Understanding the impact of DNA damage/repair mechanisms on the nuclear organization, particularly on the regulation of transcription and cell cycle, is essential to know the pathophysiology of defective DNA repair syndromes. In this work, we study the nuclear architecture and spatiotemporal organization of chromatin compartments involved in the DNA damage response (DDR) in rat sensory ganglion neurons exposed to X-ray irradiation (IR). We demonstrate that the neuronal DDR involves the formation of two categories of DNA-damage processing chromatin compartments: transient, disappearing within the 1 day post-IR, and persistent, where unrepaired DNA is accumulated. Both compartments concentrate components of the DDR pathway, including γH2AX, pATM and 53BP1. Furthermore, DNA damage does not induce neuronal apoptosis but triggers the G0-G1 cell cycle phase transition, which is mediated by the activation of the ATM-p53 pathway and increased protein levels of p21 and cyclin D1. Moreover, the run on transcription assay reveals a severe inhibition of transcription at 0.5 h post-IR, followed by its rapid recovery over the 1 day post-IR in parallel with the progression of DNA repair. Therefore, the response of healthy neurons to DNA damage involves a transcription- and cell cycle-dependent but apoptosis-independent process. Furthermore, we propose that the segregation of unrepaired DNA in a few persistent chromatin compartments preserves genomic stability of undamaged DNA and the global transcription rate in neurons.

  4. UV exposed electronically activated damage and photoreactivation repair

    Science.gov (United States)

    Bohr, Henrik; Malik, Bary

    2007-03-01

    An investigation of the possible physics underlying the damage caused to DNA by UV radiation and its subsequent repair via a photoreactivation mechanism is presented in this study. An electronic pathway starting from the initial damage to the final repair process is proposed. UV radiation is absorbed to create a hole-excited thymine or other pyrimidine that subsequently is responsible for the formation of the thymine dimer. The negative-ion of the cofactor riboflavin, FADH-, formed by the exposure of the photolyase protein to visible light interacts with the hole-excited electronic orbital of the thymine dimer inducing a photon-less Auger transition, which restores the two thymines to the ground state, thereby detaching the lesion and repairing the DNA. Due to energy balance, the process has to involve an electronic excited state (s). The mechanism involves the least amount of energy dissipation and is charge neutral. It also avoids radiation damage in the repair process, that is, is a radiationless process.

  5. 49 CFR 1242.42 - Administration, repair and maintenance, machinery repair, equipment damaged, dismantling retired...

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 9 2010-10-01 2010-10-01 false Administration, repair and maintenance, machinery repair, equipment damaged, dismantling retired property, fringe benefits, other casualties and insurance... maintenance, machinery repair, equipment damaged, dismantling retired property, fringe benefits,...

  6. Damage, DNA Repair, Aging, and Neurodegeneration

    Science.gov (United States)

    Maynard, Scott; Fang, Evandro Fei; Scheibye-Knudsen, Morten; Croteau, Deborah L.; Bohr, Vilhelm A.

    2017-01-01

    Aging in mammals is accompanied by a progressive atrophy of tissues and organs, and stochastic damage accumulation to the macromolecules DNA, RNA, proteins, and lipids. The sequence of the human genome represents our genetic blueprint, and accumulating evidence suggests that loss of genomic maintenance may causally contribute to aging. Distinct evidence for a role of imperfect DNA repair in aging is that several premature aging syndromes have underlying genetic DNA repair defects. Accumulation of DNA damage may be particularly prevalent in the central nervous system owing to the low DNA repair capacity in postmitotic brain tissue. It is generally believed that the cumulative effects of the deleterious changes that occur in aging, mostly after the reproductive phase, contribute to species-specific rates of aging. In addition to nuclear DNA damage contributions to aging, there is also abundant evidence for a causative link between mitochondrial DNA damage and the major phenotypes associated with aging. Understanding the mechanistic basis for the association of DNA damage and DNA repair with aging and age-related diseases, such as neurodegeneration, would give insight into contravening age-related diseases and promoting a healthy life span. PMID:26385091

  7. Civil liability for ecologic damage and repairing

    OpenAIRE

    Basílio, Patrícia Droeber; Faculdades de Vitória, Espírito Santo, Brasil

    2009-01-01

    This article analyses how civil liability takes position regarding situations connected to damages caused to the environment, defined ways in our legislation reprimanding damages caused and existent ways of prevention and repairing. The text contemplates how law disciplines such issue, looking for efficient and effective solutions and also checking evolution and modification from law which are relevant to the environment, the environmental law, whereas we observe it is a serious issue that ha...

  8. Radiation damage and repair in cells and cell components. Progress report, November 1, 1977--October 31, 1978. [Uv and x radiation, bacteriophages

    Energy Technology Data Exchange (ETDEWEB)

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

    1978-01-01

    Progress is reported on the following research projects: coordinate induction of mutagenesis, radioresistance, and inhibition of post-radiation DNA degradation; radioinduced filamentation; action spectrum for induction of K12 lambda phage; effects of uv radiation on cells in the frozen state; dependence of mutagenesis on wavelength of uv; and w-reactivation of x-irradiated phage lambda. (HLW)

  9. The indirect effect of radiation reduces the repair fidelity of NHEJ as verified in repair deficient CHO cell lines exposed to different radiation qualities and potassium bromate

    Energy Technology Data Exchange (ETDEWEB)

    Bajinskis, Ainars, E-mail: ainars.bajinskis@gmt.su.se [Centre for Radiation Protection Research, Department of Genetics, Microbiology and Toxicology, Stockholm University, S-10691 Stockholm (Sweden); Olsson, Gunilla; Harms-Ringdahl, Mats [Centre for Radiation Protection Research, Department of Genetics, Microbiology and Toxicology, Stockholm University, S-10691 Stockholm (Sweden)

    2012-03-01

    The complexity of DNA lesions induced by ionizing radiation is mainly dependent on radiation quality, where the indirect action of radiation may contribute to different extent depending on the type of radiation under study. The effect of indirect action of radiation can be investigated by using agents that induce oxidative DNA damage or by applying free radical scavengers. The aim of this study was to investigate the role of the indirect effect of radiation for the repair fidelity of non-homologous end-joining (NHEJ), homologous recombination repair (HRR) and base excision repair (BER) when DNA damage of different complexity was induced by gamma radiation, alpha particles or from base damages (8-oxo-dG) induced by potassium bromate (KBrO{sub 3}). CHO cells lines deficient in XRCC3 (HRR) irs1SF, XRCC7 (NHEJ) V3-3 and XRCC1 (BER) EM9 were irradiated in the absence or presence of the free radical scavenger dimethyl sulfoxide (DMSO). The endpoints investigated included rate of cell proliferation by the DRAG assay, clonogenic cell survival and the level of primary DNA damage by the comet assay. The results revealed that the indirect effect of low-LET radiation significantly reduced the repair fidelity of both NHEJ and HRR pathways. For high-LET radiation the indirect effect of radiation also significantly reduced the repair fidelity for the repair deficient cell lines. The results suggest further that the repair fidelity of the error prone NHEJ repair pathway is more impaired by the indirect effect of high-LET radiation relative to the other repair pathways studied. The response to bromate observed for the two DSB repair deficient cell lines strongly support earlier studies that bromate induces complex DNA damages. The significantly reduced repair fidelity of irs1SF and V3-3 suggests that NHEJ as well as HRR are needed for the repair, and that complex DSBs are formed after bromate exposure.

  10. Effect of chronic low dose natural radiation in human peripheral blood mononuclear cells: Evaluation of DNA damage and repair using the alkaline comet assay.

    Science.gov (United States)

    Kumar, P R Vivek; Seshadri, M; Jaikrishan, G; Das, Birajalaxmi

    2015-05-01

    This study investigates whether peripheral blood mononuclear cells (PBMCs) from inhabitants of Kerala in southwest India, exposed to chronic low dose natural radiation in vivo (>1 mSv year(-1)), respond with a radioadaptive response to a challenging dose of gamma radiation. Toward this goal, PBMCs isolated from 77 subjects from high-level natural radiation areas (HLNRA) and 37 subjects from a nearby normal level natural radiation area (NLNRA) were challenged with 2 Gy and 4 Gy gamma radiation. Subjects from HLNRA were classified based on the mean annual effective dose received, into low dose group (LDG) and high dose group (HDG) with mean annual effective doses of 2.69 mSv (N=43, range 1.07 mSv year(-1) to 5.55 mSv year(-1)) and 9.62 mSv (N = 34, range 6.07 mSv year(-1) to 17.41 mSv year(-1)), respectively. DNA strand breaks and repair kinetics (at 7 min, 15 min and 30 min after 4 Gy) were evaluated using the alkaline single cell gel electrophoresis (comet) assay. Initial levels of DNA strand breaks observed after either a 2 Gy or a 4 Gy challenging dose were significantly lower in subjects of the HDG from HLNRA compared to subjects of NLNRA (2 Gy, P = 0.01; 4 Gy, P = 0.02) and LDG (2 Gy P = 0.01; 4 Gy, P=0.05). Subjects of HDG from HLNRA showed enhanced rejoining of DNA strand breaks (HDG/NLNRA, P = 0.06) during the early stage of repair (within 7 min). However at later times a similar rate of rejoining of strand breaks was observed across the groups (HDG, LDG and NLNRA). Preliminary results from our study suggest in vivo chronic low-level natural radiation provides an initial exposure that allows an adaptation to a subsequent higher radiation exposure, perhaps through improving DNA repair via an unknown mechanism. Therefore, further investigations would be necessary in this population to understand the biological and health effects of chronic low-level natural radiation exposures. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Integration of principles of systems biology and radiation biology: toward development of in silico models to optimize IUdR-mediated radiosensitization of DNA mismatch repair-deficient (damage tolerant human cancers

    Directory of Open Access Journals (Sweden)

    Timothy James Kinsella

    2011-08-01

    Full Text Available Over the last 7 years, we have focused our experimental and computational research efforts on improving our understanding of the biochemical, molecular, and cellular processing of iododeoxyuridine (IUdR and ionizing radiation (IR induced DNA base damage by DNA mismatch repair (MMR. These coordinated research efforts, sponsored by the National Cancer Institute Integrative Cancer Biology Program (ICBP, brought together system scientists with expertise in engineering, mathematics, and complex systems theory and translational cancer researchers with expertise in radiation biology. Our overall goal was to begin to develop computational models of IUdR- and/or IR- induced base damage processing by MMR that may provide new clinical strategies to optimize IUdR-mediated radiosensitiztion in MMR deficient (MMR- damage tolerant human cancers. Using multiple scales of experimental testing, ranging from purified protein systems to in vitro (cellular and to in vivo (human tumor xenografts in athymic mice models, we have begun to integrate and interpolate these experimental data with hybrid stochastic biochemical models of MMR damage processing and probabilistic cell cycle regulation models through a systems biology approach. In this article, we highlight the results and current status of our integration of radiation biology approaches and computational modeling to enhance IUdR-mediated radiosensitization in MMR- damage tolerant cancers.

  12. Radiation Damage of Quartz Fibers

    CERN Document Server

    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 quartz clad and aluminum buffer.

  13. 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...

  14. SIRT1 promotes DNA repair activity in response to radiation

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Jae-Min; Lee, Kee-Ho [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2006-07-01

    Human SIRT1 controls various physiological responses including cell fate, stress, and aging, through deacetylation of its specific substrate protein. In processing DNA damage signaling, SIRT1 attenuates a cellular apoptotic response by deacetylation of p53 tumor suppressor. Ectopically over-expressed SIRT1 resulted in the increase of repair of DNA strand breakages produced by radiation. On the other hand, repression of endogenous SIRT1 expression by SIRT1 siRNA led to the decrease of this repair activity, indicating that SIRT1 can regulate DNA repair capacity of cells with DNA strand breaks.

  15. 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)

  16. DNA damage, repair and tanning acceleration

    NARCIS (Netherlands)

    Vink, A.A.; Berg, P.T.M. van den; Roza, L.

    1999-01-01

    Exposure of the skin to solar ultraviolet radiation (UV) leads to various adverse effects, such as the induction of cellular damage and mutations, suppression of the skin's immune system, and the induction of skin cancer. These effects are the consequence of various molecular alterations in the skin

  17. Chromatin modifications and the DNA damage response to ionizing radiation

    Science.gov (United States)

    Kumar, Rakesh; Horikoshi, Nobuo; Singh, Mayank; Gupta, Arun; Misra, Hari S.; Albuquerque, Kevin; Hunt, Clayton R.; Pandita, Tej K.

    2013-01-01

    In order to survive, cells have evolved highly effective repair mechanisms to deal with the potentially lethal DNA damage produced by exposure to endogenous as well as exogenous agents. Ionizing radiation exposure induces highly lethal DNA damage, especially DNA double-strand breaks (DSBs), that is sensed by the cellular machinery and then subsequently repaired by either of two different DSB repair mechanisms: (1) non-homologous end joining, which re-ligates the broken ends of the DNA and (2) homologous recombination, that employs an undamaged identical DNA sequence as a template, to maintain the fidelity of DNA repair. Repair of DSBs must occur within the natural context of the cellular DNA which, along with specific proteins, is organized to form chromatin, the overall structure of which can impede DNA damage site access by repair proteins. The chromatin complex is a dynamic structure and is known to change as required for ongoing cellular processes such as gene transcription or DNA replication. Similarly, during the process of DNA damage sensing and repair, chromatin needs to undergo several changes in order to facilitate accessibility of the repair machinery. Cells utilize several factors to modify the chromatin in order to locally open up the structure to reveal the underlying DNA sequence but post-translational modification of the histone components is one of the primary mechanisms. In this review, we will summarize chromatin modifications by the respective chromatin modifying factors that occur during the DNA damage response. PMID:23346550

  18. GENETIC AND MOLECULAR ANALYSIS OF DNA DAMAGE REPAIR AND TOLERANCE PATHWAYS.

    Energy Technology Data Exchange (ETDEWEB)

    SUTHERLAND, B.M.

    2001-07-26

    Radiation can damage cellular components, including DNA. Organisms have developed a panoply of means of dealing with DNA damage. Some repair paths have rather narrow substrate specificity (e.g. photolyases), which act on specific pyrimidine photoproducts in a specific type (e.g., DNA) and conformation (double-stranded B conformation) of nucleic acid. Others, for example, nucleotide excision repair, deal with larger classes of damages, in this case bulky adducts in DNA. A detailed discussion of DNA repair mechanisms is beyond the scope of this article, but one can be found in the excellent book of Friedberg et al. [1] for further detail. However, some DNA damages and paths for repair of those damages important for photobiology will be outlined below as a basis for the specific examples of genetic and molecular analysis that will be presented below.

  19. Chromatin Modifications and the DNA Damage Response to Ionizing Radiation

    Directory of Open Access Journals (Sweden)

    Tej K Pandita

    2013-01-01

    Full Text Available In order to survive, cells have evolved highly effective repair mechanisms to deal with the potentially lethal DNA damage produced by exposure to endogenous as well as exogenous agents. Ionizing radiation exposure induces highly lethal DNA damage, especially DNA double strand breaks (DSBs, that is sensed by the cellular machinery and then subsequently repaired by either of two different DSB repair mechanisms: 1 non-homologous end-joining (NHEJ, which re-ligates the broken ends of the DNA and 2 homologous recombination (HR, that employs an undamaged identical DNA sequence as a template, to maintain the fidelity of DNA repair. Repair of DSBs must occur within the natural context of the cellular DNA which, along with specific proteins, is organized to form chromatin, the overall structure of which can impede DNA damage site access by repair proteins. The chromatin complex is a dynamic structure and is known to change as required for ongoing cellular processes such as gene transcription or DNA replication. Similarly, during the process of DNA damage sensing and repair, chromatin needs to undergo several changes in order to facilitate accessibility of the repair machinery. Cells utilize several factors to modify the chromatin in order to locally open up the structure to reveal the underlying DNA sequence but posttranslational modification (PTMs of the histone components is one of the primary mechanisms. In this review, we will summarize chromatin modification by t

  20. A progression of damage repair capability in self-repairing composites

    Science.gov (United States)

    Dry, Carolyn

    2014-04-01

    This paper covers several projects in which the author sought to determine the extent of damage against which self repair would be effective. So far no limits have been reached beyond those of the fiber/matrix itself. Starting with repair of barely visible damage in airplane wings consisting of graphite fiber/resin matrix composites progression was next to self repair of ballistic damage to vinyl ester walls and epoxy resin walls and finally blast damage self repair of walls and then blast and ballistic damage were combined.

  1. Radiation damage in silicon detectors

    CERN Document Server

    Lindström, G

    2003-01-01

    Radiation damage effects in silicon detectors under severe hadron and gamma-irradiation are surveyed, focusing on bulk effects. Both macroscopic detector properties (reverse current, depletion voltage and charge collection) as also the underlying microscopic defect generation are covered. Basic results are taken from the work done in the CERN-RD48 (ROSE) collaboration updated by results of recent work. Preliminary studies on the use of dimerized float zone and Czochralski silicon as detector material show possible benefits. An essential progress in the understanding of the radiation-induced detector deterioration had recently been achieved in gamma irradiation, directly correlating defect analysis data with the macroscopic detector performance.

  2. [Studies of the repair of radiation-induced genetic damage in Drosophila]. Annual progress report, February 1, 1993--November 1, 1994

    Energy Technology Data Exchange (ETDEWEB)

    Hawley, R.S.

    1998-09-01

    This research focuses on two repair deficient mutations in Drosophila melanogaster, namely mei-9, mei-41. In addition, the authors propose to extend this study to include the mus-312 mutation. They expect these studies to provide substantial insights into both the molecular mechanisms of DNA repair in Drosophila and the role these genes play in normal biological processes.

  3. [Studies of the repair of radiation-induced genetic damage in Drosophila]. Annual progress report, February 1, 1993--November 1, 1994

    Energy Technology Data Exchange (ETDEWEB)

    Hawley, R.S.

    1998-09-01

    This research focuses on two repair deficient mutations in Drosophila melanogaster, namely mei-9, mei-41. In addition, the authors propose to extend this study to include the mus-312 mutation. They expect these studies to provide substantial insights into both the molecular mechanisms of DNA repair in Drosophila and the role these genes play in normal biological processes.

  4. 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,...

  5. 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...

  6. Radiation damage in multiphase ceramics

    Energy Technology Data Exchange (ETDEWEB)

    Men, Danju [Department of Chemical Engineering and Materials Science, University of California, Irvine, CA 92697-2575 (United States); Patel, Maulik K.; Usov, Igor O. [Materials Science and Technology Division, Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Toiammou, Moidi; Monnet, Isabelle [CIMAP, CEA/CNRS/ENSICAEN/Universite de Caen-Basse Normandie, Bd Henri Becquerel, BP 5133, F-14070 Caen Cedex 5 (France); Pivin, Jean Claude [Centre de Spectrometrie Nucleaire et de Spectrometrie de Masse, CNRS-IN2P3-Universite Paris Sud, UMR 8609, Bat. 108, 91405 Orsay (France); Porter, John R. [Materials Department, University of California, Santa Barbara, CA 93106-5050 (United States); Mecartney, Martha L., E-mail: martham@uci.edu [Department of Chemical Engineering and Materials Science, University of California, Irvine, CA 92697-2575 (United States)

    2013-11-15

    Graphical abstract: Display Omitted -- Abstract: Four-phase ceramic composites containing 3 mol% Y{sub 2}O{sub 3} stabilized ZrO{sub 2} (3Y-TZP), Al{sub 2}O{sub 3}, MgAl{sub 2}O{sub 4}, and LaPO{sub 4} were synthesized as model materials representing inert matrix fuel with enhanced thermal conductivity and decreased radiation-induced microstructural damage with respect to single-phase UO{sub 2}. This multi-phase concept, if successful, could be applied to design advanced nuclear fuels which could then be irradiated to higher burn-ups. 3Y-TZP in the composite represents a host (fuel) phase with the lowest thermal conductivity and Al{sub 2}O{sub 3} is the high thermal conductivity phase. The role of MgAl{sub 2}O{sub 4} and LaPO{sub 4} was to stabilize the structure under irradiation. The radiation response was evaluated by ion irradiation at 500 °C with 10 MeV Au ions and at 800 °C with 92 MeV Xe ions, to simulate damage due to primary knock-on atoms and fission fragments, respectively. Radiation damage and microstructural changes were characterized by X-ray diffraction, scanning electron microscopy and transmission electron microscopy and computational modeling. Al{sub 2}O{sub 3}, Y{sub 2}O{sub 3} stabilized ZrO{sub 2} and MgAl{sub 2}O{sub 4} phases exhibit high amorphization resistance and remain stable when irradiated with both Au and Xe ions. A monoclinic-to-tetragonal phase transformation, however, is promoted by Xe and Au ion irradiation in 3Y-TZP. The LaPO{sub 4} monazite phase appears to melt, dewet the other phases, and recrystallize under Au irradiation, but does not change under Xe irradiation.

  7. 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

  8. Repair of damaged supraglottic airway devices: A novel method

    Directory of Open Access Journals (Sweden)

    Kapoor Dheeraj

    2010-06-01

    Full Text Available Abstract Damage of laryngeal mask airway and other supraglottic airway devices has always been a matter of concern. Although manufacturer recommends maximum 40 uses of LMA (and its congeners but damage before 40 uses needs to be evaluated. We hereby, describe a novel method of repair of supraglottic devices when damage occurs at mask inflation line or pilot balloon valve assembly.

  9. Suppressed expression of non-DSB repair genes inhibits gamma-radiation-induced cytogenetic repair and cell cycle arrest.

    Science.gov (United States)

    Zhang, Ye; Rohde, Larry H; Emami, Kamal; Hammond, Dianne; Casey, Rachael; Mehta, Satish K; Jeevarajan, Antony S; Pierson, Duane L; Wu, Honglu

    2008-11-01

    Changes of gene expression profile are one of the most important biological responses in living cells after ionizing radiation (IR) exposure. Although some studies have shown that genes up-regulated by IR may play important roles in DNA damage repair, the relationship between the regulation of gene expression by IR, particularly genes not known for their roles in double-strand break (DSB) repair, and its impact on cytogenetic responses has not been well studied. The purpose of this study is to identify new roles of IR inducible genes in regulating DSB repair and cell cycle progression. In this study, the expression of 25 genes selected on the basis of their transcriptional changes in response to IR was individually knocked down by small interfering RNA in human fibroblast cells. Frequency of micronuclei (MN) formation and chromosome aberrations were measured to determine efficiency of cytogenetic repair, especially DSB repair. In response to IR, the formation of MN was significantly increased by suppressed expression of five genes: Ku70 (DSB repair pathway), XPA (nucleotide excision repair pathway), RPA1 (mismatch repair pathway), RAD17 and RBBP8 (cell cycle control). Knocked-down expression of four genes (MRE11A, RAD51 in the DSB pathway, SESN1, and SUMO1) significantly inhibited cell cycle progression, possibly because of severe impairment of DNA damage repair. Moreover, decreased XPA, p21, or MLH1 expression resulted in both significantly enhanced cell cycle progression and increased yields of chromosome aberrations, indicating that these gene products modulate both cell cycle control and DNA damage repair. Nine of these eleven genes, whose knock-down expression affected cytogenetic repair, were up-regulated in cells exposed to gamma radiation, suggesting that genes transcriptionally modulated by IR were critical to regulate IR-induced biological consequences. Furthermore, eight non-DBS repair genes showed involvement in regulating DSB repair, indicating that

  10. Damage diagnosis and compatible repair mortars

    NARCIS (Netherlands)

    Hees, R.P.J. van

    1999-01-01

    Mortars for repair and maintenance of historic masonry have to meet specific requirements. Several authors have made contributions, however many cases of failure show that there still is quite a lack of knowledge on the compatibility of repair mortars for historic masonry. The diagnosis of the cause

  11. Defense mechanisms against radiation induced teratogenic damage in mice

    Energy Technology Data Exchange (ETDEWEB)

    Kato, F.; Ootsuyama, A.; Nomoto, S.; Norimura, T. [Univ. of Occupational and Environmental Health, Kitakyushu, (Japan)

    2002-07-01

    Experimental studies with mice have established that fetuses at midgestational stage are highly susceptible to malformation at high, but not low, doses of radiation. When DNA damage is produced by a small amount of radiation, it is efficiently eliminated by DNA repair. However, DNA repair is not perfect. There must be defense mechanisms other than DNA repair. In order to elucidate the essential role of p53 gene in apoptotic tissue repair, we compared the incidence of radiation-induced malformations and deaths (deaths after day 10) in wild-type p53 (+/+) mice and null p53 (-/-) mice. For p53 (+/+) mice, an X-ray dose of 2 Gy given at a high dose-rate (450 mGy/min) to fetuses at 9.5 days of gestation was highly lethal and considerably teratogenic whereas it was only slightly lethal but highly teratogenic for p53 (-/-) fetuses. This reciprocal relationship of radiosensitivity to malformations and deaths supports the notion that fetal tissues have a p53 -dependent idguardianln of the tissue that aborts cells bearing radiation-induced teratogenic DNA damage. When an equal dose of 2 Gy given at a 400-fold lower dose-rate (1.2 mGy/min), this dose became not teratogenic for p53 (+/+) fetuses exhibiting p53 -dependent apoptosis, whereas this dose remained teratogenic for p53 (-/-) fetuses unable to carry out apoptosis. Furthermore, when the dose was divided into two equal dose fractions (1+1 Gy) at high dose rate, separated by 24 hours, the incidences of malformations were equal with control level for p53 (+/+), but higher for p53 (-/-) mice. Hence, complete elimination of teratogenic damage from irradiated tissues requires a concerted cooperation of two mechanisms; proficient DNA repair and p53-dependent apoptotic tissue repair.

  12. Choreography of oxidative damage repair in mammalian genomes.

    Science.gov (United States)

    Mitra, Sankar; Izumi, Tadahide; Boldogh, Istvan; Bhakat, Kishor K; Hill, Jeff W; Hazra, Tapas K

    2002-07-01

    The lesions induced by reactive oxygen species in both nuclear and mitochondrial genomes include altered bases, abasic (AP) sites, and single-strand breaks, all repaired primarily via the base excision repair (BER) pathway. Although the basic BER process (consisting of five sequential steps) could be reconstituted in vitro with only four enzymes, it is now evident that repair of oxidative damage, at least in mammalian cell nuclei, is more complex, and involves a number of additional proteins, including transcription- and replication-associated factors. These proteins may be required in sequential repair steps in concert with other cellular changes, starting with nuclear targeting of the early repair enzymes in response to oxidative stress, facilitation of lesion recognition, and access by chromatin unfolding via histone acetylation, and formation of metastable complexes of repair enzymes and other accessory proteins. Distinct, specific subclasses of protein complexes may be formed for repair of oxidative lesions in the nucleus in transcribed vs. nontranscribed sequences in chromatin, in quiescent vs. cycling cells, and in nascent vs. parental DNA strands in replicating cells. Characterizing the proteins for each repair subpathway, their signaling-dependent modifications and interactions in the nuclear as well as mitochondrial repair complexes, will be a major focus of future research in oxidative damage repair.

  13. Human longevity and variation in DNA damage response and repair

    DEFF Research Database (Denmark)

    Debrabant, Birgit; Soerensen, Mette; Flachsbart, Friederike

    2014-01-01

    others. Data were applied on 592 SNPs from 77 genes involved in nine sub-processes: DNA-damage response, base excision repair (BER), nucleotide excision repair, mismatch repair, non-homologous end-joining, homologous recombinational repair (HRR), RecQ helicase activities (RECQ), telomere functioning...... and mitochondrial DNA processes. The study population was 1089 long-lived and 736 middle-aged Danes. A self-contained set-based test of all SNPs displayed association with longevity (P-value=9.9 × 10-5), supporting that the overall pathway could affect longevity. Investigation of the nine sub-processes using...

  14. [Studies of the repair of radiation-induced genetic damage in Drosophila]. Annual progress report, June 1, 1992--June 30, 1993

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-09-01

    The most interesting discovery made over the past year derives from sequence analysis of cDNAs from the putative mus308 gene. The theoretical translation product of this gene contains a DNA polymerase domain near the carboxy terminus and DNA/RNA helicase motifs near the amino terminus. There is currently no precedent in the literature for a single polypeptide containing both of these domains. The protein appears to be a novel DNA repair enzyme which should be fruitful ground for future enzymological analysis. The authors have identified two ORFs by sequence analysis of the transforming fragment containing the mei-41 gene and of corresponding cDNAs. ORF 1 includes the P element insertion sites and encodes a peptide of 757 amino acids. ORF 2 starts 900 base pairs downstream of ORF 1 and encodes a peptide of 1,037 amino acids. This putative peptide shows homology to the yeast DNA repair genes, rad50 of S. cerevisiae and rad3 of S. pombe.

  15. In vitro sublethal damage repair in tumour subpopulations from a heterogeneous human colon tumour

    Energy Technology Data Exchange (ETDEWEB)

    Leith, J.T.; Vayer, A.V. Jr.; DeWyngaert, J.K.; Amols, H.; Peck, R.A. Jr.; Glicksman, A.S. (Rhode Island Hospital (USA); Brown Univ., Providence, RI (USA))

    1984-01-01

    The repair of sublethal radiation damage in two asynchronously growing tumour cell subpopulations (clones A and D) obtained from a single human adenocarcinoma biopsy specimen has been studied. The survival data found after generation of complete survival curves from split dose experiments in which exposures were separated by 3, 6, 12, or 24 h were examined. It was found that the method of performing irradiations (e.g., suspension cultures versus monolayer cultures) affected the shape of the single dose response curves, and as a result the interpretation of the amount of sublethal damage repair occurring after split dose irradiation.

  16. DNA damage response and repair data with pharmacological modulators of Tousled

    Directory of Open Access Journals (Sweden)

    Prakash Srinivasan Timiri Shanmugam

    2016-06-01

    Full Text Available Human Tousled kinase 1 (TLK1 plays an important role in chromatin remodeling, replication, and DNA damage response and repair. TLK1 activity is immediately, but transiently, downregulated after genotoxic insult, and its recovery is important for exit from checkpoint arrest and cell survival after radiation. The data in this article compliments research presented in the paper titled, “Tousled kinase activator, gallic acid, promotes DNA repair and suppresses radiation cytotoxicity in salivary gland cells” [1]. The identification of small molecule activators and inhibitors of TLK1 provided an opportunity to pharmacologically alter the protein׳s activity to elucidate its role in DNA damage response pathways. TLK1 effectors, gallic acid (GA and thioridazine (THD activate and inhibit the kinase, respectively, and the data report on the impact of these compounds and the significance of TLK1 to DNA break repair and the survival of human salivary acinar cells.

  17. [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.

  18. Damage tolerance of bonded composite aircraft repairs for metallic structures

    Science.gov (United States)

    Clark, Randal John

    This thesis describes the development and validation of methods for damage tolerance substantiation of bonded composite repairs applied to cracked plates. This technology is used to repair metal aircraft structures, offering improvements in fatigue life, cost, manufacturability, and inspectability when compared to riveted repairs. The work focuses on the effects of plate thickness and bending on repair life, and covers fundamental aspects of fracture and fatigue of cracked plates and bonded joints. This project falls under the UBC Bonded Composite Repair Program, which has the goal of certification and widespread use of bonded repairs in civilian air transportation. This thesis analyses the plate thickness and transverse stress effects on fracture of repaired plates and the related problem of induced geometrically nonlinear bending in unbalanced (single-sided) repairs. The author begins by developing a classification scheme for assigning repair damage tolerance substantiation requirements based upon stress-based adhesive fracture/fatigue criteria and the residual strength of the original structure. The governing equations for bending of cracked plates are then reformulated and line-spring models are developed for linear and nonlinear coupled bending and extension of reinforced cracks. The line-spring models were used to correct the Wang and Rose energy method for the determination of the long-crack limit stress intensity, and to develop a new interpolation model for repaired cracks of arbitrary length. The analysis was validated using finite element models and data from mechanical tests performed on hybrid bonded joints and repair specimens that are representative of an in-service repair. This work will allow designers to evaluate the damage tolerance of the repaired plate, the adhesive, and the composite patch, which is an airworthiness requirement under FAR (Federal Aviation Regulations) 25.571. The thesis concludes by assessing the remaining barriers to

  19. Repair of ultraviolet-light-induced damage

    Energy Technology Data Exchange (ETDEWEB)

    Sutherland, B.M.

    1981-01-01

    Studies are reviewed which present three major new findings in the photobiology of skin. First, detectable numbers of dimers are formed even at sub-erythymal doses. Second, excision of dimers is much more rapid than would be predicted from results obtained in cell culture. Third, comparison of the rates of excision and photoreactivation in skin indicates that in normal sunlight exposure, photoreactivation may well be the predominant repair pathway in skin. (ACR)

  20. Repairing Damaged Power-Cable Insulation

    Science.gov (United States)

    Baker, G. E.

    1984-01-01

    Simple method saves time, money, and material. In new method cable remains in place while new insulation is applied to damaged portion. Method results in new terminations with safety factor equal to that of any portion of cable.

  1. Differential repair of UV damage in Saccharomyces cerevisiae.

    Science.gov (United States)

    Terleth, C; van Sluis, C A; van de Putte, P

    1989-06-26

    Preferential repair of UV-induced damage is a phenomenon by which mammalian cells might enhance their survival. This paper presents the first evidence that preferential repair occurs in the lower eukaryote Saccharomyces cerevisiae. Moreover an unique approach is reported to compare identical sequences present on the same chromosome and only differing in expression. We determined the removal of pyrimidine dimers from two identical alpha-mating type loci and we were able to show that the active MAT alpha locus is repaired preferentially to the inactive HML alpha locus. In a sir-3 mutant, in which both loci are active this preference is not observed.

  2. Biomarkers of oxidative damage to DNA and repair

    DEFF Research Database (Denmark)

    Loft, Steffen; Høgh Danielsen, Pernille; Mikkelsen, Lone

    2008-01-01

    Oxidative-stress-induced damage to DNA includes a multitude of lesions, many of which are mutagenic and have multiple roles in cancer and aging. Many lesions have been characterized by MS-based methods after extraction and digestion of DNA. These preparation steps may cause spurious base oxidation...... DNA glycosylase 1), responsible for repair of 8-oxodG, by genotyping. Products of repair in DNA or the nucleotide pool, such as 8-oxodG, excreted into the urine can be assessed by MS-based methods and generally reflects the rate of damage. Experimental and population-based studies indicate that many...

  3. Monitoring Radiation Damage in the ATLAS Pixel Detector

    CERN Document Server

    Schorlemmer, André Lukas; Große-Knetter, Jörn; Rembser, Christoph; Di Girolamo, Beniamino

    2014-11-05

    Radiation hardness is one of the most important features of the ATLAS pixel detector in order to ensure a good performance and a long lifetime. Monitoring of radiation damage is crucial in order to assess and predict the expected performance of the detector. Key values for the assessment of radiation damage in silicon, such as the depletion voltage and depletion depth in the sensors, are measured on a regular basis during operations. This thesis summarises the monitoring program that is conducted in order to assess the impact of radiation damage and compares it to model predictions. In addition, the physics performance of the ATLAS detector highly depends on the amount of disabled modules in the ATLAS pixel detector. A worrying amount of module failures was observed during run I. Thus it was decided to recover repairable modules during the long shutdown (LS1) by extracting the pixel detector. The impact of the module repairs and module failures on the detector performance is analysed in this thesis.

  4. MOF and H4 K16 Acetylation Play Important Roles in DNA Damage Repair by Modulating Recruitment of DNA Damage Repair Protein Mdc1 ▿

    Science.gov (United States)

    Li, Xiangzhi; Corsa, Callie Ann Sprunger; Pan, Patricia W.; Wu, Lipeng; Ferguson, David; Yu, Xiaochun; Min, Jinrong; Dou, Yali

    2010-01-01

    MOF (MYST1) is the major enzyme to catalyze acetylation of histone H4 lysine 16 (K16) and is highly conserved through evolution. Using a conditional knockout mouse model and the derived mouse embryonic fibroblast cell lines, we showed that loss of Mof led to a global reduction of H4 K16 acetylation, severe G2/M cell cycle arrest, massive chromosome aberration, and defects in ionizing radiation-induced DNA damage repair. We further showed that although early DNA damage sensing and signaling by ATM were normal in Mof-null cells, the recruitment of repair mediator protein Mdc1 and its downstream signaling proteins 53bp1 and Brca1 to DNA damage foci was completely abolished. Mechanistic studies suggested that Mof-mediated H4 K16 acetylation and an intact acidic pocket on H2A.X were essential for the recruitment of Mdc1. Removal of Mof and its associated proteins phenocopied a charge-neutralizing mutant of H2A.X. Given the well-characterized H4-H2A trans interactions in regulating higher-order chromatin structure, our study revealed a novel chromatin-based mechanism that regulates the DNA damage repair process. PMID:20837706

  5. DNA repair and damage pathway related cancer suppressor genes in low-dose-rate irradiated AKR/J an IR mice

    Energy Technology Data Exchange (ETDEWEB)

    Bang, Hyun Soon; Bong, Jin Jong; Kang, Yumi; Choi, Moo Hyun; Lee, Hae Un; Yoo, Jae Young; Choi, Seung Jin; Kim, Hee Sun [Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd, Gyeongju (Korea, Republic of); Lee, Kyung Mi [Global Research Lab, BAERI Institute, Dept. of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul (Korea, Republic of)

    2012-11-15

    It has been reported that low-dose-rate radiation stimulates the immune response, prolongs life span and inhibits carcinogenesis. The high dose-rate radiation influences the expression of DNA repair and damage-related genes. In contrast, DNA repair and damage signaling triggered by low-dose-rate irradiation remain unclear. In the present study, we investigated the differential expression of DNA repair and damage pathway related genes in the thymus of AKR/J and ICR mice after 100th day low-dose-rate irradiation. Our findings demonstrated that low-dose-rate γ -radiation suppressed tumorigenesis.

  6. Determination of the adaptive response induced In vivo by gamma radiation and its relation with the sensibility to the damage induction in the DNA and with the repairing capacity; Determinacion de la respuesta adaptativa inducida In vivo por radiacion gamma y su relacion con la sensibilidad a la induccion de dano en el ADN y con la capacidad de reparacion

    Energy Technology Data Exchange (ETDEWEB)

    Mendiola C, M.T

    2002-07-01

    The kinetics of damage induction and repair at different doses as well as the adaptive response induced by gamma ray exposure were determined in murine leukocytes in vivo. The damage-repair kinetics were established after the exposure to 0.5, 1.0 or 2.0 Gy in a {sup 137}Cs source. Peripheral blood samples were obtained from the tails of mice, the percentage of damaged cells and the DNA migration in each one were analyzed by the single cell gel electrophoresis (SCG) technique or comet assay. Results indicated that there was an induction of approximately 75% comets with the doses of 1.0 and 2.0 Gy, which was considerably reduced to 22% and 42% respectively during the first 15 minutes. This evidences the presence of a rapid repair process and suggests that leucocytes are genetically well prepared to repair this kind of damage. After 15 minutes, a second increase in the percentage of damaged cells that was proportional to dose occurred, which seems to represent the breaks produced during the repair of other kind of lesions. After that a second reduction was observed, reaching values near to the basal ones, except with the dose of 2.0 Gy. The kinetics obtained with the dose of 0.5 Gy was similar to that established with 1.0 Gy, but in this case the initial damage was 50 % lower. Besides, the adaptive response was observed after the exposure of the mice to an adaptive dose of 0.01 Gy and to a challenge dose of 1.0 Gy 60 minutes later. The pretreatment reduced the percentage of damaged cells caused by the challenge dose to one third approximately, and also diminished this parameter produced during the late repair process. This indicates that the early adaptive response is caused, instead of by an increment in repair, by the induction of a process that protects DNA from damage induction by radiation, i.e synthesis of substances that increase the scavenging of free radicals. (Author)

  7. Estimating the effect of human base excision repair protein variants on the repair of oxidative DNA base damage.

    Science.gov (United States)

    Sokhansanj, Bahrad A; Wilson, David M

    2006-05-01

    Epidemiologic studies have revealed a complex association between human genetic variance and cancer risk. Quantitative biological modeling based on experimental data can play a critical role in interpreting the effect of genetic variation on biochemical pathways relevant to cancer development and progression. Defects in human DNA base excision repair (BER) proteins can reduce cellular tolerance to oxidative DNA base damage caused by endogenous and exogenous sources, such as exposure to toxins and ionizing radiation. If not repaired, DNA base damage leads to cell dysfunction and mutagenesis, consequently leading to cancer, disease, and aging. Population screens have identified numerous single-nucleotide polymorphism variants in many BER proteins and some have been purified and found to exhibit mild kinetic defects. Epidemiologic studies have led to conflicting conclusions on the association between single-nucleotide polymorphism variants in BER proteins and cancer risk. Using experimental data for cellular concentration and the kinetics of normal and variant BER proteins, we apply a previously developed and tested human BER pathway model to (i) estimate the effect of mild variants on BER of abasic sites and 8-oxoguanine, a prominent oxidative DNA base modification, (ii) identify ranges of variation associated with substantial BER capacity loss, and (iii) reveal nonintuitive consequences of multiple simultaneous variants. Our findings support previous work suggesting that mild BER variants have a minimal effect on pathway capacity whereas more severe defects and simultaneous variation in several BER proteins can lead to inefficient repair and potentially deleterious consequences of cellular damage.

  8. Damage and repair of ancient DNA

    DEFF Research Database (Denmark)

    Mitchell, David; Willerslev, Eske; Hansen, Anders

    2005-01-01

    , and extensive degradation. In the course of this review, we will discuss the current aDNA literature describing the importance of aDNA studies as they relate to important biological questions and the difficulties associated with extracting useful information from highly degraded and damaged substrates derived......Under certain conditions small amounts of DNA can survive for long periods of time and can be used as polymerase chain reaction (PCR) substrates for the study of phylogenetic relationships and population genetics of extinct plants and animals, including hominids. Because of extensive DNA...... degradation, these studies are limited to species that lived within the past 10(4)-10(5) years (Late Pleistocene), although DNA sequences from 10(6) years have been reported. Ancient DNA (aDNA) has been used to study phylogenetic relationships of protists, fungi, algae, plants, and higher eukaryotes...

  9. Radiation damage in rat kidney microvasculature.

    Science.gov (United States)

    Nelson, A C; Shah-Yukich, A; Babayan, R

    1984-01-01

    Scanning electron microscopy (SEM) combined with a specialized polymer injection casting technique permits the analysis of radiation induced damage in rat kidney glomeruli. A lead shielding device is constructed to enable the irradiation of the living rat left kidney, while the remainder of the animal is shielded from the dose, the right kidney serves as a control. The source of radiation is 137Cs which produces 0.66 MeV gamma-rays to achieve a kidney dose of 100 rad and 5000 rad in these experiments. Radiation damage to kidney glomeruli is assessed at intervals of 0, 1, 3 and 7 days post-irradiation at the two dose levels. It is found that radiation damage to kidney glomeruli is expressed morphologically at 7 days post-irradiation at the 100 rad dose level, while glomerular damage is apparent as early as 3 days post-irradiation at the 5000 rad dose level. Moreover, by 7 days post-irradiation with a 5000 rad dose, the kidney glomerulus thoroughly degenerates to a leaky fused mass of vessels. From a morphological viewpoint, kidney glomeruli are significantly more sensitive to radiation than surrounding vasculature. The methods developed here for assessment of radiation damage are highly repeatable and could serve as a standard technique in radiobiology.

  10. Decreased repair of gamma damaged DNA in progeria

    Energy Technology Data Exchange (ETDEWEB)

    Rainbow, A.J.; Howes, M.

    1977-01-01

    A sensitive host-cell reactivation technique was used to examine the DNA repair ability of fibroblasts from two patients with classical progeria. Fibroblasts were infected with either non-irradiated or gamma-irradiated adenovirus type 2 and at 48 hrs after infection cells were examined for the presence of viral structural antigens using immunofluorescent staining. The production of viral structural antigens was considerably reduced in the progeria lines as compared to normal fibroblasts when gamma-irradiated virus was used, indicating a defect in the repair of gamma ray damaged DNA in the progeria cells.

  11. Protein damage and repair controlling seed vigor and longevity.

    Science.gov (United States)

    Ogé, Laurent; Broyart, Caroline; Collet, Boris; Godin, Béatrice; Jallet, Denis; Bourdais, Gildas; Job, Dominique; Grappin, Philippe

    2011-01-01

    The formation of abnormal isoaspartyl residues derived from aspartyl or asparaginyl residues is a major source of spontaneous protein misfolding in cells. The repair enzyme protein L: -isoaspartyl methyltransferase (PIMT) counteracts such damage by catalyzing the conversion of abnormal isoaspartyl residues to their normal aspartyl forms. Thus, this enzyme contributes to the survival of many organisms, including plants. Analysis of the accumulation of isoaspartyl-containing proteins and its modulation by the PIMT repair pathway, using germination tests, immunodetection, enzymatic assays, and HPLC analysis, gives new insights in understanding controlling mechanisms of seed longevity and vigor.

  12. Countermeasure for Radiation Protection and Repair

    Science.gov (United States)

    2008-01-01

    Exposure to ionizing radiation during long-duration space missions is expected to cause short-term illness and increase long-term risk of cancer for astronauts. Radiation-induced free radicals overload the antioxidant defense mechanisms and lead to cellular damage at the membrane, enzyme, and chromosome levels. A large number of radioprotective agents were screened, but most had significant side effects. But there is increasing evidence that significant radioprotective benefit is achieved by increasing the dietary intake of foods with high antioxidant potential. Early plant-growing systems for space missions will be limited in both size and volume to minimize power and mass requirements. These systems will be well suited to producing plants containing high concentrations of bioprotective antioxidants. This project explored whether the production of bioprotective compounds could be increased by altering the lighting system, without increasing the space or power requirements for production, and evaluated the effects of environmental conditions (light quantity, light quality, and carbon dioxide [CO2] concentration) on the production of bioprotective compounds in lettuce, which provide a biological countermeasure for radiation exposure. The specific deliverables were to develop a database of bioprotectant compounds in plants that are suitable for use on longduration space missions, develop protocols for maintaining and increasing bioprotectant production under light emitting diodes (LEDs), recommend lighting requirements to produce dietary countermeasures of radiation, and publish results in the Journal of the American Society for Horticultural Science.

  13. Anhydrobiosis-associated nuclear DNA damage and repair in the sleeping chironomid: linkage with radioresistance.

    Directory of Open Access Journals (Sweden)

    Oleg Gusev

    Full Text Available Anhydrobiotic chironomid larvae can withstand prolonged complete desiccation as well as other external stresses including ionizing radiation. To understand the cross-tolerance mechanism, we have analyzed the structural changes in the nuclear DNA using transmission electron microscopy and DNA comet assays in relation to anhydrobiosis and radiation. We found that dehydration causes alterations in chromatin structure and a severe fragmentation of nuclear DNA in the cells of the larvae despite successful anhydrobiosis. Furthermore, while the larvae had restored physiological activity within an hour following rehydration, nuclear DNA restoration typically took 72 to 96 h. The DNA fragmentation level and the recovery of DNA integrity in the rehydrated larvae after anhydrobiosis were similar to those of hydrated larvae irradiated with 70 Gy of high-linear energy transfer (LET ions ((4He. In contrast, low-LET radiation (gamma-rays of the same dose caused less initial damage to the larvae, and DNA was completely repaired within within 24 h. The expression of genes encoding the DNA repair enzymes occurred upon entering anhydrobiosis and exposure to high- and low-LET radiations, indicative of DNA damage that includes double-strand breaks and their subsequent repair. The expression of antioxidant enzymes-coding genes was also elevated in the anhydrobiotic and the gamma-ray-irradiated larvae that probably functions to reduce the negative effect of reactive oxygen species upon exposure to these stresses. Indeed the mature antioxidant proteins accumulated in the dry larvae and the total activity of antioxidants increased by a 3-4 fold in association with anhydrobiosis. We conclude that one of the factors explaining the relationship between radioresistance and the ability to undergo anhydrobiosis in the sleeping chironomid could be an adaptation to desiccation-inflicted nuclear DNA damage. There were also similarities in the molecular response of the larvae to

  14. DNA Repair and Photoprotection: Mechanisms of Overcoming Environmental Ultraviolet Radiation Exposure in Halophilic Archaea

    Directory of Open Access Journals (Sweden)

    Daniel L. Jones

    2017-09-01

    Full Text Available Halophilic archaea push the limits of life at several extremes. In particular, they are noted for their biochemical strategies in dealing with osmotic stress, low water activity and cycles of desiccation in their hypersaline environments. Another feature common to their habitats is intense ultraviolet (UV radiation, which is a challenge that microorganisms must overcome. The consequences of high UV exposure include DNA lesions arising directly from bond rearrangement of adjacent bipyrimidines, or indirectly from oxidative damage, which may ultimately result in mutation and cell death. As such, these microorganisms have evolved a number of strategies to navigate the threat of DNA damage, which we differentiate into two categories: DNA repair and photoprotection. Photoprotection encompasses damage avoidance strategies that serve as a “first line of defense,” and in halophilic archaea include pigmentation by carotenoids, mechanisms of oxidative damage avoidance, polyploidy, and genomic signatures that make DNA less susceptible to photodamage. Photolesions that do arise are addressed by a number of DNA repair mechanisms that halophilic archaea efficiently utilize, which include photoreactivation, nucleotide excision repair, base excision repair, and homologous recombination. This review seeks to place DNA damage, repair, and photoprotection in the context of halophilic archaea and the solar radiation of their hypersaline environments. We also provide new insight into the breadth of strategies and how they may work together to produce remarkable UV-resistance for these microorganisms.

  15. Homologous recombination in DNA repair and DNA damage tolerance

    Institute of Scientific and Technical Information of China (English)

    Xuan Li; Wolf-Dietrich Heyer

    2008-01-01

    Homologous recombination (HR) comprises a series of interrelated pathways that function in the repair of DNA double-stranded breaks (DSBs) and interstrand crosslinks (ICLs). In addition, recombination provides critical sup-port for DNA replication in the recovery of stalled or broken replication forks, contributing to tolerance of DNA damage. A central core of proteins, most critically the RecA homolog Rad51, catalyzes the key reactions that typify HR: homology search and DNA strand invasion. The diverse functions of recombination are reflected in the need for context-specific factors that perform supplemental functions in conjunction with the core proteins. The inability to properly repair complex DNA damage and resolve DNA replication stress leads to genomic instability and contributes to cancer etiology. Mutations in the BRCA2 recombination gene cause predisposition to breast and ovarian cancer as well as Fanconi anemia, a cancer predisposition syndrome characterized by a defect in the repair of DNA interstrand crosslinks. The cellular functions of recombination are also germane to DNA-based treatment modaUties of cancer, which target replicating cells by the direct or indirect induction of DNA lesions that are substrates for recombination pathways. This review focuses on mechanistic aspects of HR relating to DSB and ICL repair as well as replication fork support.

  16. [Study on repair capacity of DNA damage associated with chronic benzene poisoning].

    Science.gov (United States)

    Xing, Cai-hong; Ji, Zhi-ying; Li, Gui-lan; Yin, Song-nian

    2006-07-01

    To explore the repair capacity of DNA damage associated with chronic benzene poisonings. 63 workers suffered from chronic benzene poisonings and 45 workers exposed to benzene, who were engaged in the same job title, were investigated. Comet assay and cytokinesis-block micronucleus (CBMN) detection were used to evaluate gamma-radiation-induced DNA and chromosomal damage and repair capacity in peripheral blood lymphocyte. The comet tail length difference of the benzene poisoning group (4.64 +/- 1.57 microm) was significantly higher than that of the control group (3.77 +/- 1.30 microm) (P = 0.0029). There was no significant difference of the 3AB index between the poisoning group and the control group. The relative risk of benzene poisoning in the subject with comet tail length difference > 3.81 was significantly higher than that in the subject with comet tail length difference poisoning in the subject with 3AB index or = 0.20. DNA repair capacity on DNA-strand level might tightly associate with chronic benzene poisoning. The DNA repair capacity on DNA-strand level would be worse, and the benzene poisoning risk could be higher. There was no clear relation between the DNA repair capacity on chromosome level and the benzene poisoning risk.

  17. Characterization of oxidative guanine damage and repair in mammalian telomeres.

    Directory of Open Access Journals (Sweden)

    Zhilong Wang

    2010-05-01

    Full Text Available 8-oxo-7,8-dihydroguanine (8-oxoG and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG are among the most common oxidative DNA lesions and are substrates for 8-oxoguanine DNA glycosylase (OGG1-initiated DNA base excision repair (BER. Mammalian telomeres consist of triple guanine repeats and are subject to oxidative guanine damage. Here, we investigated the impact of oxidative guanine damage and its repair by OGG1 on telomere integrity in mice. The mouse cells were analyzed for telomere integrity by telomere quantitative fluorescence in situ hybridization (telomere-FISH, by chromosome orientation-FISH (CO-FISH, and by indirect immunofluorescence in combination with telomere-FISH and for oxidative base lesions by Fpg-incision/Southern blot assay. In comparison to the wild type, telomere lengthening was observed in Ogg1 null (Ogg1(-/- mouse tissues and primary embryonic fibroblasts (MEFs cultivated in hypoxia condition (3% oxygen, whereas telomere shortening was detected in Ogg1(-/- mouse hematopoietic cells and primary MEFs cultivated in normoxia condition (20% oxygen or in the presence of an oxidant. In addition, telomere length abnormalities were accompanied by altered telomere sister chromatid exchanges, increased telomere single- and double-strand breaks, and preferential telomere lagging- or G-strand losses in Ogg1(-/- mouse cells. Oxidative guanine lesions were increased in telomeres in Ogg1(-/- mice with aging and primary MEFs cultivated in 20% oxygen. Furthermore, oxidative guanine lesions persisted at high level in Ogg1(-/- MEFs after acute exposure to hydrogen peroxide, while they rapidly returned to basal level in wild-type MEFs. These findings indicate that oxidative guanine damage can arise in telomeres where it affects length homeostasis, recombination, DNA replication, and DNA breakage repair. Our studies demonstrate that BER pathway is required in repairing oxidative guanine damage in telomeres and maintaining telomere integrity

  18. The expected radiation damage of CSNS target

    Science.gov (United States)

    Yin, W.; Yu, Q. Z.; Lu, Y. L.; Wang, S. L.; Tong, J. F.; Liang, T. J.

    2012-12-01

    The radiation damage to the tungsten target and its SS316 vessel for Chinese Spallation Neutron Source (CSNS) has been estimated with a Monte-Carlo simulation code MCNPX2.5.0. We compare the effects on the radiation damage due to two different proton beam profiles: a uniform distribution and a Gaussian distribution. We also discuss the dependence of the radiation damage estimation on different physics models. The results show the peak displacement productions in vessel and the fourth target plate are 2.5 and 5.5 dpa/y, respectively, under a Gaussian proton beam. The peak helium productions in the vessel and the fourth target are 305 and 353 appm/y, respectively, under the same proton beam. Based on these results and the allowable dpa values we have estimated the lifetime of the tungsten target and its vessel.

  19. 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.

  20. Regulation of Ceramide Synthase-Mediated Crypt Epithelium Apoptosis by DNA Damage Repair Enzymes

    Science.gov (United States)

    Rotolo, Jimmy A.; Mesicek, Judith; Maj, Jerzy; Truman, Jean-Philip; Haimovitz-Friedman, Adriana; Kolesnick, Richard; Fuks, Zvi

    2015-01-01

    Acute endothelial cell apoptosis and microvascular compromise couple GI tract irradiation to reproductive death of intestinal crypt stem cell clonogens (SCCs) following high-dose radiation. Genetic or pharmacologic inhibition of endothelial apoptosis prevents intestinal damage, but as the radiation dose is escalated, SCCs become directly susceptible to an alternate cell death mechanism, mediated via ceramide synthase (CS)-stimulated de novo synthesis of the pro-apoptotic sphingolipid ceramide, and p53-independent apoptosis of crypt SCCs. We previously reported that ATM deficiency resets the primary radiation lethal pathway, allowing CS-mediated apoptosis at the low-dose range of radiation. The mechanism for this event, termed target reordering, remains unknown. Here we show that inactivation of DNA damage repair pathways signal CS-mediated apoptosis in crypt SCCs, presumably via persistent unrepaired DNA double strand breaks (DSBs). Genetic loss-of-function of sensors and transducers of DNA DSB repair confers the CS-mediated lethal pathway in intestines of sv129/B6Mre11ATLD1/ATLD1 and C57BL/6Prkdc/SCID (SCID) mice exposed to low-dose radiation. In contrast, CS-mediated SCC lethality was mitigated in irradiated gain-of-function Rad50S/S mice, and epistasis studies order Rad50 upstream of Mre11. These studies suggest unrepaired DNA DSBs as causative in target re-ordering in intestinal SCCs. As such, we provide an in vivo model of DNA damage repair that is standardized, can be exploited to understand allele-specific regulation in intact tissue, and is pharmacologically tractable. PMID:20086180

  1. 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.

  2. Inhibition of non-homologous end joining repair impairs pancreatic cancer growth and enhances radiation response.

    Directory of Open Access Journals (Sweden)

    Ying-Hua Li

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC is amongst the deadliest of human cancers, due to its late diagnosis as well as its intense resistance to currently available therapeutics. To identify mechanisms as to why PDAC are refractory to DNA damaging cytoxic chemotherapy and radiation, we performed a global interrogation of the DNA damage response of PDAC. We find that PDAC cells generally harbor high levels of spontaneous DNA damage. Inhibition of Non-Homologous End Joining (NHEJ repair either pharmacologically or by RNAi resulted in a further accumulation of DNA damage, inhibition of growth, and ultimately apoptosis even in the absence of exogenous DNA damaging agents. In response to radiation, PDAC cells rely on the NHEJ pathway to rapidly repair DNA double strand breaks. Mechanistically, when NHEJ is inhibited there is a compensatory increase in Homologous Recombination (HR. Despite this upregulation of HR, DNA damage persists and cells are significantly more sensitive to radiation. Together, these findings support the incorporation of NHEJ inhibition into PDAC therapeutic approaches, either alone, or in combination with DNA damaging therapies such as radiation.

  3. Evaluation of radioinduced damage and repair capacity in blood lymphocytes of breast cancer patients

    Directory of Open Access Journals (Sweden)

    P.A. Nascimento

    2001-02-01

    Full Text Available Genetic damage caused by ionizing radiation and repair capacity of blood lymphocytes from 3 breast cancer patients and 3 healthy donors were investigated using the comet assay. The comets were analyzed by two parameters: comet tail length and visual classification. Blood samples from the donors were irradiated in vitro with a 60Co source at a dose rate of 0.722 Gy/min, with a dose range of 0.2 to 4.0 Gy and analyzed immediately after the procedure and 3 and 24 h later. The basal level of damage and the radioinduced damage were higher in lymphocytes from breast cancer patients than in lymphocytes from healthy donors. The radioinduced damage showed that the two groups had a similar response when analyzed immediately after the irradiations. Therefore, while the healthy donors presented a considerable reduction of damage after 3 h, the patients had a higher residual damage even 24 h after exposure. The repair capacity of blood lymphocytes from the patients was slower than that of lymphocytes from healthy donors. The possible influence of age, disease stage and mutations in the BRCA1 and BRCA2 genes are discussed. Both parameters adopted proved to be sensitive and reproducible: the dose-response curves for DNA migration can be used not only for the analysis of cellular response but also for monitoring therapeutic interventions. Lymphocytes from the breast cancer patients presented an initial radiosensitivity similar to that of healthy subjects but a deficient repair mechanism made them more vulnerable to the genotoxic action of ionizing radiation. However, since lymphocytes from only 3 patients and 3 normal subjects were analyzed in the present paper, additional donors will be necessary for a more accurate evaluation.

  4. Clustered DNA damages induced in human hematopoietic cells by low doses of ionizing radiation

    Science.gov (United States)

    Sutherland, Betsy M.; Bennett, Paula V.; Cintron-Torres, Nela; Hada, Megumi; Trunk, John; Monteleone, Denise; Sutherland, John C.; Laval, Jacques; Stanislaus, Marisha; Gewirtz, Alan

    2002-01-01

    Ionizing radiation induces clusters of DNA damages--oxidized bases, abasic sites and strand breaks--on opposing strands within a few helical turns. Such damages have been postulated to be difficult to repair, as are double strand breaks (one type of cluster). We have shown that low doses of low and high linear energy transfer (LET) radiation induce such damage clusters in human cells. In human cells, DSB are about 30% of the total of complex damages, and the levels of DSBs and oxidized pyrimidine clusters are similar. The dose responses for cluster induction in cells can be described by a linear relationship, implying that even low doses of ionizing radiation can produce clustered damages. Studies are in progress to determine whether clusters can be produced by mechanisms other than ionizing radiation, as well as the levels of various cluster types formed by low and high LET radiation.

  5. Radiation damage effect on avalanche photodiodes

    CERN Document Server

    Baccaro, S; Cavallari, F; Da Ponte, V; Deiters, K; Denes, P; Diemoz, M; Kirn, Th; Lintern, A L; Longo, E; Montecchi, M; Musienko, Y; Pansart, J P; Renker, D; Reucroft, S; Rosi, G; Rusack, R; Ruuska, D; Stephenson, R; Torbet, M J

    1999-01-01

    Avalanche Photodiodes have been chosen as photon sensors for the electromagnetic calorimeter of the CMS experiment at the LHC. These sensors should operate in the 4T magnetic field of the experiment. Because of the high neutron radiation in the detector extensive studies have been done by the CMS collaboration on the APD neutron radiation damage. The characteristics of these devices after irradiation have been analized, with particular attention to the quantum efficiency and the dark current. The recovery of the radiation induced dark current has been studied carefully at room temperature and at slightly lower and higher temperatures. The temperature dependence of the defects decay-time has been evaluated.

  6. Modeling damage complexity-dependent non-homologous end-joining repair pathway.

    Directory of Open Access Journals (Sweden)

    Yongfeng Li

    Full Text Available Non-homologous end joining (NHEJ is the dominant DNA double strand break (DSB repair pathway and involves several repair proteins such as Ku, DNA-PKcs, and XRCC4. It has been experimentally shown that the choice of NHEJ proteins is determined by the complexity of DSB. In this paper, we built a mathematical model, based on published data, to study how NHEJ depends on the damage complexity. Under an appropriate set of parameters obtained by minimization technique, we can simulate the kinetics of foci track formation in fluorescently tagged mammalian cells, Ku80-EGFP and DNA-PKcs-YFP for simple and complex DSB repair, respectively, in good agreement with the published experimental data, supporting the notion that simple DSB undergo fast repair in a Ku-dependent, DNA-PKcs-independent manner, while complex DSB repair requires additional DNA-PKcs for end processing, resulting in its slow repair, additionally resulting in slower release rate of Ku and the joining rate of complex DNA ends. Based on the numerous experimental descriptions, we investigated several models to describe the kinetics for complex DSB repair. An important prediction of our model is that the rejoining of complex DSBs is through a process of synapsis formation, similar to a second order reaction between ends, rather than first order break filling/joining. The synapsis formation (SF model allows for diffusion of ends before the synapsis formation, which is precluded in the first order model by the rapid coupling of ends. Therefore, the SF model also predicts the higher number of chromosomal aberrations observed with high linear energy transfer (LET radiation due to the higher proportion of complex DSBs compared to low LET radiation, and an increased probability of misrejoin following diffusion before the synapsis is formed, while the first order model does not provide a mechanism for the increased effectiveness in chromosomal aberrations observed.

  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. Ion-biomolecule interactions and radiation damage

    NARCIS (Netherlands)

    Schlathölter, T.A.; Alvarado Chacon, F.; Hoekstra, R.A.

    2005-01-01

    Ionization and fragmentation of DNA and its constituents is it primary step in biological radiation damage. In this paper we investigate the response of nucleobases upon interaction with keV singly and multiply charged ions. The dependence of ionization and fragmentation on ion atomic number Z, char

  9. 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.

  10. 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.

  11. Repair-dependent cell radiation survival and transformation: an integrated theory.

    Science.gov (United States)

    Sutherland, John C

    2014-09-07

    The repair-dependent model of cell radiation survival is extended to include radiation-induced transformations. The probability of transformation is presumed to scale with the number of potentially lethal damages that are repaired in a surviving cell or the interactions of such damages. The theory predicts that at doses corresponding to high survival, the transformation frequency is the sum of simple polynomial functions of dose; linear, quadratic, etc, essentially as described in widely used linear-quadratic expressions. At high doses, corresponding to low survival, the ratio of transformed to surviving cells asymptotically approaches an upper limit. The low dose fundamental- and high dose plateau domains are separated by a downwardly concave transition region. Published transformation data for mammalian cells show the high-dose plateaus predicted by the repair-dependent model for both ultraviolet and ionizing radiation. For the neoplastic transformation experiments that were analyzed, the data can be fit with only the repair-dependent quadratic function. At low doses, the transformation frequency is strictly quadratic, but becomes sigmodial over a wider range of doses. Inclusion of data from the transition region in a traditional linear-quadratic analysis of neoplastic transformation frequency data can exaggerate the magnitude of, or create the appearance of, a linear component. Quantitative analysis of survival and transformation data shows good agreement for ultraviolet radiation; the shapes of the transformation components can be predicted from survival data. For ionizing radiations, both neutrons and x-rays, survival data overestimate the transforming ability for low to moderate doses. The presumed cause of this difference is that, unlike UV photons, a single x-ray or neutron may generate more than one lethal damage in a cell, so the distribution of such damages in the population is not accurately described by Poisson statistics. However, the complete

  12. Probing and repairing damaged surfaces with nanoparticle-containing microcapsules

    Science.gov (United States)

    Kratz, Katrina; Narasimhan, Amrit; Tangirala, Ravisubhash; Moon, Sungcheal; Revanur, Ravindra; Kundu, Santanu; Kim, Hyun Suk; Crosby, Alfred J.; Russell, Thomas P.; Emrick, Todd; Kolmakov, German; Balazs, Anna C.

    2012-02-01

    Nanoparticles have useful properties, but it is often important that they only start working after they are placed in a desired location. The encapsulation of nanoparticles allows their function to be preserved until they are released at a specific time or location, and this has been exploited in the development of self-healing materials and in applications such as drug delivery. Encapsulation has also been used to stabilize and control the release of substances, including flavours, fragrances and pesticides. We recently proposed a new technique for the repair of surfaces called `repair-and-go'. In this approach, a flexible microcapsule filled with a solution of nanoparticles rolls across a surface that has been damaged, stopping to repair any defects it encounters by releasing nanoparticles into them, then moving on to the next defect. Here, we experimentally demonstrate the repair-and-go approach using droplets of oil that are stabilized with a polymer surfactant and contain CdSe nanoparticles. We show that these microcapsules can find the cracks on a surface and selectively deliver the nanoparticle contents into the crack, before moving on to find the next crack. Although the microcapsules are too large to enter the cracks, their flexible walls allow them to probe and adhere temporarily to the interior of the cracks. The release of nanoparticles is made possible by the thin microcapsule wall (comparable to the diameter of the nanoparticles) and by the favourable (hydrophobic-hydrophobic) interactions between the nanoparticle and the cracked surface.

  13. Both Complexity and Location of DNA Damage Contribute to Cellular Senescence Induced by Ionizing Radiation.

    Directory of Open Access Journals (Sweden)

    Xurui Zhang

    Full Text Available Persistent DNA damage is considered as a main cause of cellular senescence induced by ionizing radiation. However, the molecular bases of the DNA damage and their contribution to cellular senescence are not completely clear. In this study, we found that both heavy ions and X-rays induced senescence in human uveal melanoma 92-1 cells. By measuring senescence associated-β-galactosidase and cell proliferation, we identified that heavy ions were more effective at inducing senescence than X-rays. We observed less efficient repair when DNA damage was induced by heavy ions compared with X-rays and most of the irreparable damage was complex of single strand breaks and double strand breaks, while DNA damage induced by X-rays was mostly repaired in 24 hours and the remained damage was preferentially associated with telomeric DNA. Our results suggest that DNA damage induced by heavy ion is often complex and difficult to repair, thus presents as persistent DNA damage and pushes the cell into senescence. In contrast, persistent DNA damage induced by X-rays is preferentially associated with telomeric DNA and the telomere-favored persistent DNA damage contributes to X-rays induced cellular senescence. These findings provide new insight into the understanding of high relative biological effectiveness of heavy ions relevant to cancer therapy and space radiation research.

  14. DNA damage and repair in white blood cells at occupational exposure

    Energy Technology Data Exchange (ETDEWEB)

    Georgieva, R T; Zaharieva, E K; Rupova, I M; Acheva, A R; Nikolov, V N [Department of Radiobiology, National Center of Radiobiology and Radiation Protection, Sofia, 1756 (Bulgaria)], E-mail: r.georgieva@ncrrp.org

    2008-02-01

    : The present work was aimed at finding appropriate biomarkers applicable in molecular epidemiological surveys of occupationally exposed individuals and/or population in order to prove low dose effects. Blood samples were taken from NPP workers, in the 'strict regimen' area (exposed group) and from the administration staff (control group). The spontaneous and induced (exposed to a challenge dose of 2,0 Gy gamma irradiation) DNA repair synthesis in leucocytes, the level of DNA damage by single cell gel-electrophoresis in lymphocytes and the concentration of malonedialdehyde in blood serum, were analyzed. A significant decrease of potentially lethal damage in leucocytes as well as reduction of DNA double strand breaks level in lymphocytes of persons with 'mean annual dose' lower or equal to 5 mSv/a was found, compared to the control group. A higher repair capacity corresponding to elevated protein synthesis after a challenging dose of 2,0 Gy gamma rays and a significant decrease in the level of oxidative stress in the blood plasma were established in persons from the same group. The present investigation showed that annual doses not higher than twice the natural radiation background exert positive effects on DNA damage and repair, increase cellular resistance and decrease oxidative stress.

  15. The Role of Altered Nucleotide Excision Repair and UVB-Induced DNA Damage in Melanomagenesis

    Directory of Open Access Journals (Sweden)

    Timothy Budden

    2013-01-01

    Full Text Available UVB radiation is the most mutagenic component of the UV spectrum that reaches the earth’s surface and causes the development of DNA damage in the form of cyclobutane pyrimidine dimers and 6-4 photoproducts. UV radiation usually results in cellular death, but if left unchecked, it can affect DNA integrity, cell and tissue homeostasis and cause mutations in oncogenes and tumour-suppressor genes. These mutations, if unrepaired, can lead to abnormal cell growth, increasing the risk of cancer development. Epidemiological data strongly associates UV exposure as a major factor in melanoma development, but the exact biological mechanisms involved in this process are yet to be fully elucidated. The nucleotide excision repair (NER pathway is responsible for the repair of UV-induced lesions. Patients with the genetic disorder Xeroderma Pigmentosum have a mutation in one of eight NER genes associated with the XP complementation groups XP-A to XP-G and XP variant (XP-V. XP is characterized by diminished repair capacity, as well as a 1000-fold increase in the incidence of skin cancers, including melanoma. This has suggested a significant role for NER in melanoma development as a result of UVB exposure. This review discusses the current research surrounding UVB radiation and NER capacity and how further investigation of NER could elucidate the role of NER in avoiding UV-induced cellular death resulting in melanomagenesis.

  16. DNA repair gene polymorphisms in relation to chromosome aberration frequencies in retired radiation workers

    Energy Technology Data Exchange (ETDEWEB)

    Wilding, Craig S. [Genetics Department, Westlakes Research Institute, Westlakes Science and Technology Park, Moor Row, Cumbria CA24 3JY (United Kingdom)]. E-mail: craig.wilding@westlakes.ac.uk; Relton, Caroline L. [Genetics Department, Westlakes Research Institute, Westlakes Science and Technology Park, Moor Row, Cumbria CA24 3JY (United Kingdom); Paediatric and Lifecourse Epidemiology Research Group, School of Clinical Medical Sciences (Child Health), Newcastle University, Sir James Spence Institute, Royal Victoria Infirmary, Newcastle-upon-Tyne NE1 4LP (United Kingdom); Rees, Gwen S. [Genetics Department, Westlakes Research Institute, Westlakes Science and Technology Park, Moor Row, Cumbria CA24 3JY (United Kingdom); Tarone, Robert E. [International Epidemiology Institute, 1455 Research Boulevard, Suite 550, Rockville, MD 20850 (United States); Whitehouse, Caroline A. [Genetics Department, Westlakes Research Institute, Westlakes Science and Technology Park, Moor Row, Cumbria CA24 3JY (United Kingdom); Tawn, E. Janet [Genetics Department, Westlakes Research Institute, Westlakes Science and Technology Park, Moor Row, Cumbria CA24 3JY (United Kingdom)

    2005-02-15

    Polymorphic variation in DNA repair genes was examined in a group of retired workers from the British Nuclear Fuels plc facility at Sellafield in relation to previously determined translocation frequencies in peripheral blood lymphocytes. Variation at seven polymorphisms in four genes involved in the base excision repair (XRCC1 R194W, R399Q and a [AC]{sub n} microsatellite in the 3' UTR) and double strand break repair (XRCC3 T241M and a [AC]{sub n} microsatellite in intron 3 of XRCC3, XRCC4 I134T, and a GACTAn microsatellite located 120kb 5' of XRCC5) pathways was determined for 291 retired radiation workers who had received cumulative occupational external radiation doses of between 0 and 1873mSv. When the interaction between radiation dose and each DNA repair gene polymorphism was examined in relation to translocation frequency there was no evidence for any of the polymorphisms studied influencing the response to occupational exposure. A positive interaction observed between genotype (individuals with at least one allele >=20 repeat units) at a microsatellite locus in the XRCC3 gene and smoking status should be interpreted cautiously because interactions were investigated for seven polymorphisms and two exposures. Nonetheless, further research is warranted to examine whether this DNA repair gene variant might be associated with a sub-optimal repair response to smoking-induced DNA damage and hence an increased frequency of translocations.

  17. Calculation of Radiation Damage in SLAC Targets

    Energy Technology Data Exchange (ETDEWEB)

    Wirth, B D; Monasterio, P; Stein, W

    2008-04-03

    Ti-6Al-4V alloys are being considered as a positron producing target in the Next Linear Collider, with an incident photon beam and operating temperatures between room temperature and 300 C. Calculations of displacement damage in Ti-6Al-4V alloys have been performed by combining high-energy particle FLUKA simulations with SPECTER calculations of the displacement cross section from the resulting energy-dependent neutron flux plus the displacements calculated from the Lindhard model from the resulting energy-dependent ion flux. The radiation damage calculations have investigated two cases, namely the damage produced in a Ti-6Al-4V SLAC positron target where the irradiation source is a photon beam with energies between 5 and 11 MeV. As well, the radiation damage dose in displacements per atom, dpa, has been calculated for a mono-energetic 196 MeV proton irradiation experiment performed at Brookhaven National Laboratory (BLIP experiment). The calculated damage rate is 0.8 dpa/year for the Ti-6Al-4V SLAC photon irradiation target, and a total damage exposure of 0.06 dpa in the BLIP irradiation experiment. In both cases, the displacements are predominantly ({approx}80%) produced by recoiling ions (atomic nuclei) from photo-nuclear collisions or proton-nuclear collisions, respectively. Approximately 25% of the displacement damage results from the neutrons in both cases. Irradiation effects studies in titanium alloys have shown substantial increases in the yield and ultimate strength of up to 500 MPa and a corresponding decrease in uniform ductility for neutron and high energy proton irradiation at temperatures between 40 and 300 C. Although the data is limited, there is an indication that the strength increases will saturate by doses on the order of a few dpa. Microstructural investigations indicate that the dominant features responsible for the strength increases were dense precipitation of a {beta} (body-centered cubic) phase precipitate along with a high number density

  18. DNA Mismatch Repair and Oxidative DNA Damage: Implications for Cancer Biology and Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Bridge, Gemma; Rashid, Sukaina; Martin, Sarah A., E-mail: sarah.martin@qmul.ac.uk [Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ (United Kingdom)

    2014-08-05

    Many components of the cell, including lipids, proteins and both nuclear and mitochondrial DNA, are vulnerable to deleterious modifications caused by reactive oxygen species. If not repaired, oxidative DNA damage can lead to disease-causing mutations, such as in cancer. Base excision repair and nucleotide excision repair are the two DNA repair pathways believed to orchestrate the removal of oxidative lesions. However, recent findings suggest that the mismatch repair pathway may also be important for the response to oxidative DNA damage. This is particularly relevant in cancer where mismatch repair genes are frequently mutated or epigenetically silenced. In this review we explore how the regulation of oxidative DNA damage by mismatch repair proteins may impact on carcinogenesis. We discuss recent studies that identify potential new treatments for mismatch repair deficient tumours, which exploit this non-canonical role of mismatch repair using synthetic lethal targeting.

  19. DNA damage and its repair in Dictyostelium discoideum irradiated by health lamp light (UV-B)

    Energy Technology Data Exchange (ETDEWEB)

    Okaichi, K.; Kajitani, N.; Nakajima, K.; Nozu, K.; Ohnishi, T. (Nara Medical Univ., Kashihara (Japan))

    1989-07-01

    Irradiation by health lamp (HL) light (280-320 nm) more efficiently induced cell killing and mutation in a radiation sensitive mutant (TW8) of Dictyostelium discoideum as compared with the parental wild-type strain (NC4). This light as well as a germicidal lamp-light (254 nm) produced pyrimidine dimers. The dimers were removed from DNA molecules by excision repair in NC4, but more slowly in TW8. It is suggested that pyrimidine dimers are the main DNA damage caused by HL light in D. discoideum, and that this results in cell killing and induced mutation. (author).

  20. 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 \

  1. 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...

  2. Interplay between mechanisms of damage and repair in multiple sclerosis.

    Science.gov (United States)

    Stadelmann, Christine; Brück, Wolfgang

    2008-03-01

    The neuropathology of multiple sclerosis is characterised by focal damage to white matter. However, tissue damage is also present in the cortical grey matter, with a particularly high prevalence of cortical demyelination being observed in secondary progressive and primary progressive forms of the disease. The presence of meningeal B-cell follicle-like structures, which frequently appear during the secondary progressive phase of disease, may be involved in the formation of these subpial cortical lesions. Diffuse white matter inflammation accompanied by axonal damage can also be observed in normal appearing white matter and, again, this is more prominent in chronic progressive forms of multiple sclerosis than in acute stages of disease. Axonal damage is a particularly important component of the pathology of multiple sclerosis and appears to be a critical determinant of clinical outcome. Axons appear to become vulnerable to injury as a result of loss of their myelin sheaths. Remyelination represents an important mechanism of tissue repair in multiple sclerosis and already occurs at an early stage of lesion development and in both white and grey matter lesions. The extent of remyelination appears to be greater in cortical lesions and in lesions further from the ventricles. There is important heterogeneity between patients in terms of the extent of remyelination, which may reflect underlying differences in pathogenetic mechanisms between patients.

  3. Recombinant human erythropoietin for repair of white matter damage

    Institute of Scientific and Technical Information of China (English)

    Wei Zhou; Xiao Rong; Li Tao; Weineng Lu

    2011-01-01

    Erythropoietin has been shown to exhibit neuroprotective effects in animal models. A neonatal rat model of hypoxic-ischemic white matter damage was established via bilateral carotid artery ligation in 4-day-old Sprague-Dawley rats. The rats were subsequently treated with recombinant human erythropoietin to observe pathological changes in the brain and long-term neurobehavioral functions before and after intervention. Results showed that the number of myelin basic protein-positive cells, which reflected myelin/oligodendrocyte damage, significantly increased, although the number of amyloid precursor protein-positive cells, which reflected axonal injury, significantly decreased in periventricular white matter at 72 hours and 7 days following erythropoietin intervention. The number of glial fibrillary acidic protein-positive cells, indicating astrocytic damage, significantly decreased in periventricular white matter of erythropoietin-treated rats at 48 hours, 72 hours, 7 days, and 26 days. Following erythropoietin intervention in the 30-day-old rats, head-turning time in the slope test was shortened and open-field test scores increased. These results suggested that erythropoietin promoted repair of white matter damage, as well as improved neurobehavioral functions in a rat model of hypoxic-ischemic injury.

  4. Evaluation of radioinduced damage and repair capacity in human breast cancer cells, MCDF-7 and T4-D

    Energy Technology Data Exchange (ETDEWEB)

    Valgode, F.G.S.; Soares, C.R.J.; Bartolini, P.; Okazaki, K. [Instituto de Pesquisas Energeticas e Nucleares IPEN/CNEN-SP, Sao Paulo, SP (Brazil)]. E-mail: kokazaki@ipen.br

    2007-07-01

    Ionizing radiation is an established etiologic agent for breast cancer, but on the other hand it is a therapeutic modality used in cancer treatment. Accumulation of DNA damage and deficient DNA repair are considered as factors of susceptibility that predispose individuals to breast cancer development. In the present study, genetic damage induced by gamma radiation and repair capacity in the target cells, i.e. cells originating of breast cancer, were analyzed using micronucleus test and comet assay (single-cell alkaline gel electrophoresis). So, two breast tumor cell line, MCF-7 and T-47D were irradiated in a {sup 60}Co source (0.722 Gy/min) with various doses (0.5; 1.0; 2.0; 4.0 and 5.0 Gy). Cytogenetic data showed similar spontaneous damage of two cell lines, the radioinduced damage, however, was higher in T-47D, starting from 2 Gy, with a more accelerated proliferation rate than MCF- 7 at all doses analyzed. Both tumor cell lines were capable to repair a considerable part of radioinduced damage within 1 hour after exposure, indicating a relative radioresistance of theses cell lines to the genotoxic action of ionizing radiation. (author)

  5. An immunochemical approach to the study of DNA damage and repair

    Energy Technology Data Exchange (ETDEWEB)

    Wallace, S.S. (Vermont Univ., Burlington, VT (United States). Dept. of Microbiology and Molecular Genetics); Erlanger, B.F. (Columbia Univ., New York, NY (United States). Dept. of Microbiology)

    1992-05-01

    The overall objective of this project has been to develop immunochemical methods to quantitate unique DNA base damages in order to facilitate studies on radiation-induced damage production and repair. Specifically, we have been using antibodies raised to damaged bases to quantitate unique lesions in model systems in order to evaluate their potential biological consequences. Our approach has been to synthesize modified nucleotides or nucleosides, conjugate them to protein carriers, and use the conjugates as immunogens in rabbits or to prepare monoclonal antibodies. We have been studying damages that are stable radiolysis products found in X-irradiated DNA and thus of potential biological consequence. Our aim is to build an in vitro and in vivo data base on the interactions between model DNA lesions and such cellular enzymes as DNA polymerases and repair endonucleases. Initial studies have focused on pyrimidine ring saturation products (thymine glycol.and dihydrothymine), products resulting from ring fragmentation or base loss (urea, {Beta}-ureidoisobutyric acid, abasic sites), 7-hydro-8-oxopurines, and more recently, cytosine radiolysis products. These modified bases serve as useful models for examining the potential lethal and/or mutagenic (carcinogenic) effects of the products of DNA radiolysis.

  6. Radiation Damage in Polarized Ammonia Solids

    CERN Document Server

    Slifer, K

    2007-01-01

    Solid NH3 and ND3 provide a highly polarizable, radiation resistant source of polarized protons and deuterons and have been used extensively in high luminosity experiments investigating the spin structure of the nucleon. Over the past twenty years, the UVA polarized target group has been instrumental in producing and polarizing much of the material used in these studies, and many practical considerations have been learned in this time. In this discussion, we analyze the polarization performance of the solid ammonia targets used during the recent JLab Eg4 run. Topics include the rate of polarization decay with accumulated charge, the annealing procedure for radiation damaged targets to recover polarization, and the radiation induced change in optimum microwave frequency used to polarize the sample. We also discuss the success we have had in implementing frequency modulation of the polarizing microwave frequency.

  7. Radiation damage of insulating crystals induced by electronic excitation

    Energy Technology Data Exchange (ETDEWEB)

    Itoh, Noriaki

    1988-05-01

    A review is given on radiation damage of insulating crystals arising from energy imparted to solids into electronic excitation. Emphasis is placed in describing the mechanism. The role of the exciton-phonon interaction in the production of radiation damage is described and the radiation damage processes in a few typical insulators such as alkali halides, alkali earth fluorides and silicon dioxide are described.

  8. DNA repair and cell cycle biomarkers of radiation exposure and inflammation stress in human blood.

    Directory of Open Access Journals (Sweden)

    Helen Budworth

    Full Text Available DNA damage and repair are hallmarks of cellular responses to ionizing radiation. We hypothesized that monitoring the expression of DNA repair-associated genes would enhance the detection of individuals exposed to radiation versus other forms of physiological stress. We employed the human blood ex vivo radiation model to investigate the expression responses of DNA repair genes in repeated blood samples from healthy, non-smoking men and women exposed to 2 Gy of X-rays in the context of inflammation stress mimicked by the bacterial endotoxin lipopolysaccharide (LPS. Radiation exposure significantly modulated the transcript expression of 12 genes of 40 tested (2.2E-06radiation. Three genes of this panel (CDKN1A, FDXR and BBC3 were also highly sensitive to LPS treatment in the absence of radiation exposure, and LPS co-treatment significantly affected their radiation responses. At the protein level, BAX and pCHK2-thr68 were elevated after radiation exposure, but the pCHK2-thr68 response was significantly decreased in the presence of LPS. Our combined panel yields an estimated 4-group accuracy of ∼90% to discriminate between radiation alone, inflammation alone, or combined exposures. Our findings suggest that DNA repair gene expression may be helpful to identify biodosimeters of exposure to radiation, especially within high-complexity exposure scenarios.

  9. RadA: A protein involved in DNA damage repair processes of Deinococcus radiodurans R1

    Institute of Scientific and Technical Information of China (English)

    ZHOU Qing; ZHANG Xinjue; XU Hong; XU Bujin; HUA Yuejin

    2006-01-01

    RadA is highly conserved in bacteria and belongs to the RecA/RadA/Rad51 protein superfamily found in bacteria, archaea and eukarya. In Archaea, it plays a critical role in homologous recombination process due to its RecA-like function. In Escherichia coli, it takes part in conjugational recombination and DNA repair but is not as important as that of archaea. Using PSI-BLAST searches, we found that Deinococcus radiodurans RadA had a higher similarity to that of bacteria than archaea and eukarya. Disruption of radA gene in D. radiodurans resulted in a modestly decreased resistance to gamma radiation and ultraviolet, but had no effect on the resistance to hydrogen peroxide. Complementation of the radA disruptant by both E. coli radA and D.radiodurans radA could fully restore its resistance to gamma radiation and ultraviolet irradiation. Further domain function analyses of D. radiodurans RadA showed that the absence of the zinc finger domain resulted in a slightly more sensitive phenotype togamma and UV radiation than that of the radA mutant,while the absence of the Lon protease domain exhibited a slightly increased resistance to gamma and UV radiation. These data suggest that D. radiodurans RadA does play an important role in the DNA damage repair processes and its three different domains have different functions.

  10. DNA damage induced by boron neutron capture therapy is partially repaired by DNA ligase IV.

    Science.gov (United States)

    Kondo, Natsuko; Sakurai, Yoshinori; Hirota, Yuki; Tanaka, Hiroki; Watanabe, Tsubasa; Nakagawa, Yosuke; Narabayashi, Masaru; Kinashi, Yuko; Miyatake, Shin-ichi; Hasegawa, Masatoshi; Suzuki, Minoru; Masunaga, Shin-ichiro; Ohnishi, Takeo; Ono, Koji

    2016-03-01

    Boron neutron capture therapy (BNCT) is a particle radiation therapy that involves the use of a thermal or epithermal neutron beam in combination with a boron ((10)B)-containing compound that specifically accumulates in tumor. (10)B captures neutrons and the resultant fission reaction produces an alpha ((4)He) particle and a recoiled lithium nucleus ((7)Li). These particles have the characteristics of high linear energy transfer (LET) radiation and therefore have marked biological effects. High-LET radiation is a potent inducer of DNA damage, specifically of DNA double-strand breaks (DSBs). The aim of the present study was to clarify the role of DNA ligase IV, a key player in the non-homologous end-joining repair pathway, in the repair of BNCT-induced DSBs. We analyzed the cellular sensitivity of the mouse embryonic fibroblast cell lines Lig4-/- p53-/- and Lig4+/+ p53-/- to irradiation using a thermal neutron beam in the presence or absence of (10)B-para-boronophenylalanine (BPA). The Lig4-/- p53-/- cell line had a higher sensitivity than the Lig4+/+ p53-/-cell line to irradiation with the beam alone or the beam in combination with BPA. In BNCT (with BPA), both cell lines exhibited a reduction of the 50 % survival dose (D 50) by a factor of 1.4 compared with gamma-ray and neutron mixed beam (without BPA). Although it was found that (10)B uptake was higher in the Lig4+/+ p53-/- than in the Lig4-/- p53-/- cell line, the latter showed higher sensitivity than the former, even when compared at an equivalent (10)B concentration. These results indicate that BNCT-induced DNA damage is partially repaired using DNA ligase IV.

  11. International congress on DNA damage and repair: Book of abstracts

    Energy Technology Data Exchange (ETDEWEB)

    1987-01-01

    This document contains the abstracts of 105 papers presented at the Congress. Topics covered include the Escherichia coli nucleotide excision repair system, DNA repair in malignant transformations, defective DNA repair, and gene regulation. (TEM)

  12. Reduced Activity of Double-Strand Break Repair Genes in Prostate Cancer Patients With Late Normal Tissue Radiation Toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Oorschot, Bregje van, E-mail: b.vanoorschot@amc.uva.nl [Laboratory for Experimental Oncology and Radiobiology (LEXOR), Center for Molecular Medicine (CEMM), Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Hovingh, Suzanne E. [Laboratory for Experimental Oncology and Radiobiology (LEXOR), Center for Molecular Medicine (CEMM), Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Moerland, Perry D. [Bioinformatics Laboratory, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Medema, Jan Paul; Stalpers, Lukas J.A. [Laboratory for Experimental Oncology and Radiobiology (LEXOR), Center for Molecular Medicine (CEMM), Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Vrieling, Harry [Department of Toxicogenetics, Leiden University Medical Center, Leiden (Netherlands); Franken, Nicolaas A.P. [Laboratory for Experimental Oncology and Radiobiology (LEXOR), Center for Molecular Medicine (CEMM), Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands)

    2014-03-01

    Purpose: To investigate clinical parameters and DNA damage response as possible risk factors for radiation toxicity in the setting of prostate cancer. Methods and Materials: Clinical parameters of 61 prostate cancer patients, 34 with (overresponding, OR) and 27 without (non-responding, NR) severe late radiation toxicity were assembled. In addition, for a matched subset the DNA damage repair kinetics (γ-H2AX assay) and expression profiles of DNA repair genes were determined in ex vivo irradiated lymphocytes. Results: Examination of clinical data indicated none of the considered clinical parameters to be correlated with the susceptibility of patients to develop late radiation toxicity. Although frequencies of γ-H2AX foci induced immediately after irradiation were similar (P=.32), significantly higher numbers of γ-H2AX foci were found 24 hours after irradiation in OR compared with NR patients (P=.03). Patient-specific γ-H2AX foci decay ratios were significantly higher in NR patients than in OR patients (P<.0001). Consequently, NR patients seem to repair DNA double-strand breaks (DSBs) more efficiently than OR patients. Moreover, gene expression analysis indicated several genes of the homologous recombination pathway to be stronger induced in NR compared with OR patients (P<.05). A similar trend was observed in genes of the nonhomologous end-joining repair pathway (P=.09). This is congruent with more proficient repair of DNA DSBs in patients without late radiation toxicity. Conclusions: Both gene expression profiling and DNA DSB repair kinetics data imply that less-efficient repair of radiation-induced DSBs may contribute to the development of late normal tissue damage. Induction levels of DSB repair genes (eg, RAD51) may potentially be used to assess the risk for late radiation toxicity.

  13. Potentially lethal damage repair by total and quiescent tumor cells following various DNA-damaging treatments

    Energy Technology Data Exchange (ETDEWEB)

    Masunaga, Shin-ichiro; Ono, Koji; Suzuki, Minoru; Kinashi, Yuko; Takagaki, Masao [Kyoto Univ., Kumatori, Osaka (Japan). Research Reactor Inst; Hori, Hitoshi; Kasai, Soko; Nagasawa, Hideko; Uto, Yoshihiro

    1999-08-01

    After continuous labeling of proliferating (P) cells with 5-bromo-2'-deoxyuridine (BrdU) for 5 days, SCC VII tumor-bearing mice received various kinds of DNA-damaging treatments: gamma-ray irradiation, tirapazamine (TPZ, hypoxia-specific cytotoxin) administration, or cisplatin injection. From 0.5 to 72 hr after treatment, tumors were excised, minced, and trypsinized. Single tumor cell suspensions were incubated for 48 hr with a cytokinesis-blocker, cytochalasin-B. Then, the micronucleus (MN) frequency for BrdU-unlabeled cells, quiescent (Q) cells at treatment, was determined using immunofluorescence staining for BrdU. The MN frequency for total (P+Q) cells was obtained from tumors that were not pretreated with BrdU labeling. The sensitivity to each DNA-damaging treatment was evaluated in terms of the frequency of induced micronuclei in binuclear tumor cells (MN frequency). Treatment with gamma-rays or cisplatin resulted in a larger MN frequency in total cells than in Q cells. In contrast, TPZ treatment produced a smaller MN frequency in total cells than in Q cells. Regardless of the treatment used, Q cells showed greater repair capacities than total cells. However, TPZ caused much smaller repair capacity in both total and Q cells, compared with gamma-rays or cisplatin. Gamma-rays and cisplatin produced similar repair patterns. Differences in sensitivity between total and Q cells and repair patterns of the two cell populations were thought to depend on differences between the two cell populations in the toxicity of the DNA-damaging treatment and distribution pattern of the anticancer agent. (author)

  14. Repair of postirradiation damage to colorectum: a progress report

    Energy Technology Data Exchange (ETDEWEB)

    Bricker, E.M.; Johnston, W.D.; Patwardhan, R.V.

    1981-05-01

    The results of 21 operations for repair of rectovaginal fistula and/or stricture secondary to irradiation for pelvic cancer are presented. The operations rely on the use of proximal nonirradiated colon with normal blood supply for effecting the repair. In patients having had a previous colostomy, it is possible to use the proximal end of the bypassed colon for this purpose. There is minimal dissection of the rectal ampulla and the presacral space is never entered. Continuity is established by anastomosis to the anterior rectal wall via an abdominal approach alone, or by a combined abdominovaginal or abdominoperineal approach. It has been found that nonirradiated colon of normal vascularity can be expected to heal to irradiated colon or rectum, thus making the extensive resections associated with correction of these abnormalities unnecessary. The functional result in 18 of 19 patients who underwent this procedure was satisfactory to excellent. One patient had a poor result because of partial rectal incontinence. Two operations out of the 21 were total failures and one of these patients died of complications secondary to irradiation damage to the small intestine. One patient has not yet had final colostomy closure. The results are considered promising enough to warrant continued trial.

  15. Visualizing the search for radiation-damaged DNA bases in real time

    Science.gov (United States)

    Lee, Andrea J.; Wallace, Susan S.

    2016-11-01

    The Base Excision Repair (BER) pathway removes the vast majority of damages produced by ionizing radiation, including the plethora of radiation-damaged purines and pyrimidines. The first enzymes in the BER pathway are DNA glycosylases, which are responsible for finding and removing the damaged base. Although much is known about the biochemistry of DNA glycosylases, how these enzymes locate their specific damage substrates among an excess of undamaged bases has long remained a mystery. Here we describe the use of single molecule fluorescence to observe the bacterial DNA glycosylases, Nth, Fpg and Nei, scanning along undamaged and damaged DNA. We show that all three enzymes randomly diffuse on the DNA molecule and employ a wedge residue to search for and locate damage. The search behavior of the Escherichia coli DNA glycosylases likely provides a paradigm for their homologous mammalian counterparts.

  16. 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.

  17. 49 CFR 192.713 - Transmission lines: Permanent field repair of imperfections and damages.

    Science.gov (United States)

    2010-10-01

    ... Maintenance § 192.713 Transmission lines: Permanent field repair of imperfections and damages. (a) Each imperfection or damage that impairs the serviceability of pipe in a steel transmission line operating at or... 49 Transportation 3 2010-10-01 2010-10-01 false Transmission lines: Permanent field repair...

  18. Role of Rad54, Rad54b and Snm1 in DNA damage repair

    NARCIS (Netherlands)

    J. Wesoly (Joanna)

    2003-01-01

    textabstractThe aim of this thesis is to investigate the function of a number of genes involved in mammalian DNA damage repair, in particular in repair of DNA double-strand breaks (DSBs). Among a large number of different damages that can be introduced to DNA, DSBs are especially toxic. If left unre

  19. Role of Rad54, Rad54b and Snm1 in DNA damage repair

    NARCIS (Netherlands)

    J. Wesoly (Joanna)

    2003-01-01

    textabstractThe aim of this thesis is to investigate the function of a number of genes involved in mammalian DNA damage repair, in particular in repair of DNA double-strand breaks (DSBs). Among a large number of different damages that can be introduced to DNA, DSBs are especially toxic. If

  20. Mystery of DNA repair: the role of the MRN complex and ATM kinase in DNA damage repair.

    Science.gov (United States)

    Czornak, Kamila; Chughtai, Sanaullah; Chrzanowska, Krystyna H

    2008-01-01

    Genomes are subject to a number of exogenous or endogenous DNA-damaging agents that cause DNA double-strand breaks (DSBs). These critical DNA lesions can result in cell death or a wide variety of genetic alterations, including deletions, translocations, loss of heterozygosity, chromosome loss, or chromosome fusions, which enhance genome instability and can trigger carcinogenesis. The cells have developed an efficient mechanism to cope with DNA damages by evolving the DNA repair machinery. There are 2 major DSB repair mechanisms: nonhomologous end joining (NHEJ) and homologous recombination (HR). One element of the repair machinery is the MRN complex, consisting of MRE11, RAD50 and NBN (previously described as NBS1), which is involved in DNA replication, DNA repair, and signaling to the cell cycle checkpoints. A number of kinases, like ATM (ataxia-telangiectasia mutated), ATR (ataxia-telangiectasia and Rad-3-related), and DNA PKcs (DNA protein kinase catalytic subunit), phosphorylate various protein targets in order to repair the damage. If the damage cannot be repaired, they direct the cell to apoptosis. The MRN complex as well as repair kinases are also involved in telomere maintenance and genome stability. The dysfunction of particular elements involved in the repair mechanisms leads to genome instability disorders, like ataxia telangiectasia (A-T), A-T-like disorder (ATLD) and Nijmegen breakage syndrome (NBS). The mutated genes responsible for these disorders code for proteins that play key roles in the process of DNA repair. Here we present a detailed review of current knowledge on the MRN complex, kinases engaged in DNA repair, and genome instability disorders.

  1. Stochastic modeling of p53-regulated apoptosis upon radiation damage

    CERN Document Server

    Bhatt, Divesh; Bahar, Ivet

    2011-01-01

    We develop and study the evolution of a model of radiation induced apoptosis in cells using stochastic simulations, and identified key protein targets for effective mitigation of radiation damage. We identified several key proteins associated with cellular apoptosis using an extensive literature survey. In particular, we focus on the p53 transcription dependent and p53 transcription independent pathways for mitochondrial apoptosis. Our model reproduces known p53 oscillations following radiation damage. The key, experimentally testable hypotheses that we generate are - inhibition of PUMA is an effective strategy for mitigation of radiation damage if the treatment is administered immediately, at later stages following radiation damage, inhibition of tBid is more effective.

  2. Radiation damage in zircon and monazite

    Energy Technology Data Exchange (ETDEWEB)

    Meldrum, A.; Boatner, L.A. [Oak Ridge National Lab., TN (United States). Solid state Div.; Weber, W.J. [Pacific Northwest National Lab., Richland, WA (United States); Ewing, R.C. [Univ. of Michigan, Ann Arbor, MI (United States). Dept. of Nuclear Engineering and Radiological Sciences

    1998-07-01

    Monazite and zircon respond differently to ion irradiation and to thermal and irradiation-enhanced annealing. The damage process (i.e., elastic interactions leading to amorphization) in radioactive minerals (metamictization) is basically the same as for the ion-beam-irradiated samples with the exception of the dose rate which is much lower in the case of natural samples. The crystalline-to-metamict transition in natural samples with different degrees of damage, from almost fully crystalline to completely metamict, is compared to the sequence of microstructures observed for ion-beam-irradiated monazite and zircon. The damage accumulation process, representing the competing effects of radiation-induced structural disorder and subsequent annealing mechanisms (irradiation-enhanced and thermal) occurs at much higher temperatures for zircon than for monazite. The amorphization dose, expressed as displacements per atom, is considerably higher in the natural samples, and the atomic-scale process leading to metamictization appears to develop differently. Ion-beam-induced amorphization data were used to calculate the {alpha}-decay-event dose required for amorphization in terms of a critical radionuclide concentration, i.e., the concentration above which a sample of a given age will become metamict at a specific temperature. This equation was applied to estimate the reliability of U-Pb ages, to provide a qualitative estimate of the thermal history of high-U natural zircons, and to predict whether actinide-bearing zircon or monazite nuclear waste forms will become amorphous (metamict) over long timescales.

  3. A matter of life or death: modeling DNA damage and repair in bacteria.

    Science.gov (United States)

    Karschau, Jens; de Almeida, Camila; Richard, Morgiane C; Miller, Samantha; Booth, Ian R; Grebogi, Celso; de Moura, Alessandro P S

    2011-02-16

    DNA damage is a hazard all cells must face, and evolution has created a number of mechanisms to repair damaged bases in the chromosome. Paradoxically, many of these repair mechanisms can create double-strand breaks in the DNA molecule which are fatal to the cell. This indicates that the connection between DNA repair and death is far from straightforward, and suggests that the repair mechanisms can be a double-edged sword. In this report, we formulate a mathematical model of the dynamics of DNA damage and repair, and we obtain analytical expressions for the death rate. We predict a counterintuitive relationship between survival and repair. We can discriminate between two phases: below a critical threshold in the number of repair enzymes, the half-life decreases with the number of repair enzymes, but becomes independent of the number of repair enzymes above the threshold. We are able to predict quantitatively the dependence of the death rate on the damage rate and other relevant parameters. We verify our analytical results by simulating the stochastic dynamics of DNA damage and repair. Finally, we also perform an experiment with Escherichia coli cells to test one of the predictions of our model.

  4. Particle fluence measurements by activation technique for radiation damage studies

    CERN Document Server

    León-Florián, E; Furetta, C; Leroy, Claude

    1995-01-01

    High-level radiation environment can produce radiation damage in detectors and their associate electronic components. The establishment of a correlation between damage, irradiation level and absorbed dose requires a precise measurement of the fluence of particles causing the damage. The activation technique is frequently used for performing particle fluence measurements. A review of this technique is presented.

  5. A cell-free system for studying a priming factor involved in repair of bleomycin-damaged DNA.

    Directory of Open Access Journals (Sweden)

    Seki,Shuji

    1989-04-01

    Full Text Available A simple cell-free system for studying a priming factor involved in the repair of bleomycin-damaged DNA was established. The template-primer used for the repair DNA synthesis was prepared by treating the closed circular, superhelical form of pUC19 plasmid DNA with 2.2 microM bleomycin and 20 microM ferrous ions. Single-strand breaks were introduced into pUC19 DNA by the bleomycin treatment, and the DNA was consequently converted largely into the open circular form. A system for repair of this bleomycin-damaged DNA was constructed with a priming factor, DNA polymerase (DNA polymerase beta or Klenow fragment of DNA polymerase I, ATP, T4 DNA ligase and four deoxynucleoside triphosphates. After incubation, the conformation of the DNA was analyzed by agarose gel electrophoresis and electron microscopy. The open circular DNA was largely converted to the closed circular DNA, indicating that the single-strand breaks of DNA were repaired. When the priming factor was omitted, DNA repair did not occur. The present system seemed to be applicable to the study of priming factors involved in the repair of DNA with single-strand breaks caused not only by bleomycin but also by ionizing radiation or active oxygen.

  6. Cytogenetic Response to Ionizing Radiation Exposure in Human Fibroblasts with Suppressed Expression of Non-DSB Repair Genes

    Science.gov (United States)

    Zhang, Ye; Rohde, Larry H.; Emami, Kamal; Hammond, Dianne; Mehta, Satish K.; Jeevarajan, Antony S.; Pierson, Duane L.; Wu, Honglu

    2009-01-01

    Changes of gene expression profile are one of the most important biological responses in living cells after ionizing radiation (IR) exposure. Although some studies have shown that genes up-regulated by IR may play important roles in DNA damage repair, the relationship between the regulation of gene expression by IR, particularly genes not known for their roles in double-strand break (DSB) repair, and its impact on cytogenetic responses has not been well studied. The purpose of this study is to identify new roles of IR inducible genes in radiation-induced chromosome aberrations and micronuclei formation. In the study, the expression of 25 genes selected on the basis of their transcriptional changes in response to IR was individually knocked down by small interfering RNA in human fibroblast cells. Frequencies of micronuclei (MN) formation and chromosome aberrations were measured to determine the efficiency of cytogenetic repair, and the fraction of bi-nucleated cells in the MN analysis was used as a marker for cell cycle progression. In response to gamma radiation, the formation of MN was significantly increased by suppressed expression of five genes: Ku70 (DSB repair pathway), XPA (nucleotide excision repair pathway), RPA1 (mismatch repair pathway), RAD17 and RBBP8 (cell cycle control). Knocked-down expression of four genes (MRE11A, RAD51 in the DSB pathway, SESN1, and SUMO1) significantly inhibited cell cycle progression, possibly because of severe impairment of DNA damage repair. Moreover, decreased XPA, p21, or MLH1 expression resulted in both significantly enhanced cell cycle progression and increased yields of chromosome aberrations, indicating that these gene products modulate both cell cycle control and DNA damage repair. Nine of these eleven genes, whose knock-down expression affected cytogenetic repair, were up-regulated in cells exposed to gamma radiation, suggesting that genes transcriptionally modulated by IR were critical to regulate IR

  7. Cytogenetic Response to Ionizing Radiation Exposure in Human Fibroblasts with Suppressed Expression of Non-DSB Repair Genes

    Science.gov (United States)

    Zhang, Ye; Rohde, Larry H.; Emami, Kamal; Hammond, Dianne; Mehta, Satish K.; Jeevarajan, Antony S.; Pierson, Duane L.; Wu, Honglu

    2009-01-01

    Changes of gene expression profile are one of the most important biological responses in living cells after ionizing radiation (IR) exposure. Although some studies have shown that genes up-regulated by IR may play important roles in DNA damage repair, the relationship between the regulation of gene expression by IR, particularly genes not known for their roles in double-strand break (DSB) repair, and its impact on cytogenetic responses has not been well studied. The purpose of this study is to identify new roles of IR inducible genes in radiation-induced chromosome aberrations and micronuclei formation. In the study, the expression of 25 genes selected on the basis of their transcriptional changes in response to IR was individually knocked down by small interfering RNA in human fibroblast cells. Frequencies of micronuclei (MN) formation and chromosome aberrations were measured to determine the efficiency of cytogenetic repair, and the fraction of bi-nucleated cells in the MN analysis was used as a marker for cell cycle progression. In response to gamma radiation, the formation of MN was significantly increased by suppressed expression of five genes: Ku70 (DSB repair pathway), XPA (nucleotide excision repair pathway), RPA1 (mismatch repair pathway), RAD17 and RBBP8 (cell cycle control). Knocked-down expression of four genes (MRE11A, RAD51 in the DSB pathway, SESN1, and SUMO1) significantly inhibited cell cycle progression, possibly because of severe impairment of DNA damage repair. Moreover, decreased XPA, p21, or MLH1 expression resulted in both significantly enhanced cell cycle progression and increased yields of chromosome aberrations, indicating that these gene products modulate both cell cycle control and DNA damage repair. Nine of these eleven genes, whose knock-down expression affected cytogenetic repair, were up-regulated in cells exposed to gamma radiation, suggesting that genes transcriptionally modulated by IR were critical to regulate IR

  8. Detection and repair of ionizing radiation induced DNA double strand breaks: new developments in non-homologous end joining

    OpenAIRE

    Wang, Chen; Lees-Miller, Susan P.

    2013-01-01

    DNA double-strand breaks (DSBs) are considered the most cytotoxic form of DNA damage. In human cells, the major pathway for the repair of ionizing radiation (IR)-induced DSBs is non-homologous end joining (NHEJ). Here we discuss recent developments in our understanding of the mechanism of NHEJ, the proteins involved and its regulation.

  9. 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.

  10. Biological consequences of potential repair intermediates of clustered base damage site in Escherichia coli

    Energy Technology Data Exchange (ETDEWEB)

    Shikazono, Naoya, E-mail: shikazono.naoya@jaea.go.jp [Japan Atomic Energy Agency, Advanced Research Science Center, 2-4 Shirakata-Shirane, Tokai-mura, Naka-gun, Ibaraki 319-1195 (Japan); O' Neill, Peter [Gray Institute for Radiation Oncology and Biology, University of Oxford, Roosevelt Drive, Oxford OX3 7DQ (United Kingdom)

    2009-10-02

    Clustered DNA damage induced by a single radiation track is a unique feature of ionizing radiation. Using a plasmid-based assay in Escherichia coli, we previously found significantly higher mutation frequencies for bistranded clusters containing 7,8-dihydro-8-oxoguanine (8-oxoG) and 5,6-dihydrothymine (DHT) than for either a single 8-oxoG or a single DHT in wild type and in glycosylase-deficient strains of E. coli. This indicates that the removal of an 8-oxoG from a clustered damage site is most likely retarded compared to the removal of a single 8-oxoG. To gain further insights into the processing of bistranded base lesions, several potential repair intermediates following 8-oxoG removal were assessed. Clusters, such as DHT + apurinic/apyrimidinic (AP) and DHT + GAP have relatively low mutation frequencies, whereas clusters, such as AP + AP or GAP + AP, significantly reduce the number of transformed colonies, most probably through formation of a lethal double strand break (DSB). Bistranded AP sites placed 3' to each other with various interlesion distances also blocked replication. These results suggest that bistranded base lesions, i.e., single base lesions on each strand, but not clusters containing only AP sites and strand breaks, are repaired in a coordinated manner so that the formation of DSBs is avoided. We propose that, when either base lesion is initially excised from a bistranded base damage site, the remaining base lesion will only rarely be converted into an AP site or a single strand break in vivo.

  11. Ultraviolet damage, DNA repair and vitamin D in nonmelanoma skin cancer and in malignant melanoma: an update.

    Science.gov (United States)

    Reichrath, Jörg; Rass, Knuth

    2014-01-01

    Skin exposure with UV radiation (UV) is the main cause of skin cancer development. Epidemiological data indicate that excessive or cumulative UV exposure takes place years and decades before the resulting malignancies arise. The most important defense mechanisms that protect human skin against UV radiation involve melanin synthesis and active repair mechanisms. DNA is the major target of direct or indirect UV-induced cellular damage. Low pigmentation capacity in white Caucasians and rare congenital defects in DNA repair are mainly responsible for protection failures. The important function of nucleotide excision DNA repair (NER) to protect against skin cancer becomes obvious by the rare genetic disease xeroderma pigmentosum, in which diverse NER genes are mutated. In animal models, it has been demonstrated that UVB is more effective to induce skin cancer than UVA. UV-induced DNA photoproducts are able to cause specific mutations (UV-signature) in susceptible genes for squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). In SCC development, UV-signature mutations in the p53 tumor suppressor gene are the most common event, as precancerous lesions reveal -80% and SCCs > 90% UV-specific p53 mutations. Mutations in Hedgehog pathway related genes, especially PTCH1, are well known to represent the most significant pathogenic event in BCC. However, specific UV-induced mutations can be found only in -50% of sporadic BCCs. Thus, cumulative UVB radiation cannot be considered to represent the only etiologic risk factor for BCC development. During the last decades, experimental animal models, including genetically engineered mice, the Xiphophorus hybrid fish, the South American oppossum and human skin xenografts, have further elucidated the important role of the DNA repair system in the multi-step process of UV-induced melanomagenesis. An increasing body of evidence now indicates that nucleotide excision repair is not the only DNA repair pathway that is involved in UV

  12. 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.

  13. Simulation of radiation damage in gadolinium pyrochlores

    Science.gov (United States)

    Todorov, Ilian T.; Purton, John A.; Allan, Neil L.; Dove, Martin T.

    2006-02-01

    We report molecular dynamics simulations of the production of radiation cascades in pyrochlores. We consider the apparently similar systems Gd2Ti2O7, Gd2Zr2O7 and Gd2Pb2O7, the first two of which have been put forward as potential materials for high-level radioactive waste storage. The effects of changing the mass of the 'primary knock-on' atom are also examined and we investigate whether the change in behaviour from Ti to Zr to Pb is largely due to the mass or the size difference between the elements. Problems associated with analysing the cascades and the damage created are discussed. There are clear differences between the three compounds. The simulations see no direct amorphization but rather a transition to the fluorite structure which is more pronounced for the Zr and Pb compounds than the Ti system. Underlying chemical trends are examined.

  14. 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.

  15. DNA damage by reactive species: Mechanisms, mutation and repair.

    Science.gov (United States)

    Jena, N R

    2012-07-01

    DNA is continuously attacked by reactive species that can affect its structure and function severely. Structural modifications to DNA mainly arise from modifications in its bases that primarily occur due to their exposure to different reactive species. Apart from this, DNA strand break, inter- and intra-strand crosslinks and DNA-protein crosslinks can also affect the structure of DNA significantly. These structural modifications are involved in mutation, cancer and many other diseases. As it has the least oxidation potential among all the DNA bases, guanine is frequently attacked by reactive species, producing a plethora of lethal lesions. Fortunately, living cells are evolved with intelligent enzymes that continuously protect DNA from such damages. This review provides an overview of different guanine lesions formed due to reactions of guanine with different reactive species. Involvement of these lesions in inter- and intra-strand crosslinks, DNA-protein crosslinks and mutagenesis are discussed. How certain enzymes recognize and repair different guanine lesions in DNA are also presented.

  16. DNA damage by reactive species: Mechanisms, mutation and repair

    Indian Academy of Sciences (India)

    N R Jena

    2012-07-01

    DNA is continuously attacked by reactive species that can affect its structure and function severely. Structural modifications to DNA mainly arise from modifications in its bases that primarily occur due to their exposure to different reactive species. Apart from this, DNA strand break, inter- and intra-strand crosslinks and DNA–protein crosslinks can also affect the structure of DNA significantly. These structural modifications are involved in mutation, cancer and many other diseases. As it has the least oxidation potential among all the DNA bases, guanine is frequently attacked by reactive species, producing a plethora of lethal lesions. Fortunately, living cells are evolved with intelligent enzymes that continuously protect DNA from such damages. This review provides an overview of different guanine lesions formed due to reactions of guanine with different reactive species. Involvement of these lesions in inter- and intra-strand crosslinks, DNA–protein crosslinks and mutagenesis are discussed. How certain enzymes recognize and repair different guanine lesions in DNA are also presented.

  17. Reduction of arsenite-enhanced ultraviolet radiation-induced DNA damage by supplemental zinc

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, Karen L.; King, Brenee S.; Sandoval, Monica M.; Liu, Ke Jian; Hudson, Laurie G., E-mail: lhudson@salud.unm.edu

    2013-06-01

    Arsenic is a recognized human carcinogen and there is evidence that arsenic augments the carcinogenicity of DNA damaging agents such as ultraviolet radiation (UVR) thereby acting as a co-carcinogen. Inhibition of DNA repair is one proposed mechanism to account for the co-carcinogenic actions of arsenic. We and others find that arsenite interferes with the function of certain zinc finger DNA repair proteins. Furthermore, we reported that zinc reverses the effects of arsenite in cultured cells and a DNA repair target protein, poly (ADP-ribose) polymerase-1. In order to determine whether zinc ameliorates the effects of arsenite on UVR-induced DNA damage in human keratinocytes and in an in vivo model, normal human epidermal keratinocytes and SKH-1 hairless mice were exposed to arsenite, zinc or both before solar-simulated (ss) UVR exposure. Poly (ADP-ribose) polymerase activity, DNA damage and mutation frequencies at the Hprt locus were measured in each treatment group in normal human keratinocytes. DNA damage was assessed in vivo by immunohistochemical staining of skin sections isolated from SKH-1 hairless mice. Cell-based findings demonstrate that ssUVR-induced DNA damage and mutagenesis are enhanced by arsenite, and supplemental zinc partially reverses the arsenite effect. In vivo studies confirm that zinc supplementation decreases arsenite-enhanced DNA damage in response to ssUVR exposure. From these data we can conclude that zinc offsets the impact of arsenic on ssUVR-stimulated DNA damage in cells and in vivo suggesting that zinc supplementation may provide a strategy to improve DNA repair capacity in arsenic exposed human populations. - Highlights: • Low levels of arsenite enhance UV-induced DNA damage in human keratinocytes. • UV-initiated HPRT mutation frequency is enhanced by arsenite. • Zinc supplementation offsets DNA damage and mutation frequency enhanced by arsenite. • Zinc-dependent reduction of arsenite enhanced DNA damage is confirmed in vivo.

  18. DNA damage and radical reactions: Mechanistic aspects, formation in cells and repair studies

    Energy Technology Data Exchange (ETDEWEB)

    Cadet, J.; Ravanat, J.L. [CEA Grenoble, Inst Nanosci and Cryogenie, SCIB-UMR-E 3, Lab Les Acides Nucl, UJF, F-38054 Grenoble 9 (France); Carell, T. [Univ Munich, Dept Chem and Biochem, Ctr Integrat Prot Sci, D-81377 Munich (Germany); Cellai, L. [CNR, Ist Cristalog, Monterotondo Stn, I-00016 Rome (Italy); Chatgilialoglu, Ch. [CNR, ISOF, I-40129 Bologna, (Italy); Gimisis, Th. [Univ Athens, Dept Chem, Organ Chem Lab, Athens 15784, (Greece); Miranda, M. [Univ Politecn Valencia, Inst Technol Quim, Dept Quim, Valencia 46022 (Spain); O' Neill, P. [Univ Oxford, Oxford OX3 7DQ (United Kingdom); Robert, M. [Univ Paris 07, CNRS, UMR 7591, Electrochim Mol Lab, F-75251 Paris 05 (France)

    2008-07-01

    Several examples of oxidative and reductive reactions of DNA components that lead to single and tandem modifications are discussed in this review. These include nucleophilic addition reactions of the one-electron oxidation-mediated guanine radical cation and the one-electron reduced intermediate of 8-bromo-purine 2'-de-oxy-ribo-nucleosides that give rise to either an oxidizing guanine radical or related 5',8-cyclo-purine nucleosides. In addition, mechanistic insights into the reductive pathways involved in the photolyase induced reversal of cyclo-buta-cli-pyrimidine and pyrimidine (6-4) pyrimidone photoproducts are provided. Evidence for the occurrence and validation in cellular DNA of (OH){sup {center_dot}} radical degradation pathways of guanine that have been established in model systems has been gained from the accurate measurement of degradation products. Relevant information on biochemical aspects of the repair of single and clustered oxidatively generated damage to DNA has been gained from detailed investigations that rely on the synthesis of suitable modified probes. Thus the preparation of stable carbocyclic derivatives of purine nucleoside containing defined sequence oligonucleotides has allowed detailed crystallographic studies of the recognition step of the base damage by enzymes implicated in the base excision repair (BER) pathway. Detailed insights are provided on the BER processing of non-double strand break bi-stranded clustered damage that may consist of base lesions, a single strand break or abasic sites and represent one of the main deleterious classes of radiation-induced DNA damage. (authors)

  19. Monte carlo simulation of base and nucleotide excision repair of clustered DNA damage sites. II. Comparisons of model predictions to measured data.

    Science.gov (United States)

    Semenenko, V A; Stewart, R D

    2005-08-01

    Clustered damage sites other than double-strand breaks (DSBs) have the potential to contribute to deleterious effects of ionizing radiation, such as cell killing and mutagenesis. In the companion article (Semenenko et al., Radiat. Res. 164, 180-193, 2005), a general Monte Carlo framework to simulate key steps in the base and nucleotide excision repair of DNA damage other than DSBs is proposed. In this article, model predictions are compared to measured data for selected low-and high-LET radiations. The Monte Carlo model reproduces experimental observations for the formation of enzymatic DSBs in Escherichia coli and cells of two Chinese hamster cell lines (V79 and xrs5). Comparisons of model predictions with experimental values for low-LET radiation suggest that an inhibition of DNA backbone incision at the sites of base damage by opposing strand breaks is active over longer distances between the damaged base and the strand break in hamster cells (8 bp) compared to E. coli (3 bp). Model estimates for the induction of point mutations in the human hypoxanthine guanine phosphoribosyl transferase (HPRT) gene by ionizing radiation are of the same order of magnitude as the measured mutation frequencies. Trends in the mutation frequency for low- and high-LET radiation are predicted correctly by the model. The agreement between selected experimental data sets and simulation results provides some confidence in postulated mechanisms for excision repair of DNA damage other than DSBs and suggests that the proposed Monte Carlo scheme is useful for predicting repair outcomes.

  20. Alterations in phosphate metabolism during cellular recovery of radiation damage in yeast

    Energy Technology Data Exchange (ETDEWEB)

    Holahan, P.K.; Knizner, S.A.; Gabriel, C.M.; Swenberg, C.E.

    1988-01-01

    Alterations were examined in phosphate pools during cellular recovery from radiation damage in intact, wild-type diploid yeast cells using phosphorus 31 nuclear magnetic resonance (NMR) spectroscopy. Concurrent cell survival analysis was determined following exposure to cobalt 60 gamma radiation. Cells held in citrate-buffered saline (CBS) showed increased survival with increasing time after irradiation (liquid holding recovery, LHR) with no further recovery beyond 48 h. Addition of 100 mmol/cu. dm glucose to the recovery medium resulted in greater recovery. In the presence of 5 mmol/cu. dm 2-deoxyglucose (2-DG), LHR was completely inhibited. ATP was observable by NMR only when glucose was present in the recovery medium. In control cells, ATP concentrations increased and plateaued with increasing recovery time. With increasing radiation dose, the increase in ATP was of lesser magnitude, and after 2000 Gy no increase was observed. The observations suggest that either the production of ATP in irradiated cells is suppressed, or there is enhanced ATP utilization for repair of radiation damage. In CBS with 100 mmol/cu. dm glucose, a dose-dependent decrease in polyphosphate (polyP) was detectable with no concurrent increase in inorganic phosphate (p sub i). When 2-DG was present in the recovery medium, polyP decreased, but there was a simultaneous increase in p sub i with increasing radiation dose and recovery time. This suggests that the polyP are hydrolyzed as a source of phosphates for repair of radiation damage.

  1. Modeling of DSBs Generation and Repair Process under Ion Radiation

    Institute of Scientific and Technical Information of China (English)

    QI Jin-peng; SHAO Shi-huang; XIE Jin-li; BAI Hui

    2007-01-01

    Under acute perturbations from outside, cell can trigger the self-defense mechanisms in fighting against these genome stresses. To simulate the investigation of the complicated mechanisms of cellular responding DNA damage at single cell level, a model of the double strand breaks (DSBs) generation and repair process is proposed under continuous effect of acute IR. Under different IR dose domains, this model can be used to simulate the complicated interactions among vital components within the cell, and the plausible outcomes of cellular response in fighting against DNA damage.

  2. Bridging Plant and Human Radiation Response and DNA Repair through an In Silico Approach

    Directory of Open Access Journals (Sweden)

    Zacharenia Nikitaki

    2017-06-01

    Full Text Available The mechanisms of response to radiation exposure are conserved in plants and animals. The DNA damage response (DDR pathways are the predominant molecular pathways activated upon exposure to radiation, both in plants and animals. The conserved features of DDR in plants and animals might facilitate interdisciplinary studies that cross traditional boundaries between animal and plant biology in order to expand the collection of biomarkers currently used for radiation exposure monitoring (REM in environmental and biomedical settings. Genes implicated in trans-kingdom conserved DDR networks often triggered by ionizing radiation (IR and UV light are deposited into biological databases. In this study, we have applied an innovative approach utilizing data pertinent to plant and human genes from publicly available databases towards the design of a ‘plant radiation biodosimeter’, that is, a plant and DDR gene-based platform that could serve as a REM reliable biomarker for assessing environmental radiation exposure and associated risk. From our analysis, in addition to REM biomarkers, a significant number of genes, both in human and Arabidopsis thaliana, not yet characterized as DDR, are suggested as possible DNA repair players. Last but not least, we provide an example on the applicability of an Arabidopsis thaliana—based plant system monitoring the role of cancer-related DNA repair genes BRCA1, BARD1 and PARP1 in processing DNA lesions.

  3. Microvesicle shedding and lysosomal repair fulfill divergent cellular needs during the repair of streptolysin O-induced plasmalemmal damage.

    Directory of Open Access Journals (Sweden)

    Alexander P Atanassoff

    Full Text Available Pathogenic bacteria secrete pore-forming toxins that permeabilize the plasma membrane of host cells. Nucleated cells possess protective mechanisms that repair toxin-damaged plasmalemma. Currently two putative repair scenarios are debated: either the isolation of the damaged membrane regions and their subsequent expulsion as microvesicles (shedding or lysosome-dependent repair might allow the cell to rid itself of its toxic cargo and prevent lysis. Here we provide evidence that both mechanisms operate in tandem but fulfill diverse cellular needs. The prevalence of the repair strategy varies between cell types and is guided by the severity and the localization of the initial toxin-induced damage, by the morphology of a cell and, most important, by the incidence of the secondary mechanical damage. The surgically precise action of microvesicle shedding is best suited for the instant elimination of individual toxin pores, whereas lysosomal repair is indispensable for mending of self-inflicted mechanical injuries following initial plasmalemmal permeabilization by bacterial toxins. Our study provides new insights into the functioning of non-immune cellular defenses against bacterial pathogens.

  4. Escherichia coli radD (yejH) gene: a novel function involved in radiation resistance and double-strand break repair

    OpenAIRE

    Chen, Stefanie H.; Byrne, Rose T.; Wood, Elizabeth A; Cox, Michael M.

    2015-01-01

    A transposon insertion screen implicated the yejH gene in the repair of ionizing radiation-induced damage. The yejH gene, which exhibits significant homology to the human transcription-coupled DNA repair gene XPB, is involved in the repair of double strand DNA breaks. Deletion of yejH significantly sensitized cells to agents that cause double strand breaks (ionizing radiation, UV radiation, ciprofloxacin). In addition, deletion of both yejH and radA hypersensitized the cells to ionizing radia...

  5. Spectrum of Radiation-Induced Clustered Non-DSB Damage - A Monte Carlo Track Structure Modeling and Calculations.

    Science.gov (United States)

    Watanabe, Ritsuko; Rahmanian, Shirin; Nikjoo, Hooshang

    2015-05-01

    The aim of this report is to present the spectrum of initial radiation-induced cellular DNA damage [with particular focus on non-double-strand break (DSB) damage] generated by computer simulations. The radiation types modeled in this study were monoenergetic electrons (100 eV-1.5 keV), ultrasoft X-ray photons Ck, AlK and TiK, as well as some selected ions including 3.2 MeV/u proton; 0.74 and 2.4 MeV/u helium ions; 29 MeV/u nitrogen ions and 950 MeV/u iron ions. Monte Carlo track structure methods were used to simulate damage induction by these radiation types in a cell-mimetic condition from a single-track action. The simulations took into account the action of direct energy deposition events and the reaction of hydroxyl radicals on atomistic linear B-DNA segments of a few helical turns including the water of hydration. Our results permitted the following conclusions: a. The absolute levels of different types of damage [base damage, simple and complex single-strand breaks (SSBs) and DSBs] vary depending on the radiation type; b. Within each damage class, the relative proportions of simple and complex damage vary with radiation type, the latter being higher with high-LET radiations; c. Overall, for both low- and high-LET radiations, the ratios of the yields of base damage to SSBs are similar, being about 3.0 ± 0.2; d. Base damage contributes more to the complexity of both SSBs and DSBs, than additional SSB damage and this is true for both low- and high-LET radiations; and e. The average SSB/DSB ratio for low-LET radiations is about 18, which is about 5 times higher than that for high-LET radiations. The hypothesis that clustered DNA damage is more difficult for cells to repair has gained currency among radiobiologists. However, as yet, there is no direct in vivo experimental method to validate the dependence of kinetics of DNA repair on DNA damage complexity (both DSB and non-DSB types). The data on the detailed spectrum of DNA damage presented here, in particular

  6. 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

  7. Self-repairing of material damage. Sonsho wo jiko shufuku yokushisuru zairyo

    Energy Technology Data Exchange (ETDEWEB)

    Matsuoka, S. (National Research Inst. for Metals, Tsukuba (Japan))

    1994-07-01

    In order to control the damage like crack or void formed during the use of structural material by the material itself, it is required to self-detect the damage, to self-judge the state of damage, and to self-control or self-repair the damage finally. Based on the parameter of length, the repair and control is classified into the 1mm-scale functional fine wire and thin film utilization type, 1[mu]m-scale microcapsule type, and 1nm-scale trace element utilization type. For the damage repair and control of functional fine wire and thin film utilization type, the damage is repaired and controlled by pasting thin film or by embedding fine wire of functional material, such as shape memory alloy, Ti-Ni, and piezoelectric ceramics PZT (lead zirconate titanate), on the material surface or inside the material. For the damage repair and control of microcapsule type, is illustrated the control mechanism of high temperature fatigue crack propagation by Y2O3 particles dispersed in the Fe-20Cr alloy. Furthermore, the formation mechanism of self-repairing film by the trace element is also illustrated. 13 refs., 5 figs.

  8. Radiation Damage in Electronic Memory Devices

    OpenAIRE

    Irfan Fetahović; Milić Pejović; Miloš Vujisić

    2013-01-01

    This paper investigates the behavior of semiconductor memories exposed to radiation in order to establish their applicability in a radiation environment. The experimental procedure has been used to test radiation hardness of commercial semiconductor memories. Different types of memory chips have been exposed to indirect ionizing radiation by changing radiation dose intensity. The effect of direct ionizing radiation on semiconductor memory behavior has been analyzed by using Monte Carlo simula...

  9. REPAIR TECHNOLOGY OF THE COMPOSITE WING OF A LIGHT PLANE DAMAGED DURING AN AIRCRAFT CRASH

    Directory of Open Access Journals (Sweden)

    Andrzej ŚWIĄTONIOWSKI

    2016-09-01

    Full Text Available The increasing use of composite structures in aircraft constructions has made it necessary to develop repair methods that will restore the component’s original design strength without compromising its structural integrity. In this paper, the complex repair technology of the composite wing of a light plane, which was damaged during an aircraft crash, is described. The applied repair scheme should meet all the original design requirements for the plane structure.

  10. Chemistry of radiation damage to wire chambers

    Energy Technology Data Exchange (ETDEWEB)

    Wise, J.

    1992-08-01

    Proportional counters are used to study aspects of radiation damage to wire chambers (wire aging). Principles of low-pressure, rf plasma chemistry are used to predict the plasma chemistry in electron avalanches (1 atm, dc). (1) Aging is studied in CF{sub 4}/iC{sub 4}H{sub 10} gas mixtures. Wire deposits are analyzed by Auger electron spectroscopy. An apparent cathode aging process resulting in loss of gain rather than in a self-sustained current is observed in CF{sub 4}-rich gases. A four-part model considering plasma polymerization of the hydrocarbon, etching of wire deposits by CF{sub 4}, acceleration of deposition processes in strongly etching environments, and reactivity of the wire surface is developed to understand anode wire aging in CF{sub 4}/iC{sub 4}H{sub 10} gases. Practical guidelines suggested by the model are discussed. (2) Data are presented to suggest that trace amounts of Freons do not affect aging rates in either dimethyl ether or Ar/C{sub 2}H{sub 6}. Apparent loss of gain is explained by attachment of primary electrons to a continuously increasing concentration of Freon 11 (CCl{sub 3}F) in the counter gas. An increase in the concentration of Freon 11 in dimethyl ether is caused by a distillation process in the gas supply bottle and is a natural consequence of the unequal volatilities of the two compounds.

  11. Study on Repaired Earthquake-Damaged Bridge Piers under Seismic Load

    Directory of Open Access Journals (Sweden)

    Jun Deng

    2015-01-01

    Full Text Available The concrete bridge pier damaged during earthquakes need be repaired to meet the design standards. Steel tube as a traditional material or FRP as a novel material has become popular to repair the damaged reinforced concrete (RC bridge piers. In this paper, experimental and finite element (FE studies are employed to analyze the confinement effectiveness of the different repair materials. The FE method was used to calculate the hysteretic behavior of three predamaged circle RC bridge piers repaired with steel tube, basalt fiber reinforced polymer (BFRP, and carbon fiber reinforced polymer (CFRP, respectively. Meanwhile, the repaired predamaged circle concrete bridge piers were tested by pseudo-static cyclic loading to study the seismic behavior and evaluate the confinement effectiveness of the different repair materials and techniques. The FE analysis and experimental results showed that the repaired piers had similar hysteretic curves with the original specimens and all the three repair techniques can restore the seismic performance of the earthquake-damaged piers. Steel tube jacketing can significantly improve the lateral stiffness and peak load of the damaged pier, while the BFRP and CFRP sheets cannot improve these properties due to their thin thickness.

  12. The REPAIR Project: Examining the Biological Impacts of Sub-Background Radiation Exposure within SNOLAB, a Deep Underground Laboratory.

    Science.gov (United States)

    Thome, Christopher; Tharmalingam, Sujeenthar; Pirkkanen, Jake; Zarnke, Andrew; Laframboise, Taylor; Boreham, Douglas R

    2017-07-19

    Considerable attention has been given to understanding the biological effects of low-dose ionizing radiation exposure at levels slightly above background. However, relatively few studies have been performed to examine the inverse, where natural background radiation is removed. The limited available data suggest that organisms exposed to sub-background radiation environments undergo reduced growth and an impaired capacity to repair genetic damage. Shielding from background radiation is inherently difficult due to high-energy cosmic radiation. SNOLAB, located in Sudbury, Ontario, Canada, is a unique facility for examining the effects of sub-background radiation exposure. Originally constructed for astroparticle physics research, the laboratory is located within an active nickel mine at a depth of over 2,000 m. The rock overburden provides shielding equivalent to 6,000 m of water, thereby almost completely eliminating cosmic radiation. Additional features of the facility help to reduce radiological contamination from the surrounding rock. We are currently establishing a biological research program within SNOLAB: Researching the Effects of the Presence and Absence of Ionizing Radiation (REPAIR project). We hypothesize that natural background radiation is essential for life and maintains genomic stability, and that prolonged exposure to sub-background radiation environments will be detrimental to biological systems. Using a combination of whole organism and cell culture model systems, the effects of exposure to a sub-background environment will be examined on growth and development, as well as markers of genomic damage, DNA repair capacity and oxidative stress. The results of this research will provide further insight into the biological effects of low-dose radiation exposure as well as elucidate some of the processes that may drive evolution and selection in living systems. This Radiation Research focus issue contains reviews and original articles, which relate to the

  13. Repair of corrosion-damaged columns using FRP wraps

    Science.gov (United States)

    Baiyasi, Mohamad Imad

    Many bridge columns in Michigan are damaged by chloride contamination resulting in the corrosion of the steel reinforcement, and swelling and spalling of the concrete and use of the bridges is typically continued. This in itself may not be a serious problem since most columns in Michigan are over-designed and the loss of strength is not a significant issue. However, the lack of any method to minimize or prevent corrosion of the steel results in continued deterioration and unsightly columns. Polymer composite (also known as fiber-reinforced polymer or FRP) jackets offer a possible remedy to this problem. They offer a rapid repair technique with the potential to enhance the longterm durability and compression strength of damaged columns due to the confinement that is provided when fibers are oriented in the hoop direction. Fibers oriented in the vertical direction can enhance the bending strength. Experiments were conducted to assess the effects of using FRP wraps with fibers oriented in the hoop direction for rehabilitating corrosion-damaged columns. Issues that were explored are: (1) effect of freeze-thaw and wet-dry cycles on the properties of FRP panels; (2) freeze-thaw durability of concrete square and cylindrical specimens wrapped with glass and carbon FRP and subjected to an internal expansive force; and (3) effect of wrapping on the rate of corrosion in an accelerated corrosion test. The results of the freeze-thaw experiment indicate that freeze-thaw cycles have no statistically significant effect on the compressive strength of glass and carbon wrapped specimens. For round specimens, glass and carbon wraps increased the strength by a factor of about 2.3 and 2.6, respectively. For square specimens, glass and carbon wraps increased the strength by a factor of 1.4--1.5. Freeze-thaw conditioning generally reduced the longitudinal failure strain of wrapped specimens. The square wrapped specimens had lower compressive strength compared to the round specimens, even

  14. BRCA1-associated exclusion of 53BP1 from DNA damage sites underlies temporal control of DNA repair

    Science.gov (United States)

    Chapman, J. Ross; Sossick, Alex J.; Boulton, Simon J.; Jackson, Stephen P.

    2012-01-01

    Summary Following irradiation, numerous DNA-damage-responsive proteins rapidly redistribute into microscopically visible subnuclear aggregates, termed ionising-radiation-induced foci (IRIF). How the enrichment of proteins on damaged chromatin actually relates to DNA repair remains unclear. Here, we use super-resolution microscopy to examine the spatial distribution of BRCA1 and 53BP1 proteins within single IRIF at subdiffraction-limit resolution, yielding an unprecedented increase in detail that was not previously apparent by conventional microscopy. Consistent with a role for 53BP1 in promoting DNA double-strand break repair by non-homologous end joining, 53BP1 enrichment in IRIF is most prominent in the G0/G1 cell cycle phases, where it is enriched in dense globular structures. By contrast, as cells transition through S phase, the recruitment of BRCA1 into the core of IRIF is associated with an exclusion of 53BP1 to the focal periphery, leading to an overall reduction of 53BP1 occupancy at DNA damage sites. Our data suggest that the BRCA1-associated IRIF core corresponds to chromatin regions associated with repair by homologous recombination, and the enrichment of BRCA1 in IRIF represents a temporal switch in the DNA repair program. We propose that BRCA1 antagonises 53BP1-dependent DNA repair in S phase by inhibiting its interaction with chromatin proximal to damage sites. Furthermore, the genomic instability exhibited by BRCA1-deficient cells might result from a failure to efficiently exclude 53BP1 from such regions during S phase. PMID:22553214

  15. Radiation Damage in Electronic Memory Devices

    Directory of Open Access Journals (Sweden)

    Irfan Fetahović

    2013-01-01

    Full Text Available This paper investigates the behavior of semiconductor memories exposed to radiation in order to establish their applicability in a radiation environment. The experimental procedure has been used to test radiation hardness of commercial semiconductor memories. Different types of memory chips have been exposed to indirect ionizing radiation by changing radiation dose intensity. The effect of direct ionizing radiation on semiconductor memory behavior has been analyzed by using Monte Carlo simulation method. Obtained results show that gamma radiation causes decrease in threshold voltage, being proportional to the absorbed dose of radiation. Monte Carlo simulations of radiation interaction with material proved to be significant and can be a good estimation tool in probing semiconductor memory behavior in radiation environment.

  16. 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)

  17. Repair of the radiation induced rectovaginal fistulas without or with interposition of the bulbocavernosus muscle (Martius procedure)

    Energy Technology Data Exchange (ETDEWEB)

    Aartsen, E.J.; Sindram, I.S.

    1988-04-01

    Two local repair procedures, one without (9) and the other with (14) a bulbocavernosus muscle graft were performed on 20 patients with a radiation induced rectovaginal fistula. Four patients had two procedures successively. The initial success rate of both procedures was 7/9 and 14/14 respectively. Though the initial result of the bulbocavernosus graft was obviously better, in many of the local repair procedures, subclinical radiation damage progressed, resulting in recurrence of rectovaginal fistula (5), rectovesical fistula (4), pararectal abscess (2) etc. After a mean follow up of around 10 years, the success rate of fistula repair decreased to 5/9 and 13/14 and only 2/9 and 6/14 finally remained without a colostomy. A local repair operation should be restricted to carefully selected cases. The musculus gracilis is proposed as a better vascular graft. If the general condition of the patient does not allow more aggressive reconstructive procedures, fistula repair is better cancelled because there is a high risk of subsequent radiation damage.

  18. Analyses of the secondary particle radiation and the DNA damage it causes to human keratinocytes

    Energy Technology Data Exchange (ETDEWEB)

    Lebel E.; Rusek A.; Sivertz, M.; Yip, K.; Thompson, K.; Tafrov, S.

    2011-11-22

    High-energy protons, and high mass and energy ions, along with the secondary particles they produce, are the main contributors to the radiation hazard during space explorations. Skin, particularly the epidermis, consisting mainly of keratinocytes with potential for proliferation and malignant transformation, absorbs the majority of the radiation dose. Therefore, we used normal human keratinocytes to investigate and quantify the DNA damage caused by secondary radiation. Its manifestation depends on the presence of retinol in the serum-free media, and is regulated by phosphatidylinositol 3-kinases. We simulated the generation of secondary radiation after the impact of protons and iron ions on an aluminum shield. We also measured the intensity and the type of the resulting secondary particles at two sample locations; our findings agreed well with our predictions. We showed that secondary particles inflict DNA damage to different extents, depending on the type of primary radiation. Low-energy protons produce fewer secondary particles and cause less DNA damage than do high-energy protons. However, both generate fewer secondary particles and inflict less DNA damage than do high mass and energy ions. The majority of cells repaired the initial damage, as denoted by the presence of 53BPI foci, within the first 24 hours after exposure, but some cells maintained the 53BP1 foci longer.

  19. Analyses of the Secondary Particle Radiation and the DNA Damage it Causes to Human Keratinocytes

    Energy Technology Data Exchange (ETDEWEB)

    Lebel E. A.; Tafrov S.; Rusek, A.; Sivertz, M. B.; Yip, K.; Thompson, K. H.

    2011-11-01

    High-energy protons, and high mass and energy ions, along with the secondary particles they produce, are the main contributors to the radiation hazard during space explorations. Skin, particularly the epidermis, consisting mainly of keratinocytes with potential for proliferation and malignant transformation, absorbs the majority of the radiation dose. Therefore, we used normal human keratinocytes to investigate and quantify the DNA damage caused by secondary radiation. Its manifestation depends on the presence of retinol in the serum-free media, and is regulated by phosphatidylinositol 3-kinases. We simulated the generation of secondary radiation after the impact of protons and iron ions on an aluminum shield. We also measured the intensity and the type of the resulting secondary particles at two sample locations; our findings agreed well with our predictions. We showed that secondary particles inflict DNA damage to different extents, depending on the type of primary radiation. Low-energy protons produce fewer secondary particles and cause less DNA damage than do high-energy protons. However, both generate fewer secondary particles and inflict less DNA damage than do high mass and energy ions. The majority of cells repaired the initial damage, as denoted by the presence of 53BPI foci, within the first 24 hours after exposure, but some cells maintained the 53BP1 foci longer.

  20. PARP-1: Friend or Foe of DNA Damage and Repair in Tumorigenesis?

    Energy Technology Data Exchange (ETDEWEB)

    Swindall, Amanda F.; Stanley, Jennifer A. [Department of Radiation Oncology Comprehensive Cancer Center, University of Alabama at Birmingham School of Medicine, 176F HSROC Suite 2232B, 1700 6th Avenue South, Birmingham, AL 35249 (United States); Yang, Eddy S., E-mail: eyang@uab.edu [Department of Radiation Oncology Comprehensive Cancer Center, University of Alabama at Birmingham School of Medicine, 176F HSROC Suite 2232B, 1700 6th Avenue South, Birmingham, AL 35249 (United States); Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL 35249 (United States); Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL 35249 (United States)

    2013-07-26

    Oxidative stress induced by reactive oxygen species can result in DNA damage within cells and subsequently increase risk for carcinogenesis. This may be averted by repair of DNA damage through the base or nucleotide excision repair (BER/NER) pathways. PARP, a BER protein, is known for its role in DNA-repair. However, multiple lesions can occur within a small range of DNA, known as oxidative clustered DNA lesions (OCDLs), which are difficult to repair and may lead to the more severe DNA double-strand break (DSB). Inefficient DSB repair can then result in increased mutagenesis and neoplastic transformation. OCDLs occur more frequently within a variety of tumor tissues. Interestingly, PARP is highly expressed in several human cancers. Additionally, chronic inflammation may contribute to tumorigenesis through ROS-induced DNA damage. Furthermore, PARP can modulate inflammation through interaction with NFκB and regulating the expression of inflammatory signaling molecules. Thus, the upregulation of PARP may present a double-edged sword. PARP is needed to repair ROS-induced DNA lesions, but PARP expression may lead to increased inflammation via upregulation of NFκB signaling. Here, we discuss the role of PARP in the repair of oxidative damage versus the formation of OCDLs and speculate on the feasibility of PARP inhibition for the treatment and prevention of cancers by exploiting its role in inflammation.

  1. Regulation of ATM in DNA double strand break repair accounts for the radiosensitivity in human cells exposed to high linear energy transfer ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Xue Lian, E-mail: xuelian@suda.edu.cn [School of Radiation Medicine and Public Health, Medical College of Soochow University, No. 199, Ren' ai Road, Suzhou 215123 (China); Yu Dong, E-mail: ydong@ncc.go.jp [Tumor Endocrinology Project, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Furusawa, Yoshiya; Okayasu, Ryuichi [Heavy-Ion Radiobiology Research Group, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba-shi 263-8555 (Japan); Tong Jian; Cao Jianping; Fan Saijun [School of Radiation Medicine and Public Health, Medical College of Soochow University, No. 199, Ren' ai Road, Suzhou 215123 (China)

    2009-11-02

    High linear energy transfer (LET) radiation shows different biological effects from low-LET radiation. The complex nature of high LET radiation-induced damage, especially the clustered DNA damage, brings about slow repair of DNA double strand breaks (DSBs), which finally lead to higher lethality and chromosome aberration. Ionizing radiation (IR) induced DNA DSBs are repaired by both non-homologous end-joining (NHEJ) and homologous recombination repair (HRR) pathways in mammalian cells. The novel function of ataxia telangiectasia-mutated (ATM) protein is its involvement in the DSB repair of slow kinetics for 'dirty' breaks rejoining by NHEJ, this suggests that ATM may play a more important role in high LET radiation-induced DNA damage. We show here that KU55933, an ATM inhibitor could distinctly lower the clonogenic survival in normal human skin fibroblast cells exposed to carbon ion radiation and dramatically impair the normal process for DSB repair. We also implicated the involvement of ATM in the two pathways of DNA DSB repair, with DNA-PKcs and Rad51 as the representative proteins. The phosphorylation of DNA-PKcs at Thr-2609 with both immunoblotting and immunofluorescent staining indicated an ATM-dependent change, while for Rad51, KU55933 pretreatment could postpone the formation of nuclear Rad51 foci. Interestingly, we also found that pretreatment with chloroquine, an ATM stimulator could protect cells from carbon ion radiation only at lower doses. For doses over 1 Gy, protection was no longer observed. There was a dose-dependent increase for ATM kinase activity, with saturation at about 1 Gy. Chloroquine pretreatment prior to 1 Gy of carbon ion radiation did not enhance the autophosphorylation of ATM at serine 1981. The function of ATM in G2/M checkpoint arrest facilitated DSB repair in high-LET irradiation. Our results provide a possible mechanism for the direct involvement of ATM in DSB repair by high-LET irradiation.

  2. Lung Basal Stem Cells Rapidly Repair DNA Damage Using the Error-Prone Nonhomologous End-Joining Pathway.

    Science.gov (United States)

    Weeden, Clare E; Chen, Yunshun; Ma, Stephen B; Hu, Yifang; Ramm, Georg; Sutherland, Kate D; Smyth, Gordon K; Asselin-Labat, Marie-Liesse

    2017-01-01

    Lung squamous cell carcinoma (SqCC), the second most common subtype of lung cancer, is strongly associated with tobacco smoking and exhibits genomic instability. The cellular origins and molecular processes that contribute to SqCC formation are largely unexplored. Here we show that human basal stem cells (BSCs) isolated from heavy smokers proliferate extensively, whereas their alveolar progenitor cell counterparts have limited colony-forming capacity. We demonstrate that this difference arises in part because of the ability of BSCs to repair their DNA more efficiently than alveolar cells following ionizing radiation or chemical-induced DNA damage. Analysis of mice harbouring a mutation in the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a key enzyme in DNA damage repair by nonhomologous end joining (NHEJ), indicated that BSCs preferentially repair their DNA by this error-prone process. Interestingly, polyploidy, a phenomenon associated with genetically unstable cells, was only observed in the human BSC subset. Expression signature analysis indicated that BSCs are the likely cells of origin of human SqCC and that high levels of NHEJ genes in SqCC are correlated with increasing genomic instability. Hence, our results favour a model in which heavy smoking promotes proliferation of BSCs, and their predilection for error-prone NHEJ could lead to the high mutagenic burden that culminates in SqCC. Targeting DNA repair processes may therefore have a role in the prevention and therapy of SqCC.

  3. DNA Repair and the Accumulation of Oxidatively Damaged DNA Are Affected by Fruit Intake in Mice

    DEFF Research Database (Denmark)

    Croteau, Deborah L; de Souza-Pinto, Nadja C; Harboe, Charlotte

    2010-01-01

    Aging is associated with elevated oxidative stress and DNA damage. To achieve healthy aging, we must begin to understand how diet affects cellular processes. We postulated that fruit-enriched diets might initiate a program of enhanced DNA repair and thereby improve genome integrity. C57Bl/6 J mice...... were fed for 14 weeks a control diet or a diet with 8% peach or nectarine extract. The activities of DNA repair enzymes, the level of DNA damage, and gene expression changes were measured. Our study showed that repair of various oxidative DNA lesions was more efficient in liver extracts derived from......-fed mice. Taken together, these results suggest that an increased intake of fruits might modulate the efficiency of DNA repair, resulting in altered levels of DNA damage....

  4. Rapid repair of severely earthquake-damaged bridge piers with flexural-shear failure mode

    Science.gov (United States)

    Sun, Zhiguo; Wang, Dongsheng; Du, Xiuli; Si, Bingjun

    2011-12-01

    An experimental study was conducted to investigate the feasibility of a proposed rapid repair technique for severely earthquake-damaged bridge piers with flexural-shear failure mode. Six circular pier specimens were first tested to severe damage in flexural-shear mode and repaired using early-strength concrete with high-fluidity and carbon fiber reinforced polymers (CFRP). After about four days, the repaired specimens were tested to failure again. The seismic behavior of the repaired specimens was evaluated and compared to the original specimens. Test results indicate that the proposed repair technique is highly effective. Both shear strength and lateral displacement of the repaired piers increased when compared to the original specimens, and the failure mechanism of the piers shifted from flexural-shear failure to ductile flexural failure. Finally, a simple design model based on the Seible formulation for post-earthquake repair design was compared to the experimental results. It is concluded that the design equation for bridge pier strengthening before an earthquake could be applicable to seismic repairs after an earthquake if the shear strength contribution of the spiral bars in the repaired piers is disregarded and 1.5 times more FRP sheets is provided.

  5. Radiation damage to nucleoprotein complexes in macromolecular crystallography

    Energy Technology Data Exchange (ETDEWEB)

    Bury, Charles; Garman, Elspeth F.; Ginn, Helen Mary [University of Oxford, South Parks Road, Oxford OX1 3QU (United Kingdom); Ravelli, Raimond B. G. [Maastricht University, PO Box 616, Maastricht 6200 MD (Netherlands); Carmichael, Ian [University of Notre Dame, Notre Dame, IN 46556 (United States); Kneale, Geoff; McGeehan, John E., E-mail: john.mcgeehan@port.ac.uk [University of Portsmouth, King Henry 1st Street, Portsmouth PO1 2DY (United Kingdom)

    2015-01-30

    Quantitative X-ray induced radiation damage studies employing a model protein–DNA complex revealed a striking partition of damage sites. The DNA component was observed to be far more resistant to specific damage compared with the protein. Significant progress has been made in macromolecular crystallography over recent years in both the understanding and mitigation of X-ray induced radiation damage when collecting diffraction data from crystalline proteins. In contrast, despite the large field that is productively engaged in the study of radiation chemistry of nucleic acids, particularly of DNA, there are currently very few X-ray crystallographic studies on radiation damage mechanisms in nucleic acids. Quantitative comparison of damage to protein and DNA crystals separately is challenging, but many of the issues are circumvented by studying pre-formed biological nucleoprotein complexes where direct comparison of each component can be made under the same controlled conditions. Here a model protein–DNA complex C.Esp1396I is employed to investigate specific damage mechanisms for protein and DNA in a biologically relevant complex over a large dose range (2.07–44.63 MGy). In order to allow a quantitative analysis of radiation damage sites from a complex series of macromolecular diffraction data, a computational method has been developed that is generally applicable to the field. Typical specific damage was observed for both the protein on particular amino acids and for the DNA on, for example, the cleavage of base-sugar N{sub 1}—C and sugar-phosphate C—O bonds. Strikingly the DNA component was determined to be far more resistant to specific damage than the protein for the investigated dose range. At low doses the protein was observed to be susceptible to radiation damage while the DNA was far more resistant, damage only being observed at significantly higher doses.

  6. Temperature effects on radiation damage to silicon detectors

    Energy Technology Data Exchange (ETDEWEB)

    Barberis, E.; Cartiglia, N.; Leslie, J.; Pitzl, D.; Rowe, W.A.; Sadrozinski, H.F.W. (SCIPP, Univ. California, Santa Cruz, CA (United States)); Boissevain, J.G.; Ferguson, P.; Holzscheiter, K.; Kapustinsky, J.S.; Palounek, A.P.T.; Sommer, W.F.; Sondheim, W.E.; Ziock, H.J. (Los Alamos National Lab., NM (United States)); Ellison, J.A.; Fleming, J.K.; Jerger, S.; Joyce, D.; Lietzke, C.; Wimpenny, S.J. (Univ. California, Riverside, CA (United States)); Matthews, J.A.J.; Skinner, D. (Univ. New Mexico, Albuquerque, NM (United States))

    1993-03-01

    Motivated by the large particle fluences anticipated for the SSC and LHC, we are performing a systematic study of radiation damage to silicon microstrip detectors. Here we report radiation effects on detectors cooled to 0deg C (the proposed operating point for a large SSC silicon tracker) including leakage currents and change in depletion voltage. We also present results on the annealing behavior of the radiation damage. Finally, we report results of charge collection measurements of the damaged detectors made with an [sup 241]Am [alpha] source. (orig.).

  7. [Damage and functional recovery of the mouse retina after exposure to ionizing radiation and methylnitrosourea].

    Science.gov (United States)

    Vinogradova, Iu V; Tronov, V A; Liakhova, K N; Poplinskaia, V A; Ostrovskiĭ, M A

    2014-01-01

    The eye retina consists of terminally differentiated cells that have lost their ability to proliferate. The death of these cells leads tothe loss of sight. The mice retina is characterized by relatively high resistance to radiation, which is provided by its ability to repair damage caused by environmental factors. The aim of our work was to assess the damaging effect of ionizing radiation and methylnitrosourea (MNU) on the DNA structure in the mouse retina, the functional activity of the retina, and its ability to recover in vivo. The results confirm the ability of the mature retina to structural and functional recovery. Adapting influence of low dose chemical agent increases retina resistance to cytotoxic dose of genotoxicants and prevents degeneration of photoreceptor layer of the retina. The results show the possibility of neurohormesis effect in the mice retina after exposure to ionizing radiation and chemicals.

  8. Skin-resident T cells sense ultraviolet radiation-induced injury and contribute to DNA repair.

    Science.gov (United States)

    MacLeod, Amanda S; Rudolph, Ross; Corriden, Ross; Ye, Ivan; Garijo, Olivia; Havran, Wendy L

    2014-06-15

    Skin-resident T cells have been shown to play important roles in tissue homeostasis and wound repair, but their role in UV radiation (UVR)-mediated skin injury and subsequent tissue regeneration is less clear. In this study, we demonstrate that acute UVR rapidly activates skin-resident T cells in humans and dendritic epidermal γδ T cells (DETCs) in mice through mechanisms involving the release of ATP from keratinocytes. Following UVR, extracellular ATP leads to an increase in CD69 expression, proliferation, and IL-17 production, and to changes in DETC morphology. Furthermore, we find that the purinergic receptor P2X7 and caspase-1 are necessary for UVR-induced IL-1 production in keratinocytes, which increases IL-17 secretion by DETCs. IL-17, in turn, induces epidermal TNF-related weak inducer of apoptosis and growth arrest and DNA damage-associated gene 45, two molecules linked to the DNA repair response. Finally, we demonstrate that DETCs and human skin-resident T cells limit DNA damage in keratinocytes. Taken together, our findings establish a novel role for skin-resident T cells in the UVR-associated DNA repair response and underscore the importance of skin-resident T cells to overall skin regeneration.

  9. DNA repair decline during mouse spermiogenesis results in the accumulation of heritable DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Marchetti, Francesco; Marchetti, Francesco; Wryobek, Andrew J

    2008-02-21

    The post-meiotic phase of mouse spermatogenesis (spermiogenesis) is very sensitive to the genomic effects of environmental mutagens because as male germ cells form mature sperm they progressively lose the ability to repair DNA damage. We hypothesized that repeated exposures to mutagens during this repair-deficient phase result in the accumulation of heritable genomic damage in mouse sperm that leads to chromosomal aberrations in zygotes after fertilization. We used a combination of single or fractionated exposures to diepoxybutane (DEB), a component of tobacco smoke, to investigate how differential DNA repair efficiencies during the three weeks of spermiogenesis affected the accumulation of DEB-induced heritable damage in early spermatids (21-15 days before fertilization, dbf), late spermatids (14-8 dbf) and sperm (7- 1 dbf). Analysis of chromosomalaberrations in zygotic metaphases using PAINT/DAPI showed that late spermatids and sperm are unable to repair DEB-induced DNA damage as demonstrated by significant increases (P<0.001) in the frequencies of zygotes with chromosomal aberrations. Comparisons between single and fractionated exposures suggested that the DNA repair-deficient window during late spermiogenesis may be less than two weeks in the mouse and that during this repair-deficient window there is accumulation of DNA damage in sperm. Finally, the dose-response study in sperm indicated a linear response for both single and repeated exposures. These findings show that the differential DNA repair capacity of post-meioitic male germ cells has a major impact on the risk of paternally transmitted heritable damage and suggest that chronic exposures that may occur in the weeks prior to fertilization because of occupational or lifestyle factors (i.e, smoking) can lead to an accumulation of genetic damage in sperm and result in heritable chromosomal aberrations of paternal origin.

  10. DNA Repair Decline During Mouse Spermiogenesis Results in the Accumulation of Heritable DNA Damage

    Energy Technology Data Exchange (ETDEWEB)

    Marchetti, Francesco; Marchetti, Francesco; Wyrobek, Andrew J.

    2007-12-01

    The post-meiotic phase of mouse spermatogenesis (spermiogenesis) is very sensitive to the genomic effects of environmental mutagens because as male germ cells form mature sperm they progressively lose the ability to repair DNA damage. We hypothesized that repeated exposures to mutagens during this repair-deficient phase result in the accumulation of heritable genomic damage in mouse sperm that leads to chromosomal aberrations in zygotes after fertilization. We used a combination of single or fractionated exposures to diepoxybutane (DEB), a component of tobacco smoke, to investigate how differential DNA repair efficiencies during the three weeks of spermiogenesis affected the accumulation of DEB-induced heritable damage in early spermatids (21-15 days before fertilization, dbf), late spermatids (14-8 dbf) and sperm (7-1 dbf). Analysis of chromosomal aberrations in zygotic metaphases using PAINT/DAPI showed that late spermatids and sperm are unable to repair DEB-induced DNA damage as demonstrated by significant increases (P<0.001) in the frequencies of zygotes with chromosomal aberrations. Comparisons between single and fractionated exposures suggested that the DNA repair-deficient window during late spermiogenesis may be less than two weeks in the mouse and that during this repair-deficient window there is accumulation of DNA damage in sperm. Finally, the dose-response study in sperm indicated a linear response for both single and repeated exposures. These findings show that the differential DNA repair capacity of post-meioitic male germ cells has a major impact on the risk of paternally transmitted heritable damage and suggest that chronic exposures that may occur in the weeks prior to fertilization because of occupational or lifestyle factors (i.e, smoking) can lead to an accumulation of genetic damage in sperm and result in heritable chromosomal aberrations of paternal origin.

  11. Dose-response relationship of induction kinetics of In vivo DNA damage and repair in mouse leukocytes exposed to gamma radiation; Relacion dosis-respuesta de la cinetica de induccion de dano y reparacion del ADN In vivo en leucocitos de raton expuestos a radiacion gamma

    Energy Technology Data Exchange (ETDEWEB)

    Mendiola C, M.T.; Morales, R.P. [Instituto Nacional de Investigaciones Nucleares, Gerencia de Investigacion Basica, Departamento de Biologia, A.P. 18-1027, 11801 Mexico D.F. (Mexico)

    2000-07-01

    The Unicellular electrophoresis in gel technique is a useful tool in the determination of simple ruptures and labile sites to the alkali in DNA of eucariontes cells. The determination of the induction kinetics of damage and repair of DNA can give more information. The objective of this work was to determine whether the analysis of the area under the damage/repair induction kinetics curve in comets percent or the comets frequency in the two peaks of maximum induction is adequate for determining the dose-response relationship. The mice were exposed at the doses of 0.5, 1.0, 2.0 Gy. (Author)

  12. [Influence of Detector Radiation Damage on CR Mammography Quality Control].

    Science.gov (United States)

    Moriwaki, Atsumi; Ishii, Mie; Terazono, Shiho; Arao, Keiko; Ishii, Rie; Sanada, Taizo; Yoshida, Akira

    2016-05-01

    Recently, radiation damage to the detector apparatus employed in computed radiography (CR) mammography has become problematic. The CR system and the imaging plate (IP) applied to quality control (QC) program were also used in clinical mammography in our hospital, and the IP to which radiation damage has occurred was used for approximately 5 years (approximately 13,000 exposures). We considered using previously acquired QC image data, which is stored in a server, to investigate the influence of radiation damage to an IP. The mammography unit employed in this study was a phase contrast mammography (PCM) Mermaid (KONICA MINOLTA) system. The QC image was made newly, and it was output in the film, and thereafter the optical density of the step-phantom image was measured. An input (digital value)-output (optical density) conversion curve was plotted using the obtained data. The digital values were then converted to optical density values using a reference optical density vs. digital value curve. When a high radiation dose was applied directly, radiation damage occurred at a position on the IP where no object was present. Daily QC for mammography is conducted using an American College of Radiology (ACR) accreditation phantom and acrylic disc, and an environmental background density measurement is performed as one of the management indexes. In this study, the radiation damage sustained by the acrylic disc was shown to differ from that of the background. Thus, it was revealed that QC results are influenced by radiation damage.

  13. Cyclobutane pyrimidine dimers photolyase from extremophilic microalga: Remarkable UVB resistance and efficient DNA damage repair

    Energy Technology Data Exchange (ETDEWEB)

    Li, Chongjie [Key Laboratory of Marine Bioactive Substance, The First Institute of Oceanography, State Oceanic Administration, Qingdao 266061 (China); Ma, Li [Key Laboratory of Biofuels, and Shandong Provincial Key Laboratory of Energy Genetics, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao 266101 (China); Mou, Shanli [Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao (China); Wang, Yibin, E-mail: wangyibin@fio.org.cn [Key Laboratory of Marine Bioactive Substance, The First Institute of Oceanography, State Oceanic Administration, Qingdao 266061 (China); Zheng, Zhou; Liu, Fangming; Qi, Xiaoqing; An, Meiling; Chen, Hao [Key Laboratory of Marine Bioactive Substance, The First Institute of Oceanography, State Oceanic Administration, Qingdao 266061 (China); Miao, Jinlai, E-mail: miaojinlai@163.com [Key Laboratory of Marine Bioactive Substance, The First Institute of Oceanography, State Oceanic Administration, Qingdao 266061 (China); State Key Laboratory of Biological Fermentation Engineering of Beer (In Preparation), Qingdao (China)

    2015-03-15

    Highlights: • Chlamydomonas sp. ICE-L photolyase gene PHR2 is first cloned and expressed in E. coli. • PHR2 complemented E. coli could efficiently survival from UV radiation. • Expressed PHR2 photolyase has distinct photo-reactivation activity in vitro. - Abstract: Bacteria living in the Antarctic region have developed several adaptive features for growth and survival under extreme conditions. Chlamydomonas sp. ICE-Lis well adapted to high levels of solar UV radiation. A putative photolyase was identified in the Chlamydomonas sp. ICE-L transcriptome. The complete cDNA sequence was obtained by RACE-PCR. This PHR encoding includes a polypeptide of 579 amino acids with clear photolyase signatures belonging to class II CPD-photolyases, sharing a high degree of homology with Chlamydomonas reinhardtii (68%). Real-time PCR was performed to investigate the potential DNA damage and responses following UVB exposure. CPD photolyase mRNA expression level increased over 50-fold in response to UVB radiation for 6 h. Using photolyase complementation assay, we demonstrated that DNA photolyase increased photo-repair more than 116-fold in Escherichia coli strain SY2 under 100 μw/cm{sup 2} UVB radiation. To determine whether photolyase is active in vitro, CPD photolyase was over-expressed. It was shown that pyrimidine dimers were split by the action of PHR2. This study reports the unique structure and high activity of the enzyme. These findings are relevant for further understanding of molecular mechanisms of photo-reactivation, and will accelerate the utilization of photolyase in the medical field.

  14. 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;...

  15. Damage induced by continued corrosion in concrete repair systems

    NARCIS (Netherlands)

    Luckovic, M.; Savija, B.; Schlangen, E.

    2014-01-01

    Corrosion of steel reinforcement is the main cause of deterioration in reinforced concrete structures. After the repair, corrosion of the steel might continue and even accelerate. While the development of the corrosion cell depends on many parameters and is difficult to control, the occurrence of vi

  16. Molecular dynamics investigation of radiation damage in semiconductors

    Science.gov (United States)

    Good, Brian S.

    1991-01-01

    Results of a molecular dynamics investigation of the effects of radiation damage on the crystallographic structure of semiconductors are reported. Particular cosiderastion is given to the formation of point defects and small defect complexes in silicon at the end of a radiation-damage cascade. The calculations described make use of the equivalent crystal theory of Smith and Banerjea (1988). Results on the existence of an atomic displacement threshold, the defect formation energy, and some crystallographic information on the defects observed are reported.

  17. Molecular dynamics investigation of radiation damage in semiconductors

    Science.gov (United States)

    Good, Brian S.

    1991-01-01

    Results of a molecular dynamics investigation of the effects of radiation damage on the crystallographic structure of semiconductors are reported. Particular cosiderastion is given to the formation of point defects and small defect complexes in silicon at the end of a radiation-damage cascade. The calculations described make use of the equivalent crystal theory of Smith and Banerjea (1988). Results on the existence of an atomic displacement threshold, the defect formation energy, and some crystallographic information on the defects observed are reported.

  18. 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.

  19. Nucleotide Excision Repair and Transcription-coupled DNA Repair Abrogate the Impact of DNA Damage on Transcription.

    Science.gov (United States)

    Nadkarni, Aditi; Burns, John A; Gandolfi, Alberto; Chowdhury, Moinuddin A; Cartularo, Laura; Berens, Christian; Geacintov, Nicholas E; Scicchitano, David A

    2016-01-01

    DNA adducts derived from carcinogenic polycyclic aromatic hydrocarbons like benzo[a]pyrene (B[a]P) and benzo[c]phenanthrene (B[c]Ph) impede replication and transcription, resulting in aberrant cell division and gene expression. Global nucleotide excision repair (NER) and transcription-coupled DNA repair (TCR) are among the DNA repair pathways that evolved to maintain genome integrity by removing DNA damage. The interplay between global NER and TCR in repairing the polycyclic aromatic hydrocarbon-derived DNA adducts (+)-trans-anti-B[a]P-N(6)-dA, which is subject to NER and blocks transcription in vitro, and (+)-trans-anti-B[c]Ph-N(6)-dA, which is a poor substrate for NER but also blocks transcription in vitro, was tested. The results show that both adducts inhibit transcription in human cells that lack both NER and TCR. The (+)-trans-anti-B[a]P-N(6)-dA lesion exhibited no detectable effect on transcription in cells proficient in NER but lacking TCR, indicating that NER can remove the lesion in the absence of TCR, which is consistent with in vitro data. In primary human cells lacking NER, (+)-trans-anti-B[a]P-N(6)-dA exhibited a deleterious effect on transcription that was less severe than in cells lacking both pathways, suggesting that TCR can repair the adduct but not as effectively as global NER. In contrast, (+)-trans-anti-B[c]Ph-N(6)-dA dramatically reduces transcript production in cells proficient in global NER but lacking TCR, indicating that TCR is necessary for the removal of this adduct, which is consistent with in vitro data showing that it is a poor substrate for NER. Hence, both global NER and TCR enhance the recovery of gene expression following DNA damage, and TCR plays an important role in removing DNA damage that is refractory to NER.

  20. 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.)

  1. 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.)

  2. Bleomycin and radiation-induced lung damage in mice

    Energy Technology Data Exchange (ETDEWEB)

    Collis, C.H.; Down, J.D.; Pearson, A.E.; Steel, G.G. (Institute of Cancer Research, Sutton (UK). Surrey Branch)

    1983-01-01

    Bleomycin-induced lung damage was assessed using both a functional end-point and mortality. The extent of lung damage was found to depend on the schedule, mode of administration and dose of the drug. Greater damage occurred following twice-weekly administration than when the same dose was given as a single injection. Intravenous administration resulted in greater damage than intraperitoneal administration. When bleomycin was given with thoracic irradiation lung damage occurred earlier and at lower radiation doses than with radiation alone. Similar responses were obtained whether bleomycin was given four weeks before, with or four weeks after irradiation. Thus although there was enhanced damage from the combined treatment, there was no evidence of a time-dependent interaction.

  3. Analysis of DNA repair and protection in the Tardigrade Ramazzottius varieornatus and Hypsibius dujardini after exposure to UVC radiation.

    Directory of Open Access Journals (Sweden)

    Daiki D Horikawa

    Full Text Available Tardigrades inhabiting terrestrial environments exhibit extraordinary resistance to ionizing radiation and UV radiation although little is known about the mechanisms underlying the resistance. We found that the terrestrial tardigrade Ramazzottius varieornatus is able to tolerate massive doses of UVC irradiation by both being protected from forming UVC-induced thymine dimers in DNA in a desiccated, anhydrobiotic state as well as repairing the dimers that do form in the hydrated animals. In R. varieornatus accumulation of thymine dimers in DNA induced by irradiation with 2.5 kJ/m(2 of UVC radiation disappeared 18 h after the exposure when the animals were exposed to fluorescent light but not in the dark. Much higher UV radiation tolerance was observed in desiccated anhydrobiotic R. varieornatus compared to hydrated specimens of this species. On the other hand, the freshwater tardigrade species Hypsibius dujardini that was used as control, showed much weaker tolerance to UVC radiation than R. varieornatus, and it did not contain a putative phrA gene sequence. The anhydrobiotes of R. varieornatus accumulated much less UVC-induced thymine dimers in DNA than hydrated one. It suggests that anhydrobiosis efficiently avoids DNA damage accumulation in R. varieornatus and confers better UV radiation tolerance on this species. Thus we propose that UV radiation tolerance in tardigrades is due to the both high capacities of DNA damage repair and DNA protection, a two-pronged survival strategy.

  4. Analysis of DNA repair and protection in the Tardigrade Ramazzottius varieornatus and Hypsibius dujardini after exposure to UVC radiation.

    Science.gov (United States)

    Horikawa, Daiki D; Cumbers, John; Sakakibara, Iori; Rogoff, Dana; Leuko, Stefan; Harnoto, Raechel; Arakawa, Kazuharu; Katayama, Toshiaki; Kunieda, Takekazu; Toyoda, Atsushi; Fujiyama, Asao; Rothschild, Lynn J

    2013-01-01

    Tardigrades inhabiting terrestrial environments exhibit extraordinary resistance to ionizing radiation and UV radiation although little is known about the mechanisms underlying the resistance. We found that the terrestrial tardigrade Ramazzottius varieornatus is able to tolerate massive doses of UVC irradiation by both being protected from forming UVC-induced thymine dimers in DNA in a desiccated, anhydrobiotic state as well as repairing the dimers that do form in the hydrated animals. In R. varieornatus accumulation of thymine dimers in DNA induced by irradiation with 2.5 kJ/m(2) of UVC radiation disappeared 18 h after the exposure when the animals were exposed to fluorescent light but not in the dark. Much higher UV radiation tolerance was observed in desiccated anhydrobiotic R. varieornatus compared to hydrated specimens of this species. On the other hand, the freshwater tardigrade species Hypsibius dujardini that was used as control, showed much weaker tolerance to UVC radiation than R. varieornatus, and it did not contain a putative phrA gene sequence. The anhydrobiotes of R. varieornatus accumulated much less UVC-induced thymine dimers in DNA than hydrated one. It suggests that anhydrobiosis efficiently avoids DNA damage accumulation in R. varieornatus and confers better UV radiation tolerance on this species. Thus we propose that UV radiation tolerance in tardigrades is due to the both high capacities of DNA damage repair and DNA protection, a two-pronged survival strategy.

  5. QUANTIFYING LOCAL RADIATION-INDUCED LUNG DAMAGE FROM COMPUTED TOMOGRAPHY

    NARCIS (Netherlands)

    Ghobadi, Ghazaleh; Hogeweg, Laurens E.; Faber, Hette; Tukker, Wim G. J.; Schippers, Jacobus M.; Brandenburg, Sytze; Langendijk, Johannes A.; Coppes, Robert P.; van Luijk, Peter

    2010-01-01

    Purpose: Optimal implementation of new radiotherapy techniques requires accurate predictive models for normal tissue complications. Since clinically used dose distributions are nonuniform, local tissue damage needs to be measured and related to local tissue dose. In lung, radiation-induced damage re

  6. An immunochemical approach to the study of DNA damage and repair. Technical progress report, May 1, 1989--April 30, 1992

    Energy Technology Data Exchange (ETDEWEB)

    Wallace, S.S. [Vermont Univ., Burlington, VT (United States). Dept. of Microbiology and Molecular Genetics; Erlanger, B.F. [Columbia Univ., New York, NY (United States). Dept. of Microbiology

    1992-05-01

    The overall objective of this project has been to develop immunochemical methods to quantitate unique DNA base damages in order to facilitate studies on radiation-induced damage production and repair. Specifically, we have been using antibodies raised to damaged bases to quantitate unique lesions in model systems in order to evaluate their potential biological consequences. Our approach has been to synthesize modified nucleotides or nucleosides, conjugate them to protein carriers, and use the conjugates as immunogens in rabbits or to prepare monoclonal antibodies. We have been studying damages that are stable radiolysis products found in X-irradiated DNA and thus of potential biological consequence. Our aim is to build an in vitro and in vivo data base on the interactions between model DNA lesions and such cellular enzymes as DNA polymerases and repair endonucleases. Initial studies have focused on pyrimidine ring saturation products (thymine glycol.and dihydrothymine), products resulting from ring fragmentation or base loss (urea, {Beta}-ureidoisobutyric acid, abasic sites), 7-hydro-8-oxopurines, and more recently, cytosine radiolysis products. These modified bases serve as useful models for examining the potential lethal and/or mutagenic (carcinogenic) effects of the products of DNA radiolysis.

  7. Early mechanisms in radiation-induced biological damage

    Energy Technology Data Exchange (ETDEWEB)

    Powers, E.L.

    1983-01-01

    An introduction to the mechanisms of radiation action in biological systems is presented. Several questions about the nature of the radiation damage process are discussed, including recognition of the oxygen effects, dose-response relationships, and the importance of the hydroxyl radical. (ACR)

  8. Living with cracks: Damage and repair in human bone

    Science.gov (United States)

    Taylor, David; Hazenberg, Jan G.; Lee, T. Clive

    2007-04-01

    Our bones are full of cracks, which form and grow as a result of daily loading activities. Bone is the major structural material in our bodies. Although weaker than many engineering materials, it has one trick that keeps it ahead - it can repair itself. Small cracks, which grow under cyclic stresses by the mechanism of fatigue, can be detected and removed before they become long enough to be dangerous. This article reviews the work that has been done to understand how cracks form and grow in bone, and how they can be detected and repaired in a timely manner. This is truly an interdisciplinary research field, requiring the close cooperation of materials scientists, biologists and engineers.

  9. Radiation damage of LHCb electromagnetic calorimeter

    CERN Document Server

    Barsuk, S; Kirichenko, V; Korolko, I; Malyshev, S; Rusinov, V Yu; Tarkovski, E

    2000-01-01

    Addressed is an extensive irradiation test program carried on to establish proper design and materials to build electromagnetic calorimeter that matches radiation conditions of the LHCb experiment at CERN. The results obtained are compared with measurements by other groups.

  10. The Cartography of UV-induced DNA Damage Formation and DNA Repair.

    Science.gov (United States)

    Hu, Jinchuan; Adar, Sheera

    2017-01-01

    DNA damage presents a barrier to DNA-templated biochemical processes, including gene expression and faithful DNA replication. Compromised DNA repair leads to mutations, enhancing the risk for genetic diseases and cancer development. Conventional experimental approaches to study DNA damage required a researcher to choose between measuring bulk damage over the entire genome, with little or no resolution regarding a specific location, and obtaining data specific to a locus of interest, without a global perspective. Recent advances in high-throughput genomic tools overcame these limitations and provide high-resolution measurements simultaneously across the genome. In this review, we discuss the available methods for measuring DNA damage and their repair, focusing on genomewide assays for pyrimidine photodimers, the major types of damage induced by ultraviolet irradiation. These new genomic assays will be a powerful tool in identifying key components of genome stability and carcinogenesis. © 2016 The American Society of Photobiology.

  11. Comparative DNA Damage and Repair in Echinoderm Coelomocytes Exposed to Genotoxicants

    OpenAIRE

    El-Bibany, Ameena H.; Bodnar, Andrea G.; Reinardy, Helena C.

    2014-01-01

    The capacity to withstand and repair DNA damage differs among species and plays a role in determining an organism's resistance to genotoxicity, life history, and susceptibility to disease. Environmental stressors that affect organisms at the genetic level are of particular concern in ecotoxicology due to the potential for chronic effects and trans-generational impacts on populations. Echinoderms are valuable organisms to study the relationship between DNA repair and resistance to genotoxic st...

  12. Radiation damage in charge-coupled devices.

    Science.gov (United States)

    Bassler, Niels

    2010-08-01

    Due to their high sensitivity and signal-to-noise ratio, charge-coupled devices (CCDs) have been the preferred optical photon detectors of astronomers for several decades. CCDs are flown in space as the main detection instrument on several well-known missions, such as the Hubble Space Telescope, XMM-Newton or the Cassini Probe. Also, CCDs are frequently used in satellite star trackers which provide attitude information to the satellite orientation system. However, one major drawback is their extreme vulnerability to radiation, which is readily abundant in space. Here, we shall give a brief overview of the radiation effects on CCDs, and mention ways how to mitigate the effects in other ways than merely increase shielding, such as cooling and annealing. As an example, we have investigated the radiation hardness of a particular CCD, the so-called CCD47-20 from Marconi Applied Technologies (now E2V), by exposing it to radiation fields representing the radiation environment found in a highly elliptic orbit crossing the Van-Allen radiation belts. Two engineering-grade CCDs were irradiated with proton beams and photons, and effects of increased bulk dark current, surface dark current and inversion threshold voltage shifts were observed and are quantified.

  13. 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.

  14. Association between age and repair of oxidatively damaged DNA in human peripheral blood mononuclear cells

    DEFF Research Database (Denmark)

    Løhr, Mille; Jensen, Annie; Eriksen, Louise

    2015-01-01

    It has been hypothesised that positive associations between age and levels of oxidative stress-generated damage to DNA may be related to an age-dependent decline in DNA repair activity. The objective of this study was to investigate the association between age and repair activity of oxidatively...... assay. There was an inverse association between age and DNA repair activity with a 0.65% decline in activity per year from age 18 to 83 (95% confidence interval: 0.16-1.14% per year). Univariate regression analysis also indicated inverse associations between DNA repair activity and waist-hip ratio (P...... indicating that the decline in repair activity was not mediated by metabolic risk factors. In summary...

  15. The 2015 Nobel Prize in Chemistry The Discovery of Essential Mechanisms that Repair DNA Damage.

    Science.gov (United States)

    Lindahl, Tomas; Modrich, Paul; Sancar, Aziz

    2016-01-01

    The Royal Swedish Academy awarded the Nobel Prize in Chemistry for 2015 to Tomas Lindahl, Paul Modrich and Aziz Sancar for their discoveries in fundamental mechanisms of DNA repair. This pioneering research described three different essential pathways that correct DNA damage, safeguard the integrity of the genetic code to ensure its accurate replication through generations, and allow proper cell division. Working independently of each other, Tomas Lindahl, Paul Modrich and Aziz Sancar delineated the mechanisms of base excision repair, mismatch repair and nucleotide excision repair, respectively. These breakthroughs challenged and dismissed the early view that the DNA molecule was very stable, paving the way for the discovery of human hereditary diseases associated with distinct DNA repair deficiencies and a susceptibility to cancer. It also brought a deeper understanding of cancer as well as neurodegenerative or neurological diseases, and let to novel strategies to treat cancer.

  16. Optical modulation study of repaired damage morphologies of fused silica by scalar diffraction theory

    Science.gov (United States)

    Li, Bo; Zhou, Qingyan; Jiang, Yong; Xiang, Xia; Liao, Wei; Jiang, Xiaolong; Wang, Haijun; Luan, Xiaoyu; Zheng, Wanguo; Yuan, Xiaodong

    2017-01-01

    The cone and Gaussian repaired damage craters are two typical morphologies induced by CO2 laser evaporation and nonevaporation technologies. The mathematical models are built for these two types of repaired craters, and the light modulation at 355 nm induced by the millimeter-scale repaired damage morphology is studied by scalar diffraction theory. The results show that the modulation of the Gaussian repaired morphology has one peak and then decreases with the increasing distance from 0 to 30 cm. While the modulation for cone repaired morphology remains stable after decreasing quickly with the increasing distance. When the horizontal radius increases, the modulation looks like a saw-tooth. However, the modulation has irregular variations for two kinds of morphologies with the increasing vertical depth. The simulated results agree well with experimental results. The horizontal and vertical dimensions, and downstream distance have different influences on the modulation. The risk of damage to downstream optical components can be suppressed to improve the stability of the optical system if the shape and size of repaired craters are well controlled and the positions of downstream optical components are selected appropriately.

  17. Photodynamic DNA damage induced by phycocyanin and its repair in Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    M. Pádula

    1999-09-01

    Full Text Available In the present study, we analyzed DNA damage induced by phycocyanin (PHY in the presence of visible light (VL using a set of repair endonucleases purified from Escherichia coli. We demonstrated that the profile of DNA damage induced by PHY is clearly different from that induced by molecules that exert deleterious effects on DNA involving solely singlet oxygen as reactive species. Most of PHY-induced lesions are single strand breaks and, to a lesser extent, base oxidized sites, which are recognized by Nth, Nfo and Fpg enzymes. High pressure liquid chromatography coupled to electrochemical detection revealed that PHY photosensitization did not induce 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo at detectable levels. DNA repair after PHY photosensitization was also investigated. Plasmid DNA damaged by PHY photosensitization was used to transform a series of Saccharomyces cerevisiae DNA repair mutants. The results revealed that plasmid survival was greatly reduced in rad14 mutants, while the ogg1 mutation did not modify the plasmid survival when compared to that in the wild type. Furthermore, plasmid survival in the ogg1 rad14 double mutant was not different from that in the rad14 single mutant. The results reported here indicate that lethal lesions induced by PHY plus VL are repaired differently by prokaryotic and eukaryotic cells. Morever, nucleotide excision repair seems to play a major role in the recognition and repair of these lesions in Saccharomyces cerevisiae.

  18. Tousled kinase activator, gallic acid, promotes homologous recombinational repair and suppresses radiation cytotoxicity in salivary gland cells.

    Science.gov (United States)

    Timiri Shanmugam, Prakash Srinivasan; Nair, Renjith Parameshwaran; De Benedetti, Arrigo; Caldito, Gloria; Abreo, Fleurette; Sunavala-Dossabhoy, Gulshan

    2016-04-01

    Accidental or medical radiation exposure of the salivary glands can gravely impact oral health. Previous studies have shown the importance of Tousled-like kinase 1 (TLK1) and its alternate start variant TLK1B in cell survival against genotoxic stresses. Through a high-throughput library screening of natural compounds, the phenolic phytochemical, gallic acid (GA), was identified as a modulator of TLK1/1B. This small molecule possesses anti-oxidant and free radical scavenging properties, but in this study, we report that in vitro it promotes survival of human salivary acinar cells, NS-SV-AC, through repair of ionizing radiation damage. Irradiated cells treated with GA show improved clonogenic survival compared to untreated controls. And, analyses of DNA repair kinetics by alkaline single-cell gel electrophoresis and γ-H2AX foci immunofluorescence indicate rapid resolution of DNA breaks in drug-treated cells. Study of DR-GFP transgene repair indicates GA facilitates homologous recombinational repair to establish a functional GFP gene. In contrast, inactivation of TLK1 or its shRNA knockdown suppressed resolution of radiation-induced DNA tails in NS-SV-AC, and homology directed repair in DR-GFP cells. Consistent with our results in culture, animals treated with GA after exposure to fractionated radiation showed better preservation of salivary function compared to saline-treated animals. Our results suggest that GA-mediated transient modulation of TLK1 activity promotes DNA repair and suppresses radiation cytoxicity in salivary gland cells.

  19. Radiation damage in ceramic plasma-facing materials

    Energy Technology Data Exchange (ETDEWEB)

    Itoh, Noriaki; Morita, Kenji

    1988-07-01

    The present status of the studies of radiation damage of plasma-facing materials is reviewed. Emphasis is placed on the extent of the understanding in terms of the critical issues for materials in use as plasma interactive components. Understanding of the basic problems of radiation effects, which are important for long term development of fusion reactors, is also emphasized. It is pointed out that for low-Z materials radiation damage by fission neutrons is a good measure of the effects of radiation damage by fusion neutrons. The understanding of the fission neutron damage of major candidate materials is surveyed. Existing data on the effects of transmuted helium gas in beryllium are inferred and the data needs for the He effects on graphite are stressed. For radiation damage by plasma particles, the importance of understanding of the dynamic behaviors of the materials which are composite because of redeposition and hydrogen implantation. Some of the features of such composite materials under radiation are presented.

  20. 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.

  1. 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.

  2. Injection technologies for the repair of damaged concrete structures

    CERN Document Server

    Panasyuk, V V; Sylovanyuk, V P

    2014-01-01

    This book analyzes the most important achievements in science and engineering practice concerning operational factors that cause damage to concrete and reinforced concrete structures. It includes methods for assessing their strength and service life, especially those that are based on modern concepts of the fracture mechanics of materials. It also includes basic approaches to the prediction of the remaining service life for long-term operational structures. Much attention is paid to injection technologies for restoring the serviceability of damaged concrete and reinforced concrete structures. In particular, technologies for remedying holes, cracks, corrosion damages etc. The books contains sample cases in which the above technologies have been used to restore structural integrity and extend the reliable service life of concrete and reinforced concrete constructions, especially NPPs, underground railways, bridges, seaports and historical relics.

  3. 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 of this ......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...... of this interaction is therefore of vital importance to the medical community, but even after decades of thorough investigation the breakdown pattern of radiation damage has not yet been completely deciphered. This thesis represents a very comprehensive attempt at drawing conclusions on the initial step....... Considering this there is much novelty in the results drawn from the present study, as conclusions based also on the kinetics of the system imply that the hydrogen abstraction pathways are of equal importance for the possible reactions preceding the radiation damage. The purine nucleobases are found to favour...

  4. Probing Radiation Damage in Plutonium Alloys with Multiple Measurement Techniques

    Energy Technology Data Exchange (ETDEWEB)

    McCall, S K; Fluss, M J; Chung, B W

    2010-04-21

    A material subjected to radiation damage will usually experience changes in its physical properties. Measuring these changes in the physical properties provides a basis to study radiation damage in a material which is important for a variety of real world applications from reactor materials to semiconducting devices. When investigating radiation damage, the relative sensitivity of any given property can vary considerably based on the concentration and type of damage present as well as external parameters such as the temperature and starting material composition. By measuring multiple physical properties, these differing sensitivities can be leveraged to provide greater insight into the different aspects of radiation damage accumulation, thereby providing a broader understanding of the mechanisms involved. In this report, self-damage from {alpha}-particle decay in Pu is investigated by measuring two different properties: magnetic susceptibility and resistivity. The results suggest that while the first annealing stage obeys second order chemical kinetics, the primary mechanism is not the recombination of vacancy-interstitial close pairs.

  5. Typical Cell Signaling Response to Ionizing Radiation:DNA Damage and Extranuclear Damage

    Institute of Scientific and Technical Information of China (English)

    Hui Yu

    2012-01-01

    To treat many types of cancer,ionizing radiation (IR) is primarily used as external-beam radiotherapy,brachytherapy,and targeted radionuclide therapy.Exposure of tumor cells to IR can induce DNA damage as well as generation of reactiveoxygen species (ROS) and reactive nitrogen species (RNS) which can cause non-DNA lesions or extracellular damage like lipid perioxidation.The initial radiation-induced cell responses to DNA damage and ROS like the proteolytic processing,as well as synthesis and releasing ligands (such as growth factors,cytokines,and hormone) can cause the delayed secondary responses in irradiated and unirradiated bystander cells through paracrine and autocrine pathways.

  6. Glycolipid biosurfactants, mannosylerythritol lipids, repair the damaged hair.

    Science.gov (United States)

    Morita, Tomotake; Kitagawa, Masaru; Yamamoto, Shuhei; Sogabe, Atsushi; Imura, Tomohiro; Fukuoka, Tokuma; Kitamoto, Dai

    2010-01-01

    Mannosylerythritol lipids (MELs), are produced from feedstock by the genus Pseudozyma, and are the most promising biosurfactants known due to its versatile interfacial and biochemical actions. In order to broaden the application in cosmetics, the hair care properties of MELs were investigated using damaged hair. On electron microscopic observation, the damaged hair was dramatically recovered with applying MEL-A and MEL-B. The tensile strength of the damaged hair increased by treatment with MEL-A (122.0 +/- 13.5 gf/p), MEL-B (119.4 +/- 7.6 gf/p) and ceramide (100.7 +/- 15.9 gf/p) compared with only lauryl glucoside (96.7 +/- 12.7 gf/p), indicating the advantage of MELs on hair care treatment. In addition, the average friction coefficient of the damaged hair was maintained after treatment with MEL-A (0.108 +/- 0.002), MEL-B (0.107 +/- 0.003) and the ceramide (0.111 +/- 0.003), although lauryl glucoside treatment increased the average friction coefficient (0.126 +/- 0.003). The increase of bending rigidity by treatment with lauryl glucoside (0.204 +/- 0.002) was prevented by treatment with MEL-A (0.129 +/- 0.002), MEL-B (0.176 +/- 0.003) and the ceramide (0.164 +/- 0.002). Consequently, MELs are proposed to be the new hair care ingredient, which are the highly useful agent for not only for the recovery of damaged hair but also for providing the smooth and flexible hair.

  7. Animal Models of Ionizing Radiation Damage

    Science.gov (United States)

    1992-01-01

    Haggbloom, and R.A. Gazzara, Effects of Hippocampal X-irradiation-Produced Granule-Cell Agenesis on Instrumental Runway Performance in Rats, Physiol...Bowden, and J.P. Wyatt, A Pathway To Pulmonary Fibrosis: An Ultrastructural Study Of Mouse and Rat Following Radiation to the Whole Body and Hemithorax...532-536, 1956. 27. Brooks, P.M., E.O. Richey, and J.E. Pickering, Prompt Pulmonary Ventilation and Oxygen Consumption Changes in Rhesus Monkeys

  8. Deoxycytidine kinase augments ATM-Mediated DNA repair and contributes to radiation resistance.

    Directory of Open Access Journals (Sweden)

    Yuri L Bunimovich

    Full Text Available Efficient and adequate generation of deoxyribonucleotides is critical to successful DNA repair. We show that ataxia telangiectasia mutated (ATM integrates the DNA damage response with DNA metabolism by regulating the salvage of deoxyribonucleosides. Specifically, ATM phosphorylates and activates deoxycytidine kinase (dCK at serine 74 in response to ionizing radiation (IR. Activation of dCK shifts its substrate specificity toward deoxycytidine, increases intracellular dCTP pools post IR, and enhances the rate of DNA repair. Mutation of a single serine 74 residue has profound effects on murine T and B lymphocyte development, suggesting that post-translational regulation of dCK may be important in maintaining genomic stability during hematopoiesis. Using [(18F]-FAC, a dCK-specific positron emission tomography (PET probe, we visualized and quantified dCK activation in tumor xenografts after IR, indicating that dCK activation could serve as a biomarker for ATM function and DNA damage response in vivo. In addition, dCK-deficient leukemia cell lines and murine embryonic fibroblasts exhibited increased sensitivity to IR, indicating that pharmacologic inhibition of dCK may be an effective radiosensitization strategy.

  9. Role of Nicotinamide in DNA Damage, Mutagenesis, and DNA Repair

    Directory of Open Access Journals (Sweden)

    Devita Surjana

    2010-01-01

    Full Text Available Nicotinamide is a water-soluble amide form of niacin (nicotinic acid or vitamin B3. Both niacin and nicotinamide are widely available in plant and animal foods, and niacin can also be endogenously synthesized in the liver from dietary tryptophan. Nicotinamide is also commercially available in vitamin supplements and in a range of cosmetic, hair, and skin preparations. Nicotinamide is the primary precursor of nicotinamide adenine dinucleotide (NAD+, an essential coenzyme in ATP production and the sole substrate of the nuclear enzyme poly-ADP-ribose polymerase-1 (PARP-1. Numerous in vitro and in vivo studies have clearly shown that PARP-1 and NAD+ status influence cellular responses to genotoxicity which can lead to mutagenesis and cancer formation. This paper will examine the role of nicotinamide in the protection from carcinogenesis, DNA repair, and maintenance of genomic stability.

  10. Heat induced damage detection in composite materials by terahertz radiation

    Science.gov (United States)

    Radzieński, Maciej; Mieloszyk, Magdalena; Rahani, Ehsan Kabiri; Kundu, Tribikram; Ostachowicz, Wiesław

    2015-03-01

    In recent years electromagnetic Terahertz (THz) radiation or T-ray has been increasingly used for nondestructive evaluation of various materials such as polymer composites and porous foam tiles in which ultrasonic waves cannot penetrate but T-ray can. Most of these investigations have been limited to mechanical damage detection like inclusions, cracks, delaminations etc. So far only a few investigations have been reported on heat induced damage detection. Unlike mechanical damage the heat induced damage does not have a clear interface between the damaged part and the surrounding intact material from which electromagnetic waves can be reflected back. Difficulties associated with the heat induced damage detection in composite materials using T-ray are discussed in detail in this paper. T-ray measurements are compared for different levels of heat exposure of composite specimens.

  11. Resveratrol affects DNA damage induced by ionizing radiation in human lymphocytes in vitro.

    Science.gov (United States)

    Basso, Emiliano; Regazzo, Giulia; Fiore, Mario; Palma, Valentina; Traversi, Gianandrea; Testa, Antonella; Degrassi, Francesca; Cozzi, Renata

    2016-08-01

    Resveratrol (3,4',5-trihydroxystilbene; RSV) acts on cancer cells in several ways, inducing cell cycle delay and apoptotic death, and enhancing ionizing radiation (IR)-mediated responses. However, fewer studies have examined RSV effects on normal cells. We have treated human lymphocytes in vitro with RSV, either alone or combined with IR, to evaluate its potential use as a radioprotector. We measured the effects of RSV on induction of DNA damage, repair kinetics, and modulation of histone deacetylase activity. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Self-repairing control for damaged robotic manipulators

    Energy Technology Data Exchange (ETDEWEB)

    Eisler, G.R.; Robinett, R.D.; Dohrmann, C.R.; Driessen, B.J. [and others

    1997-03-01

    Algorithms have been developed allowing operation of robotic systems under damaged conditions. Specific areas addressed were optimal sensor location, adaptive nonlinear control, fault-tolerant robot design, and dynamic path-planning. A seven-degree-of-freedom, hydraulic manipulator, with fault-tolerant joint design was also constructed and tested. This report completes this project which was funded under the Laboratory Directed Research and Development program.

  13. Influence of radiation damage on BGO scintillation properties

    Energy Technology Data Exchange (ETDEWEB)

    Georgii, R.; Meissl, R.; Lichti, G.G.; Schoenfelder, V. [Max-Planck-Institut fuer Extraterrestrische Physik, Garching (Germany); Hajdas, W. [Paul-Scherrer Institut, CH-5232 Villigen (Switzerland); Henschel, H. [Fraunhofer-Institut fuer Naturwissenschaftlich-Technische Trendanalyse, D-53879 Euskirchen (Germany); Graef, H.-D.; Neumann-Cosel, P. von; Richter, A. [Institut fuer Kernphysik, Technische Universitaet Darmstadt, D-64289 Darmstadt (Germany)

    1998-08-11

    Aboard INTEGRAL, the next medium-size {gamma}-ray mission of the European Space Agency (ESA), a high-resolution Ge-spectrometer array with a BGO anticoincidence shield and imaging capability will be flown. The influence of the radiation damage on the photoelectron yield of the BGO scintillators due to the radiation environment in the orbit, i.e. {gamma}-rays, electrons and protons from the radiation, belts and the cosmic diffuse radiation, was investigated. Irradiation tests with doses equivalent to the orbit conditions were performed and the photoelectron yields of different BGO crystals were measured. It was found that for equal doses the reduction of the photoelectron yield varies strongly for the crystals of different manufacturers. Furthermore, electromagnetic radiation affects the photoelectron yield much stronger than particle radiation. A possible explanation is given by interpreting the effect due to {gamma}-rays primarily as damage of the electronic structure of the BGO, whereas the particle radiation damages mainly the crystal structure. (orig.) 19 refs.

  14. Damage Pattern as a Function of Various Types of Radiation

    Directory of Open Access Journals (Sweden)

    R.G. Ahmed

    2006-01-01

    Full Text Available The number of reports on the effects of various types of radiation is gradually increasing because of weakening of the immune system. Radiation can penetrate into living cells and result in the transfer of radiation energy to the biological material. The absorbed energy can increase the reactive oxygen species and break chemical bonds and cause ionization of different biologically essential macromolecules, such as DNA membrane lipids and proteins. Damage to the cellular membrane release the hydrolytic enzymes responsible for various catabolic processes in the tissues and leads to cell death. An understanding of the pattern in critical cellular structures such as DNA is an important prerequisite for a mechanistic assessment of primary radiation injury. The DNA damage induced by radiation such as base alterations, cross linking, strands breaker chromosomal aberration which may in turn lead to mutations. In order to further explore the harmful effects of radiation. I have produced a variety of effects of radiation on the apoptosis and necrosis. Indeed, the present review has shown that the increase in the oxidative stress (increased endogenous production of the free radicals due to radiation may be a reason for such a damage of the cell membrane, and may lead to harming the cellular elements (such as DNA. Here, one can hypothesize that, the cells with increased sensitivity to oxidative stress may be more susceptible to damage by radiation compared to normal cells. The ultimate biological consequences of this effect are subsequently processed by these cells. Much work remains to be done to firmly establish this concept.

  15. High-energy radiation damage in zirconia: modeling results

    Energy Technology Data Exchange (ETDEWEB)

    Zarkadoula, Eva; Devanathan, Ram; Weber, William J.; Seaton, Michael; Todorov, Ilian; Nordlund, Kai; Dove, Martin T.; Trachenko, Kostya

    2014-02-28

    Zirconia has been viewed as a material of exceptional resistance to amorphization by radiation damage, and was consequently proposed as a candidate to immobilize nuclear waste and serve as a nuclear fuel matrix. Here, we perform molecular dynamics simulations of radiation damage in zirconia in the range of 0.1-0.5 MeV energies with the account of electronic energy losses. We find that the lack of amorphizability co-exists with a large number of point defects and their clusters. These, importantly, are largely disjoint from each other and therefore represent a dilute damage that does not result in the loss of long-range structural coherence and amorphization. We document the nature of these defects in detail, including their sizes, distribution and morphology, and discuss practical implications of using zirconia in intense radiation environments.

  16. High-energy radiation damage in zirconia: modeling results

    Energy Technology Data Exchange (ETDEWEB)

    Zarkadoula, Evangelia [Queen Mary, University of London; Devanathan, Ram [Pacific Northwest National Laboratory (PNNL); Weber, William J [ORNL; Seaton, M [Daresbury Laboratory, UK; Todorov, I T [Daresbury Laboratory, UK; Nordlund, Kai [University of Helsinki; Dove, Martin T [Queen Mary, University of London; Trachenko, Kostya [Queen Mary, University of London

    2014-01-01

    Zirconia is viewed as a material of exceptional resistance to amorphization by radiation damage, and consequently proposed as a candidate to immobilize nuclear waste and serve as an inert nuclear fuel matrix. Here, we perform molecular dynamics simulations of radiation damage in zirconia in the range of 0.1-0.5 MeV energies with account of electronic energy losses. We nd that the lack of amorphizability co-exists with a large number of point defects and their clusters. These, importantly, are largely isolated from each other and therefore represent a dilute damage that does not result in the loss of long-range structural coherence and amorphization. We document the nature of these defects in detail, including their sizes, distribution and morphology, and discuss practical implications of using zirconia in intense radiation environments.

  17. High-energy radiation damage in zirconia: Modeling results

    Energy Technology Data Exchange (ETDEWEB)

    Zarkadoula, E., E-mail: zarkadoulae@ornl.gov [School of Physics and Astronomy, Queen Mary University of London, Mile End Road, London E1 4NS (United Kingdom); SEPnet, Queen Mary University of London, Mile End Road, London E1 4NS (United Kingdom); Materials Science and Technology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831 (United States); Devanathan, R. [Nuclear Sciences Division, Pacific Northwest National Laboratory, Richland, Washington 99352 (United States); Weber, W. J. [Materials Science and Technology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831 (United States); Department of Materials Science and Engineering, University of Tennessee, Knoxville, Tennessee 37996 (United States); Seaton, M. A.; Todorov, I. T. [STFC Daresbury Laboratory, Scientific Computing Department, Keckwick Lane, Daresbury, Warrington, Cheshire WA4 4AD (United Kingdom); Nordlund, K. [University of Helsinki, P.O. Box 43, FIN-00014 Helsinki (Finland); Dove, M. T. [School of Physics and Astronomy, Queen Mary University of London, Mile End Road, London E1 4NS (United Kingdom); Trachenko, K. [School of Physics and Astronomy, Queen Mary University of London, Mile End Road, London E1 4NS (United Kingdom); SEPnet, Queen Mary University of London, Mile End Road, London E1 4NS (United Kingdom)

    2014-02-28

    Zirconia is viewed as a material of exceptional resistance to amorphization by radiation damage, and consequently proposed as a candidate to immobilize nuclear waste and serve as an inert nuclear fuel matrix. Here, we perform molecular dynamics simulations of radiation damage in zirconia in the range of 0.1–0.5 MeV energies with account of electronic energy losses. We find that the lack of amorphizability co-exists with a large number of point defects and their clusters. These, importantly, are largely isolated from each other and therefore represent a dilute damage that does not result in the loss of long-range structural coherence and amorphization. We document the nature of these defects in detail, including their sizes, distribution, and morphology, and discuss practical implications of using zirconia in intense radiation environments.

  18. New discoveries linking transcription to DNA repair and damage tolerance pathways.

    Science.gov (United States)

    Cohen, Susan E; Walker, Graham C

    2011-01-01

    In Escherichia coli, the transcription elongation factor NusA is associated with all elongating RNA polymerases where it functions in transcription termination and antitermination. Here, we review our recent results implicating NusA in the recruitment of DNA repair and damage tolerance mechanisms to sites of stalled transcription complexes.

  19. The Fanconi anemia DNA damage repair pathway in the spotlight for germline predisposition to colorectal cancer

    Science.gov (United States)

    Esteban-Jurado, Clara; Franch-Expósito, Sebastià; Muñoz, Jenifer; Ocaña, Teresa; Carballal, Sabela; López-Cerón, Maria; Cuatrecasas, Miriam; Vila-Casadesús, Maria; Lozano, Juan José; Serra, Enric; Beltran, Sergi; Brea-Fernández, Alejandro; Ruiz-Ponte, Clara; Castells, Antoni; Bujanda, Luis; Garre, Pilar; Caldés, Trinidad; Cubiella, Joaquín; Balaguer, Francesc; Castellví-Bel, Sergi

    2016-01-01

    Colorectal cancer (CRC) is one of the most common neoplasms in the world. Fanconi anemia (FA) is a very rare genetic disease causing bone marrow failure, congenital growth abnormalities and cancer predisposition. The comprehensive FA DNA damage repair pathway requires the collaboration of 53 proteins and it is necessary to restore genome integrity by efficiently repairing damaged DNA. A link between FA genes in breast and ovarian cancer germline predisposition has been previously suggested. We selected 74 CRC patients from 40 unrelated Spanish families with strong CRC aggregation compatible with an autosomal dominant pattern of inheritance and without mutations in known hereditary CRC genes and performed germline DNA whole-exome sequencing with the aim of finding new candidate germline predisposition variants. After sequencing and data analysis, variant prioritization selected only those very rare alterations, producing a putative loss of function and located in genes with a role compatible with cancer. We detected an enrichment for variants in FA DNA damage repair pathway genes in our familial CRC cohort as 6 families carried heterozygous, rare, potentially pathogenic variants located in BRCA2/FANCD1, BRIP1/FANCJ, FANCC, FANCE and REV3L/POLZ. In conclusion, the FA DNA damage repair pathway may play an important role in the inherited predisposition to CRC. PMID:27165003

  20. Differential contributions of mammalian Rad54 paralogs to recombination, DNA damage repair, and meiosis.

    NARCIS (Netherlands)

    J. Wesoly (Joanna); S. Agarwal (Sheba); S. Sigurdsson (Stefan); W. Bussen (Wendy); S. Komen (Stephen); J. Qin (Jian); H. van Steeg (Harry); J. van Benthem (Jan); E. Wassenaar (Evelyne); W.M. Baarends (Willy); M. Ghazvini (Mehrnaz); A. Tafel (Agnieszka); H. Heath (Helen); N.J. Galjart (Niels); J. Essers (Jeroen); J.A. Grootegoed (Anton); N. Arnheim (Norman); O.Y. Bezzubova (Olga); J-M. Buerstedde; P. Sung (Patrick); R. Kanaar (Roland)

    2006-01-01

    textabstractHomologous recombination is a versatile DNA damage repair pathway requiring Rad51 and Rad54. Here we show that a mammalian Rad54 paralog, Rad54B, displays physical and functional interactions with Rad51 and DNA that are similar to those of Rad54. While ablation of Rad54 in mouse embryoni

  1. A bivariate optimal replacement policy with cumulative repair cost limit under cumulative damage model

    Indian Academy of Sciences (India)

    MIN-T SAI LAI; SHIH-CHIH CHEN

    2016-05-01

    In this paper, a bivariate replacement policy (n, T) for a cumulative shock damage process is presented that included the concept of cumulative repair cost limit. The arrival shocks can be divided into two kinds of shocks. Each type-I shock causes a random amount of damage and these damages are additive. When the total damage exceeds a failure level, the system goes into serious failure. Type-II shock causes the system into minor failure and such a failure can be corrected by minimal repair. When a minor failure occurs, the repaircost will be evaluated and minimal repair is executed if the accumulated repair cost is less than a predetermined limit L. The system is replaced at scheduled time T, at n-th minor failure, or at serious failure. The long-term expected cost per unit time is derived using the expected costs as the optimality criterion. The minimum-cost policy is derived, and existence and uniqueness of the optimal n* and T* are proved. This bivariate optimal replacement policy (n, T) is showed to be better than the optimal T* and the optimal n* policy.

  2. Human embryonic stem cells have enhanced repair of multiple forms of DNA damage

    DEFF Research Database (Denmark)

    Maynard, Scott; Swistowska, Anna Maria; Lee, Jae Wan

    2008-01-01

    fibroblasts (WI-38, hs27) and, with the exception of UV-C damage, HeLa cells. Microarray gene expression analysis showed that mRNA levels of several DNA repair genes are elevated in human embryonic stem cells compared with their differentiated forms (embryoid bodies). These data suggest that genomic...

  3. Human papillomavirus mediated inhibition of DNA damage sensing and repair drives skin carcinogenesis

    NARCIS (Netherlands)

    M. Hufbauer (Martin); J. Cooke (James); G.T.J. van der Horst (Gijsbertus); H. Pfister (Herbert); A. Storey (Alan); B. Akgül (Baki)

    2015-01-01

    textabstractBackground: The failure to mount an effective DNA damage response to repair UV induced cyclobutane pyrimidine dimers (CPDs) results in an increased propensity to develop cutaneous squamous cell carcinoma (cSCC). High-risk patient groups, such as organ transplant recipients (OTRs)

  4. Expression of MLL-AF4 or AF4-MLL fusions does not impact the efficiency of DNA damage repair.

    Science.gov (United States)

    Castaño, Julio; Herrero, Ana B; Bursen, Aldeheid; González, Federico; Marschalek, Rolf; Gutiérrez, Norma C; Menendez, Pablo

    2016-05-24

    The most frequent rearrangement of the human MLL gene fuses MLL to AF4 resulting in high-risk infant B-cell acute lymphoblastic leukemia (B-ALL). MLL fusions are also hallmark oncogenic events in secondary acute myeloid leukemia. They are a direct consequence of mis-repaired DNA double strand breaks (DNA-DSBs) due to defects in the DNA damage response associated with exposure to topoisomerase-II poisons such as etoposide. It has been suggested that MLL fusions render cells susceptible to additional chromosomal damage upon exposure to etoposide. Conversely, the genome-wide mutational landscape in MLL-rearranged infant B-ALL has been reported silent. Thus, whether MLL fusions compromise the recognition and/or repair of DNA damage remains unanswered. Here, the fusion proteins MLL-AF4 (MA4) and AF4-MLL (A4M) were CRISPR/Cas9-genome edited in the AAVS1 locus of HEK293 cells as a model to study MLL fusion-mediated DNA-DSB formation/repair. Repair kinetics of etoposide- and ionizing radiation-induced DSBs was identical in WT, MA4- and A4M-expressing cells, as revealed by flow cytometry, by immunoblot for γH2AX and by comet assay. Accordingly, no differences were observed between WT, MA4- and A4M-expressing cells in the presence of master proteins involved in non-homologous end-joining (NHEJ; i.e.KU86, KU70), alternative-NHEJ (Alt-NHEJ; i.e.LigIIIa, WRN and PARP1), and homologous recombination (HR, i.e.RAD51). Moreover, functional assays revealed identical NHEJ and HR efficiency irrespective of the genotype. Treatment with etoposide consistently induced cell cycle arrest in S/G2/M independent of MA4/A4M expression, revealing a proper activation of the DNA damage checkpoints. Collectively, expression of MA4 or A4M does neither influence DNA signaling nor DNA-DSB repair.

  5. Kinetic model for the pathogenesis of radiation lung damage

    Energy Technology Data Exchange (ETDEWEB)

    Collis, C.H. (Institute of Cancer Research, Sutton (UK). Surrey Branch)

    1982-09-01

    The development of radiation-induced lung damage can be explained by a kinetic model, based on the assumption that this damage becomes manifest only when a critical proportion (K) of essential cells have ceased to function, and that the rate of loss of these cells following irradiation is linear and dose-dependent. The kinetic model relates the surviving fraction to the time to manifestation of radiation-induced lung damage and to constants, K and the cell cycle time, T. Predictions made from the model about the nature of the response to irradiation are, for the most part, fulfilled. The model can also be used to interpret the response to combined treatment with irradiation and cytotoxic drugs, including the much earlier manifestation of lung damage sometimes seen with such treatment.

  6. Low cost CCD camera protection against neutron radiation damage.

    Science.gov (United States)

    Kok, J G M

    2005-01-01

    At a radiotherapy department cancer patients are treated with high energy electron and photon beams. These beams are produced by a linear accelerator. A closed circuit television system is used to monitor patients during treatment. Although CCD cameras are rather resistant to stray radiation, they are damaged by the low flux of neutrons which are produced by the linac as a side effect. PVC can be used to reduce damage to CCD cameras induced by neutron radiation. A box with 6 cm thick walls will extend the life of the camera at least by a factor of two. A PVC neutron shield is inexpensive. PVC is easy to obtain and the box is simple to construct. A similar box made out of PE will not reduce neutron damage to a CCD camera. Although PE is a good medium to moderate faster neutrons, thereby reducing some of the bulk defects, it will not capture thermal neutrons which induce surface damage.

  7. Are glutathione S transferases involved in DNA damage signalling? Interactions with DNA damage and repair revealed from molecular epidemiology studies

    Energy Technology Data Exchange (ETDEWEB)

    Dusinska, Maria, E-mail: Maria.DUSINSKA@nilu.no [CEE-Health Effects Group, NILU - Norwegian Institute for Air Research, Kjeller (Norway); Staruchova, Marta; Horska, Alexandra [Department of Experimental and Applied Genetics, Slovak Medical University, Bratislava (Slovakia); Smolkova, Bozena [Laboratory of Cancer Genetics, Cancer Research Institute of the Slovak Academy of Sciences, Bratislava (Slovakia); Collins, Andrew [Department of Nutrition, Faculty of Medicine, University of Oslo (Norway); Bonassi, Stefano [Unit of Clinical and Molecular Epidemiology, IRCCS San Raffaele Pisana, Rome (Italy); Volkovova, Katarina [Department of Experimental and Applied Genetics, Slovak Medical University, Bratislava (Slovakia)

    2012-08-01

    Glutathione S-transferases (GSTs) are members of a multigene family of isoenzymes that are important in the control of oxidative stress and in phase II metabolism. Acting non-enzymically, GSTs can modulate signalling pathways of cell proliferation, cell differentiation and apoptosis. Using a molecular epidemiology approach, we have investigated a potential involvement of GSTs in DNA damage processing, specifically the modulation of DNA repair in a group of 388 healthy adult volunteers; 239 with at least 5 years of occupational exposure to asbestos, stone wool or glass fibre, and 149 reference subjects. We measured DNA damage in lymphocytes using the comet assay (alkaline single cell gel electrophoresis): strand breaks (SBs) and alkali-labile sites, oxidised pyrimidines with endonuclease III, and oxidised purines with formamidopyrimidine DNA glycosylase. We also measured GST activity in erythrocytes, and the capacity for base excision repair (BER) in a lymphocyte extract. Polymorphisms in genes encoding three GST isoenzymes were determined, namely deletion of GSTM1 and GSTT1 and single nucleotide polymorphism Ile105Val in GSTP1. Consumption of vegetables and wine correlated negatively with DNA damage and modulated BER. GST activity correlated with oxidised bases and with BER capacity, and differed depending on polymorphisms in GSTP1, GSTT1 and GSTM1. A significantly lower BER rate was associated with the homozygous GSTT1 deletion in all asbestos site subjects and in the corresponding reference group. Multifactorial analysis revealed effects of sex and exposure in GSTP1 Ile/Val heterozygotes but not in Ile/Ile homozygotes. These variants affected also SBs levels, mainly by interactions of GSTP1 genotype with exposure, with sex, and with smoking habit; and by an interaction between sex and smoking. Our results show that GST polymorphisms and GST activity can apparently influence DNA stability and repair of oxidised bases, suggesting a potential new role for these

  8. Participation of DNA-PKcs in DSB repair after exposure to high- and low-LET radiation.

    Science.gov (United States)

    Anderson, Jennifer A; Harper, Jane V; Cucinotta, Francis A; O'Neill, Peter

    2010-08-01

    Cellular lesions (e.g. DSBs) are induced into DNA upon exposure to radiation, with DSB complexity increasing with radiation ionization density. Using M059K and M059J human glioblastoma cells (proficient and deficient in DNA-PKcs activity, respectively), we investigated the repair of DNA damage, including DSBs, induced by high- and low-LET radiation [gamma rays, alpha particles and high-charge and energy (HZE) ions]. In the absence of DNA-PKcs activity, less DSB repair and increased recruitment of RAD51 was seen at 24 h. After exposure to (56)Fe heavy ions, the number of cells with RAD51 tracks was less than the number of cells with gamma-H2AX at 24 h with both cell lines. Using alpha particles, comparable numbers of cells with visible gamma-H2AX and RAD51 were seen at 24 h in both cell lines. M059J cells irradiated with alpha particles accumulated in S phase, with a greater number of cyclin A and RAD51 co-stained cells seen at 24 h compared with M059K cells, where an S-phase block is absent. It is proposed that DNA-PKcs plays a role in the repair of some frank DSBs, which are longer-lived in NHEJ-deficient cells, and some non-DSB clustered damage sites that are converted into DSBs at replication as the cell cycles through to S phase.

  9. Location of DNA damage by charge exchanging repair enzymes: effects of cooperativity on location time

    Directory of Open Access Journals (Sweden)

    Eriksen Kasper

    2005-04-01

    Full Text Available Abstract Background How DNA repair enzymes find the relatively rare sites of damage is not known in great detail. Recent experiments and molecular data suggest that individual repair enzymes do not work independently of each other, but interact with each other through charges exchanged along the DNA. A damaged site in the DNA hinders this exchange. The hypothesis is that the charge exchange quickly liberates the repair enzymes from error-free stretches of DNA. In this way, the sites of damage are located more quickly; but how much more quickly is not known, nor is it known whether the charge exchange mechanism has other observable consequences. Results Here the size of the speed-up gained from this charge exchange mechanism is calculated and the characteristic length and time scales are identified. In particular, for Escherichia coli, I estimate the speed-up is 50000/N, where N is the number of repair enzymes participating in the charge exchange mechanism. Even though N is not exactly known, a speed-up of order 10 is not entirely unreasonable. Furthermore, upon over expression of all the repair enzymes, the location time only varies as N-1/2 and not as 1/N. Conclusion The revolutionary hypothesis that DNA repair enzymes use charge exchange along DNA to locate damaged sites more efficiently is actually sound from a purely theoretical point of view. Furthermore, the predicted collective behavior of the location time is important in assessing the impact of stress-ful and radioactive environments on individual cell mutation rates.

  10. 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).

  11. Monte Carlo simulation of base and nucleotide excision repair of clustered DNA damage sites. I. Model properties and predicted trends

    Energy Technology Data Exchange (ETDEWEB)

    Semenenko, Vladimir; Stewart, Robert D.; Ackerman, Eric J.

    2005-12-31

    Single-cell irradiators and new experimental assays are rapidly expanding our ability to quantify the molecular mechanisms responsible for phenomena such as toxicant-induced adaptations in DNA repair and signal-mediated changes to the genome stability of cells not directly damaged by radiation (i.e., bystander cells). To advance our understanding of, and ability to predict and mitigate, the potentially harmful effects of radiological agents, effective strategies must be devised to incorporate information from molecular and cellular studies into mechanism-based, hierarchical models. A key advantage of the hierarchical modeling approach is that information from DNA repair and other in vitro assays can be systematically integrated into higher-level cell transformation and, eventually, carcinogenesis models. This presentation will outline the hierarchical modeling strategy used to integrate information from in vitro studies into the Virtual Cell (VC) radiobiology software (see Endnote). A new multi-path genomic instability model will be introduced and used to link biochemical processing of double strand breaks (DSBs) to neoplastic cell transformation. Bystander and directly damaged cells are treated explicitly in the model using a microdosimetric approach, although many of the details of the bystander response model are of a necessarily preliminary nature. The new model will be tested against several published radiobiological datasets. Results illustrating how hypothesized bystander mechanisms affect the shape of dose-response curves for neoplastic transformation as a function of Linear Energy Transfer (LET) will be presented. EndNote: R.D. Stewart, Virtual Cell (VC) Radiobiology Software. PNNL-13579, July 2001. Available at http://www.pnl.gov/berc/kbem/vc/ The DNA repair model used in the VC computer program is based on the Two-Lesion Kinetic (TLK) model [Radiat. Res. 156(4), 365-378 October 2001].

  12. Systematic analysis of DNA damage induction and DNA repair pathway activation by continuous wave visible light laser micro-irradiation

    Directory of Open Access Journals (Sweden)

    Britta Muster

    2017-02-01

    Full Text Available Laser micro-irradiation can be used to induce DNA damage with high spatial and temporal resolution, representing a powerful tool to analyze DNA repair in vivo in the context of chromatin. However, most lasers induce a mixture of DNA damage leading to the activation of multiple DNA repair pathways and making it impossible to study individual repair processes. Hence, we aimed to establish and validate micro-irradiation conditions together with inhibition of several key proteins to discriminate different types of DNA damage and repair pathways using lasers commonly available in confocal microscopes. Using time-lapse analysis of cells expressing fluorescently tagged repair proteins and also validation of the DNA damage generated by micro-irradiation using several key damage markers, we show that irradiation with a 405 nm continuous wave laser lead to the activation of all repair pathways even in the absence of exogenous sensitization. In contrast, we found that irradiation with 488 nm laser lead to the selective activation of non-processive short-patch base excision and single strand break repair, which were further validated by PARP inhibition and metoxyamine treatment. We conclude that these low energy conditions discriminated against processive long-patch base excision repair, nucleotide excision repair as well as double strand break repair pathways.

  13. Essential and distinct roles of the F-box and helicase domains of Fbh1 in DNA damage repair

    Directory of Open Access Journals (Sweden)

    Shinagawa Hideo

    2008-03-01

    Full Text Available Abstract Background DNA double-strand breaks (DSBs are induced by exogenous insults such as ionizing radiation and chemical exposure, and they can also arise as a consequence of stalled or collapsed DNA replication forks. Failure to repair DSBs can lead to genomic instability or cell death and cancer in higher eukaryotes. The Schizosaccharomyces pombe fbh1 gene encodes an F-box DNA helicase previously described to play a role in the Rhp51 (an orthologue of S. cerevisiae RAD51-dependent recombinational repair of DSBs. Fbh1 fused to GFP localizes to discrete nuclear foci following DNA damage. Results To determine the functional roles of the highly conserved F-box and helicase domains, we have characterized fbh1 mutants carrying specific mutations in these domains. We show that the F-box mutation fbh1-fb disturbs the nuclear localization of Fbh1, conferring an fbh1 null-like phenotype. Moreover, nuclear foci do not form in fbh1-fb cells with DNA damage even if Fbh1-fb is targeted to the nucleus by fusion to a nuclear localization signal sequence. In contrast, the helicase mutation fbh1-hl causes the accumulation of Fbh1 foci irrespective of the presence of DNA damage and confers damage sensitivity greater than that conferred by the null allele. Additional mutation of the F-box alleviates the hypermorphic phenotype of the fbh1-hl mutant. Conclusion These results suggest that the F-box and DNA helicase domains play indispensable but distinct roles in Fbh1 function. Assembly of the SCFFbh1 complex is required for both the nuclear localization and DNA damage-induced focus formation of Fbh1 and is therefore prerequisite for the Fbh1 recombination function.

  14. Determination of damage and In vivo DNA repairing through the unicellular in gel electrophoresis technique; Determinacion del dano y la reparacion del ADN In vivo mediante la tecnica de electroforesis unicelular en gel

    Energy Technology Data Exchange (ETDEWEB)

    Mendiola C, M.T.; Morales R, P. [Instituto Nacional de Investigaciones Nucleares, A.P. 18-1027, 11801 Mexico D.F. (Mexico)

    1997-07-01

    The experimental conditions were standardized for the unicellular in gel electrophoresis technique setting up (EUG) at the Cellular Radiobiology laboratory. Preliminary experiments were realized with human cells and mouse which were exposed to ionizing radiation or hydroxide peroxide (H{sub 2}O{sub 2}) to induce DNA damage and to verify the technique performance. It was analysed the In vivo repairing kinetics of induced damage by gamma radiation in mouse leukocytes which were exposed to {sup 137} Cs source and taking samples of peripheric blood of the tail of each mouse at different exposure times and processing them for EUG. In function of the cells proportion with damage in each time it was determined the existence of fast repairing mechanism at the first 15 minutes followed by a slight increase in the damage and a late repairing stage between 30 and 90 minutes. It was analysed this behavior and the potentiality of this In vivo system. (Author)

  15. Proton-radiation damage in Gunn oscillators

    Science.gov (United States)

    Johnson, J. W.; Fales, C. L., Jr.

    1973-01-01

    The irradiation effects of 22 MeV protons on the electrical characteristics of GaAs continuous-wave Gunn oscillators was studied. The radio frequency power output was reduced by 3 decibels at proton fluences in the neighborhood of 1.5 x 10 to the 12th power protons/sq cm. Conductance measurements indicate that the carrier removal rate at high electric fields remained roughly 40 percent less than at low fields. Diode efficiencies of two device groups were found to be monotonically descreasing functions of fluence. Frequency modulation noise was generally unaffected by radiation, but the magnitude of the noise in the noise power spectrum increased significantly. These effects are partially accounted for, in a qualitative fashion, by a model of electron traps having field-dependent net-carrier capture rates and various response times.

  16. Simulating radiation damage in {delta}-plutonium

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, M. [Department of Mathematical Sciences, Loughborough University, Loughborough, LE11 3TU (United Kingdom)], E-mail: m.robinson@lboro.ac.uk; Kenny, S.D.; Smith, R. [Department of Mathematical Sciences, Loughborough University, Loughborough, LE11 3TU (United Kingdom); Storr, M.T.; McGee, E. [Atomic Weapons Establishment, Aldermaston, Reading, RG7 4PR (United Kingdom)

    2009-09-15

    Radiation events in {delta}-Pu (fcc) have been simulated in an attempt to understand the fundamental mechanisms that contribute to the Pu ageing process. The Pu interactions are modelled using a potential based on the modified embedded atom method (MEAM). The energetics of point defects have been investigated using static calculations together with molecular dynamics (MD) to simulate radiation events. All MD simulations were carried out with Pu initially in the face-centred-cubic (fcc) structure, although this is not the lowest energy configuration for the pure metal. The point defect study suggests that the mono-vacancy has the lowest formation energy (0.46 eV), with interstitial defects favouring the <100> - split orientation over occupation of the native fcc octahedral site. Displacement threshold energy calculations at room temperature give a minimum value of between 5 and 6 eV, increasing to 8-14 eV along the major crystallographic directions. Low energy collision cascades, initiated with energies in the range of 0.4-1 keV, show that the cascades form in a similar manner to other fcc metals with a vacancy rich zone at the cascade core, surrounded by isolated interstitial defects. Higher energy cascades show similar features but with occasional channelling of energetic atoms and sub-cascade branching which significantly reduces defect production. A common trait observed across all the cascades was the relatively slow annealing period, compared to cascades in other fcc metals, with simulations at energies above 5 keV requiring many 10's of picoseconds before the ballistic phase was completed.

  17. Oxidative DNA damage background estimated by a system model of base excision repair.

    Science.gov (United States)

    Sokhansanj, Bahrad A; Wilson, David M

    2004-08-01

    Human DNA can be damaged by natural metabolism through free radical production. It has been suggested that the equilibrium between innate damage and cellular DNA repair results in an oxidative DNA damage background that potentially contributes to disease and aging. Efforts to quantitatively characterize the human oxidative DNA damage background level, based on measuring 8-oxoguanine lesions as a biomarker, have led to estimates that vary over three to four orders of magnitude, depending on the method of measurement. We applied a previously developed and validated quantitative pathway model of human DNA base excision repair, integrating experimentally determined endogenous damage rates and model parameters from multiple sources. Our estimates of at most 100 8-oxoguanine lesions per cell are consistent with the low end of data from biochemical and cell biology experiments, a result robust to model limitations and parameter variation. Our findings show the power of quantitative system modeling to interpret composite experimental data and make biologically and physiologically relevant predictions for complex human DNA repair pathway mechanisms and capacity.

  18. Oxidative DNA damage background estimated by a system model of base excision repair

    Energy Technology Data Exchange (ETDEWEB)

    Sokhansanj, B A; Wilson, III, D M

    2004-05-13

    Human DNA can be damaged by natural metabolism through free radical production. It has been suggested that the equilibrium between innate damage and cellular DNA repair results in an oxidative DNA damage background that potentially contributes to disease and aging. Efforts to quantitatively characterize the human oxidative DNA damage background level based on measuring 8-oxoguanine lesions as a biomarker have led to estimates varying over 3-4 orders of magnitude, depending on the method of measurement. We applied a previously developed and validated quantitative pathway model of human DNA base excision repair, integrating experimentally determined endogenous damage rates and model parameters from multiple sources. Our estimates of at most 100 8-oxoguanine lesions per cell are consistent with the low end of data from biochemical and cell biology experiments, a result robust to model limitations and parameter variation. Our results show the power of quantitative system modeling to interpret composite experimental data and make biologically and physiologically relevant predictions for complex human DNA repair pathway mechanisms and capacity.

  19. Inducible HSP70 Protects Radiation-Induced Salivary Gland Damage

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hae-June; Lee, Yoon-Jin; Kwon, Hee-Choong; Lee, Su-Jae; Bae, Sang-Woo; Lee, Yun-Sil [Korea Institute of Radiological Medical Sciences, Seoul (Korea, Republic of); Kim, Sung-Ho [Chonnam National University, Gwangju (Korea, Republic of)

    2006-07-01

    Irradiation (IR) delivered to the head and neck is a common treatment for malignancies. Salivary glands in the irradiation field are severely damaged, and consequently this resulted in marked salivary hypofunction. While the exact mechanism of salivary gland damage remains enigmatic, fluid secreting acinar cells are lost, and saliva output is dramatically reduced. Previously we have reported that inducible heat shock protein 70 (HSP70i) induced radioresistance in vitro. Moreover, HSP70i localized to salivary glands by gene transfer has great potential for the treatment of salivary gland. Herein, we investigated whether HSP70 can use as radio protective molecules for radiation-induced salivary gland damage in vivo.

  20. Relationships between chromatin remodeling and DNA damage repair induced by 8-methoxypsoralen and UVA in yeast Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Lavínia Almeida Cruz

    2012-01-01

    Full Text Available Eukaryotic cells have developed mechanisms to prevent genomic instability, such as DNA damage detection and repair, control of cell cycle progression and cell death induction. The bifunctional compound furocumarin 8-methoxy-psoralen (8-MOP is widely used in the treatment of various inflammatory skin diseases. In this review, we summarize recent data about the role of chromatin remodeling in the repair of DNA damage induced by treatment with 8-methoxypsoralen plus UVA (8-MOP+UVA, focusing on repair proteins in budding yeast Saccharomyces cerevisiae, an established model system for studying DNA repair pathways. The interstrand crosslinks (ICL formed by the 8-MOP+UVA treatment are detrimental lesions that can block transcription and replication, leading to cell death if not repaired. Current data show the involvement of different pathways in ICL processing, such as nucleotide excision repair (NER, base excision repair (BER, translesion repair (TLS and double-strand break repair. 8-MOP+UVA treatment in yeast enhances the expression of genes involved in the DNA damage response, double strand break repair by homologous replication, as well as genes related to cell cycle regulation. Moreover, alterations in the expression of subtelomeric genes and genes related to chromatin remodeling are consistent with structural modifications of chromatin relevant to DNA repair. Taken together, these findings indicate a specific profile in 8-MOP+UVA responses related to chromatin remodeling and DNA repair.

  1. Experimental assessment of concrete damage due to exposure to high temperature and efficacy of the repair system

    Directory of Open Access Journals (Sweden)

    Guruprasad Y.K.

    2013-09-01

    Full Text Available The present study experimentally evaluates the performance of control (standard cylinder specimen, damaged (mechanical loading after thermal exposure and repaired / retrofitted normal plain concrete cylinders using different repair schemes such as on use of FRP wraps, Geo-polymers, etc., to restore the capacity of damaged structural concrete elements. The control-companion specimen in the series provides the reference frame against which both, specimen damage levels were quantified and the benefits of a specimen repaired subsequent to damage were assessed.

  2. Radiation damage in nonmetallic solids under dense electronic excitation

    Energy Technology Data Exchange (ETDEWEB)

    Itoh, Noriaki; Tanimura, Katsumi; Nakai, Yasuo (Dept. of Physics, Nagoya Univ. (Japan))

    1992-03-01

    Basic processes of radiation damage of insulators by dense electronic excitation are reviewed. First it is pointed out that electronic excitation of nonmetallic solids produces the self-trapped excitons and defect-related metastable states having relatively long lifetimes, and that the excitation of these metastable states, produces stable defects. The effects of irradiation with heavy ions, including track registration, are surveyed on the basis of the microscopic studies. It is pointed out also that the excitation of the metastable states plays a role in laser-induced damage at relatively low fluences, while the laser damage has been reported to be governed by heating of free electrons produced by multiphoton excitation. Difference in the contributions of the excitation of metastable defects to laser-induced damage of surfaces, or laser ablation, and laser-induced bulk damage is stressed. (orig.).

  3. Radiation Damage Studies of Silicon Photomultipliers

    CERN Document Server

    Bohn, P; Hazen, E.; Heering, A.; Rohlf, J.; Freeman, J.; Los, Sergey V.; Cascio, E.; Kuleshov, S.; Musienko, Y.; Piemonte, C.

    2008-01-01

    We report on the measurement of the radiation hardness of silicon photomultipliers (SiPMs) manufactured by Fondazione Bruno Kessler in Italy (1 mm$^2$ and 6.2 mm$^2$), Center of Perspective Technology and Apparatus in Russia (1 mm$^2$ and 4.4 mm$^2$), and Hamamatsu Corporation in Japan (1 mm$^2$). The SiPMs were irradiated using a beam of 212 MeV protons at Massachusetts General Hospital, receiving fluences of up to $3 \\times 10^{10}$ protons per cm$^2$ with the SiPMs at operating voltage. Leakage currents were read continuously during the irradiation. The delivery of the protons was paused periodically to record scope traces in response to calibrated light pulses to monitor the gains, photon detection efficiencies, and dark counts of the SiPMs. The leakage current and dark noise are found to increase with fluence. Te leakage current is found to be proportional to the mean square deviation of the noise distribution, indicating the dark counts are due to increased random individual pixel activation, while SiPM...

  4. Radiation damage aspects of the Chernobyl accident

    Energy Technology Data Exchange (ETDEWEB)

    Parmentier, N.; Nenot, J.C. (CEA Centre d' Etudes Nucleaires de Fontenay-aux-Roses, 92 (France). Inst. de Protection et de Surete Nucleaire)

    1989-01-01

    During the night of 25 to 26 April 1986, the most severe nuclear accident occurred at the Chernobyl power stations. It resulted in the irradiation of 237 workers at dose levels justifying medical care. The most severe cases (115) were hospitalized in Moscow, with 20 patients with doses higher than 6 Gy. In most cases, the treatment was classical, based on transfusion of red cells and platelets, and heavy supportive therapy. For 19 patients with severe aplasia, transplantations of bone marrow (13) or foetal liver (6) were decided. Of these patients only one survived, which justifies the statement from U.S.S.R. physicians: after an accident the indications of grafting are limited and its risks may not justify its use. Most of the complications were related to radiation burns which involved 56 victims and resulted in fatal outcomes in at least 19 patients. The population was evacuated from a 30 km zone around the site; based on direct measurements and calculations, the collective dose was evaluated at 1.6 x 10{sup 4} man Sv, with an individual average lower than 250 mSv. The European part of U.S.S.R. with 75 million persons is supposed to have received a collective dose likely to increase the natural mortality by less than 0.1%. The numbers with cancer in the Northern Hemisphere might increase by 0.004% over the next 50 years.

  5. Radiation damage aspects of the chernobyl accident

    Science.gov (United States)

    Parmentier, N.; Nenot, J. C.

    During the night of 25 to 26 April 1986, the most severe nuclear accident occurred at the Chernobyl power station, about 150km north of Kiev, in the Ukraine. It resulted in the irradiation of 237 workers at dose levels justifying medical care. The most severe cases (115) were hospitalized in Moscow, with 20 patients with doses higher than 6 Gy. In most cases, the treatment was classical, based on transfusion of red cells and platelets, and heavy supportive therapy. For 19 patients with severe aplasia, transplantations of bone marrow (13) or foetal liver (6) were decided. Of these patients only one survived, which justifies the statement from U.S.S.R. physicians: after an accident the indications of grafting are limited and its risks may not justify its use. Most of the complications were related to radiation burns which involved 56 victims and resulted in fatal outcomes in at least 19 patients. The population was evacuated from a 30 km zone around the site; based on direct measurements and calculations, the collective dose was evaluated at 1.6 × 10 4 man Sv, with an individual average lower than 250 mSv. The European part of U.S.S.R. with 75 million persons is supposed to have received a collective dose likely to increase the natural mortality by less than 0.1%. The numbers with cancer in the Northern Hemisphere might increase by 0.004% over the next 50 years.

  6. 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...

  7. Repair Machinery for Radiation-Induced DNA Damage

    Science.gov (United States)

    2000-07-01

    titrations, different pHs were maintained with a buffer mixture of constant ionic strength composed of 25 mM of acetic acids and MES, and 50 mM of Trizma base...the region 1lq23.1-11q23.2. accession number P39287). IMAGE clone 663460 was chosen, se- Buffers and Reagents-All reagents were purchased from Sigma...was obtained quenced Tagged Site" data base at National Cancer Biology Institute, from Dharmacon Research (Boulder, CO). L buffer (Lysis buffer ) con

  8. Regulators of global genome repair do not respond to DNA damaging therapy but correlate with survival in melanoma.

    Directory of Open Access Journals (Sweden)

    Nikola A Bowden

    Full Text Available Nucleotide excision repair (NER orchestrates the repair of helix distorting DNA damage, induced by both ultraviolet radiation (UVR and cisplatin. There is evidence that the global genome repair (GGR arm of NER is dysfunctional in melanoma and it is known to have limited induction in melanoma cell lines after cisplatin treatment. The aims of this study were to examine mRNA transcript levels of regulators of GGR and to investigate the downstream effect on global transcript expression in melanoma cell lines after cisplatin treatment and in melanoma tumours. The GGR regulators, BRCA1 and PCNA, were induced in melanocytes after cisplatin, but not in melanoma cell lines. Transcripts associated with BRCA1, BRCA2, ATM and CHEK2 showed altered expression in melanoma cell lines after cisplatin treatment. In melanoma tumour tissue BRCA1 transcript expression correlated with poor survival and XPB expression correlated with solar elastosis levels. Taken together, these findings provide evidence of the mechanisms underlying NER deficiency in melanoma.

  9. Neutron dosimetry and radiation damage calculations for HFBR

    Energy Technology Data Exchange (ETDEWEB)

    Greenwood, L.R.; Ratner, R.T. [Pacific Northwest National Lab., TN (United States)

    1998-03-01

    Neutron dosimetry measurements have been conducted for various positions of the High Flux Beam Reactor (HFBR) at Brookhaven National Laboratory (BNL) in order to measure the neutron flux and energy spectra. Neutron dosimetry results and radiation damage calculations are presented for positions V10, V14, and V15.

  10. A new mechanism for radiation damage processes in alkali halides

    NARCIS (Netherlands)

    Dubinko, V.I.; Turkin, A.A.; Vainshtein, D.I.; Hartog, H.W. den

    1999-01-01

    We present a theory of radiation damage formation in alkali halides based on a new mechanism of dislocation climb, which involves the production of VF centers (self-trapped hole neighboring a cation vacancy) as a result of the absorption of H centers of dislocation lines. We consider the evolution o

  11. Genomic damage in children accidentally exposed to ionizing radiation

    DEFF Research Database (Denmark)

    Fucic, A; Brunborg, G; Lasan, R

    2007-01-01

    doses of radiation; (b) effects on children from combined exposure to low doses of radiation and chemical agents from food, water and air; and (c) specific effects from exposure during early childhood (radioisotopes from water, radon in homes). Special consideration should also be given to a possible......, environmental radiation pollution and indoor accidental contamination reveals consistently increased chromosome aberration and micronuclei frequency in exposed than in referent children. Future research in this area should be focused on studies providing information on: (a) effects on children caused by low...... 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...

  12. Human telomeres are hypersensitive to UV-induced DNA Damage and refractory to repair.

    Directory of Open Access Journals (Sweden)

    Patrick J Rochette

    2010-04-01

    Full Text Available Telomeric repeats preserve genome integrity by stabilizing chromosomes, a function that appears to be important for both cancer and aging. In view of this critical role in genomic integrity, the telomere's own integrity should be of paramount importance to the cell. Ultraviolet light (UV, the preeminent risk factor in skin cancer development, induces mainly cyclobutane pyrimidine dimers (CPD which are both mutagenic and lethal. The human telomeric repeat unit (5'TTAGGG/CCCTAA3' is nearly optimal for acquiring UV-induced CPD, which form at dipyrimidine sites. We developed a ChIP-based technique, immunoprecipitation of DNA damage (IPoD, to simultaneously study DNA damage and repair in the telomere and in the coding regions of p53, 28S rDNA, and mitochondrial DNA. We find that human telomeres in vivo are 7-fold hypersensitive to UV-induced DNA damage. In double-stranded oligonucleotides, this hypersensitivity is a property of both telomeric and non-telomeric repeats; in a series of telomeric repeat oligonucleotides, a phase change conferring UV-sensitivity occurs above 4 repeats. Furthermore, CPD removal in the telomere is almost absent, matching the rate in mitochondria known to lack nucleotide excision repair. Cells containing persistent high levels of telomeric CPDs nevertheless proliferate, and chronic UV irradiation of cells does not accelerate telomere shortening. Telomeres are therefore unique in at least three respects: their biophysical UV sensitivity, their prevention of excision repair, and their tolerance of unrepaired lesions. Utilizing a lesion-tolerance strategy rather than repair would prevent double-strand breaks at closely-opposed excision repair sites on opposite strands of a damage-hypersensitive repeat.

  13. The Comet-FISH assay for the analysis of DNA damage and repair.

    Science.gov (United States)

    Spivak, Graciela

    2010-01-01

    In this chapter, I describe the alkaline single-cell gel electrophoresis (Comet assay) combined with fluorescence in situ hybridization (FISH) technology, used in our laboratory, to study the incidence and repair of lesions induced in human cells by ultraviolet light. The Comet-FISH method permits the simultaneous and comparative analysis of DNA damage and its repair throughout the genome and in defined chromosomal regions. This very sensitive approach can be applied to any lesion, such as those induced by chemical carcinogens and products of cellular metabolism that can be converted to DNA single- or double-strand breaks. The unique advantages and limitations of the method for particular applications are discussed.

  14. Neuromuscular Damage and Repair after Dry Needling in Mice

    Directory of Open Access Journals (Sweden)

    Ares Domingo

    2013-01-01

    Full Text Available Objective. Some dry needling treatments involve repetitive and rapid needle insertions into myofascial trigger points. This type of treatment causes muscle injury and can also damage nerve fibers. The aim of this study is to determine the injury caused by 15 repetitive punctures in the muscle and the intramuscular nerves in healthy mouse muscle and its ulterior regeneration. Methods. We repeatedly needled the levator auris longus muscle of mice, and then the muscles were processed with immunohistochemistry, methylene blue, and electron microscopy techniques. Results. Three hours after the dry needling procedure, the muscle fibers showed some signs of an inflammatory response, which progressed to greater intensity 24 hours after the procedure. Some inflammatory cells could still be seen when the muscle regeneration was almost complete seven days after the treatment. One day after the treatment, some changes in the distribution of receptors could be observed in the denervated postsynaptic component. Reinnervation was complete by the third day after the dry needling procedure. We also saw very fine axonal branches reinnervating all the postsynaptic components and some residual sprouts the same day. Conclusion. Repeated dry needling punctures in muscle do not perturb the different stages of muscle regeneration and reinnervation.

  15. Radiation induced crystallinity damage in poly(L-lactic acid)

    CERN Document Server

    Kantoglu, O

    2002-01-01

    The radiation-induced crystallinity damage in poly(L-lactic acid) (PLLA) in the presence of air and in vacuum, is studied. From the heat of fusion enthalpy values of gamma irradiated samples, some changes on the thermal properties were determined. To identify these changes, first the glass transition temperature (T sub g) of L-lactic acid polymers irradiated to various doses in air and vacuum have been investigated and it is found that it is independent of irradiation atmosphere and dose. The fraction of damaged units of PLLA per unit of absorbed energy has been measured. For this purpose, SAXS and differential scanning calorimetry methods were used, and the radiation yield of number of damaged units (G(-u)) is found to be 0.74 and 0.58 for PLLA samples irradiated in vacuum and air, respectively.

  16. Recent results of radiation damage studies in silicon

    Energy Technology Data Exchange (ETDEWEB)

    Bates, S.J.; Munday, D.J.; Parker, M.A.; Anghinolfi, F.; Chilingarov, A.; Ciasnohova, A.; Glaser, M.; Heijne, E.; Jarron, P.; Lemeilleur, F.; Santiard, J.C.; Bonino, R.; Clark, A.G.; Kambara, H.; Goessling, C.; Lisowski, B.; Rolf, A.; Pilath, S.; Feick, H.; Fretwurst, E.; Lindstroem, G.; Schulz, T.; Bardos, R.A.; Gorfine, G.W.; Moorhead, G.F.; Taylor, G.N.; Tovey, S.N. (Cavendish Lab., Univ. of Cambridge (United Kingdom) CERN, Geneva (Switzerland) DPNC, Univ. de Geneve (Switzerland) Inst. fuer Physik, Univ. Dortmund (Germany) 1. Inst. fuer Experimentalphysik, Univ. Hamburg (Germany) School of Physics, Univ. of Melbourne (Australia))

    1994-04-21

    The RD2 Collaboration is making preliminary studies on a silicon tracking detector for use at the LHC. It is a priority that this detector should withstand the high level of radiation to be expected for LHC operation. Therefore systematic studies on the change of the detector performance due to radiation damage have been made, or are in progress. Well established results on neutron related damage at room temperature have been extended to lower temperatures, as foreseen for operation at LHC. For comparison proton damage studies have also been started. The detector properties under investigation include the reverse current, the depletion voltage and the charge collection efficiency. With a compressed 10 year LHC operational scenario we have successfully checked the ability of silicon detectors to survive the period influences of high fluence irradiation and subsequent annealing. (orig.)

  17. Suppression of Jab1/CSN5 induces radio- and chemo-sensitivity in nasopharyngeal carcinoma through changes to the DNA damage and repair pathways.

    Science.gov (United States)

    Pan, Y; Zhang, Q; Atsaves, V; Yang, H; Claret, F X

    2013-05-30

    Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus-associated malignancy most common in East Asia and Africa. Radiotherapy and cisplatin-based chemotherapy are the main treatment options. Unfortunately, disease response to concurrent chemoradiotherapy varies among patients with NPC, and many cases are resistant to cisplatin. Increased DNA damage repair is one of the mechanisms contributing to this resistance. Jab1/CSN5 is a multifunctional protein that participates in controlling cell proliferation and the stability of multiple proteins. Jab1 overexpression has been found to correlate with poor prognosis in several tumor types. However, the biological significance of Jab1 activity in response to cancer treatment is unclear. In this study, we used three NPC cell lines (CNE1, CNE2 and HONE1) to investigate the hypothesis that Jab1 positively regulates the DNA repair protein Rad51 and, in turn, cellular response to treatment with DNA-damaging agents such as cisplatin, ionizing radiation (IR) and ultraviolet (UV) radiation. We found that Jab1 was overexpressed in two relatively cisplatin-, IR- and UV-resistant NPC cell lines, and knocking down its expression conferred sensitivity to cisplatin, IR and UV radiation. By contrast, exogenous Jab1 expression enhanced the resistance of NPC cells to cisplatin, IR and UV radiation. Moreover, we provide a mechanism by which Jab1 positively regulated Rad51 through p53-dependent pathway, and increased ectopic expression of Rad51 conferred cellular resistance to cisplatin, IR and UV radiation in Jab1-deficient cells. Taken together, our findings suggest that Jab1 has an important role in the cellular response to cisplatin and irradiation by regulating DNA damage and repair pathways. Therefore, Jab1 is a novel biomarker for predicting the outcome of patients with NPC who are treated with DNA-damaging agents.

  18. Role of protein synthesis in the repair of sublethal x-ray damage in a mutant Chinese hamster ovary cell line

    Energy Technology Data Exchange (ETDEWEB)

    Yezzi, M.J.

    1985-04-01

    A temperature-sensitive mutant for protein synthesis, CHO-TSH1, has been compared to the wild-type cell, CHO-sC1, in single- and split-radiation-dose schemes. When the exponentially growing TS mutant and the wild-type cells were treated at 40/sub 0/C for up to 2 hrs prior to graded doses of x rays, the survival curves were identical and were the same as those obtained without heat treatment. If the cultures were incubated at 40/sup 0/C for 2 hrs before a first dose and maintained at 40/sup 0/C during a 2 hr dose fractionation interval, repair of radiation damage was reduced in the mutant compared to the wild type. These observations implied that a pool of proteins was involved in the repair of sublethal x-ray damage. However, if repair was measured by the alkaline-unwinding technique under the same time and temperature schemes, no difference in the kientics of DNA strand rejoining was observed. Misrepair processes may permit restoration of DNA strand integrity but not allow functional repair. The effect of diminished repair under conditions of inhibition of protein synthesis was found to be cell-cycle dependent in survival studies with synchronized mutant cell populations. Repair was found to be almost completely eliminated if the temperature sequence described above was applied in the middle of the DNA synthetic phase. Treatment of cell populations in the middle of G/sub 1/-phase yielded repair inhibition comparable to that observed with the asynchronous cells. Splitdose experiments were done using pre-incubation with cycloheximide to chemically inhibit protein synthesis. WT cells and TS cells were treated with cycloheximide at 35/sup 0/C for 2 hrs before a first dose and during a 2 hr dose fractionation interval. 23 figs., 7 tabs.

  19. Modelling radiation damage to ESA's Gaia satellite CCDs

    CERN Document Server

    Seabroke, G M; Cropper, M S

    2008-01-01

    The Gaia satellite is a high-precision astrometry, photometry and spectroscopic ESA cornerstone mission, currently scheduled for launch in late 2011. Its primary science drivers are the composition, formation and evolution of the Galaxy. Gaia will achieve its scientific requirements with detailed calibration and correction for radiation damage. Microscopic models of Gaia's CCDs are being developed to simulate the charge trapping effect of radiation damage, which causes charge transfer inefficiency. The key to calculating the probability of a photoelectron being captured by a trap is the 3D electron density within each CCD pixel. However, this has not been physically modelled for Gaia CCD pixels. In this paper, the first of a series, we motivate the need for such specialised 3D device modelling and outline how its future results will fit into Gaia's overall radiation calibration strategy.

  20. From repairing the damaged landscape to restoration project

    Directory of Open Access Journals (Sweden)

    Céline Granjou

    2010-10-01

    Full Text Available The study adopts an empirical sociological approach to analyse how the objectives behind the revegetation of ski trails and runs in the French alpine resort of Alpe d’Huez have evolved since the 1970s. A revegetation programme was first introduced to repair the scars left by the works conducted to equip the resort with infrastructures, and then, over time, it became a more complex restoration project. At first, revegetation techniques were developed to fight soil erosion, but soon also became associated with the idea of “turning the mountain green again”. Now, 40 years later, revegetation is aimed at restoring both a natural ecosystem and a cultural landscape. The ski resort’s managers, local farmers, technicians, and those conducting research in the area share a common desire to promote autochthony, which in some cases runs the risk of reproducing folklore. Far from adopting an overriding ethical perspective, the study suggests that the area’s physical characteristics, specific history and configuration of local actors have shaped and continue to shape both the manner in which ecological restoration is implemented, through political choices and technical decisions, and the debates it gives rise to. The study concludes by examining the specificity of the findings for Alpe d’Huez and discussing their validity for other alpine ski resorts.A partir d’une approche sociologique empirique, ce texte propose une analyse de la mise en œuvre de la revégétalisation sur la station de l’Alpe d’Huez depuis les années 1970. Il montre comment la revégétalisation est passée d’un objectif de réparation des cicatrices provoquées par les aménagements à une entreprise plus complexe de restauration. S’il s’agissait au départ de répondre à un objectif technique de lutte contre l’érosion, la revégétalisation a pris rapidement une tournure paysagère (reverdissement ; elle a ensuite été pensée dans une perspective de

  1. Dietary Berries and Ellagic Acid Prevent Oxidative DNA Damage and Modulate Expression of DNA Repair Genes

    Directory of Open Access Journals (Sweden)

    Ramesh C. Gupta

    2008-03-01

    Full Text Available DNA damage is a pre-requisite for the initiation of cancer and agents that reduce this damage are useful in cancer prevention. In this study, we evaluated the ability of whole berries and berry phytochemical, ellagic acid to reduce endogenous oxidative DNA damage. Ellagic acid was selected based on > 95% inhibition of 8-oxodeoxyguosine (8-oxodG and other unidentified oxidative DNA adducts induced by 4-hydroxy-17B;-estradiol and CuCl2 in vitro. Inhibition of the latter occurred at lower concentrations (10 u(microM than that for 8-oxodG (100 u(microM. In the in vivo study, female CD-1 mice (n=6 were fed either a control diet or diet supplemented with ellagic acid (400 ppm and dehydrated berries (5% w/w with varying ellagic acid contents -- blueberry (low, strawberry (medium and red raspberry (high, for 3 weeks. Blueberry and strawberry diets showed moderate reductions in endogenous DNA adducts (25%. However, both red raspberry and ellagic acid diets showed a significant reduction of 59% (p < 0.001 and 48% (p < 0.01, respectively. Both diets also resulted in a 3-8 fold over-expression of genes involved in DNA repair such as xeroderma pigmentosum group A complementing protein (XPA, DNA excision repair protein (ERCC5 and DNA ligase III (DNL3. These results suggest that red raspberry and ellagic acid reduce endogenous oxidative DNA damage by mechanisms which may involve increase in DNA repair.

  2. Repair of Damaged M-Chromium-Aluminum-Yttrium Coatings Targeting Petroleum Industry Applications

    Science.gov (United States)

    Farhat, Rabab

    The increase in efficiency of furnace and refinery components in petroleum industries has been the target of many studies. However, the repair technology for damaged pieces is still to be developed. During prolonged service, a degradation of developed coatings occurs as a result of the harsh environment. Therefore, a repair technology, which can extend the life of the coatings, is now under consideration. In this work, electrospark deposition (ESD) has been investigated to understand the solidification behavior and its possibility to repair damaged MCrAlY coatings. Ni-based alloys with different compositions were deposited on Ni substrate using ESD to understand crystal structure of the solidified deposit and the effect of the dissimilar weld composition on dilution. The electrode samples were prepared by spark plasma sintering (SPS). Firstly, different coatings with single and bi-phase microstructure were deposited on pure Ni substrate. Secondly, NiCoCrAlY and CoNiCrAlY were deposited on the damaged spot of the oxidized NiCoCrAlY and CoNiCrAlY respectively. A fine microstructure of metastable phases obtained from each deposit. Also, it was found that an epitaxial growth of NiCoCrAlY and CoNiCrAlY were obtained on the damaged spots. In addition, α-Al 2O3 was obtained on the surface of the deposit after 24hr oxidation at 1000°C.

  3. Post-irradiation chemical processing of DNA damage generates double-strand breaks in cells already engaged in repair

    Science.gov (United States)

    Singh, Satyendra K.; Wang, Minli; Staudt, Christian; Iliakis, George

    2011-01-01

    In cells exposed to ionizing radiation (IR), double-strand breaks (DSBs) form within clustered-damage sites from lesions disrupting the DNA sugar–phosphate backbone. It is commonly assumed that these DSBs form promptly and are immediately detected and processed by the cellular DNA damage response (DDR) apparatus. This assumption is questioned by the observation that after irradiation of naked DNA, a fraction of DSBs forms minutes to hours after exposure as a result of temperature dependent, chemical processing of labile sugar lesions. Excess DSBs also form when IR-exposed cells are processed at 50°C, but have been hitherto considered method-related artifact. Thus, it remains unknown whether DSBs actually develop in cells after IR exposure from chemically labile damage. Here, we show that irradiation of ‘naked’ or chromatin-organized mammalian DNA produces lesions, which evolve to DSBs and add to those promptly induced, after 8–24 h in vitro incubation at 37°C or 50°C. The conversion is more efficient in chromatin-associated DNA, completed within 1 h in cells and delayed in a reducing environment. We conclude that IR generates sugar lesions within clustered-damage sites contributing to DSB formation only after chemical processing, which occurs efficiently at 37°C. This subset of delayed DSBs may challenge DDR, may affect the perceived repair kinetics and requires further characterization. PMID:21745815

  4. Incident laser modulation of a repaired damage site with a rim in fused silica rear subsurface

    Institute of Scientific and Technical Information of China (English)

    Li Li; Xiang Xia; Zu Xiao-Tao; Yuan Xiao-Dong; He Shao-Bo; Jiang Xiao-Dong; Zheng Wan-Guo

    2012-01-01

    Local CO2 laser treatment has proved to be an effective method to prevent the 351-nm laser-induced damage sitesin a fused silica surface from exponentially growing,which is responsible for limiting the lifetime of optics in high fluence laser systems.However,the CO2 laser induced ablation crater is often surrounded by a raised rim at the edge,which can also result in the intensification of transmitted ultraviolet light that may damage the downstream optics.In this work,the three-dimensional finite-difference time-domain method is developed to simulate the distribution of electrical field intensity in the vicinity of the CO2 laser mitigated damage site located in the exit subsurface of fused silica.The simulated results show that the repaired damage sites with raised rims cause more notable modulation to the incident laser than those without rims.Specifically,we present a theoretical model of using dimpled patterning to control the rim structure around the edge of repaired damage sites to avoid damage to downstream optics.The calculated results accord well with previous experimental results and the underlying physical mechanism is analysed in detail.

  5. UVA radiation is highly mutagenic in cells that are unable to repair 7,8-dihydro-8-oxoguanine in Saccharomyces cerevisiae.

    Science.gov (United States)

    Kozmin, S; Slezak, G; Reynaud-Angelin, A; Elie, C; de Rycke, Y; Boiteux, S; Sage, E

    2005-09-20

    UVA (320-400 nm) radiation constitutes >90% of the environmentally relevant solar UV radiation, and it has been proposed to have a role in skin cancer and aging. Because of the popularity of UVA tanning beds and prolonged periods of sunbathing, the potential deleterious effect of UVA has emerged as a source of concern for public health. Although generally accepted, the impact of DNA damage on the cytotoxic, mutagenic, and carcinogenic effect of UVA radiation remains unclear. In the present study, we investigated the sensitivity of a panel of yeast mutants affected in the processing of DNA damage to the lethal and mutagenic effect of UVA radiation. The data show that none of the major DNA repair pathways, such as base excision repair, nucleotide excision repair, homologous recombination, and postreplication repair, efficiently protect yeast from the lethal action of UVA radiation. In contrast, the results show that the Ogg1 DNA glycosylase efficiently prevents UVA-induced mutagenesis, suggesting the formation of oxidized guanine residues. Furthermore, sequence analysis of UVA-induced canavanine-resistant mutations reveals a bias in favor of GC-->TA events when compared with spontaneous or H(2)O(2)-, UVC-, and gamma-ray- induced canavanine-resistant mutations in the WT strain. Taken together, our data point out a major role of oxidative DNA damage, mostly 7,8-dihydro-8-oxoguanine, in the genotoxicity of UVA radiation in the yeast Saccharomyces cerevisiae. Therefore, the capacity of skin cells to repair 7,8-dihydro-8-oxoguanine may be a key parameter in the mutagenic and carcinogenic effect of UVA radiation in humans.

  6. GUI to Facilitate Research on Biological Damage from Radiation

    Science.gov (United States)

    Cucinotta, Frances A.; Ponomarev, Artem Lvovich

    2010-01-01

    A graphical-user-interface (GUI) computer program has been developed to facilitate research on the damage caused by highly energetic particles and photons impinging on living organisms. The program brings together, into one computational workspace, computer codes that have been developed over the years, plus codes that will be developed during the foreseeable future, to address diverse aspects of radiation damage. These include codes that implement radiation-track models, codes for biophysical models of breakage of deoxyribonucleic acid (DNA) by radiation, pattern-recognition programs for extracting quantitative information from biological assays, and image-processing programs that aid visualization of DNA breaks. The radiation-track models are based on transport models of interactions of radiation with matter and solution of the Boltzmann transport equation by use of both theoretical and numerical models. The biophysical models of breakage of DNA by radiation include biopolymer coarse-grained and atomistic models of DNA, stochastic- process models of deposition of energy, and Markov-based probabilistic models of placement of double-strand breaks in DNA. The program is designed for use in the NT, 95, 98, 2000, ME, and XP variants of the Windows operating system.

  7. Seasonal variation of DNA damage and repair in patients with non-melanoma skin cancer and referents with and without psoriasis

    DEFF Research Database (Denmark)

    Møller, P; Knudsen, Lisbeth E.; Frentz, G;

    1998-01-01

    Quadruples of skin cancer patients with and without psoriasis and referents with and without psoriasis (4 x 20 study persons) were identified and examined for DNA damage by single cell gel electrophoresis (comet-assay) and DNA-repair by UV-induced unscheduled DNA synthesis (UDS) in mononuclear...... to solar radiation. When the comet tail moment data were stratified by sampling period, an interaction between psoriasis and skin cancer was detected, with patients with psoriasis and skin cancer exhibiting more DNA damage. Patients with psoriasis and skin cancer also had lower UDS compared to healthy...

  8. PTH1–34 Blocks Radiation-induced Osteoblast Apoptosis by Enhancing DNA Repair through Canonical Wnt Pathway*

    Science.gov (United States)

    Chandra, Abhishek; Lin, Tiao; Zhu, Ji; Tong, Wei; Huo, Yanying; Jia, Haoruo; Zhang, Yejia; Liu, X. Sherry; Cengel, Keith; Xia, Bing; Qin, Ling

    2015-01-01

    Focal radiotherapy for cancer patients has detrimental effects on bones within the radiation field and the primary clinical signs of bone damage include the loss of functional osteoblasts. We reported previously that daily injection of parathyroid hormone (PTH, 1–34) alleviates radiation-induced osteopenia in a preclinical radiotherapy model by improving osteoblast survival. To elucidate the molecular mechanisms, we irradiated osteoblastic UMR 106-01 cells and calvarial organ culture and demonstrated an anti-apoptosis effect of PTH1–34 on these cultures. Inhibitor assay indicated that PTH exerts its radioprotective action mainly through protein kinase A/β-catenin pathway. γ-H2AX foci staining and comet assay revealed that PTH efficiently promotes the repair of DNA double strand breaks (DSBs) in irradiated osteoblasts via activating the β-catenin pathway. Interestingly, Wnt3a alone also blocked cell death and accelerated DNA repair in primary osteoprogenitors, osteoblastic and osteocytic cells after radiation through the canonical signaling. Further investigations revealed that both Wnt3a and PTH increase the amount of Ku70, a core protein for initiating the assembly of DSB repair machinery, in osteoblasts after radiation. Moreover, down-regulation of Ku70 by siRNA abrogated the prosurvival effect of PTH and Wnt3a on irradiated osteoblasts. In summary, our results identify a novel role of PTH and canonical Wnt signaling in regulating DSB repair machinery and apoptosis in osteoblasts and shed light on using PTH1–34 or Wnt agonist as possible therapy for radiation-induced osteoporosis. PMID:25336648

  9. Rad54 and Mus81 cooperation promotes DNA damage repair and restrains chromosome missegregation

    DEFF Research Database (Denmark)

    Ghamrasni, S El; Cardoso, R; Li, L;

    2016-01-01

    Rad54 and Mus81 mammalian proteins physically interact and are important for the homologous recombination DNA repair pathway; however, their functional interactions in vivo are poorly defined. Here, we show that combinatorial loss of Rad54 and Mus81 results in hypersensitivity to DNA......-damaging agents, defects on both the homologous recombination and non-homologous DNA end joining repair pathways and reduced fertility. We also observed that while Mus81 deficiency diminished the cleavage of common fragile sites, very strikingly, Rad54 loss impaired this cleavage to even a greater extent....... The inefficient repair of DNA double-strand breaks (DSBs) in Rad54(-/-)Mus81(-/-) cells was accompanied by elevated levels of chromosome missegregation and cell death. Perhaps as a consequence, tumor incidence in Rad54(-/-)Mus81(-/-) mice remained comparable to that in Mus81(-/-) mice. Our study highlights...

  10. Pim-3 contributes to radioresistance through regulation of the cell cycle and DNA damage repair in pancreatic cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Xiang-Yuan; Wang, Zhen [Cancer Research Institute, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai (China); Li, Bei [Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai (China); Zhang, Ying-Jian, E-mail: yjzhang111@aliyun.com [Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai (China); Li, Ying-Yi, E-mail: liyingyi@fudan.edu.cn [Cancer Research Institute, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai (China)

    2016-04-22

    Resistance of cancer cells to chemoradiotherapy is a major clinical problem in pancreatic cancer treatment. Therefore, understanding the molecular basis of cellular resistance and identifying novel targets are essential for improving treatment efficacy for pancreatic cancer patients. Previous studies have demonstrated a significant role for Pim-3 in pancreatic cancer survival against gemcitabine-induced genotoxic stress. Here, we observed that radiation treatment enhanced Pim-3 expression in human pancreatic cancer cells in vitro. Stable overexpression of Pim-3 in pancreatic cancer cells significantly protected cells against radiation treatment by attenuating G2/M phase cell cycle arrest and DNA damage response. Silencing of Pim-3 expression significantly elevated the phosphorylation of histone variant H2AX, a marker of DNA double strand breaks, and decreased the activation of ataxia-telangiectasia-mutated (ATM) kinase, along with its downstream targets, eventually enhancing the radiosensitivity of human pancreatic cancer cells in vitro and in vivo. Hence, we demonstrated a novel function for Pim-3 in human pancreatic cancer cell survival against radiation. Targeting Pim-3 may be a promising way to improve treatment efficacy in combination with radiotherapy in human pancreatic cancer. - Highlights: • This is first study to demonstrate that Pim-3 is endogenously induced by ionizing radiation in pancreatic cancer cells, and Pim-3 overexpression enhanced radioresistance of pancreatic cancer cells both in vitro and in vivo. • This is first study to provide evidence that radioresistance induced by Pim-3 is mainly attributed to Pim-3 induces activation of ATM, which subsequently activates checkpoint 1, leading to amplification of DNA repair through cell cycle arrest and DNA repair pathways. • This is first study to indicate that targeting Pim-3 may be a promising strategy to provide better treatment efficacy in combination with radiotherapy in human pancreatic

  11. 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

  12. 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.)

  13. Repair work continues on the external tank of Space Shuttle Discovery after damage from hail

    Science.gov (United States)

    1999-01-01

    In the Vehicle Assembly Building (VAB), United Space Alliance technician Robert Williams sands the repaired areas near the top of Space Shuttle Discovery's external tank. Repairs were required for damage caused by hail during recent storms. Because access to all of the damaged areas was not possible at the pad, the Shuttle was rolled back from Pad 39B to the VAB. The work is expected to take two to three days, allowing Discovery to roll back to the pad late this week for launch of mission STS-96, the 94th launch in the Space Shuttle Program. Liftoff will occur no earlier than May 27. STS-96 is a logistics and resupply mission for the International Space Station, carrying such payloads as a Russian crane, the Strela; a U.S.-built crane; the Spacehab Oceaneering Space System Box (SHOSS), a logistics items carrier; and STARSHINE, a student-shared experiment.

  14. Arsenic Biotransformation as a Cancer Promoting Factor by Inducing DNA Damage and Disruption of Repair Mechanisms

    Directory of Open Access Journals (Sweden)

    Victor D. Martinez

    2011-01-01

    Full Text Available Chronic exposure to arsenic in drinking water poses a major global health concern. Populations exposed to high concentrations of arsenic-contaminated drinking water suffer serious health consequences, including alarming cancer incidence and death rates. Arsenic is biotransformed through sequential addition of methyl groups, acquired from s-adenosylmethionine (SAM. Metabolism of arsenic generates a variety of genotoxic and cytotoxic species, damaging DNA directly and indirectly, through the generation of reactive oxidative species and induction of DNA adducts, strand breaks and cross links, and inhibition of the DNA repair process itself. Since SAM is the methyl group donor used by DNA methyltransferases to maintain normal epigenetic patterns in all human cells, arsenic is also postulated to affect maintenance of normal DNA methylation patterns, chromatin structure, and genomic stability. The biological processes underlying the cancer promoting factors of arsenic metabolism, related to DNA damage and repair, will be discussed here.

  15. Increasing Melanoma—Too Many Skin Cell Damages or Too Few Repairs?

    Directory of Open Access Journals (Sweden)

    Örjan Hallberg

    2013-02-01

    Full Text Available Skin melanoma rates have been increasing for a long time in many Western countries. The object of this study was to apply modern problem-solving theory normally used to clear industrial problems to search for roots and causes of this medical question. Increasing cancer rates can be due to too many cell damage incidents or to too few repairs. So far, it has been assumed that the melanoma epidemic mainly is caused by increasing sun tanning habits. In order to explore this problem in more detail, we used cancer statistics from several countries over time and space. Detailed analysis of data obtained and a model study to evaluate the effects from increased damages or decreased repairs clearly indicate that the main reason behind the melanoma problem is a disturbed immune system. The possibility to introduce efficient corrective actions is apparent.

  16. Oxidatively damaged DNA and its repair after experimental exposure to wood smoke in healthy humans

    DEFF Research Database (Denmark)

    Danielsen, Pernille Høgh; Bräuner, Elvira Vaclavik; Barregard, Lars

    2008-01-01

    Particulate matter from wood smoke may cause health effects through generation of oxidative stress with resulting damage to DNA. We investigated oxidatively damaged DNA and related repair capacity in peripheral blood mononuclear cells (PBMC) and measured the urinary excretion of repair products...... after controlled short-term exposure of human volunteers to wood smoke. Thirteen healthy adults were exposed first to clean air and then to wood smoke in a chamber during 4h sessions, 1 week apart. Blood samples were taken 3h after exposure and on the following morning, and urine was collected after...... chromatography with mass spectrometry. The morning following exposure to wood smoke the PBMC levels of SB were significantly decreased and the mRNA levels of hOGG1 significantly increased. FPG sites, hOGG1 activity, expression of hNUDT1 and hHO1, urinary excretion of 8-oxodG and 8-oxoGua did not change...

  17. Granular Effect of Fly Ash Repairs Damage of Recycled Coarse Aggregate

    Institute of Scientific and Technical Information of China (English)

    LI Jiu-su; XIAO Han-ning; GONG Jian-qing

    2008-01-01

    Repairing effect of fly ash (FA) on damage of recycled coarse aggregate was evaluated by characteristics of pores and cracks in the vicinity of interracial transition zone (ITZ). The interracial structure between the virgin aggregate and the attached old mortar was investigated and compared with ITZ of recycled aggregate concrete in the presence of FA or ultra-fine FA(UFA) by means of scanning electron microscope (SEM). Diam- eter and plumpness frequency distribution of pores as well as width of the old ITZ, length of contacting points and cracks density were analyzed. The SEM results reveal that the diameter of pores is decreases significantly but pores plumpness increases. A decreased ITZ width and cracks density as well as an increased bonding zone length can also been observed, which indicates that FA or UFA repairs damage of recycled coarse aggregate due to its granular effect.

  18. Rotator Interval Lesion and Damaged Subscapularis Tendon Repair in a High School Baseball Player

    Directory of Open Access Journals (Sweden)

    Tomoyuki Muto

    2015-01-01

    Full Text Available In 2013, a 16-year-old baseball pitcher visited Nobuhara Hospital complaining of shoulder pain and limited range of motion in his throwing shoulder. High signal intensity in the rotator interval (RI area (ball sign, injured subscapularis tendon, and damage to both the superior and middle glenohumeral ligaments were identified using magnetic resonance imaging (MRI. Repair of the RI lesion and partially damaged subscapularis tendon was performed in this pitcher. During surgery, an opened RI and dropping of the subscapularis tendon were observed. The RI was closed in a 90° externally rotated and abducted position. To reconfirm the exact repaired state of the patient, arthroscopic examination was performed from behind. However, suture points were not visible in the >30° externally rotated position, which indicates that the RI could not be correctly repaired with the arthroscopic procedure. One year after surgery, the patient obtained full function of the shoulder and returned to play at a national convention. Surgical repair of the RI lesion should be performed in exactly the correct position of the upper extremity.

  19. Repair of damage to wind turbine foundations. Nondestructive ultrasonic testing; Sanierung von Fundamentschaeden. Zerstoerungsfreie Pruefung mittels Ultraschall

    Energy Technology Data Exchange (ETDEWEB)

    Zimmer, Hans-Peter [CONCRETE CARE, Berlin (Germany)

    2009-07-01

    Damage of foundations is often not visible from the surface. And even visible cracks do not show how far they reach inside the foundation. Prior to any repair measures, detailed analysis and a careful and precise description of the damage pattern are required. The biggest challenge is the detection of hidden damage and its correct description. Nondestructive methods are the method of choice. (orig.)

  20. 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.

  1. DNA Damage Response and DNA Repair in Skeletal Myocytes From a Mouse Model of Spinal Muscular Atrophy.

    Science.gov (United States)

    Fayzullina, Saniya; Martin, Lee J

    2016-09-01

    We studied DNA damage response (DDR) and DNA repair capacities of skeletal muscle cells from a mouse model of infantile spinal muscular atrophy (SMA) caused by loss-of-function mutation of survival of motor neuron (Smn). Primary myocyte cultures derived from skeletal muscle satellite cells of neonatal control and mutant SMN mice had similar myotube length, myonuclei, satellite cell marker Pax7 and differentiated myotube marker myosin, and acetylcholine receptor clustering. DNA damage was induced in differentiated skeletal myotubes by γ-irradiation, etoposide, and methyl methanesulfonate (MMS). Unexposed control and SMA myotubes had stable genome integrity. After γ-irradiation and etoposide, myotubes repaired most DNA damage equally. Control and mutant myotubes exposed to MMS exhibited equivalent DNA damage without repair. Control and SMA myotube nuclei contained DDR proteins phospho-p53 and phospho-H2AX foci that, with DNA damage, dispersed and then re-formed similarly after recovery. We conclude that mouse primary satellite cell-derived myotubes effectively respond to and repair DNA strand-breaks, while DNA alkylation repair is underrepresented. Morphological differentiation, genome stability, genome sensor, and DNA strand-break repair potential are preserved in mouse SMA myocytes; thus, reduced SMN does not interfere with myocyte differentiation, genome integrity, and DNA repair, and faulty DNA repair is unlikely pathogenic in SMA.

  2. Low velocity impact response and damage evolution in unreinforced resin systems and self-repairing polymer matrix composites

    Science.gov (United States)

    Motuku, Molefi

    The low velocity impact response and damage evolution in unreinforced polymer matrices, conventional polymer matrix composites, and self-repairing polymer matrix composites was investigated. The impact response study of unreinforced matrices and conventional laminates was undertaken because the failure initiation energies, threshold energy levels, failure characteristics and damage evolution in both the matrix material (unreinforced resin plaques) and the composite are intrinsic to proper design of a self-repairing composite. The self-repairing concept was investigated due to its attractive potential to alleviate damage problems in polymer matrix composites. Self-repairing composites, which fall under the category of passive smart polymer composites, have the potential to self repair both micro- and macro-damage resulting from impacts as well as non-impact loading. The self-repairing mechanism is achieved through the incorporation of hollow fibers in addition to the normal solid reinforcing fibers. The hollow fibers store the damage-repairing solution or chemicals that are released into the matrix or damaged zone upon fiber failure to repair and/or arrest damage progression. The room temperature low velocity impact response and damage evolution in DERAKANE 411-350 and 411-C50 vinyl ester unreinforced resin systems was investigated as a function of impact energy level, sample thickness, matrix material and catalyst system. The low velocity impact response of conventional and self-repairing glass reinforced polymer composites was investigated by addressing the fabrication and some of the parameters that influence their response to low velocity impact loading. Specific issues addressed by this study include developing a process to fabricate self-repairing laminates, processing quality; selection of storage material for the repairing solution; release and transportation of repairing solution; the effect of the number, type and spatial distribution of the repairing

  3. Maintaining Genetic Integrity Under Extreme Conditions: Novel DNA Damage Repair Biology in the Archaea

    Science.gov (United States)

    2013-11-23

    DeRuggiero (Johns Hopkins University). Chromosome behaviour was monitored in wild-type and ∆nreA cells treated with MMC for 1 hour and during a 10...MacNeill, undergraduate students Agnieszka Janska and Jason Woodier) In bacteria , RecJ has an important role in DNA damage repair, in particular in...is an NAD-dependent enzyme the gene for which was apparently acquired by lateral gene transfer from bacteria . Biochemical analysis of LigN function

  4. Human POLD1 modulates cell cycle progression and DNA damage repair

    OpenAIRE

    Song, Jing; Hong, Ping; Liu, Chengeng; Zhang, Yueqi; Wang, Jinling; Wang, Peichang

    2015-01-01

    Background The activity of eukaryotic DNA polymerase delta (Pol ?) plays an essential role in genome stability through its effects on DNA replication and repair. The p125 catalytic subunit of Pol ? is encoded by POLD1 gene in human cells. To clarify biological functions of POLD1, we investigated the effects of POLD1 overexpression or downregulation on cell proliferation, cell cycle progression, DNA synthesis and oxidative DNA damage induced by H2O2. Methods HEK293 cells were transfected with ...

  5. Involvement of Caveolin-1 in repair of DNA damage through both homologous recombination and non-homologous end joining.

    Directory of Open Access Journals (Sweden)

    Hua Zhu

    Full Text Available BACKGROUND: Caveolin-1 (Cav-1, the major component of caveolae, is a 21-24 kDa integral membrane protein that interacts with a number of signaling molecules. By acting as a scaffolding protein, Cav-1 plays crucial roles in the regulation of various physiologic and patho-physiologic processes including oncogenic transformation and tumorigenesis, and tumor invasion and metastasis. METHODOLOGY/PRINCIPAL FINDINGS: In the present study we sought to explore the role of Cav-1 in response to DNA damage and the mechanism involved. We found that the level of Cav-1 was up-regulated rapidly in cells treated with ionizing radiation. The up-regulation of Cav-1 following DNA damage occurred only in cells expressing endogenous Cav-1, and was associated with the activation of DNA damage response pathways. Furthermore, we demonstrated that the expression of Cav-1 protected cells against DNA damage through modulating the activities of both the homologous recombination (HR and non-homologous end joining (NHEJ repair systems, as evidenced by the inhibitory effects of the Cav-1-targeted siRNA on cell survival, HR frequency, phosphorylation of DNA-dependent protein kinase (DNA-PK, and nuclear translocation of epidermal growth factor receptor (EGFR following DNA damage, and by the stimulatory effect of the forced expression of Cav-1 on NHEJ frequency. CONCLUSION/SIGNIFICANCE: Our results indicate that Cav-1 may play a critical role in sensing genotoxic stress and in orchestrating the response of cells to DNA damage through regulating the important molecules involved in maintaining genomic integrity.

  6. Influence of LET on repair of DNA damages in Deinococcus radiodurans

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Y.; Tanaka, A.; Kikuchi, M.; Shimizu, T.; Watanabe, H. [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment; Cao, J.P.; Taucher-Scholz, G.

    1997-03-01

    Inactivation caused by heavy ions was studied in dry cells of radioresistant bacterium Deinococcus radiodurans. All survival curves were characterized by a large shoulder of the curves. No final slopes of the exponential part of survival curves for heavy ion irradiation were steeper than that for 2.0 MeV electron irradiation. The plots of RBE versus LET showed no obvious peaks, suggesting that this bacterium can repair not only DNA double strand breaks (DSBs) but also clustered damage in DNA which may be induced by heavy ions. The genomic DNA of D. radiodurans was cleaved into large fragments with restriction enzyme Not I after post-irradiation incubation and the fragments were separated using pulsed-field gel electrophoresis (PFGE). DSBs induction and rejoining process were analyzed by detection of the reappearance of ladder pattern of DNA fragments. The required repair time after heavy ions irradiation was longer than the repair time for electrons at the same dose of irradiation, however, the rate of repair enzyme induction was almost similar to each other between electrons and heavy ions, suggesting that the same repair system is likely to be used after both low and high LET irradiations. (author)

  7. Proton induced radiation damage in fast crystal scintillators

    Science.gov (United States)

    Yang, Fan; Zhang, Liyuan; Zhu, Ren-Yuan; Kapustinsky, Jon; Nelson, Ron; Wang, Zhehui

    2016-07-01

    This paper reports proton induced radiation damage in fast crystal scintillators. A 20 cm long LYSO crystal, a 15 cm long CeF3 crystal and four liquid scintillator based sealed quartz capillaries were irradiated by 800 MeV protons at Los Alamos up to 3.3 ×1014 p /cm2. Four 1.5 mm thick LYSO plates were irradiated by 24 GeV protons at CERN up to 6.9 ×1015 p /cm2. The results show an excellent radiation hardness of LYSO crystals against charged hadrons.

  8. Non-Thermal Electromagnetic Radiation Damage to Lens Epithelium

    OpenAIRE

    Bormusov, Elvira; P.Andley, Usha; Sharon, Naomi; Schächter, 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...

  9. Radiation Damage Study on the Electrical Properties of Si Diodes

    Science.gov (United States)

    Pascoalino, Kelly C. S.; Gonçalves, Josemary A. C.; Tobias, Carmen C. B.

    2011-08-01

    The aim of this work was to study the radiation damage effects on the electrical properties of Float Zone (FZ) and Magnetic Czochralski (MCz) diodes. The effects were evaluated by measuring the reverse current and capacitance of these devices as a function of the reverse voltage. The irradiation was performed in the Radiation Technology Center (CTR) at IPEN-CNEN/SP using a 60Co irradiator (Gammacell 220-Nordion) with a dose rate of about 2 kGy/h. Samples were irradiated at room temperature in five steps up to an accumulated dose of 603 kGy.

  10. Comparative DNA damage and repair in echinoderm coelomocytes exposed to genotoxicants.

    Science.gov (United States)

    El-Bibany, Ameena H; Bodnar, Andrea G; Reinardy, Helena C

    2014-01-01

    The capacity to withstand and repair DNA damage differs among species and plays a role in determining an organism's resistance to genotoxicity, life history, and susceptibility to disease. Environmental stressors that affect organisms at the genetic level are of particular concern in ecotoxicology due to the potential for chronic effects and trans-generational impacts on populations. Echinoderms are valuable organisms to study the relationship between DNA repair and resistance to genotoxic stress due to their history and use as ecotoxicological models, little evidence of senescence, and few reported cases of neoplasia. Coelomocytes (immune cells) have been proposed to serve as sensitive bioindicators of environmental stress and are often used to assess genotoxicity; however, little is known about how coelomocytes from different echinoderm species respond to genotoxic stress. In this study, DNA damage was assessed (by Fast Micromethod) in coelomocytes of four echinoderm species (sea urchins Lytechinus variegatus, Echinometra lucunter lucunter, and Tripneustes ventricosus, and a sea cucumber Isostichopus badionotus) after acute exposure to H2O2 (0-100 mM) and UV-C (0-9999 J/m2), and DNA repair was analyzed over a 24-hour period of recovery. Results show that coelomocytes from all four echinoderm species have the capacity to repair both UV-C and H2O2-induced DNA damage; however, there were differences in repair capacity between species. At 24 hours following exposure to the highest concentration of H2O2 (100 mM) and highest dose of UV-C (9999 J/m2) cell viability remained high (>94.6 ± 1.2%) but DNA repair ranged from 18.2 ± 9.2% to 70.8 ± 16.0% for H2O2 and 8.4 ± 3.2% to 79.8 ± 9.0% for UV-C exposure. Species-specific differences in genotoxic susceptibility and capacity for DNA repair are important to consider when evaluating ecogenotoxicological model organisms and assessing overall impacts of genotoxicants in the environment.

  11. Comparative DNA damage and repair in echinoderm coelomocytes exposed to genotoxicants.

    Directory of Open Access Journals (Sweden)

    Ameena H El-Bibany

    Full Text Available The capacity to withstand and repair DNA damage differs among species and plays a role in determining an organism's resistance to genotoxicity, life history, and susceptibility to disease. Environmental stressors that affect organisms at the genetic level are of particular concern in ecotoxicology due to the potential for chronic effects and trans-generational impacts on populations. Echinoderms are valuable organisms to study the relationship between DNA repair and resistance to genotoxic stress due to their history and use as ecotoxicological models, little evidence of senescence, and few reported cases of neoplasia. Coelomocytes (immune cells have been proposed to serve as sensitive bioindicators of environmental stress and are often used to assess genotoxicity; however, little is known about how coelomocytes from different echinoderm species respond to genotoxic stress. In this study, DNA damage was assessed (by Fast Micromethod in coelomocytes of four echinoderm species (sea urchins Lytechinus variegatus, Echinometra lucunter lucunter, and Tripneustes ventricosus, and a sea cucumber Isostichopus badionotus after acute exposure to H2O2 (0-100 mM and UV-C (0-9999 J/m2, and DNA repair was analyzed over a 24-hour period of recovery. Results show that coelomocytes from all four echinoderm species have the capacity to repair both UV-C and H2O2-induced DNA damage; however, there were differences in repair capacity between species. At 24 hours following exposure to the highest concentration of H2O2 (100 mM and highest dose of UV-C (9999 J/m2 cell viability remained high (>94.6 ± 1.2% but DNA repair ranged from 18.2 ± 9.2% to 70.8 ± 16.0% for H2O2 and 8.4 ± 3.2% to 79.8 ± 9.0% for UV-C exposure. Species-specific differences in genotoxic susceptibility and capacity for DNA repair are important to consider when evaluating ecogenotoxicological model organisms and assessing overall impacts of genotoxicants in the environment.

  12. 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

  13. Ion irradiation and biomolecular radiation damage II. Indirect effect

    CERN Document Server

    Wang, Wei; Su, Wenhui

    2010-01-01

    It has been reported that damage of genome in a living cell by ionizing radiation is about one-third direct and two-thirds indirect. The former which has been introduced in our last paper, concerns direct energy deposition and ionizing reactions in the biomolecules; the latter results from radiation induced reactive species (mainly radicals) in the medium (mainly water) surrounding the biomolecules. In this review, a short description of ion implantation induced radical formation in water is presented. Then we summarize the aqueous radical reaction chemistry of DNA, protein and their components, followed by a brief introduction of biomolecular damage induced by secondary particles (ions and electron). Some downstream biological effects are also discussed.

  14. Thermal spray and weld repair alloys for the repair of cavitation damage in turbines and pumps: A technical note

    Science.gov (United States)

    Kumar, Ashok; Boy, J.; Zatorski, Ray; Stephenson, L. D.

    2005-06-01

    The cavitation and erosion resistance of 21 thermal spray coatings and four weld repair materials were investigated in the laboratory using cavitation jet and slurry erosion testing. Of the thermal spray coatings, Stellite® 6 deposited by the high velocity oxyfuel (HVOF) process had the lowest cavitation rate (11.7 mg/h). This was higher than the corresponding cavitation rate (3.2 mg/h) of 308 stainless steel weld metal currently used as a reference. In the slurry erosion testing, the volume loss of Stellite® 6 applied by the HVOF process was 5.33 cubic mm/h, much lower than the corresponding loss (11.17 cubic mm/h) in the currently used stainless steel 304 reference. Furthermore, the electrochemical potential difference between the carbon steel and HVOF sprayed Stellite 6 coating was 0.25 volts, half the potential difference between the 304 stainless steel carbon steel substrate, and will result in reduced galvanic corrosion of the substrate near the contact areas. Stellite 6 deposited by the HVOF process was recommended for repair of damage resulting from erosion and subsequent cavitation by caused by surface roughening.

  15. 11th International Conference of Radiation Research

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-07-18

    Topics discussed in the conference included the following: Radiation Physics, Radiation Chemistry and modelling--Radiation physics and dosimetry; Electron transfer in biological media; Radiation chemistry; Biophysical and biochemical modelling; Mechanisms of DNA damage; Assays of DNA damage; Energy deposition in micro volumes; Photo-effects; Special techniques and technologies; Oxidative damage. Molecular and cellular effects-- Photobiology; Cell cycle effects; DNA damage: Strand breaks; DNA damage: Bases; DNA damage Non-targeted; DNA damage: other; Chromosome aberrations: clonal; Chromosomal aberrations: non-clonal; Interactions: Heat/Radiation/Drugs; Biochemical effects; Protein expression; Gene induction; Co-operative effects; ``Bystander'' effects; Oxidative stress effects; Recovery from radiation damage. DNA damage and repair -- DNA repair genes; DNA repair deficient diseases; DNA repair enzymology; Epigenetic effects on repair; and Ataxia and ATM.

  16. 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.

  17. The effect of aging on the DNA damage and repair capacity in 2BS cells undergoing oxidative stress.

    Science.gov (United States)

    Wang, Jin-Ling; Wang, Pei-Chang

    2012-01-01

    Aging is associated with a reduction in the DNA repair capacity under oxidative stress. However, whether the DNA damage and repair capacity can be a biomarker of aging remains controversial. In this study, we demonstrated two cause-and-effect relationships, the one is between the DNA damage and repair capacity and the cellular age, another is between DNA damage and repair capacity and the level of oxidative stress in human embryonic lung fibroblasts (2BS) exposed to different doses of hydrogen peroxide (H2O2). To clarify the mechanisms of the age-related reduction in DNA damage and repair capacity, we preliminarily evaluated the expressions of six kinds of pivotal enzymes involved in the two classical DNA repair pathways. The DNA repair capacity was observed in human fibroblasts cells using the comet assay; the age-related DNA repair enzymes were selected by RT-PCR and then verified by Western blot in vitro. Results showed that the DNA repair capacity was negatively and linearly correlated with (i) cumulative population doubling (PD) levels only in the group of low concentration of hydrogen peroxide treatment, (ii) with the level of oxidative stress only in the group of young PD cells. The mRNA expression of DNA polymerase δ1 decreased substantially in senescent cells and showed negative linear-correlation with PD levels; the protein expression level was well consistent with the mRNA level. Taken together, DNA damage and repair capacity can be a biomarker of aging. Reduced expression of DNA polymerase δ1 may be responsible for the decrease of DNA repair capacity in senescent cells.

  18. The LHCb Vertex Locator – Performance and Radiation Damage

    CERN Document Server

    Oblakowska-Mucha, A

    2014-01-01

    LHCb is a dedicated flavour physics experiment at the Large Hadron Collider at CERN. The Vertex Locator (VELO) is an important part of a LHCb tracking system, enabling precision measurement of beauty and charm mesons’ flight distance. The VELO consist of a set of silicon micro-strip detectors, arranged in two retractable halves, operating only 7 mm from the interac- tion region. In these proceedings the VELO performance during the Run 1 is summarised and radiation damage studies are presented.

  19. Site-selective radiation damage of collapsed carbon nanotubes

    Energy Technology Data Exchange (ETDEWEB)

    Crespi, V.H. [Department of Physics, 104 Davey Lab, The Pennsylvania State University, University Park, Pennsylvania 16802-6300 (United States); Chopra, N.G.; Cohen, M.L.; Zettl, A. [Department of Physics, University of California at Berkeley and Materials Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720 (United States); Radmilovic, V. [Department of Physical Metallurgy, University of Belgrade Karnegijeva 4, P.O. Box 494, Belgrade, 11001 (Yugoslavia)

    1998-10-01

    Carbon nanotubes can flatten into collapsed tubes with bulbs along either edge. The strong anisotropy in the graphitic radiation damage threshold both explains the rapid destruction of face-on flattened nanotubes and can be exploited to selectively modify the structure of edge-on flattened nanotubes, thereby creating one-dimensional sp{sup 2} carbon with noncontinuous transverse boundary conditions. {copyright} {ital 1998 American Institute of Physics.}

  20. DNA-damage foci to detect and characterize DNA repair alterations in children treated for pediatric malignancies.

    Directory of Open Access Journals (Sweden)

    Nadine Schuler

    Full Text Available PURPOSE: In children diagnosed with cancer, we evaluated the DNA damage foci approach to identify patients with double-strand break (DSB repair deficiencies, who may overreact to DNA-damaging radio- and chemotherapy. In one patient with Fanconi anemia (FA suffering relapsing squamous cell carcinomas of the oral cavity we also characterized the repair defect in biopsies of skin, mucosa and tumor. METHODS AND MATERIALS: In children with histologically confirmed tumors or leukemias and healthy control-children DSB repair was investigated by counting γH2AX-, 53BP1- and pATM-foci in blood lymphocytes at defined time points after ex-vivo irradiation. This DSB repair capacity was correlated with treatment-related normal-tissue responses. For the FA patient the defective repair was also characterized in tissue biopsies by analyzing DNA damage response proteins by light and electron microscopy. RESULTS: Between tumor-children and healthy control-children we observed significant differences in mean DSB repair capacity, suggesting that childhood cancer is based on genetic alterations affecting DNA repair. Only 1 out of 4 patients with grade-4 normal-tissue toxicities revealed an impaired DSB repair capacity. The defective DNA repair in FA patient was verified in irradiated blood lymphocytes as well as in non-irradiated mucosa and skin biopsies leading to an excessive accumulation of heterochromatin-associated DSBs in rapidly cycling cells. CONCLUSIONS: Analyzing human tissues we show that DSB repair alterations predispose to cancer formation at younger ages and affect the susceptibility to normal-tissue toxicities. DNA damage foci analysis of blood and tissue samples allows one to detect and characterize DSB repair deficiencies and enables identification of patients at risk for high-grade toxicities. However, not all treatment-associated normal-tissue toxicities can be explained by DSB repair deficiencies.

  1. 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

  2. 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.

  3. High background radiation areas of Ram sar in Iran: evaluation of DNA damage by alkaline single cell gel electrophoresis (SCE)

    Energy Technology Data Exchange (ETDEWEB)

    Masoomi, J.R. [Biophysics Department, College of Sciences, Tarbiat Modarres University, Tehran (Iran, Islamic Republic of); Mohammadi, Sh. [Radiation Molecular Genetic Laboratory, National Radiation Protection Department (NRPD), Iranian Nuclear Regulatory Authority (INRA), P.O. Box 14155-4494, Tehran (Iran, Islamic Republic of); Amini, M. [Faculty of Pharmacy, Azad University of Tehran (Iran, Islamic Republic of); Ghiassi-Nejad, M. [Biophysics Department, College of Sciences, Tarbiat Modarres University, Tehran (Iran, Islamic Republic of)]. E-mail: ghiassi@mailcity.com

    2006-07-01

    The hot springs in special areas in Ram sar, a northern coastal town in Iran, contain {sup 226}Ra and {sup 222}Rn. The natural radiation effects, radiosensitivity or adaptive responses, on the inhabitants of high natural radiation in Ram sar 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 {sup 6}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.

  4. Radiation damage measurements on CZT drift strip detectors

    Energy Technology Data Exchange (ETDEWEB)

    Kuvvetli, I. E-mail: irfan@dsri.dk; Budtz-Joergensen, C. E-mail: carl@dsri.dk; Korsbech, U.; Jensen, H.J

    2003-10-11

    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 range from 2x10{sup 8} to 60x10{sup 8} p{sup +}/cm{sup 2}. Even for the highest fluences, which had a dramatic effect on the spectroscopic performance, we were able to recover the detectors after an appropriate annealing procedure. The radiation damage was studied as a function of depth inside the detector material. A numerical model that emulates the physical processes of the charge transport in the CZT detector was used to derive the charge trapping parameter, {mu}{tau}{sub e} (the product of charge mobility and trapping time) as a function of fluence. The analysis showed that the electron trapping increased proportionately with the proton dose. The radiation contribution to the electron trapping was found to obey the following relation: ({mu}{tau}{sub e}{sup -1}){sub rad}=(2.5{+-}0.2)x10{sup -7}xPHI (V/cm){sup 2} with the proton fluence, PHI in p{sup +}/cm{sup 2}. The trapping depth dependence, however, did not agree well with the damage profile calculated using the standard Monte Carlo simulations, TRIM , for the proton-induced radiation effects. The present results suggest that proton-induced nuclear reactions contribute significantly to the radiation damage. Further work will elaborate on these effects.

  5. Radiation damage measurements on CZT drift strip detectors

    Science.gov (United States)

    Kuvvetli, I.; Budtz-Jørgensen, C.; Korsbech, U.; Jensen, H. J.

    2003-10-01

    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 range from 2×10 8 to 60×10 8 p +/cm 2. Even for the highest fluences, which had a dramatic effect on the spectroscopic performance, we were able to recover the detectors after an appropriate annealing procedure. The radiation damage was studied as a function of depth inside the detector material. A numerical model that emulates the physical processes of the charge transport in the CZT detector was used to derive the charge trapping parameter, μτe (the product of charge mobility and trapping time) as a function of fluence. The analysis showed that the electron trapping increased proportionately with the proton dose. The radiation contribution to the electron trapping was found to obey the following relation: (μτ e- 1) rad=(2.5±0.2)×10 -7×Φ ( V/cm)2 with the proton fluence, Φ in p +/cm 2. The trapping depth dependence, however, did not agree well with the damage profile calculated using the standard Monte Carlo simulations, TRIM [1], for the proton-induced radiation effects. The present results suggest that proton-induced nuclear reactions contribute significantly to the radiation damage. Further work will elaborate on these effects.

  6. Tailoring radiation damage in ZnO by surface modification

    Science.gov (United States)

    Myers, M. T.; Charnvanichborikarn, S.; Myers, M. A.; Lee, J. H.; Wang, H.; Biener, M. M.; Shao, L.; Kucheyev, S. O.

    2013-07-01

    Heavy-ion irradiation of (0 0 0 1) ZnO crystals results in unusual damage buildup, including an additional (intermediate) peak in damage-depth profiles measured by ion channeling, the formation of near-surface nanocavities, and stoichiometric imbalance. All these effects are thought to be associated with the influence of the sample surface on dynamic annealing processes. Here, by using ion channeling and transmission electron microscopy, we find that placing an ~7 nm thick AlO(OH) layer on the (0 0 0 1) ZnO surface results in (i) suppression of cavity formation, (ii) a reduced intermediate defect peak intensity, and (iii) a decreased level of disorder extending up to ~100 nm from the ZnO surface for room-temperature bombardment with 500 keV Xe ions. Our results demonstrate the potential to control radiation damage in ZnO by surface manipulation.

  7. Heat Induced Damage Detection by Terahertz (THz) Radiation

    Science.gov (United States)

    Rahani, Ehsan Kabiri; Kundu, Tribikram; Wu, Ziran; Xin, Hao

    2011-06-01

    Terahertz (THz) and sub-terahertz imaging and spectroscopy are becoming increasingly popular nondestructive evaluation techniques for damage detection and characterization of materials. THz radiation is being used for inspecting ceramic foam tiles used in TPS (Thermal Protection System), thick polymer composites and polymer tiles that are not good conductors of ultrasonic waves. Capability of THz electromagnetic waves in detecting heat induced damage in porous materials is investigated in this paper. Porous pumice stone blocks are subjected to long time heat exposures to produce heat induced damage in the block. The dielectric properties extracted from THz TDS (Time Domain Spectroscopy) measurements are compared for different levels of heat exposure. Experimental results show noticeable and consistent change in dielectric properties with increasing levels of heat exposure, well before its melting point.

  8. HSP25 Protects Radiation-Induced Salivary Gland Damage

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hae June; Lee, Yoon Jin; Kwon, Hee Choong; Lee, Su Jae; Bae, Sang Woo; Lee, Yun Sil [Korea Institute of Radiological Medical Sciences, Seoul (Korea, Republic of); Kim, Sung Ho [Chonnam National Univ., Gwangju (Korea, Republic of)

    2005-07-01

    Irradiation (IR) is a central treatment modality administered for head and neck malignancies. A significant consequence of this IR treatment is irreversible damage to salivary gland in the IR field. While the exact mechanism of salivary gland damage remains enigmatic, fluid secreting acinar cells are lost, and saliva output is dramatically reduced. Previously we have reported that heat shock protein 25 (HSP25) induced radioresistance in vitro. HSP25 interferes negatively with apoptosis through several pathways which involve its direct interaction with cytochrome c, protein kinase c delta or Akt. And localized gene transfer to salivary glands has great potential for the treatment of salivary gland. Herein, we investigated whether HSP25 can use as radio protective molecules for radiation-induced salivary gland damage in vivo.

  9. 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.

  10. 49 CFR 1242.36 - Machinery repair and equipment damaged (accounts XX-26-40 and XX-26-48).

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 9 2010-10-01 2010-10-01 false Machinery repair and equipment damaged (accounts XX-26-40 and XX-26-48). 1242.36 Section 1242.36 Transportation Other Regulations Relating to... FOR RAILROADS 1 Operating Expenses-Equipment § 1242.36 Machinery repair and equipment...

  11. DNA Damage Follows Repair Factor Depletion and Portends Genome Variation in Cancer Cells after Pore Migration.

    Science.gov (United States)

    Irianto, Jerome; Xia, Yuntao; Pfeifer, Charlotte R; Athirasala, Avathamsa; Ji, Jiazheng; Alvey, Cory; Tewari, Manu; Bennett, Rachel R; Harding, Shane M; Liu, Andrea J; Greenberg, Roger A; Discher, Dennis E

    2017-01-23

    Migration through micron-size constrictions has been seen to rupture the nucleus, release nuclear-localized GFP, and cause localized accumulations of ectopic 53BP1-a DNA repair protein. Here, constricted migration of two human cancer cell types and primary mesenchymal stem cells (MSCs) increases DNA breaks throughout the nucleoplasm as assessed by endogenous damage markers and by electrophoretic "comet" measurements. Migration also causes multiple DNA repair proteins to segregate away from DNA, with cytoplasmic mis-localization sustained for many hours as is relevant to delayed repair. Partial knockdown of repair factors that also regulate chromosome copy numbers is seen to increase DNA breaks in U2OS osteosarcoma cells without affecting migration and with nucleoplasmic patterns of damage similar to constricted migration. Such depletion also causes aberrant levels of DNA. Migration-induced nuclear damage is nonetheless reversible for wild-type and sub-cloned U2OS cells, except for lasting genomic differences between stable clones as revealed by DNA arrays and sequencing. Gains and losses of hundreds of megabases in many chromosomes are typical of the changes and heterogeneity in bone cancer. Phenotypic differences that arise from constricted migration of U2OS clones are further illustrated by a clone with a highly elongated and stable MSC-like shape that depends on microtubule assembly downstream of the transcription factor GATA4. Such changes are consistent with reversion to a more stem-like state upstream of cancerous osteoblastic cells. Migration-induced genomic instability can thus associate with heritable changes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. The role of DNA damage and repair in decitabine-mediated apoptosis in multiple myeloma.

    Science.gov (United States)

    Maes, Ken; De Smedt, Eva; Lemaire, Miguel; De Raeve, Hendrik; Menu, Eline; Van Valckenborgh, Els; McClue, Steve; Vanderkerken, Karin; De Bruyne, Elke

    2014-05-30

    DNA methyltransferase inhibitors (DNMTi) and histone deacetylase inhibitors (HDACi) are under investigation for the treatment of cancer, including the plasma cell malignancy multiple myeloma (MM). Evidence exists that DNA damage and repair contribute to the cytotoxicity mediated by the DNMTi decitabine. Here, we investigated the DNA damage response (DDR) induced by decitabine in MM using 4 human MM cell lines and the murine 5T33MM model. In addition, we explored how the HDACi JNJ-26481585 affects this DDR. Decitabine induced DNA damage (gamma-H2AX foci formation), followed by a G0/G1- or G2/M-phase arrest and caspase-mediated apoptosis. JNJ-26481585 enhanced the anti-MM effect of decitabine both in vitro and in vivo. As JNJ-26481585 did not enhance decitabine-mediated gamma-H2AX foci formation, we investigated the DNA repair response towards decitabine and/or JNJ-26481585. Decitabine augmented RAD51 foci formation (marker for homologous recombination (HR)) and/or 53BP1 foci formation (marker for non-homologous end joining (NHEJ)). Interestingly, JNJ-26481585 negatively affected basal or decitabine-induced RAD51 foci formation. Finally, B02 (RAD51 inhibitor) enhanced decitabine-mediated apoptosis. Together, we report that decitabine-induced DNA damage stimulates HR and/or NHEJ. JNJ-26481585 negatively affects RAD51 foci formation, thereby providing an additional explanation for the combinatory effect between decitabine and JNJ-26481585.

  13. Radiation- and drug-induced DNA repair in mammalian oocytes and embryos

    Energy Technology Data Exchange (ETDEWEB)

    Pedersen, R A; Brandriff, B

    1979-01-01

    A review of studies showing ultraviolet- or drug-induced unscheduled DNA synthesis in mammalian oocytes and embryos suggests that the female gamete has an excision repair capacity from the earliest stages of oocyte growth. The oocyte's demonstrable excision repair capacity decreases at the time of meiotic maturation for unknown reasons, but the fully mature oocyte maintans a repair capacity, in contrast to the mature sperm, and contributes this to the zygote. Early embryo cells maintain relatively constant levels of excision repair until late fetal stages, when they lose their capacity for excision repair. These apparent changes in excision repair capacity do not have a simple relationship to known differences in radiation sensitivity of germ cells and embryos.

  14. In vivo effects of UV radiation on multiple endpoints and expression profiles of DNA repair and heat shock protein (Hsp) genes in the cycloid copepod Paracyclopina nana

    Energy Technology Data Exchange (ETDEWEB)

    Won, Eun-Ji; Han, Jeonghoon [Department of Biological Science, College of Science, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Lee, Yeonjung; Kumar, K. Suresh; Shin, Kyung-Hoon [Department of Marine Sciences and Convergent Technology, College of Science and Technology, Hanyang University, Ansan 426-791 (Korea, Republic of); Lee, Su-Jae [Department of Life Sciences, College of Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of); Park, Heum Gi, E-mail: hgpark@gwnu.ac.kr [Department of Marine Resource Development, College of Life Sciences, Gangneung-Wonju National University, Gangneung 210-702 (Korea, Republic of); Lee, Jae-Seong, E-mail: jslee2@skku.edu [Department of Biological Science, College of Science, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of)

    2015-08-15

    Highlights: • UV-B radiation induced a significant reduction of the re-brooding rate of ovigerous females. • A dose-dependent decrease in food ingestion and the rate of assimilation to the body upon UV radiation. • Expression of base excision repair-associated and hsp chaperoning genes was significantly increased upon UV radiation in P. nana. - Abstract: To evaluate the effects of ultraviolet (UV) radiation on energy acquisition and consumption, the copepod Paracyclopina nana was irradiated with several doses (0–3 kJ/m{sup 2}) of UV. After UV radiation, we measured the re-brooding success, growth pattern of newly hatched nauplii, ingestion rate, and assimilation of diet. In addition, we checked the modulated patterns of DNA repair and heat shock protein (hsp) chaperoning genes of P. nana. UV-B radiation induced a significant reduction (7–87%) of the re-brooding rate of ovigerous females, indicating that UV-induced egg sac damage is closely correlated with a reduction in the hatching rate of UV-irradiated ovigerous female offspring. Using chlorophyll a and stable carbon isotope incubation experiments, we found a dose-dependent decrease (P < 0.05) in food ingestion and the rate of assimilation to the body in response to UV radiation, implying that P. nana has an underlying ability to shift its balanced-energy status from growth and reproduction to DNA repair and adaptation. Also, expression of P. nana base excision repair (BER)-associated genes and hsp chaperoning genes was significantly increased in response to UV radiation in P. nana. These findings indicate that even 1 kJ/m{sup 2} of UV radiation induces a reduction in reproduction and growth patterns, alters the physiological balance and inhibits the ability to cope with UV-induced damage in P. nana.

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

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Masato; Endo, Hideo [Japan Nuclear Cycle Development Inst., Tokai Works, Tokai, Ibaraki (Japan); Sugata, Hiromasa [Inspection Development Company Ltd., Tokai, Ibaraki (Japan)

    2002-12-01

    In plutonium compounds, self-radiation induces expansion of the lattice parameter as a function of time. The expansion of the lattice parameter and thermal recovery of radiation damage in plutonium and uranium mixed dioxide (MOX) were studied in this paper. The MOX powder had been kept in an ambient atmosphere for about two years. The lattice parameter of the powder saturated after an increase of about 0.23%. The change in the lattice parameter was formulated as a function of the self-radiation amount. Three thermal recovery stages of radiation damage were observed in temperature ranges below 400degC, 400-800degC and above 800degC. The recovery rate of the three stages in total lattice expansion was about 25%, 55% and 20%, respectively, and activation energy in each recovery was estimated to be 0.14 eV, 0.54 eV and 1.1 eV. (author)

  16. Functional analysis of molecular mechanisms of radiation induced apoptosis, that are not mediated by DNA damages; Funktionelle Analyse molekularer Mechanismen der strahleninduzierten Apoptose, die nicht ueber direkte DNA-Schaeden vermittelt werden

    Energy Technology Data Exchange (ETDEWEB)

    Angermeier, Marita; Moertl, Simone [Helmholtz Zentrum Muenchen, Neuherberg (Germany). Inst. fuer Strahlenbiologie

    2012-09-15

    The effects of low-dose irradiation pose new challenges on the radiation protection efforts. Enhanced cellular radiation sensitivity is displayed by disturbed cellular reactions and resulting damage like cell cycle arrest, DNA repair and apoptosis. Apoptosis serves as genetically determinate parameter for the individual radiation sensitivity. In the frame of the project the radiation-induced apoptosis was mechanistically investigated. Since ionizing radiation induced direct DNA damage and generates a reactive oxygen species, the main focus of the research was the differentiation and weighting of DNA damage mediated apoptosis and apoptosis caused by the reactive oxygen species (ROS).

  17. Delayed damage after radiation therapy for head and neck cancer

    Energy Technology Data Exchange (ETDEWEB)

    Matsumoto, Yoshiyuki [Osaka Dental Univ., Hirakata (Japan)

    2000-03-01

    I investigated radiation damage, including osteoradionecrosis, arising from tooth extraction in fields that had received radiation therapy for head and neck cancer, and evaluated the effectiveness of pilocarpine for xerostomia. Between January 1990 and April 1996, I examined 30 patients for bone changes after tooth extraction in fields irradiated at the Department of Oral Radiology, Osaka Dental University Hospital. Nineteen of the patients had been treated for nasopharyngeal cancer and 11 for oropharyngeal cancer. Between January and April 1996, 4 additional patients were given pilocarpine hydrochloride (3-mg, 6-mg and 9-mg of KSS-694 orally three times a day) for 12 weeks and evaluated every 4 weeks as a base line. One had been treated for nasopharyngeal carcinoma, two for cancer of the cheek and one for an unknown carcinoma. Eighteen of the patients (11 with nasopharyngeal carcinoma and 7 with oropharyngeal carcinoma) had extractions. Use of preoperative and postoperative radiographs indicated that damage to the bone following tooth extraction after radiation exposure was related to whether antibiotics were administered the day before the extraction, whether forceps or elevators were used, and whether the tooth was in the field of radiation. Xerostomia improved in all 4 of the patients who received 6-mg or 9-mg of pilocarpine. It improved saliva production and relieved the symptoms of xerostomia after radiation therapy for head and neck cancer, although there were minor side effects such as fever. This information can be used to improve the oral environment of patients who have received radiation therapy for head and neck cancer, and to better understand their oral environment. (author)

  18. Actualities on molecular pathogenesis and repairing processes of cerebral damage in perinatal hypoxic-ischemic encephalopathy.

    Science.gov (United States)

    Distefano, Giuseppe; Praticò, Andrea D

    2010-09-16

    Hypoxic-ischemic encephalopathy (HIE) is the most important cause of cerebral damage and long-term neurological sequelae in the perinatal period both in term and preterm infant. Hypoxic-ischemic (H-I) injuries develop in two phases: the ischemic phase, dominated by necrotic processes, and the reperfusion phase, dominated by apoptotic processes extending beyond ischemic areas. Due to selective ischemic vulnerability, cerebral damage affects gray matter in term newborns and white matter in preterm newborns with the typical neuropathological aspects of laminar cortical necrosis in the former and periventricular leukomalacia in the latter. This article summarises the principal physiopathological and biochemical processes leading to necrosis and/or apoptosis of neuronal and glial cells and reports recent insights into some endogenous and exogenous cellular and molecular mechanisms aimed at repairing H-I cerebral damage.

  19. Actualities on molecular pathogenesis and repairing processes of cerebral damage in perinatal hypoxic-ischemic encephalopathy

    Directory of Open Access Journals (Sweden)

    Praticò Andrea D

    2010-09-01

    Full Text Available Abstract Hypoxic-ischemic encephalopathy (HIE is the most important cause of cerebral damage and long-term neurological sequelae in the perinatal period both in term and preterm infant. Hypoxic-ischemic (H-I injuries develop in two phases: the ischemic phase, dominated by necrotic processes, and the reperfusion phase, dominated by apoptotic processes extending beyond ischemic areas. Due to selective ischemic vulnerability, cerebral damage affects gray matter in term newborns and white matter in preterm newborns with the typical neuropathological aspects of laminar cortical necrosis in the former and periventricular leukomalacia in the latter. This article summarises the principal physiopathological and biochemical processes leading to necrosis and/or apoptosis of neuronal and glial cells and reports recent insights into some endogenous and exogenous cellular and molecular mechanisms aimed at repairing H-I cerebral damage.

  20. Proteasome inhibition enhances resistance to DNA damage via upregulation of Rpn4-dependent DNA repair genes.

    Science.gov (United States)

    Karpov, Dmitry S; Spasskaya, Daria S; Tutyaeva, Vera V; Mironov, Alexander S; Karpov, Vadim L

    2013-09-17

    The 26S proteasome is an ATP-dependent multi-subunit protease complex and the major regulator of intracellular protein turnover and quality control. However, its role in the DNA damage response is controversial. We addressed this question in yeast by disrupting the transcriptional regulation of the PRE1 proteasomal gene. The mutant strain has decreased proteasome activity and is hyper-resistant to various DNA-damaging agents. We found that Rpn4-target genes MAG1, RAD23, and RAD52 are overexpressed in this strain due to Rpn4 stabilisation. These genes represent three different pathways of base excision, nucleotide excision and double strand break repair by homologous recombination (DSB-HR). Consistently, the proteasome mutant displays increased DSB-HR activity. Our data imply that the proteasome may have a negative role in DNA damage response.

  1. Dietary phytochemicals, HDAC inhibition, and DNA damage/repair defects in cancer cells

    Directory of Open Access Journals (Sweden)

    Rajendran Praveen

    2011-10-01

    Full Text Available Abstract Genomic instability is a common feature of cancer etiology. This provides an avenue for therapeutic intervention, since cancer cells are more susceptible than normal cells to DNA damaging agents. However, there is growing evidence that the epigenetic mechanisms that impact DNA methylation and histone status also contribute to genomic instability. The DNA damage response, for example, is modulated by the acetylation status of histone and non-histone proteins, and by the opposing activities of histone acetyltransferase and histone deacetylase (HDAC enzymes. Many HDACs overexpressed in cancer cells have been implicated in protecting such cells from genotoxic insults. Thus, HDAC inhibitors, in addition to unsilencing tumor suppressor genes, also can silence DNA repair pathways, inactivate non-histone proteins that are required for DNA stability, and induce reactive oxygen species and DNA double-strand breaks. This review summarizes how dietary phytochemicals that affect the epigenome also can trigger DNA damage and repair mechanisms. Where such data is available, examples are cited from studies in vitro and in vivo of polyphenols, organosulfur/organoselenium compounds, indoles, sesquiterpene lactones, and miscellaneous agents such as anacardic acid. Finally, by virtue of their genetic and epigenetic mechanisms, cancer chemopreventive agents are being redefined as chemo- or radio-sensitizers. A sustained DNA damage response coupled with insufficient repair may be a pivotal mechanism for apoptosis induction in cancer cells exposed to dietary phytochemicals. Future research, including appropriate clinical investigation, should clarify these emerging concepts in the context of both genetic and epigenetic mechanisms dysregulated in cancer, and the pros and cons of specific dietary intervention strategies.

  2. Repair of skin damage during fractionated irradiation with gamma rays and low-LET carbon ions.

    Science.gov (United States)

    Ando, Koichi; Koike, Sachiko; Uzawa, Akiko; Takai, Nobuhiko; Fukawa, Takeshi; Furusawa, Yoshiya; Aoki, Mizuho; Hirayama, Ryoichi

    2006-06-01

    In clinical use of carbon-ion beams, a deep-seated tumor is irradiated with a Spread-Out Bragg peak (SOBP) with a high-LET feature, whereas surface skin is irradiated with an entrance plateau, the LET of which is lower than that of the peak. The repair kinetics of murine skin damage caused by an entrance plateau of carbon ions was compared with that caused by photons using a scheme of daily fractionated doses followed by a top-up dose. Right hind legs received local irradiations with either 20 keV/microm carbon ions or gamma rays. The skin reaction of the irradiated legs was scored every other day up to Day 35 using a scoring scale that consisted of 10 steps, ranging from 0.5 to 5.0. An isoeffect dose to produce a skin reaction score of 3.0 was used to obtain a total dose and a top-up dose for each fractionation. Dependence on a preceding dose and on the time interval of a top-up dose was examined using gamma rays. For fractionated gamma rays, the total dose linearly increased while the top-up dose linearly decreased with an increase in the number of fractions. The magnitude of damage repair depended on the size of dose per fraction, and was larger for 5.2 Gy than 12.5 Gy. The total dose of carbon ions with 5.2 Gy per fraction did not change till 2 fractions, but abruptly increased at the 3rd fraction. Factors such as rapid repopulation, induced repair and cell cycle synchronization are possible explanations for the abrupt increase. As an abrupt increase/decrease of normal tissue damage could be caused by changing the number of fractions in carbon-ion radiotherapy, we conclude that, unlike photon therapy, skin damage should be carefully studied when the number of fractions is changed in new clinical trials.

  3. Effect of caffeine and adenosine on G2 repair: mitotic delay and chromosome damage.

    Science.gov (United States)

    González-Fernández, A; Hernández, P; López-Sáez, J F

    1985-04-01

    Proliferating plant cells treated during the late S period with 5-aminouracil (AU), give the typical response that DNA-damaging agents induce, characterized by: an important mitotic delay, and a potentiation of the chromosome damage by caffeine post-treatment. The study of labelled prophases, after a tritiated thymidine pulse, allowed evaluation of the mitotic delay induced by AU as well as its reversion by caffeine, while chromosome damage was estimated by the percentage of anaphases and telophases showing chromosomal aberrations. Post-treatment with adenosine alone has shown no effect on mitotic delay or chromosomal damage. However, when cells after AU were incubated in caffeine plus adenosine, the chromosome damage potentiation was abolished without affecting the caffeine action on mitotic delay. As a consequence, we postulate that caffeine could have two effects on G2 cells with damaged DNA: the first, to cancel their mitotic delay and the second to inhibit some DNA-repair pathway(s). Only this last effect could be reversed by adenosine.

  4. Base excision repair of oxidative DNA damage and association with cancer and aging

    DEFF Research Database (Denmark)

    Maynard, Scott; Schurman, Shepherd H; Harboe, Charlotte

    2009-01-01

    Aging has been associated with damage accumulation in the genome and with increased cancer incidence. Reactive oxygen species (ROS) are produced from endogenous sources, most notably the oxidative metabolism in the mitochondria, and from exogenous sources, such as ionizing radiation. ROS attack D...

  5. Repair work begins on the external tank of Space Shuttle Discovery after damage from hail

    Science.gov (United States)

    1999-01-01

    United Space Alliance technician Don Pataky repairs one of the hail-created divots in the foam insulation on the external tank of Space Shuttle Discovery. The Shuttle was rolled back from Pad 39B to the Vehicle Assemby Building for repairs because access to all of the damaged areas was not possible at the pad. The work is expected to take two to three days, allowing Discovery to roll back to the pad late this week for launch of mission STS-96, the 94th launch in the Space Shuttle Program. Liftoff will occur no earlier than May 27. STS-96 is a logistics and resupply mission for the International Space Station, carrying such payloads as a Russian crane, the Strela; a U.S.-built crane; the Spacehab Oceaneering Space System Box (SHOSS), a logistics items carrier; and STARSHINE, a student-shared experiment.

  6. Repair work begins on the external tank of Space Shuttle Discovery after damage from hail

    Science.gov (United States)

    1999-01-01

    Standing inside a protective tent around the external tank of Space Shuttle Discovery in the Vehicle Assembly Building (VAB), United Space Alliance technician Don Pataky repairs divots caused by hail storms. The Shuttle was rolled back from Pad 39B to the VAB for repairs because access to all of the damaged areas was not possible at the pad. The work is expected to take two to three days, allowing Discovery to roll back to the pad late this week for launch of mission STS-96, the 94th launch in the Space Shuttle Program. Liftoff will occur no earlier than May 27. STS- 96 is a logistics and resupply mission for the International Space Station, carrying such payloads as a Russian crane, the Strela; a U.S.-built crane; the Spacehab Oceaneering Space System Box (SHOSS), a logistics items carrier; and STARSHINE, a student- shared experiment.

  7. 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 range...... from 2 x 10(8) to 60 x 10(8) p(+)/cm(2). Even for the highest fluences, which had a dramatic effect on the spectroscopic performance, we were able to recover the detectors after an appropriate annealing procedure. The radiation damage was studied as a function of depth inside the detector material...... with the proton dose. The radiation contribution to the electron trapping was found to obey the following relation: (mutau(e)(-1))(rad) = (2.5+/-0.2) x 10(-7) x Phi (V/cm)(2) with the proton fluence, Phi in p(+)/cm(2). The trapping depth dependence, however, did not agree well with the damage profile calculated...

  8. The evaluation of radiation damage parameter for CVD diamond

    Science.gov (United States)

    Grilj, V.; Skukan, N.; Jakšić, M.; Pomorski, M.; Kada, W.; Kamiya, T.; Ohshima, T.

    2016-04-01

    There are a few different phenomenological approaches that aim to track the dependence of signal height in irradiated solid state detectors on the fluence of damaging particles. However, none of them are capable to provide a unique radiation hardness parameter that would reflect solely the material capability to withstand high radiation environment. To extract such a parameter for chemical vapor deposited (CVD) diamond, two different diamond detectors were irradiated with proton beams in MeV energy range and subjected afterwards to ion beam induced charge (IBIC) analysis. The change in charge collection efficiency (CCE) due to defects produced was investigated in context of a theoretical model that was developed on the basis of the adjoint method for linearization of the continuity equations of electrons and holes. Detailed modeling of measured data resulted with the first known value of the kσ product for diamond, where k represents the number of charge carriers' traps created per one simulated primary lattice vacancy and σ represents the charge carriers' capture cross section. As discussed in the text, this product could be considered as a true radiation damage parameter.

  9. Radiation Damages in Aluminum Alloy SAV-1 under Neutron Irradiation

    Science.gov (United States)

    Salikhbaev, Umar; Akhmedzhanov, Farkhad; Alikulov, Sherali; Baytelesov, Sapar; Boltabaev, Azizbek

    2016-05-01

    The aim of this work was to study the effect of neutron irradiation on the kinetics of radiation damages in the SAV-1 alloy, which belongs to the group of aluminum alloys of the ternary system Al-Mg-Si. For fast-neutron irradiation by different doses up to fluence 1019 cm-2 the SAV-1 samples were placed in one of the vertical channels of the research WWR type reactor (Tashkent). The temperature dependence of the electrical resistance of the alloy samples was investigated in the range 290 - 490 K by the four-compensation method with an error about 0.1%. The experimental results were shown that at all the temperatures the dependence of the SAV-1 alloy resistivity on neutron fluence was nonlinear. With increasing neutron fluence the deviation from linearity and the growth rate of resistivity with temperature becomes more appreciable. The observed dependences are explained by means of martensitic transformations and the radiation damages in the studied alloy under neutron irradiation. The mechanisms of radiation modification of the SAV-1 alloy structure are discussed.

  10. The evaluation of radiation damage parameter for CVD diamond

    Energy Technology Data Exchange (ETDEWEB)

    Grilj, V., E-mail: vgrilj@irb.hr [Division for Experimental Physics, Ruđer Bošković Institute, 10000 Zagreb (Croatia); Skukan, N.; Jakšić, M. [Division for Experimental Physics, Ruđer Bošković Institute, 10000 Zagreb (Croatia); Pomorski, M. [CEA-LIST, Diamond Sensors Laboratory, Gif-sur-Yvette F-91191 (France); Kada, W. [Division of Electronics and Informatics, Faculty of Science and Technology, Gunma University, Kiryu, Gunma 376-8515 (Japan); Kamiya, T.; Ohshima, T. [Japan Atomic Energy Agency (JAEA), Takasaki, Gunma 370-1292 (Japan)

    2016-04-01

    There are a few different phenomenological approaches that aim to track the dependence of signal height in irradiated solid state detectors on the fluence of damaging particles. However, none of them are capable to provide a unique radiation hardness parameter that would reflect solely the material capability to withstand high radiation environment. To extract such a parameter for chemical vapor deposited (CVD) diamond, two different diamond detectors were irradiated with proton beams in MeV energy range and subjected afterwards to ion beam induced charge (IBIC) analysis. The change in charge collection efficiency (CCE) due to defects produced was investigated in context of a theoretical model that was developed on the basis of the adjoint method for linearization of the continuity equations of electrons and holes. Detailed modeling of measured data resulted with the first known value of the kσ product for diamond, where k represents the number of charge carriers’ traps created per one simulated primary lattice vacancy and σ represents the charge carriers’ capture cross section. As discussed in the text, this product could be considered as a true radiation damage parameter.

  11. 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 ...

  12. 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...

  13. Space Transportation System (STS)-117 External Tank (ET)-124 Hail Damage Repair Assessment

    Science.gov (United States)

    Wilson, Timmy R.; Gentz, Steven J.; Barth, Timothy S.; Minute, Stephen A.; Flowers, Cody P.; Hamilton, David A.; Null, Cynthia H.; Schafer, Charles F.

    2009-01-01

    Severe thunderstorms with associated hail and high winds struck the STS-117 stack on February 26, 2007. Peak winds were recorded at 62 knots with hail sizes ranging from 0.3 inch to 0.8 inch in diameter. As a result of the storm, the North Carolina Foam Institute (NCFI) type 24-124 Thermal Protection System (TPS) foam on the liquid oxygen (LO2) ogive acreage incurred significant impact damage. The NCFI on the ET intertank and the liquid hydrogen (LH2) acreage sustained hail damage. The Polymer Development Laboratory (PDL)-1034 foam of the LO2 ice frost ramps (IFRs) and the Super-Lightweight Ablator (SLA) of the LO2 cable tray also suffered minor damage. NASA Engineering and Safety Center (NESC) was asked to assess the technical feasibility of repairing the ET TPS, the reasonableness of conducting those repairs with the vehicle in a vertical, integrated configuration at the Kennedy Space Center (KSC) Vehicle Assemble Building (VAB), and to address attendant human factors considerations including worker fatigue and the potential for error. The outcome of the assessment is recorded in this document.

  14. Effect of the repaired damage morphology of fused silica on the modulation of incident laser

    Science.gov (United States)

    Gao, X.; Jiang, Y.; Qiu, R.; Zhou, Q.; Zuo, R.; Zhou, G. R.; Yao, K.

    2017-02-01

    Local CO2 laser treatment has proved to be the most promising method to extend the life-time of fused silica. However, previous experimental data show that some raised rims are observed around the mitigated sites left from the mitigation process, which will result in hazardous light modulation to the downstream optics. In this work, the morphology features of mitigated sites on the surface of fused silica optics were analyzed in detail. According to measured morphology features, a 3D analytical model for simulating the modulation value induced by mitigated site has been developed based on the scalar diffraction theory. The diffraction patterns at a discrete distance downstream from each mitigated site are measured. The influences of geometry, laser wavelength and refractive index of substrates on the modulation by repaired damage morphology at different distances are discussed, respectively. The analytical model is usable and representative to evaluate the hazardous modulation induced by repaired damage morphology to downstream optics. Results on this research suggest that the downstream intensification can be suppressed by controlling the morphology features of mitigated sites, which provides a direction for the development and improvement of the mitigated techniques of damage optics.

  15. Assessment of okadaic acid effects on cytotoxicity, DNA damage and DNA repair in human cells.

    Science.gov (United States)

    Valdiglesias, Vanessa; Méndez, Josefina; Pásaro, Eduardo; Cemeli, Eduardo; Anderson, Diana; Laffon, Blanca

    2010-07-07

    Okadaic acid (OA) is a phycotoxin produced by several types of dinoflagellates causing diarrheic shellfish poisoning (DSP) in humans. Symptoms induced by DSP toxins are mainly gastrointestinal, but the intoxication does not appear to be fatal. Despite this, this toxin presents a potential threat to human health even at concentrations too low to induce acute toxicity, since previous animal studies have shown that OA has very potent tumour promoting activity. However, its concrete action mechanism has not been described yet and the results reported with regard to OA cytotoxicity and genotoxicity are often contradictory. In the present study, the genotoxic and cytotoxic effects of OA on three different types of human cells (peripheral blood leukocytes, HepG2 hepatoma cells, and SHSY5Y neuroblastoma cells) were evaluated. Cells were treated with a range of OA concentrations in the presence and absence of S9 fraction, and MTT test and Comet assay were performed in order to evaluate cytotoxicity and genotoxicity, respectively. The possible effects of OA on DNA repair were also studied by means of the DNA repair competence assay, using bleomycin as DNA damage inductor. Treatment with OA in absence of S9 fraction induced not statistically significant decrease in cell viability and significant increase in DNA damage in all cell types at the highest concentrations investigated. However, only SHSY5Y cells showed OA induced genotoxic and cytotoxic effects in presence of S9 fraction. Furthermore, we found that OA can induce modulations in DNA repair processes when exposure was performed prior to BLM treatment, in co-exposure, or during the subsequent DNA repair process. Copyright 2010 Elsevier B.V. All rights reserved.

  16. Alpha particle induced DNA damage and repair in normal cultured thyrocytes of different proliferation status

    DEFF Research Database (Denmark)

    Lyckesvärd, Madeleine Nordén; Delle, Ulla; Kahu, Helena

    2014-01-01

    mechanism as (131)I [1], in cancer treatment has increased during recent years because of its high efficiency in inducing biological damage and beneficial dose distribution when compared to low-LET radiation. Most knowledge of the DNA damage response in thyroid is from studies using low-LET irradiation...... and much less is known of high-LET irradiation. In this paper we investigated the DNA damage response and biological consequences to photons from Cobolt-60 ((60)Co) and alpha particles from (211)At in normal primary thyrocytes of different cell cycle status. For both radiation qualities the intensity....... Increasing ratios of micronuclei per cell nuclei were seen up to 1Gy (211)At. We found that primary thyrocytes were much more sensitive to alpha particle exposure compared with low-LET photons. Calculations of the relative biological effectiveness yielded higher RBE for cycling cells compared with stationary...

  17. Repair of damaged connectors of tunneled cuffed catheters with a two-piece adaptor for peritoneal dialysis.

    Science.gov (United States)

    Letachowicz, Krzysztof; Letachowicz, Waldemar; Weyde, Waclaw; Gołębiowski, Tomasz; Kusztal, Mariusz; Wątorek, Ewa; Klinger, Marian

    2012-01-01

    Although catheter use exposes the patient to several complications, tunneled cuffed catheters are widely applied for temporary or long-term vascular access. The aim of the study was to establish the rate of tunneled dialysis catheter damage and report our experience with breakage repair. All 363 cuffed tunneled hemodialysis catheters inserted into 309 patients from May 2000 to December 2008 were followed up. When connector damage was encountered, repair with a two-piece adaptor for peritoneal dialysis was attempted. Mechanical breakage occurred in 33 (9.1%) of catheters with an incidence of 0.36/1000 catheter-days. The most frequent was connector damage, found in 25 cases (67.6%). Catheter repair using a peritoneal dialysis Luer adaptor was performed with good early and long-term outcome. Tunneled catheter breakage is a relatively rare complication. Catheter repair using the adaptor for peritoneal dialysis is easy to perform, safe, and cost-effective.

  18. Cytogenetic damage at low doses and the problem of bioindication of chronic low level radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Geras' kin, S.A.; Dikarev, V.G.; Nesterov, E.B.; Vasiliev, D.V.; Dikareva, N.S. [Russian Inst. of Agricultural Radiology and Agroecology, Obninsk (Russian Federation)

    2000-05-01

    of radioactive wastes located at Sosnovy Bor in the Leningrad region was carried out in 1995-1999. Results of this research give evidence on pronounced genotoxic influence presence in investigated sites and as against the 30-km ChNPP zone in the Sosnovy Bor region chemical toxicants make the significant contribution to pollution of the environment. The seeds collected in control and experimental population were compared by acute {gamma}-irradiation resistance. This comparison has revealed the selection toward the increase of repair system efficiency. The received results give evidence that although the cytogenetic damage frequency within low dose range cannot be used in biological dosimetry, but the indexes based on it are informative and important for the man-made effect bioindication and for identification of groups at risk of long term health consequences of radiation. (author)

  19. In vivo effects of UV radiation on multiple endpoints and expression profiles of DNA repair and heat shock protein (Hsp) genes in the cycloid copepod Paracyclopina nana.

    Science.gov (United States)

    Won, Eun-Ji; Han, Jeonghoon; Lee, Yeonjung; Kumar, K Suresh; Shin, Kyung-Hoon; Lee, Su-Jae; Park, Heum Gi; Lee, Jae-Seong

    2015-08-01

    To evaluate the effects of ultraviolet (UV) radiation on energy acquisition and consumption, the copepod Paracyclopina nana was irradiated with several doses (0-3kJ/m(2)) of UV. After UV radiation, we measured the re-brooding success, growth pattern of newly hatched nauplii, ingestion rate, and assimilation of diet. In addition, we checked the modulated patterns of DNA repair and heat shock protein (hsp) chaperoning genes of P. nana. UV-B radiation induced a significant reduction (7-87%) of the re-brooding rate of ovigerous females, indicating that UV-induced egg sac damage is closely correlated with a reduction in the hatching rate of UV-irradiated ovigerous female offspring. Using chlorophyll a and stable carbon isotope incubation experiments, we found a dose-dependent decrease (Pnana has an underlying ability to shift its balanced-energy status from growth and reproduction to DNA repair and adaptation. Also, expression of P. nana base excision repair (BER)-associated genes and hsp chaperoning genes was significantly increased in response to UV radiation in P. nana. These findings indicate that even 1kJ/m(2) of UV radiation induces a reduction in reproduction and growth patterns, alters the physiological balance and inhibits the ability to cope with UV-induced damage in P. nana.

  20. Contribution of endogenous and exogenous damage to the total radiation-induced damage in the bacterial spore

    Energy Technology Data Exchange (ETDEWEB)

    Jacobs, G.P.; Samuni, A.; Czapski, G.

    1980-01-01

    Radical scavengers such as polyethylene glycol 4000 and bovine albumin have been used to define the contribution of exogenous and endogenous damage to the total radiation-induced damage in aqueous buffered suspensions of Bacillus pumilus spores. The results indicate that this damage in the bacterial spore is predominantly endogenous.

  1. Radiation-damage study of a monocrystalline tungsten positron converter

    CERN Document Server

    Artru, X; Chehab, R; Johnson, B; Keppler, P; Major, J V; Rinolfi, Louis; Jejcic, A

    1998-01-01

    The exploitation of the enhancement of positron sources by channeling effects, in particular for Linear Colliders (LC), relies on the long term resistance of the crystal to radiation damage. Such dama ge has been tested on a 0.3 mm thick tungsten monocrystal exposed during 6 months to the 30 Gev incident electron beam of the SLAC Linear Collider (SLC). The crystal was placed in the converter region , orientated in a random direction and received an integrated flux of e- (fluence) of 2 x 10^18 e-/mm^2. The crystal was analyzed before and after irradiation by X and Gamma diffractometry. No damage was observed, the mosaic spread remained unchanged during irradiation (0.4 mrad FWHM). Implications for use of orientated crystal as converter for positron sources of future LCs are discussed.

  2. 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)

  3. DNA damage and repair activity after broccoli intake in young healthy smokers

    DEFF Research Database (Denmark)

    Riso, Patrizia; Martini, Daniela; Møller, Peter;

    2010-01-01

    Cruciferous vegetables contain compounds with antioxidant properties (e.g. carotenoids, vitamin C and folates) and can alter the activity of xenobiotic metabolism (i.e. isothiocyanates). These constituents may be particularly important for subjects who are exposed to free radicals and genotoxic....... Blood was collected before and after each period. The level of oxidatively damaged DNA lesions (formamidopyrimidine DNA glycosylase-sensitive sites), resistance to ex vivo H(2)O(2) treatment and repair of oxidised DNA lesions were measured in peripheral blood mononuclear cells (PBMCs). We also measured...

  4. Reduced inflammation accompanies diminished myelin damage and repair in the NG2 null mouse spinal cord

    Directory of Open Access Journals (Sweden)

    Kucharova Karolina

    2011-11-01

    Full Text Available Abstract Background Multiple sclerosis (MS is a demyelinating disease in which blood-derived immune cells and activated microglia damage myelin in the central nervous system. While oligodendrocyte progenitor cells (OPCs are essential for generating oligodendrocytes for myelin repair, other cell types also participate in the damage and repair processes. The NG2 proteoglycan is expressed by OPCs, pericytes, and macrophages/microglia. In this report we investigate the effects of NG2 on these cell types during spinal cord demyelination/remyelination. Methods Demyelinated lesions were created by microinjecting 1% lysolecithin into the lumbar spinal cord. Following demyelination, NG2 expression patterns in wild type mice were studied via immunostaining. Immunolabeling was also used in wild type and NG2 null mice to compare the extent of myelin damage, the kinetics of myelin repair, and the respective responses of OPCs, pericytes, and macrophages/microglia. Cell proliferation was quantified by studies of BrdU incorporation, and cytokine expression levels were evaluated using qRT-PCR. Results The initial volume of spinal cord demyelination in wild type mice is twice as large as in NG2 null mice. However, over the ensuing 5 weeks there is a 6-fold improvement in myelination in wild type mice, versus only a 2-fold improvement in NG2 null mice. NG2 ablation also results in reduced numbers of each of the three affected cell types. BrdU incorporation studies reveal that reduced cell proliferation is an important factor underlying NG2-dependent decreases in each of the three key cell populations. In addition, NG2 ablation reduces macrophage/microglial cell migration and shifts cytokine expression from a pro-inflammatory to anti-inflammatory phenotype. Conclusions Loss of NG2 expression leads to decreased proliferation of OPCs, pericytes, and macrophages/microglia, reducing the abundance of all three cell types in demyelinated spinal cord lesions. As a result

  5. Probing the molecular structures of plasma-damaged and surface-repaired low-k dielectrics.

    Science.gov (United States)

    Zhang, Xiaoxian; Myers, John N; Lin, Qinghuang; Bielefeld, Jeffery D; Chen, Zhan

    2015-10-21

    Fully understanding the effect and the molecular mechanisms of plasma damage and silylation repair on low dielectric constant (low-k) materials is essential to the design of low-k dielectrics with defined properties and the integration of low-k dielectrics into advanced interconnects of modern electronics. Here, analytical techniques including sum frequency generation vibrational spectroscopy (SFG), Fourier transform infrared spectroscopy (FTIR), contact angle goniometry (CA) and X-ray photoelectron spectroscopy (XPS) have been employed to provide a comprehensive characterization of the surface and bulk structure changes of poly(methyl)silsesquioxane (PMSQ) low-k thin films before and after O2 plasma treatment and silylation repair. O2 plasma treatment altered drastically both the molecular structures and water structures at the surfaces of the PMSQ film while no bulk structural change was detected. For example, ∼34% Si-CH3 groups were removed from the PMSQ surface, and the Si-CH3 groups at the film surface tilted toward the surface after the O2 plasma treatment. The oxidation by the O2 plasma made the PMSQ film surface more hydrophilic and thus enhanced the water adsorption at the film surface. Both strongly and weakly hydrogen bonded water were detected at the plasma-damaged film surface during exposure to water with the former being the dominate component. It is postulated that this enhancement of both chemisorbed and physisorbed water after the O2 plasma treatment leads to the degradation of low-k properties and reliability. The degradation of the PMSQ low-k film can be recovered by repairing the plasma-damaged surface using a silylation reaction. The silylation method, however, cannot fully recover the plasma induced damage at the PMSQ film surface as evidenced by the existence of hydrophilic groups, including C-O/C[double bond, length as m-dash]O and residual Si-OH groups. This work provides a molecular level picture on the surface structural changes of low

  6. Human POLD1 modulates cell cycle progression and DNA damage repair

    OpenAIRE

    Song, Jing; Hong, Ping; Liu, Chengeng; Zhang, Yueqi; Wang, Jinling; Wang, Peichang

    2015-01-01

    Background The activity of eukaryotic DNA polymerase delta (Pol δ) plays an essential role in genome stability through its effects on DNA replication and repair. The p125 catalytic subunit of Pol δ is encoded by POLD1 gene in human cells. To clarify biological functions of POLD1, we investigated the effects of POLD1 overexpression or downregulation on cell proliferation, cell cycle progression, DNA synthesis and oxidative DNA damage induced by H2O2. Methods HEK293 cells were transfected with ...

  7. Digital Restoration from Start to Finish How to repair old and damaged photographs

    CERN Document Server

    Ctein,

    2010-01-01

    Digital Restoration: Start to Finish 2nd edition guides you step-by-step through the entire process of restoring old photographs and repairing new ones using Adobe Photoshop, Picture Window, and now Elements. Nothing is left out, from choosing the right hardware and software and getting the photographs into the computer, to getting the finished photo out of the computer and preserving it for posterity.  LEARN HOW TO: Scan faded and damaged prints or films Improve snapshots with Shadow/Highlight adjustment Correct uneven exposure Fix color and skin tones quickly with Curves, plug-ins, a

  8. DNA damage and gene therapy of xeroderma pigmentosum, a human DNA repair-deficient disease

    Energy Technology Data Exchange (ETDEWEB)

    Dupuy, Aurélie [Laboratory of Genetic Instability and Oncogenesis UMR8200CNRS, Institut Gustave Roussy and University Paris-Sud, Villejuif (France); Sarasin, Alain, E-mail: alain.sarasin@gustaveroussy.fr [Laboratory of Genetic Instability and Oncogenesis UMR8200CNRS, Institut Gustave Roussy and University Paris-Sud, Villejuif (France); Service de Génétique, Institut Gustave Roussy (France)

    2015-06-15

    Graphical abstract: - Highlights: • Full correction of mutation in the XPC gene by engineered nucleases. • Meganucleases and TALENs are inhibited by 5-MeC for inducing double strand breaks. • Gene therapy of XP cells is possible using homologous recombination for DSB repair. - Abstract: Xeroderma pigmentosum (XP) is a genetic disease characterized by hypersensitivity to ultra-violet and a very high risk of skin cancer induction on exposed body sites. This syndrome is caused by germinal mutations on nucleotide excision repair genes. No cure is available for these patients except a complete protection from all types of UV radiations. We reviewed the various techniques to complement or to correct the genetic defect in XP cells. We, particularly, developed the correction of XP-C skin cells using the fidelity of the homologous recombination pathway during repair of double-strand break (DSB) in the presence of XPC wild type sequences. We used engineered nucleases (meganuclease or TALE nuclease) to induce a DSB located at 90 bp of the mutation to be corrected. Expression of specific TALE nuclease in the presence of a repair matrix containing a long stretch of homologous wild type XPC sequences allowed us a successful gene correction of the original TG deletion found in numerous North African XP patients. Some engineered nucleases are sensitive to epigenetic modifications, such as cytosine methylation. In case of methylated sequences to be corrected, modified nucleases or demethylation of the whole genome should be envisaged. Overall, we showed that specifically-designed TALE-nuclease allowed us to correct a 2 bp deletion in the XPC gene leading to patient's cells proficient for DNA repair and showing normal UV-sensitivity. The corrected gene is still in the same position in the human genome and under the regulation of its physiological promoter. This result is a first step toward gene therapy in XP patients.

  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. Radiation Damage to the Elements of the SIS300 Dipoles

    CERN Document Server

    Mustafin, Edil; Latysheva, Ludmila N; Moritz, Gebhard; Sobolevskiy, Nikolai; Walter, Gertrud

    2005-01-01

    Radiation damage to various elements of the cosine-theta type dipoles of the SIS300 synchrotron of the FAIR Project was calculated. Among the elements under consideration were the superconducting cable, insulating materials, and high-current by-pass protection diodes. The Monte-Carlo particle transport codes MARS and SHIELD were used to simulate propagation of the lost ions and protons, together with the products of nuclear interactions in the material of the elements. It was found that the lifetime of the protection diodes under irradiation is a more restrictive limit for the tolerable level of beam losses than the occurrence of magnet quenches.

  11. 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)

  12. 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).

  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.

  14. Metals far from equilibrium: From shocks to radiation damage

    CERN Document Server

    Bringa, E M; Caturla, M J; Stoelken, J; Kalantar, D

    2003-01-01

    Shock waves and high-energy particle radiation can each drive materials far from thermodynamic equilibrium and enable novel scenarios in the processing of materials. A large number of theoretical and experimental studies of shock deformation have been performed on polycrystalline materials, but shock deformation in single crystals has only recently been studied in some detail. We present molecular dynamics (MD) simulations of the shock response of single crystal copper, modeled using an embedded atom potential that reproduces both defect formation and high pressure behavior. Shock-induced plasticity will also be discussed. Predicting the in-service response of ferritic alloys in future fusion energy environments requires a detailed understanding of the mechanisms of defect accumulation and microstructure evolution in harsh radiation environments, which include a high level of He generation concurrent with primary damage production. The second half of this paper describes results of atomistic MD and kinetic Mo...

  15. Compensation of radiation damages for SOI pixel detector via tunneling

    CERN Document Server

    Yamada, Miho; Kurachi, Ikuo

    2015-01-01

    We are developing monolithic pixel detectors based on SOI technology for high energy physics, X-ray applications and so on.To employ SOI pixel detector on such radiation environments, we have to solve effects of total ionization damages (TID) for transistors which are enclosed in oxide layer.The holes which are generated and trapped in the oxide layers after irradiation affect characteristics of near-by transistors due to its positive electric field.Annealing and radiation of ultraviolet are not realistic to remove trapped holes for a fabricated detector due to thermal resistance of components and difficulty of handling. We studied compensation of TID effects by tunneling using a high-voltage. For decrease of trapped holes, applied high-voltage to buried p-well which is under oxide layer to inject the electrons into the oxide layer.In this report, recent progress of this study is shown.

  16. 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%.

  17. Readout techniques and radiation damage of undoped cesium iodide

    Energy Technology Data Exchange (ETDEWEB)

    Woody, C.L.; Levy, P.W.; Kierstead, J.A.; Skwarnicki, T.; Sobolewski, Z.; Goldberg, M.; Horwitz, N.; Souder, P.; Anderson, D.F. (Brookhaven National Lab., Upton, NY (USA); Syracuse Univ., NY (USA). Dept. of Physics; Fermi National Accelerator Lab., Batavia, IL (USA))

    1989-01-01

    Several readout techniques for undoped CsI have been studied which utilize the fast scintillation component for speed, and the high photon yield for good energy resolution. Quantum yields have been measured for samples up to 30 cm in length using photomultiplier tubes, wavelength shifters, and silicon photodiodes. A study has also been made of the scintillation properties of undoped CsI. It is found that the light output and decay time of the 310 nm fast component increases and the emission spectrum shifts to longer wavelengths at lower temperatures. The effects on the optical transmission and scintillation light output due to radiation damage from {sup 60}Co gamma rays has been measured for doses up to {approximately}10{sup 6} rad. It is found that the radiation resistance of undoped CsI is substantially higher than has been reported for thallium doped CsI. 16 refs., 11 figs., 3 tabs.

  18. 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.

  19. Radiation damage effects in standard float zone silicon diodes

    Energy Technology Data Exchange (ETDEWEB)

    Pascoalino, Kelly C.; Camargo, Fabio; Barbosa, Renata F.; Goncalves, Josemary A.C.; Tobias, Carmen C.B., E-mail: ccbueno@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2009-07-01

    The aim of this work was to study the radiation damage effects on the electrical properties of standard float zone diodes (STFZ). Such effects were evaluated by measuring the current and capacitance of these devices as a function of the reverse voltage. For comparison, current and capacitance measurements were carried out with a non-irradiated STFZ device. The irradiation was performed in the Radiation Technology Center (CTR) at IPEN/CNEN-SP using a {sup 60}Co irradiator (Gammacell 220 - Nordion) with a dose rate of about 2.2 kGy/h. Samples were irradiated at room temperature in steps variable from 50 kGy up 140 kGy which lead to an accumulated dose of 460 kGy. The results obtained have shown that the upper dose limit for a 'damageless' STFZ diode is about 50 kGy. (author)

  20. Medicinal protection with Chinese herb-compound against radiation damage

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, R.J.; Qian, J.K.; Yang, G.H.; Wang, B.Z.; Wen, X.L. (Institute of Space Medico-Engineering, Beijing (China))

    1990-08-01

    Experiments were carried out on mice and the subjects irradiated for cancer therapy to evaluate the protective efficacy of a Chinese medicinal herb-compound (CMHC). The lethality and the degree of leucopenia caused by radiation in mice medicated with CMHC were significantly less in comparison with control mice (p less than 0.01 and p less than 0.001, respectively). CMHC significantly improved the WBC and the thrombocytes in irradiated workers (p less than 0.01 and p less than 0.001, respectively). The WBC count of 40 patients under radiotherapy while treated with CMHC recovered from 3450 +/- 77/c.mm to 5425 +/- 264/c.mm (p less than 0.001); whereas, in the control group, without any medication, the WBC count dropped significantly (p less than 0.001). Our results revealed the applicabilities of CMHC in protection against radiation damage in spaceflight and in other fields.

  1. 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

  2. Genetic damage in subjects exposed to radiofrequency radiation.

    Science.gov (United States)

    Verschaeve, Luc

    2009-01-01

    Despite many research efforts and public debate there is still great concern about the possible adverse effects of radiofrequency (RF) radiation on human health. This is especially due to the enormous increase of wireless mobile telephones and other telecommunication devices throughout the world. The possible genetic effects of mobile phone radiation and other sources of radiofrequencies constitute one of the major points of concern. In the past several review papers were published on laboratory investigations that were devoted to in vitro and in vivo animal (cyto)genetic studies. However, it may be assumed that some of the most important observations are those obtained from studies with individuals that were exposed to relatively high levels of radiofrequency radiation, either as a result of their occupational activity or as frequent users of radiofrequency emitting tools. In this paper the cytogenetic biomonitoring studies of RF-exposed humans are reviewed. A majority of these studies do show that RF-exposed individuals have increased frequencies of genetic damage (e.g., chromosomal aberrations) in their lymphocytes or exfoliated buccal cells. However, most of the studies, if not all, have a number of shortcomings that actually prevents any firm conclusion. Radiation dosimetry was lacking in all papers, but some of the investigations were flawed by much more severe imperfections. Large well-coordinated multidisciplinary investigations are needed in order to reach any robust conclusion.

  3. Reduced repair capacity of a DNA clustered damage site comprised of 8-oxo-7,8-dihydro-2′-deoxyguanosine and 2-deoxyribonolactone results in an increased mutagenic potential of these lesions

    Energy Technology Data Exchange (ETDEWEB)

    Cunniffe, Siobhan [CRUK-MRC Gray Institute for Radiation Oncology and Biology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ (United Kingdom); O’Neill, Peter, E-mail: peter.oneill@oncology.ox.ac.uk [CRUK-MRC Gray Institute for Radiation Oncology and Biology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ (United Kingdom); Greenberg, Marc M. [Johns Hopkins University, Department of Chemistry, 3400 N. Charles St. , Baltimore, MD 21218 (United States); Lomax, Martine E. [CRUK-MRC Gray Institute for Radiation Oncology and Biology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ (United Kingdom)

    2014-04-15

    Highlights: • A dL lesion is not repaired as effectively as an AP site. • The repair of a cluster with dL and 8-oxodGuo lesions is compromised. • Delayed repair of the cluster leads to an increase in mutation frequency. - Abstract: A signature of ionizing radiation is the induction of DNA clustered damaged sites. Non-double strand break (DSB) clustered damage has been shown to compromise the base excision repair pathway, extending the lifetimes of the lesions within the cluster, compared to isolated lesions. This increases the likelihood the lesions persist to replication and thus increasing the mutagenic potential of the lesions within the cluster. Lesions formed by ionizing radiation include 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo) and 2-deoxyribonolactone (dL). dL poses an additional challenge to the cell as it is not repaired by the short-patch base excision repair pathway. Here we show recalcitrant dL repair is reflected in mutations observed when DNA containing it and a proximal 8-oxodGuo is replicated in Escherichia coli. 8-oxodGuo in close proximity to dL on the opposing DNA strand results in an enhanced frequency of mutation of the lesions within the cluster and a 20 base sequence flanking the clustered damage site in an E. coli based plasmid assay. In vitro repair of a dL lesion is reduced when compared to the repair of an abasic (AP) site and a tetrahydrofuran (THF), and this is due mainly to a reduction in the activity of polymerase β, leading to retarded FEN1 and ligase 1 activities. This study has given insights in to the biological effects of clusters containing dL.

  4. Cryo-EM Imaging of DNA-PK DNA Damage Repair Complexes

    Energy Technology Data Exchange (ETDEWEB)

    Phoebe L. Stewart

    2005-06-27

    Exposure to low levels of ionizing radiation causes DNA double-strand breaks (DSBs) that must be repaired for cell survival. Higher eukaryotes respond to DSBs by arresting the cell cycle, presumably to repair the DNA lesions before cell division. In mammalian cells, the nonhomologous end-joining DSB repair pathway is mediated by the 470 kDa DNA-dependent protein kinase catalytic subunit (DNA-PKcs) together with the DNA-binding factors Ku70 and Ku80. Mouse knock-out models of these three proteins are all exquisitely sensitive to low doses of ionizing radiation. In the presence of DNA ends, Ku binds to the DNA and then recruits DNA-PKcs. After formation of the complex, the kinase activity associated with DNA-PKcs becomes activated. This kinase activity has been shown to be essential for repairing DNA DSBs in vivo since expression of a kinase-dead form of DNA-PKcs in a mammalian cell line that lacks DNA-PKcs fails to complement the radiosensitive phenotype. The immense size of DNA-PKcs suggests that it may also serve as a docking site for other DNA repair proteins. Since the assembly of the DNA-PK complex onto DNA is a prerequisite for DSB repair, it is critical to obtain structural information on the complex. Cryo-electron microscopy (cryo-EM) and single particle reconstruction methods provide a powerful way to image large macromolecular assemblies at near atomic (10-15 ?) resolution. We have already used cryo-EM methods to examine the structure of the isolated DNA-PKcs protein. This structure reveals numerous cavities throughout the protein that may allow passage of single or double-stranded DNA. Pseudo two-fold symmetry was found for the monomeric protein, suggesting that DNA-PKcs may interact with two DNA ends or two Ku heterodimers simultaneously. Here we propose to study the structure of the cross-linked DNA-PKcs/Ku/DNA complex. Difference imaging with our published DNA-PKcs structure will enable us to elucidate the architecture of the complex. A second

  5. 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

  6. The chromatin-remodeling factor CHD4 coordinates signaling and repair after DNA damage

    DEFF Research Database (Denmark)

    Larsen, Dorthe Helena; Poinsignon, Catherine; Gudjonsson, Thorkell

    2010-01-01

    In response to ionizing radiation (IR), cells delay cell cycle progression and activate DNA repair. Both processes are vital for genome integrity, but the mechanisms involved in their coordination are not fully understood. In a mass spectrometry screen, we identified the adenosine triphosphate...... and extended cell cycle delay. At DNA double-strand breaks, depletion of CHD4 disrupts the chromatin response at the level of the RNF168 ubiquitin ligase, which in turn impairs local ubiquitylation and BRCA1 assembly. These cell cycle and chromatin defects are accompanied by elevated spontaneous and IR...

  7. Investigations of DNA damage induction and repair resulting from cellular exposure to high dose-rate pulsed proton beams

    Energy Technology Data Exchange (ETDEWEB)

    Renis, M.; Malfa, G.; Tomasello, B. [Drug Sciences Department, University of Catania, Catania (Italy); Borghesi, M.; Schettino, G. [Queen' s University Belfast, Northern Ireland (United Kingdom); Favetta, M.; Romano, F.; Cirrone, G. A. P. [National Institute for Nuclear Physics (INFN-LNS), Catania (Italy); Manti, L. [Physics Science Department, University of Naples Federico II, Naples, and National Institute for Nuclear Physics (INFN), Naples (Italy)

    2013-07-26

    Studies regarding the radiobiological effects of low dose radiation, microbeam irradiation services have been developed in the world and today laser acceleration of protons and heavy ions may be used in radiation therapy. The application of different facilities is essential for studying bystander effects and relating signalling phenomena in different cells or tissues. In particular the use of ion beams results advantageous in cancer radiotherapy compared to more commonly used X-rays, since the ability of ions in delivering lethal amount of doses into the target tumour avoiding or limiting damage to the contiguous healthy tissues. At the INFN-LNS in Catania, a multidisciplinary radiobiology group is strategically structured aimed to develop radiobiological research, finalised to therapeutic applications, compatible with the use of high dose laser-driven ion beams. The characteristic non-continuous dose rates with several orders of magnitude of laser-driven ion beams makes this facility very interesting in the cellular systems' response to ultra-high dose rates with non-conventional pulse time intervals cellular studies. Our group have projected to examine the effect of high dose laser-driven ion beams on two cellular types: foetal fibroblasts (normal control cells) and DU145 (prostate cancer cells), studying the modulation of some different bio-molecular parameters, in particular cell proliferation and viability, DNA damage, redox cellular status, morphological alterations of both the cytoskeleton components and some cell organelles and the possible presence of apoptotic or necrotic cell death. Our group performed preliminary experiments with high energy (60 MeV), dose rate of 10 Gy/min, doses of 1, 2, 3 Gy and LET 1 keV/μm on human foetal fibroblasts (control cells). We observed that cell viability was not influenced by the characteristics of the beam, the irradiation conditions or the analysis time. Conversely, DNA damage was present at time 0, immediately

  8. Discovery of Novel Small Molecules that Activate Satellite Cell Proliferation and Enhance Repair of Damaged Muscle.

    Science.gov (United States)

    Billin, Andrew N; Bantscheff, Marcus; Drewes, Gerard; Ghidelli-Disse, Sonja; Holt, Jason A; Kramer, Henning F; McDougal, Alan J; Smalley, Terry L; Wells, Carrow I; Zuercher, William J; Henke, Brad R

    2016-02-19

    Skeletal muscle progenitor stem cells (referred to as satellite cells) represent the primary pool of stem cells in adult skeletal muscle responsible for the generation of new skeletal muscle in response to injury. Satellite cells derived from aged muscle display a significant reduction in regenerative capacity to form functional muscle. This decrease in functional recovery has been attributed to a decrease in proliferative capacity of satellite cells. Hence, agents that enhance the proliferative abilities of satellite cells may hold promise as therapies for a variety of pathological settings, including repair of injured muscle and age- or disease-associated muscle wasting. Through phenotypic screening of isolated murine satellite cells, we identified a series of 2,4-diaminopyrimidines (e.g., 2) that increased satellite cell proliferation. Importantly, compound 2 was effective in accelerating repair of damaged skeletal muscle in an in vivo mouse model of skeletal muscle injury. While these compounds were originally prepared as c-Jun N-terminal kinase 1 (JNK-1) inhibitors, structure-activity analyses indicated JNK-1 inhibition does not correlate with satellite cell activity. Screening against a broad panel of kinases did not result in identification of an obvious molecular target, so we conducted cell-based proteomics experiments in an attempt to identify the molecular target(s) responsible for the potentiation of the satellite cell proliferation. These data provide the foundation for future efforts to design improved small molecules as potential therapeutics for muscle repair and regeneration.

  9. Radiation damage of biomolecules (RADAM) database development: current status

    Science.gov (United States)

    Denifl, S.; Garcia, G.; Huber, B. A.; Marinković, B. P.; Mason, N.; Postler, J.; Rabus, H.; Rixon, G.; Solov'yov, A. V.; Suraud, E.; Yakubovich, A. V.

    2013-06-01

    Ion beam therapy offers the possibility of excellent dose localization for treatment of malignant tumours, minimizing radiation damage in normal tissue, while maximizing cell killing within the tumour. However, as the underlying dependent physical, chemical and biological processes are too complex to treat them on a purely analytical level, most of our current and future understanding will rely on computer simulations, based on mathematical equations, algorithms and last, but not least, on the available atomic and molecular data. The viability of the simulated output and the success of any computer simulation will be determined by these data, which are treated as the input variables in each computer simulation performed. The radiation research community lacks a complete database for the cross sections of all the different processes involved in ion beam induced damage: ionization and excitation cross sections for ions with liquid water and biological molecules, all the possible electron - medium interactions, dielectric response data, electron attachment to biomolecules etc. In this paper we discuss current progress in the creation of such a database, outline the roadmap of the project and review plans for the exploitation of such a database in future simulations.

  10. 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.

  11. Radiation damage in soft X-ray microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Wang, J.; Morin, C.; Li, L. [Department of Chemistry and Brockhouse Institute for Materials Research, McMaster University, Hamilton, ON, L8S 4M1 (Canada); Hitchcock, A.P. [Department of Chemistry and Brockhouse Institute for Materials Research, McMaster University, Hamilton, ON, L8S 4M1 (Canada)], E-mail: aph@mcmaster.ca; Scholl, A.; Doran, A. [Advanced Light Source, Berkeley Lab, Berkeley, CA 94720 (United States)

    2009-03-15

    The rates of chemical transformation by radiation damage of polystyrene (PS), poly(methyl methacrylate) (PMMA), and fibrinogen (Fg) in a X-ray photoemission electron microscope (X-PEEM) and in a scanning transmission X-ray microscope (STXM) have been measured quantitatively using synchrotron radiation. As part of the method of dose evaluation in X-PEEM, the characteristic (1/e) sampling depth of X-PEEM for polystyrene in the C 1s region was measured to be 4 {+-} 1 nm. Critical doses for chemical change as monitored by changes in the X-ray absorption spectra are 80 (12), 280 (40) and 1230 (180) MGy (1 MGy = 6.242*{rho} eV/nm{sup 3}, where {rho} is the polymer density in g/cm{sup 3}) at 300 eV photon energy for PMMA, Fg and PS, respectively. The critical dose for each material is comparable in X-PEEM and STXM and the values cited are thus the mean of the values determined by X-PEEM and STXM. C 1s, N 1s and O 1s spectroscopy of the damaged materials is used to gain insight into the chemical changes that soft X-rays induce in these materials.

  12. 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.

  13. Histone deacetylase inhibitors mediate DNA damage repair in ameliorating hemorrhagic cystitis.

    Science.gov (United States)

    Haldar, Subhash; Dru, Christopher; Mishra, Rajeev; Tripathi, Manisha; Duong, Frank; Angara, Bryan; Fernandez, Ana; Arditi, Moshe; Bhowmick, Neil A

    2016-12-20

    Hemorrhagic cystitis is an inflammatory and ulcerative bladder condition associated with systemic chemotherapeutics, like cyclophosphomide. Earlier, we reported reactive oxygen species resulting from cyclophosphamide metabolite, acrolein, causes global methylation followed by silencing of DNA damage repair genes. Ogg1 (8-oxoguanine DNA glycosylase) is one such silenced base excision repair enzyme that can restore DNA integrity. The accumulation of DNA damage results in subsequent inflammation associated with pyroptotic death of bladder smooth muscle cells. We hypothesized that reversing inflammasome-induced imprinting in the bladder smooth muscle could prevent the inflammatory phenotype. Elevated recruitment of Dnmt1 and Dnmt3b to the Ogg1 promoter in acrolein treated bladder muscle cells was validated by the pattern of CpG methylation revealed by bisulfite sequencing. Knockout of Ogg1 in detrusor cells resulted in accumulation of reactive oxygen mediated 8-Oxo-dG and spontaneous pyroptotic signaling. Histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA), restored Ogg1 expression in cells treated with acrolein and mice treated with cyclophosphamide superior to the standard of care, mesna or nicotinamide-induced DNA demethylation. SAHA restored cyclophosphamide-induced bladder pathology to that of untreated control mice. The observed epigenetic imprinting induced by inflammation suggests a new therapeutic target for the treatment of hemorrhagic cystitis.

  14. Real-time fluorescence imaging of the DNA damage repair response during mitosis.

    Science.gov (United States)

    Miwa, Shinji; Yano, Shuya; Yamamoto, Mako; Matsumoto, Yasunori; Uehara, Fuminari; Hiroshima, Yukihiko; Toneri, Makoto; Murakami, Takashi; Kimura, Hiroaki; Hayashi, Katsuhiro; Yamamoto, Norio; Efimova, Elena V; Tsuchiya, Hiroyuki; Hoffman, Robert M

    2015-04-01

    The response to DNA damage during mitosis was visualized using real-time fluorescence imaging of focus formation by the DNA-damage repair (DDR) response protein 53BP1 linked to green fluorescent protein (GFP) (53BP1-GFP) in the MiaPaCa-2(Tet-On) pancreatic cancer cell line. To observe 53BP1-GFP foci during mitosis, MiaPaCa-2(Tet-On) 53BP1-GFP cells were imaged every 30 min by confocal microscopy. Time-lapse imaging demonstrated that 11.4 ± 2.1% of the mitotic MiaPaCa-2(Tet-On) 53BP1-GFP cells had increased focus formation over time. Non-mitotic cells did not have an increase in 53BP1-GFP focus formation over time. Some of the mitotic MiaPaCa-2(Tet-On) 53BP1-GFP cells with focus formation became apoptotic. The results of the present report suggest that DNA strand breaks occur during mitosis and undergo repair, which may cause some of the mitotic cells to enter apoptosis in a phenomenon possibly related to mitotic catastrophe.

  15. Histone deacetylase inhibitors mediate DNA damage repair in ameliorating hemorrhagic cystitis

    Science.gov (United States)

    Haldar, Subhash; Dru, Christopher; Mishra, Rajeev; Tripathi, Manisha; Duong, Frank; Angara, Bryan; Fernandez, Ana; Arditi, Moshe; Bhowmick, Neil A.

    2016-01-01

    Hemorrhagic cystitis is an inflammatory and ulcerative bladder condition associated with systemic chemotherapeutics, like cyclophosphomide. Earlier, we reported reactive oxygen species resulting from cyclophosphamide metabolite, acrolein, causes global methylation followed by silencing of DNA damage repair genes. Ogg1 (8-oxoguanine DNA glycosylase) is one such silenced base excision repair enzyme that can restore DNA integrity. The accumulation of DNA damage results in subsequent inflammation associated with pyroptotic death of bladder smooth muscle cells. We hypothesized that reversing inflammasome-induced imprinting in the bladder smooth muscle could prevent the inflammatory phenotype. Elevated recruitment of Dnmt1 and Dnmt3b to the Ogg1 promoter in acrolein treated bladder muscle cells was validated by the pattern of CpG methylation revealed by bisulfite sequencing. Knockout of Ogg1 in detrusor cells resulted in accumulation of reactive oxygen mediated 8-Oxo-dG and spontaneous pyroptotic signaling. Histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA), restored Ogg1 expression in cells treated with acrolein and mice treated with cyclophosphamide superior to the standard of care, mesna or nicotinamide-induced DNA demethylation. SAHA restored cyclophosphamide-induced bladder pathology to that of untreated control mice. The observed epigenetic imprinting induced by inflammation suggests a new therapeutic target for the treatment of hemorrhagic cystitis. PMID:27995963

  16. Deficiency of the DNA repair protein nibrin increases the basal but not the radiation induced mutation frequency in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Wessendorf, Petra [Institute of Medical and Human Genetics, Charité – Universitätsmedizin Berlin, Augustenburger Platz 1, D-13353 Berlin (Germany); Vijg, Jan [Albert Einstein College of Medicine, Michael F. Price Center, 1301 Morris Park Avenue, Bronx, NY 10461 (United States); Nussenzweig, André [Laboratory of Genome Integrity, National Cancer Institute, National Institute of Health, 37 Convent Drive, Room 1106, Bethesda, MD 20892 (United States); Digweed, Martin, E-mail: martin.digweed@charite.de [Institute of Medical and Human Genetics, Charité – Universitätsmedizin Berlin, Augustenburger Platz 1, D-13353 Berlin (Germany)

    2014-11-15

    Highlights: • lacZ mutant frequencies measured in vivo in mouse models of radiosensitive Nijmegen Breakage Syndrome. • Spontaneous mutation frequencies are increased in lymphatic tissue due to Nbn mutation. • Single base transitions, not deletions, dominate the mutation spectrum. • Radiation induced mutation frequencies are not increased due to Nbn mutation. - Abstract: Nibrin (NBN) is a member of a DNA repair complex together with MRE11 and RAD50. The complex is associated particularly with the repair of DNA double strand breaks and with the regulation of cell cycle check points. Hypomorphic mutation of components of the complex leads to human disorders characterised by radiosensitivity and increased tumour occurrence, particularly of the lymphatic system. We have examined here the relationship between DNA damage, mutation frequency and mutation spectrum in vitro and in vivo in mouse models carrying NBN mutations and a lacZ reporter plasmid. We find that NBN mutation leads to increased spontaneous DNA damage in fibroblasts in vitro and high basal mutation rates in lymphatic tissue of mice in vivo. The characteristic mutation spectrum is dominated by single base transitions rather than the deletions and complex rearrangements expected after abortive repair of DNA double strand breaks. We conclude that in the absence of wild type nibrin, the repair of spontaneous errors, presumably arising during DNA replication, makes a major contribution to the basal mutation rate. This applies also to cells heterozygous for an NBN null mutation. Mutation frequencies after irradiation in vivo were not increased in mice with nibrin mutations as might have been expected considering the radiosensitivity of NBS patient cells in vitro. Evidently apoptosis is efficient, even in the absence of wild type nibrin.

  17. Micronuclei in humans induced by exposure to low level of ionizing radiation: influence of polymorphisms in DNA repair genes

    Energy Technology Data Exchange (ETDEWEB)

    Angelini, Sabrina [Department of Pharmacology, University of Bologna, Via Irnerio 48, Bologna 40126 (Italy) and Department of Biosciences, Karolinska Institute, Novum, Huddinge 141 57 (Sweden)]. E-mail: angelini@biocfarm.unibo.it; Kumar, Rajiv [Department of Biosciences, Karolinska Institute, Novum, Huddinge 141 57 (Sweden); Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg (Germany); Carbone, Fabio [Department of Pharmacology, University of Bologna, Via Irnerio 48, Bologna 40126 (Italy); Maffei, Francesca [Department of Pharmacology, University of Bologna, Via Irnerio 48, Bologna 40126 (Italy); Forti, Giorgio Cantelli [Department of Pharmacology, University of Bologna, Via Irnerio 48, Bologna 40126 (Italy); Violante, Francesco Saverio [Department of Biosciences, Karolinska Institute, Novum, Huddinge 141 57 (Sweden); Occupational Medicine Unit, S. Orsola-Malpighi Hospital, Via Pelagi 9, Bologna 40100 (Italy); Lodi, Vittorio [Department of Biosciences, Karolinska Institute, Novum, Huddinge 141 57 (Sweden); Curti, Stefania [Department of Biosciences, Karolinska Institute, Novum, Huddinge 141 57 (Sweden); Hemminki, Kari [Department of Biosciences, Karolinska Institute, Novum, Huddinge 141 57 (Sweden); Hrelia, Patrizia [Department of Pharmacology, University of Bologna, Via Irnerio 48, Bologna 40126 (Italy)

    2005-02-15

    Understanding the risks deriving from protracted exposure to low doses of ionizing radiation has remarkable societal importance in view of the large number of work settings in which sources of IR are encountered. To address this question, we studied the frequency of micronuclei (MN), which is an indicator of DNA damage, in a population exposed to low levels of ionizing radiation and in matched controls. In both exposed population and controls, the possible influence of single nucleotide polymorphisms in XRCC1, XRCC3 and XPD genes on the frequency of micronuclei was also evaluated. We also considered the effects of confounding factors, like smoking status, age and gender. The results indicated that MN frequency was significantly higher in the exposed workers than in the controls [8.62 {+-} 2.80 versus 6.86 {+-} 2.65; P = 0.019]. Radiological workers with variant alleles for XRCC1 or XRCC3 polymorphisms or wild-type alleles for XPD exon 23 or 10 polymorphisms showed a significantly higher MN frequency than controls with the same genotypes. Smoking status did not affect micronuclei frequency either in exposed workers or controls, while age was associated with increased MN frequency in the exposed only. In the combined population, gender but not age exerted an influence on the yield of MN, being higher in females than in males. Even though there is a limitation in this study due to the small number of subjects, these results suggest that even exposures to low level of ionizing radiation could have genotoxic effects and that XRCC3, XRCC1 and XPD polymorphisms might contribute to the increased genetic damage in susceptible individuals occupationally exposed to chronic low levels of ionizing radiation. For a clear conclusion on the induction of DNA damage caused by protracted exposure to low doses of ionizing radiation and the possible influence of genetic polymorphism in DNA repair genes larger studies are needed.

  18. 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

    -{beta}galactosidase activity, which is detectable in senescent cells only, has been not observed in irradiated or non irradiated keratocytes. A slight increase of cell proliferation, according to the exposure, was estimated by incorporation of BrdU in place of thymidine during DNA synthesis and then detected b y immuno-assay. The infrared 1573 nm laser radiation can induce morphological nucleic abnormalities such as giant nucleus, micronuclei and apoptotic bodies. These cellular effects are mostly dose dependent on 3.9 J.cm{sup -2}. Apoptosis is confirmed by the presence of p 53 which induction has been pointed out after 1573 nm laser irradiation. When cellular damages are induced, p 53 starts the process of repair by stopping cell cycle in G 1 or G 2. If DNA damages are too import ant, p 53 can initiate an apoptosis phenomena. In conclusion, the E.D.50 determined in vivo supports the present 1 J.cm{sup -2} exposure limit but the safety margin is reduced. Preliminary assays realized in vitro have shown the possibility to use specific tests at the cellular level and that 1573 nm laser radiation could induce DNA damage. The frequency of apoptotic bodies seemed the most suitable criterion capable to reveal the cellular stress induced by laser exposure. (authors)

  19. DNA Damage/Repair and Polymorphism of the hOGG1 Gene in Lymphocytes of AMD Patients

    Directory of Open Access Journals (Sweden)

    Katarzyna Wozniak

    2009-01-01

    Full Text Available Oxidative stress is thought to play a role in the pathogenesis of age-related macular degeneration (AMD. We determined the extent of oxidative DNA damage and the kinetics of its removal as well as the genotypes of the Ser326Cys polymorphism of the hOGG1 gene in lymphocytes of 30 wet AMD patients and 30 controls. Oxidative DNA damage induced by hydrogen peroxide and its repair were evaluated by the comet assay and DNA repair enzymes. We observed a higher extent of endogenous oxidative DNA damage and a lower efficacy of its repair in AMD patients as compared with the controls. We did not find any correlation between the extent of DNA damage and efficacy of DNA repair with genotypes of the Ser326Cys polymorphism. The results obtained suggest that oxidative DNA damage and inefficient DNA repair can be associated with AMD and the variability of the hOOG1 gene may not contribute to this association.

  20. The Molecular Mechanisms and the Role of hnRNP K Protein Post- Translational Modification in DNA Damage Repair.

    Science.gov (United States)

    Lu, Jing; Gao, Feng-Hou

    2017-01-01

    DNA damage repair is a kind of cellular self-protection mechanism in which some relevant proteins are activated when DNA damage response occurs in order to maintain the intracellular function stability and structure integrity. Post-translational modifications (PTMs) of proteins can rapidly confer to them more complicated structure and sophisticated function by covalently combining different small molecules with target proteins, which in turn plays an important regulatory role in DNA damage repair. It was reported that heterogeneous nuclear ribonucleoprotein K (hnRNP K) could be involved in DNA damage repair process under the regulation of its many post-translational modifications, including methylation, ubiquitination, sumoylation and phosphorylation. Here, we reviewed molecular mechanisms of hnRNP K protein post-translational modifications and their role in DNA damage repair, which will promote our understanding of how hnRNP K participating in the repair process to maintain the normal operation of biological activities in the cells. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. 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.

  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. LNL irradiation facilities for radiation damage studies on electronic devices

    Science.gov (United States)

    Bisello, D.; Candelori, A.; Giubilato, P.; Mattiazzo, S.; Pantano, D.; Silvestrin, L.; Tessaro, M.; Wyss, J.

    2016-11-01

    In this paper we will review the wide range of irradiation facilities installed at the INFN Legnaro National Laboratories and routinely used for radiation damage studies on silicon detectors, electronic components and systems. The SIRAD irradiation facility, dedicated to Single Event Effect (SEE) and bulk damage studies, is installed at the 14MV Tandem XTU accelerator and can deliver ion beams from H up to Au in the energy range from 28MeV to 300MeV. An Ion Electron Emission Microscope, also installed at SIRAD, allows SEE testing with micrometric sensitivity. For total dose tests, two facilities are presently available: an X-rays source and a 60Co γ -ray source. The 7MV Van de Graaff CN accelerator provides 1H beams in the energy range 2-7MeV and currents up to few μA for both total dose and bulk damage studies. At this facility, very high dose rates (up to ˜ 100 krad/s (SiO2)) can be achieved. Finally, also neutron beams are available, produced at the CN accelerator, by the reaction d + Be ⇒ n + B.

  4. Recognition, signaling, and repair of DNA double-strand breaks produced by ionizing radiation in mammalian cells: the molecular choreography.

    Science.gov (United States)

    Thompson, Larry H

    2012-01-01

    The faithful maintenance of chromosome continuity in human cells during DNA replication and repair is critical for preventing the conversion of normal diploid cells to an oncogenic state. The evolution of higher eukaryotic cells endowed them with a large genetic investment in the molecular machinery that ensures chromosome stability. In mammalian and other vertebrate cells, the elimination of double-strand breaks with minimal nucleotide sequence change involves the spatiotemporal orchestration of a seemingly endless number of proteins ranging in their action from the nucleotide level to nucleosome organization and chromosome architecture. DNA DSBs trigger a myriad of post-translational modifications that alter catalytic activities and the specificity of protein interactions: phosphorylation, acetylation, methylation, ubiquitylation, and SUMOylation, followed by the reversal of these changes as repair is completed. "Superfluous" protein recruitment to damage sites, functional redundancy, and alternative pathways ensure that DSB repair is extremely efficient, both quantitatively and qualitatively. This review strives to integrate the information about the molecular mechanisms of DSB repair that has emerged over the last two decades with a focus on DSBs produced by the prototype agent ionizing radiation (IR). The exponential growth of molecular studies, heavily driven by RNA knockdown technology, now reveals an outline of how many key protein players in genome stability and cancer biology perform their interwoven tasks, e.g. ATM, ATR, DNA-PK, Chk1, Chk2, PARP1/2/3, 53BP1, BRCA1, BRCA2, BLM, RAD51, and the MRE11-RAD50-NBS1 complex. Thus, the nature of the intricate coordination of repair processes with cell cycle progression is becoming apparent. This review also links molecular abnormalities to cellular pathology as much a possible and provides a framework of temporal relationships.

  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. DNA damage and gene therapy of xeroderma pigmentosum, a human DNA repair-deficient disease.

    Science.gov (United States)

    Dupuy, Aurélie; Sarasin, Alain

    2015-06-01

    Xeroderma pigmentosum (XP) is a genetic disease characterized by hypersensitivity to ultra-violet and a very high risk of skin cancer induction on exposed body sites. This syndrome is caused by germinal mutations on nucleotide excision repair genes. No cure is available for these patients except a complete protection from all types of UV radiations. We reviewed the various techniques to complement or to correct the genetic defect in XP cells. We, particularly, developed the correction of XP-C skin cells using the fidelity of the homologous recombination pathway during repair of double-strand break (DSB) in the presence of XPC wild type sequences. We used engineered nucleases (meganuclease or TALE nuclease) to induce a DSB located at 90 bp of the mutation to be corrected. Expression of specific TALE nuclease in the presence of a repair matrix containing a long stretch of homologous wild type XPC sequences allowed us a successful gene correction of the original TG deletion found in numerous North African XP patients. Some engineered nucleases are sensitive to epigenetic modifications, such as cytosine methylation. In case of methylated sequences to be corrected, modified nucleases or demethylation of the whole genome should be envisaged. Overall, we showed that specifically-designed TALE-nuclease allowed us to correct a 2 bp deletion in the XPC gene leading to patient's cells proficient for DNA repair and showing normal UV-sensitivity. The corrected gene is still in the same position in the human genome and under the regulation of its physiological promoter. This result is a first step toward gene therapy in XP patients.

  7. 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

    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 24 h. The damage gradually decreased with time, i.e. was smaller at 48 and 72 h than at 24 h 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 reveals that gamma radiation induces single strand breaks in DNA as measured by alkaline comet assay in bivalves and comet assay serves as a sensitive and rapid method to detect genotoxicity of gamma radiation. This study further indicates that both M. casta and P. malabarica exhibit almost identical sensitivity to gamma radiation as measured by DNA damage.

  8. 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

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

    Science.gov (United States)

    Roberts, J.; Gaugliardo, P.; Farnan, I.; Zhang, M.; Vance, E. R.; Davis, J.; Karatchevtseva, I.; Knott, R. B.; Mudie, S.; Buckman, S. J.; Sullivan, J. P.

    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 ∼1019 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.

  10. UV radiation effects on a DNA repair enzyme: conversion of a [4Fe-4S](2+) cluster into a [2Fe-2S] (2+).

    Science.gov (United States)

    Folgosa, Filipe; Camacho, Inês; Penas, Daniela; Guilherme, Márcia; Fróis, João; Ribeiro, Paulo A; Tavares, Pedro; Pereira, Alice S

    2015-03-01

    Organisms are often exposed to different types of ionizing radiation that, directly or not, will promote damage to DNA molecules and/or other cellular structures. Because of that, organisms developed a wide range of response mechanisms to deal with these threats. Endonuclease III is one of the enzymes responsible to detect and repair oxidized pyrimidine base lesions. However, the effect of radiation on the structure/function of these enzymes is not clear yet. Here, we demonstrate the effect of UV-C radiation on E. coli endonuclease III through several techniques, namely UV-visible, fluorescence and Mössbauer spectroscopies, as well as SDS-PAGE and electrophoretic mobility shift assay. We demonstrate that irradiation with a UV-C source has dramatic consequences on the absorption, fluorescence, structure and functionality of the protein, affecting its [4Fe-4S] cluster and its DNA-binding ability, which results in its inactivation. An UV-C radiation-induced conversion of the [4Fe-4S](2+) into a [2Fe-2S](2+) was observed for the first time and proven by Mössbauer and UV-visible analysis. This work also shows that the DNA-binding capability of endonuclease III is highly dependent of the nuclearity of the endogenous iron-sulfur cluster. Thus, from our point of view, in a cellular context, these results strengthen the argument that cellular sensitivity to radiation can also be due to loss of radiation-induced damage repair ability.

  11. Dynamics and mechanism of UV-damaged DNA repair in indole-thymine dimer adduct: molecular origin of low repair quantum efficiency.

    Science.gov (United States)

    Guo, Xunmin; Liu, Zheyun; Song, Qinhua; Wang, Lijuan; Zhong, Dongping

    2015-02-26

    Many biomimetic chemical systems for repair of UV-damaged DNA showed very low repair efficiency, and the molecular origin is still unknown. Here, we report our systematic characterization of the repair dynamics of a model compound of indole-thymine dimer adduct in three solvents with different polarity. By resolving all elementary steps including three electron-transfer processes and two bond-breaking and bond-formation dynamics with femtosecond resolution, we observed the slow electron injection in 580 ps in water, 4 ns in acetonitrile, and 1.38 ns in dioxane, the fast back electron transfer without repair in 120, 150, and 180 ps, and the slow bond splitting in 550 ps, 1.9 ns, and 4.5 ns, respectively. The dimer bond cleavage is clearly accelerated by the solvent polarity. By comparing with the biological repair machine photolyase with a slow back electron transfer (2.4 ns) and a fast bond cleavage (90 ps), the low repair efficiency in the biomimetic system is mainly determined by the fast back electron transfer and slow bond breakage. We also found that the model system exists in a dynamic heterogeneous C-clamped conformation, leading to a stretched dynamic behavior. In water, we even identified another stacked form with ultrafast cyclic electron transfer, significantly reducing the repair efficiency. Thus, the comparison of the repair efficiency in different solvents is complicated and should be cautious, and only the dynamics by resolving all elementary steps can finally determine the total repair efficiency. Finally, we use the Marcus electron-transfer theory to analyze all electron-transfer reactions and rationalize all observed electron-transfer dynamics.

  12. Development and Evaluation of Cement-Based Materials for Repair of Corrosion-Damaged Reinforced Concrete Slabs

    OpenAIRE

    Liu, Rongtang; Olek, J.

    2001-01-01

    In this study, the results of an extensive laboratory investigation conducted to evaluate the properties of concrete mixes used as patching materials to repair reinforced concrete slabs damaged by corrosion are reported. Seven special concrete mixes containing various combinations of chemical or mineral admixtures were developed and used as a patching material to improve the durability of the repaired slabs. Physical and mechanical properties of these mixes, such as compressive strength, stat...

  13. p38γ regulates UV-induced checkpoint signaling and repair of UV-induced DNA damage.

    Science.gov (United States)

    Wu, Chia-Cheng; Wu, Xiaohua; Han, Jiahuai; Sun, Peiqing

    2010-06-01

    In eukaryotic cells, DNA damage triggers activation of checkpoint signaling pathways that coordinate cell cycle arrest and repair of damaged DNA. These DNA damage responses serve to maintain genome stability and prevent accumulation of genetic mutations and development of cancer. The p38 MAPK was previously implicated in cellular responses to several types of DNA damage. However, the role of each of the four p38 isoforms and the mechanism for their involvement in DNA damage responses remained poorly understood. In this study, we demonstrate that p38γ, but not the other p38 isoforms, contributes to the survival of UV-treated cells. Deletion of p38γ sensitizes cells to UV exposure, accompanied by prolonged S phase cell cycle arrest and increased rate of apoptosis. Further investigation reveal that p38γ is essential for the optimal activation of the checkpoint signaling caused by UV, and for the efficient repair of UV-induced DNA damage. These findings have established a novel role of p38γ in UV-induced DNA damage responses, and suggested that p38γ contributes to the ability of cells to cope with UV exposure by regulating the checkpoint signaling pathways and the repair of damaged DNA.

  14. 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.)

  15. Rapid Repair of Earthquake Damaged RC Interior Beam-wide Column Joints and Beam-wall Joints Using FRP Composites

    Institute of Scientific and Technical Information of China (English)

    LI Bing; LIM Chee Leong

    2009-01-01

    This paper studies the seismic performance of FRP-strengthened RC interior non-seismically detailed beam-wide columns and beam-wall joints after limited seismic damage. Four eccentric and concentric beam-wide column joints and two beam-wall joints, initially damaged in a previous study, were repaired and tested under constant axial loads (0. \\fc'Ag and 0. 35 fc'Ag ) and lateral cyclic loading. The rapid repair technique developed, aimed to restore the original strength and to provide minimum drift capacity. The repair schemes were characterized by the use of; (a) epoxy injections and polymer modified cementitious mortar to seal the cracks and replace spalled concrete; and (b) glass (GFRP) and carbon (CFRP) sheets to enhance the joint performance. The FRP sheets were effectively prevented against possible debonding through the use of fiber anchors. Comparison between responses of specimens before and after repair clearly indicated reasonable restoration in strength, drift capacity, stiffness and cumulative energy dissipation capacity. All specimens failed with delamination of FRP sheets at beam-column joint interfaces. The rapid repair technique developed in this study is recommended for mass upgrading or repair of earthquake damaged beam-column joints.

  16. XAFS studies of radiation damage in nuclear materials

    Science.gov (United States)

    Olive, Daniel Thomas

    The growing demand for nuclear energy places a high importance on the development of new materials capable of withstanding higher temperatures and harsher irradiation conditions than those used in existing reactors. By supporting the development of next generation reactors it also becomes possible to close the nuclear fuel cycle, greatly reducing the amount of waste sent for disposal in deep geologic repositories, where its interaction with the environment is also a matter of interest. In this thesis, X-ray absorption fine structure (XAFS) spectroscopy is used to investigate the local atomic structure of systems of interest to nuclear energy. First, two XAFS studies on environmental materials are presented. Granular activated carbon (GAC) was treated with iron to improve its water remediation properties, specifically with respect to arsenic. XAFS was used to determine the nature of iron coating on the GAC surface, and the method of arsenic bonding to the treated surface. Next, a neodymium precipitate from solubility studies carried out for the Waste Isolation Pilot Plant (WIPP) was analyzed. Neodymium was used as an analog for plutonium in brine solutions. XAFS fitting indicated that the neodymium substituted for calcium in a gypsum lattice, providing information useful for future geochemical modeling. XAFS was also used to study radiation damage in materials. A candidate material for advanced reactor structural materials, modified 9Cr--1Mo, was irradiated to 1, 4, and 10 displacements per atom (dpa). XAFS analyses were performed on the Fe, Mo, and Nb K-edges. Irradiation caused a reduction in coordination for all three elements, but the exact behavior was element specific. Damage around Fe atoms was linear with dose, while damage around Mo atoms saturated at or before 1 dpa. XAFS was shown to provide a useful atomic level description of radiation damage for a complex alloy system. Finally, zirconium carbide and zirconium nitride, candidate materials for advanced

  17. Induction of DNA repair synthesis by ultraviolet radiation and methylmethanesulphonate in cultured mouse lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Bianchi, V.; Zantedeschi, A.; Levis, A.G. (Padua Univ. (Italy). Ist. di Zoologia e Anatomia Comparata); Ronchese, F. (Inst. of Pathological Anatomy, Padua (Italy))

    1983-02-01

    The induction of DNA repair synthesis by UV-radiation and methylmethanesulphonate (MMS) was studied in mouse lymphocytes and leukemic cells by means of autoradiography and scintillation counting, after labelling in vitro with tritiated thymidine ((/sup 3/H)dThd). Repair stimulation was detected by both procedures in LSTRA AND YC8 leukemic cell lines as well as in primary fibroblasts of BALB/c and BALB/Mo mice. No stimulation was observed in primary cultures of lymphocytes from the spleen, thymus and lymph-nodes of the same mice. In primary lymphocytes neither stimulation with concanavalin A (Con A) nor pre-incubation with 5-bromodeoxyuridine (BUdR) were effective in making evident DNA repair. The data put into question the reliability of the repair test for the prediction of carcinogenic potential of chemicals.

  18. Studies of DNA repair in saccharomyces cerevisiae. I. Characterization of a new allele of RAD6. II. Investigation of events in the first cell cycle after DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Douthwright-Fasse, Jane Ann

    1979-01-01

    Studies in two independent, but related, areas of DNA repair have been carried out in Saccharomyces cerevisiae; characterization of a new allele in the RAD6 gene which suggests that the gene is multifunctional, and utilization of photoreactivation as a probe of events occurring during the first cell cycle after DNA damage. Strains carrying the new allele, designated rad6-4, are as sensitive to uv and ionizing radiation as those carrying rad6-1 or rad6-3 but, unlike them, are capable of induced mutagenesis and sporulation. Although rad6-4 may well be a missense mutation, the evidence shows that it is unlikely that this phenotype is due to leakiness. Instead, the data suggest that the RAD6 gene is multifunctional. One function is necessary to recover from DNA damage in an error-free manner, and the other is concerned with mutagenic processes and sporulation. Rad6-1 and rad6-3 strains are deficient in both of these functions, while rad6-4 strains are deficient only in the error-free function. The loss of photoreversibility (LOP) of ultraviolet induced mutations to arginine independence in an excision defective strain carrying arg4-17 examines the events occurring in the first cell cycle after DNA damage. LOP is dependent upon de novo protein synthesis. LOP begins immediately after UV irradiation, before semiconservative DNA synthesis takes place, and is complete after four hours in growth medium.There is no evidence indicating whether the normal function of the protein is involved in excision repair, or in one of the two repair processes believed to be inducible; induced mutagenesis or recombinational repair.

  19. 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.

  20. Radiation Damage Studies with Hadrons on Materials and Electronics

    Energy Technology Data Exchange (ETDEWEB)

    Spencer, J

    2004-07-01

    Many materials and electronics need to be tested for the radiation environment expected at linear colliders (LC) where the accelerator and detectors will be subjected to large fluences of hadrons, leptons and {gamma}'s over their life[1]. Examples are NdFeB magnets considered for the damping rings and final focus, electronic and electro-optical devices to be utilized in detector readout and accelerator controls and CCDs required for the vertex detector. Effects of {gamma}'s on many materials have been presented[2] and our understanding of the situation for rare earth permanent magnets at PAC2003[3]. Here we give first measurements of the fast neutron, stepped doses at the UC Davis McClellan Nuclear Reactor Center (UCD MNRC) together with the induced radioactivities. Damage appears to be proportional to the distances between the operating point and H{sub ci}.

  1. Radiation damage/activity calculation for CSNS target station

    Science.gov (United States)

    Yin, W.; Liang, T. J.; Yu, Q. Z.; Jia, X. J.

    2010-03-01

    The radiation damages have been performed for Chinese spallation neutron source (CSNS) target center components that relies on Monte Carlo simulation code MCNPX. During the calculation, Bertini intranuclear cascade model, three level-density formulation GCCI, and multistage pre-equilibrium model MPM on which are provided within MCNPX are employed. We calculate the displacement per atom (DPA) and afterheat of the tungsten target, the stainless steel target vessel window and the aluminum alloy moderator vessel. As a hundred kW-level source, these spallation center components have the lifetime more than 5 year. We also give the activity for the T0 chopper of the beam line HIPD to get the primary data for making out a maintenance scenario.

  2. Chromatin compaction protects genomic DNA from radiation damage.

    Directory of Open Access Journals (Sweden)

    Hideaki Takata

    Full Text Available Genomic DNA is organized three-dimensionally in the nucleus, and is thought to form compact chromatin domains. Although chromatin compaction is known to be essential for mitosis, whether it confers other advantages, particularly in interphase cells, remains unknown. Here, we report that chromatin compaction protects genomic DNA from radiation damage. Using a newly developed solid-phase system, we found that the frequency of double-strand breaks (DSBs in compact chromatin after ionizing irradiation was 5-50-fold lower than in decondensed chromatin. Since radical scavengers inhibited DSB induction in decondensed chromatin, condensed chromatin had a lower level of reactive radical generation after ionizing irradiation. We also found that chromatin compaction protects DNA from attack by chemical agents. Our findings suggest that genomic DNA compaction plays an important role in maintaining genomic integrity.

  3. Hypothermia postpones DNA damage repair in irradiated cells and protects against cell killing

    Energy Technology Data Exchange (ETDEWEB)

    Baird, Brandon J.; Dickey, Jennifer S.; Nakamura, Asako J.; Redon, Christophe E.; Parekh, Palak [Laboratory of Molecular Pharmacology, CCR, NCI, Bethesda, MD 20892 (United States); Griko, Yuri V. [Radiation and Space Biotechnology Branch, NASA Ames Research Center, Moffett Field, CA 94035 (United States); Aziz, Khaled; Georgakilas, Alexandros G. [Biology Department, East Carolina University, Greenville, NC 27858 (United States); Bonner, William M. [Laboratory of Molecular Pharmacology, CCR, NCI, Bethesda, MD 20892 (United States); Martin, Olga A., E-mail: sedelnio@mail.nih.gov [Laboratory of Molecular Pharmacology, CCR, NCI, Bethesda, MD 20892 (United States)

    2011-06-03

    Hibernation is an established strategy used by some homeothermic organisms to survive cold environments. In true hibernation, the core body temperature of an animal may drop to below 0 {sup o}C and metabolic activity almost cease. The phenomenon of hibernation in humans is receiving renewed interest since several cases of victims exhibiting core body temperatures as low as 13.7 {sup o}C have been revived with minimal lasting deficits. In addition, local cooling during radiotherapy has resulted in normal tissue protection. The experiments described in this paper were prompted by the results of a very limited pilot study, which showed a suppressed DNA repair response of mouse lymphocytes collected from animals subjected to 7-Gy total body irradiation under hypothermic (13 {sup o}C) conditions, compared to normothermic controls. Here we report that human BJ-hTERT cells exhibited a pronounced radioprotective effect on clonogenic survival when cooled to 13 {sup o}C during and 12 h after irradiation. Mild hypothermia at 20 and 30 {sup o}C also resulted in some radioprotection. The neutral comet assay revealed an apparent lack on double strand break (DSB) rejoining at 13 {sup o}C. Extension of the mouse lymphocyte study to ex vivo-irradiated human lymphocytes confirmed lower levels of induced phosphorylated H2AX ({gamma}-H2AX) and persistence of the lesions at hypothermia compared to the normal temperature. Parallel studies of radiation-induced oxidatively clustered DNA lesions (OCDLs) revealed partial repair at 13 {sup o}C compared to the rapid repair at 37 {sup o}C. For both {gamma}-H2AX foci and OCDLs, the return of lymphocytes to 37 {sup o}C resulted in the resumption of normal repair kinetics. These results, as well as observations made by others and reviewed in this study, have implications for understanding the radiobiology and protective mechanisms underlying hypothermia and potential opportunities for exploitation in terms of protecting normal tissues against

  4. Repair of ultraviolet-damaged transforming DNA in a mismatch repair-deficient strain of Haemophilus influenzae

    Energy Technology Data Exchange (ETDEWEB)

    Bagci, H.; Stuy, J.H. (Florida State Univ., Tallahassee (USA). Dept. of Biological Science)

    1982-03-01

    Ultraviolet inactivation of Haemophilus influenzae transforming DNA followed inverse square root kinetics in both mismatch repair-proficient (hex/sup +/) and deficient (hex-1) recipients. No DNA concentration effect was seen with UV-excision repair-deficient (uvr/sup -/) strains. Low-efficiency genetic markers remained more sensitive than high-efficiency ones when they were assayed on excision repair-deficient hex/sup +/ uvr/sup -/ strains. They were equally resistant when hex/sup -/ uvr/sup -/ recipients were used. This was explained by assuming that recombinational repair of UV lesions in the donor strand and mismatch repair of the recipient strand may overlap and cause double strand interruptions. This will eliminate low-efficiency transformants.

  5. Alpha-phellandrene-induced DNA damage and affect DNA repair protein expression in WEHI-3 murine leukemia cells in vitro.

    Science.gov (United States)

    Lin, Jen-Jyh; Wu, Chih-Chung; Hsu, Shu-Chun; Weng, Shu-Wen; Ma, Yi-Shih; Huang, Yi-Ping; Lin, Jaung-Geng; Chung, Jing-Gung

    2015-11-01

    Although there are few reports regarding α-phellandrene (α-PA), a natural compound from Schinus molle L. essential oil, there is no report to show that α-PA induced DNA damage and affected DNA repair associated protein expression. Herein, we investigated the effects of α-PA on DNA damage and repair associated protein expression in murine leukemia cells. Flow cytometric assay was used to measure the effects of α-PA on total cell viability and the results indicated that α-PA induced cell death. Comet assay and 4,6-diamidino-2-phenylindole dihydrochloride staining were used for measuring DNA damage and condensation, respectively, and the results indicated that α-PA induced DNA damage and condensation in a concentration-dependent manner. DNA gel electrophoresis was used to examine the DNA damage and the results showed that α-PA induced DNA damage in WEHI-3 cells. Western blotting assay was used to measure the changes of DNA damage and repair associated protein expression and the results indicated that α-PA increased p-p53, p-H2A.X, 14-3-3-σ, and MDC1 protein expression but inhibited the protein of p53, MGMT, DNA-PK, and BRCA-1.

  6. Bisdemethoxycurcumin induces DNA damage and inhibits DNA repair associated protein expressions in NCI-H460 human lung cancer cells.

    Science.gov (United States)

    Yu, Chien-Chih; Yang, Su-Tso; Huang, Wen-Wen; Peng, Shu-Fen; Huang, An-Cheng; Tang, Nou-Ying; Liu, Hsin-Chung; Yang, Mei-Due; Lai, Kuang-Chi; Chung, Jing-Gung

    2016-12-01

    Nonsmall cell lung carcinoma (NSCLC) is a devastating primary lung tumor resistant to conventional therapies. Bisdemethoxycurcumin (BDMC) is one of curcumin derivate from Turmeric and has been shown to induce NSCLC cell death. Although there is one report to show BDMC induced DNA double strand breaks, however, no available information to show BDMC induced DNA damage action with inhibited DNA repair protein in lung cancer cells in detail. In this study, we tested BDMC-induced DNA damage and condensation in NCI-H460 cells by using Comet assay and DAPI staining examinations, respectively and we found BDMC induced DNA damage and condension. Western blotting was used to examine the effects of BDMC on protein expression associated with DNA damage and repair and results indicated that BDMC suppressed the protein levels associated with DNA damage and repair, such as 14-3-3σ (an important checkpoint keeper of DDR), O6-methylguanine-DNA methyltransferase, DNA repair proteins breast cancer 1, early onset, mediator of DNA damage checkpoint 1 but activate phosphorylated p53 and p-H2A.X (phospho Ser140) in NCI-H460 cells. Confocal laser systems microscopy was used for examining the protein translocation and results show that BDMC increased the translocation of p-p53 and p-H2A.X (phospho Ser140) from cytosol to nuclei in NCI-H460 cells. In conclusion, BDMC induced DNA damage and condension and affect DNA repair proteins in NCI-H460 cells in vitro. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1859-1868, 2016. © 2015 Wiley Periodicals, Inc.

  7. 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.

  8. 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.)

  9. 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)

  10. 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.

  11. Direct detection and quantification of abasic sites for in vivo studies of DNA damage and repair

    Energy Technology Data Exchange (ETDEWEB)

    Wang Yanming [Division of Radiopharmaceutical Science, Case Center for Imaging Research, Department of Radiology, Case Western Reserve University, Cleveland, OH 44122 (United States)], E-mail: yanming.wang@case.edu; Liu Lili [Department of Hematology and Oncology, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44122 (United States); Wu Chunying [Division of Radiopharmaceutical Science, Case Center for Imaging Research, Department of Radiology, Case Western Reserve University, Cleveland, OH 44122 (United States); Bulgar, Alina [Department of Hematology and Oncology, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44122 (United States); Somoza, Eduardo; Zhu Wenxia [Division of Radiopharmaceutical Science, Case Center for Imaging Research, Department of Radiology, Case Western Reserve University, Cleveland, OH 44122 (United States); Gerson, Stanton L. [Department of Hematology and Oncology, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44122 (United States)

    2009-11-15

    Use of chemotherapeutic agents to induce cytotoxic DNA damage and programmed cell death is a key strategy in cancer treatments. However, the efficacy of DNA-targeted agents such as temozolomide is often compromised by intrinsic cellular responses such as DNA base excision repair (BER). Previous studies have shown that BER pathway resulted in formation of abasic or apurinic/apyrimidinic (AP) sites, and blockage of AP sites led to a significant enhancement of drug sensitivity due to reduction of DNA base excision repair. Since a number of chemotherapeutic agents also induce formation of AP sites, monitoring of these sites as a clinical correlate of drug effect will provide a useful tool in the development of DNA-targeted chemotherapies aimed at blocking abasic sites from repair. Here we report an imaging technique based on positron emission tomography (PET) that allows for direct quantification of AP sites in vivo. For this purpose, positron-emitting carbon-11 has been incorporated into methoxyamine ([{sup 11}C]MX) that binds covalently to AP sites with high specificity. The binding specificity of [{sup 11}C]MX for AP sites was demonstrated by in vivo blocking experiments. Using [{sup 11}C]MX as a radiotracer, animal PET studies have been conducted in melanoma and glioma xenografts for quantification of AP sites. Following induction of AP sites by temozolomide, both tumor models showed significant increase of [{sup 11}C]MX uptake in tumor regions in terms of radioactivity concentration as a function of time, which correlates well with conventional aldehyde reactive probe (ARP)-based bioassays for AP sites.

  12. Use of Displacement Damage Dose in an Engineering Model of GaAs Solar Cell Radiation Damage

    Science.gov (United States)

    Morton, T. L.; Chock, R.; Long, K. J.; Bailey, S.; Messenger, S. R.; Walters, R. J.; Summers, G. P.

    2005-01-01

    Current methods for calculating damage to solar cells are well documented in the GaAs Solar Cell Radiation Handbook (JPL 96-9). An alternative, the displacement damage dose (D(sub d)) method, has been developed by Summers, et al. This method is currently being implemented in the SAVANT computer program.

  13. Nonhomologous end-joining repair plays a more important role than homologous recombination repair in defining radiosensitivity after exposure to high-LET radiation.

    Science.gov (United States)

    Takahashi, Akihisa; Kubo, Makoto; Ma, Hongyu; Nakagawa, Akiko; Yoshida, Yukari; Isono, Mayu; Kanai, Tatsuaki; Ohno, Tatsuya; Furusawa, Yoshiya; Funayama, Tomoo; Kobayashi, Yasuhiko; Nakano, Takashi

    2014-09-01

    DNA double-strand breaks (DSBs) induced by ionizing radiation pose a major threat to cell survival. The cell can respond to the presence of DSBs through two major repair pathways: homologous recombination (HR) and nonhomologous end joining (NHEJ). Higher levels of cell death are induced by high-linear energy transfer (LET) radiation when compared to low-LET radiation, even at the same physical doses, due to less effective and efficient DNA repair. To clarify whether high-LET radiation inhibits all repair pathways or specifically one repair pathway, studies were designed to examine the effects of radiation with different LET values on DNA DSB repair and radiosensitivity. Embryonic fibroblasts bearing repair gene (NHEJ-related Lig4 and/or HR-related Rad54) knockouts (KO) were used and their responses were compared to wild-type cells. The cells were exposed to X rays, spread-out Bragg peak (SOBP) carbon ion beams as well as with carbon, iron, neon and argon ions. Cell survival was measured with colony-forming assays. The sensitization enhancement ratio (SER) values were calculated using the 10% survival dose of wild-type cells and repair-deficient cells. Cellular radiosensitivity was listed in descending order: double-KO cells > Lig4-KO cells > Rad54-KO cells > wild-type cells. Although Rad54-KO cells had an almost constant SER value, Lig4-KO cells showed a high-SER value when compared to Rad54-KO cells, even with increasing LET values. These results suggest that with carbon-ion therapy, targeting NHEJ repair yields higher radiosensitivity than targeting homologous recombination repair.

  14. Assessment of Damage to Nucleic Acids and Repair Machinery in Salmonella typhimurium Exposed to Chlorine

    Directory of Open Access Journals (Sweden)

    M. H. Phe

    2009-01-01

    Full Text Available Water disinfection is usually evaluated using mandatory methods based on cell culturability. However, such methods do not consider the potential of cells to recover, which should also be kept as low as possible. In this paper, we hypothesized that a successful disinfection is achieved only when the applied chlorine leads to both intracellular nucleic acid damage and strong alterations of the DNA repair machinery. Monitoring the SOS system responsiveness with a umuC'-‘lacZ reporter fusion, we found that the expression of this important cellular machinery was altered after the beginning of membrane permeabilization but prior to the total decline of both the cell culturability and the nucleic acid integrity as revealed by Sybr-II staining. Rapid measurement of such nucleic acid alterations by fluorochrome-based staining could be used as an alternative method for assessing the effectiveness of disinfection with chlorine.

  15. Repair of ultraviolet light-induced DNA damage in cholera bacteriophages

    Energy Technology Data Exchange (ETDEWEB)

    Palit, B.N.; Das, G.; Das, J. (Indian Inst. of Chemical Biology, Calcutta. Dept. of Biophysics)

    1983-08-01

    DNA repair-proficient and -deficient strains of Vibrio cholerae were used to examine host cell reactivation, Weigle reactivation and photoreactivation of u.v.-irradiated cholera bacteriophages. U.v. light-induced DNA damage in phages of different morphological and serological groups could be efficiently photoreactivated. Host cell reactivation of irradiated phages of different groups was different on the same indicator host. Phage phi149 was the most sensitive, and phi138 the most resistant to u.v. irradiation. While phi138 showed appreciable host cell reactivation, this was minimal for phi149. Attempts to demonstrate Weigle reactivation of u.v.-irradiated cholera phages were not successful, although u.v.-induced filamentation of host cells was observed.

  16. Tai chi improves oxidative stress response and DNA damage/repair in young sedentary females.

    Science.gov (United States)

    Huang, Xing-Yu; Eungpinichpong, Wichai; Silsirivanit, Atit; Nakmareong, Saowanee; Wu, Xiu-Hua

    2014-06-01

    [Purpose] This study was to examine the effects of 12 weeks of Tai Chi (TC) exercise on antioxidant capacity, and DNA damage/repair in young females who did not perform regular physical exercise. [Subjects and Methods] Ten female students from a Chinese university voluntarily participated in this program. All of them practiced the 24-form simplified Tai Chi, 5 times weekly, for 12 weeks. Plasma levels of superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA), glutathione (GSH), hydroxyl radical inhibiting capacity (OH·-IC), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and 8-oxoguanine DNA glycosylase (OGG1) were measured at 0, 8, and 12 weeks. Heart rate (HR) was monitored during the last set of the training session at 4, 8, and 12 weeks. [Results] Plasma SOD and OH·-IC levels were increased at 8 and 12 weeks compared to the baseline (0 weeks). Gpx and GSH levels did not change significantly throughout the study period. The plasma MDA level was decreased significantly at 8 weeks but not at 12 weeks compared to the baseline value. While the plasma 8-OHdG level did not change throughout the study period, the plasma OGG1 level was significantly increased at 8 and 12 weeks compared to the baseline value. [Conclusion] TC practice for 12 weeks efficiently improved the oxidative stress response in young females who did not perform regular physical exercise. The TC exercise also increased the DNA repairing capacity.

  17. The role of Holliday junction resolvases in the repair of spontaneous and induced DNA damage.

    Science.gov (United States)

    Agmon, Neta; Yovel, Moran; Harari, Yaniv; Liefshitz, Batia; Kupiec, Martin

    2011-09-01

    DNA double-strand breaks (DSBs) and other lesions occur frequently during cell growth and in meiosis. These are often repaired by homologous recombination (HR). HR may result in the formation of DNA structures called Holliday junctions (HJs), which need to be resolved to allow chromosome segregation. Whereas HJs are present in most HR events in meiosis, it has been proposed that in vegetative cells most HR events occur through intermediates lacking HJs. A recent screen in yeast has shown HJ resolution activity for a protein called Yen1, in addition to the previously known Mus81/Mms4 complex. Yeast strains deleted for both YEN1 and MMS4 show a reduction in growth rate, and are very sensitive to DNA-damaging agents. In addition, we investigate the genetic interaction of yen1 and mms4 with mutants defective in different repair pathways. We find that in the absence of Yen1 and Mms4 deletion of RAD1 or RAD52 have no further effect, whereas additional sensitivity is seen if RAD51 is deleted. Finally, we show that yeast cells are unable to carry out meiosis in the absence of both resolvases. Our results show that both Yen1 and Mms4/Mus81 play important (although not identical) roles during vegetative growth and in meiosis.

  18. Harnessing neural activity to promote repair of the damaged corticospinal system after spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    John H. Martin

    2016-01-01

    As most spinal cord injuries (SCIs) are incomplete, an important target for promoting neural repair and recovery of lost motor function is to promote the connections of spared descending spinal pathways with spinal motor circuits. Among the pathways, the corticospinal tract (CST) is most associated with skilled voluntary functions in humans and many animals. CST loss, whether at its origin in the motor cortex or in the white matter tracts subcortically and in the spinal cord, leads to movement impairments and paraly-sis. To restore motor function after injury will require repair of the damaged CST. In this review, I discuss how knowledge of activity-dependent development of the CST—which establishes connectional speci-ifcity through axon pruning, axon outgrowth, and synaptic competition among CST terminals—informed a novel activity-based therapy for promoting sprouting of spared CST axons after injur in mature animals. This therapy, which comprises motor cortex electrical stimulation with and without concurrent trans-spi-nal direct current stimulation, leads to an increase in the gray matter axon length of spared CST axons in the rat spinal cord and, after a pyramidal tract lesion, restoration of skilled locomotor movements. I discuss how this approach is now being applied to a C4 contusion rat model.

  19. Harnessing neural activity to promote repair of the damaged corticospinal system after spinal cord injury

    Directory of Open Access Journals (Sweden)

    John H Martin

    2016-01-01

    Full Text Available As most spinal cord injuries (SCIs are incomplete, an important target for promoting neural repair and recovery of lost motor function is to promote the connections of spared descending spinal pathways with spinal motor circuits. Among the pathways, the corticospinal tract (CST is most associated with skilled voluntary functions in humans and many animals. CST loss, whether at its origin in the motor cortex or in the white matter tracts subcortically and in the spinal cord, leads to movement impairments and paralysis. To restore motor function after injury will require repair of the damaged CST. In this review, I discuss how knowledge of activity-dependent development of the CST-which establishes connectional specificity through axon pruning, axon outgrowth, and synaptic competition among CST terminals-informed a novel activity-based therapy for promoting sprouting of spared CST axons after injur in mature animals. This therapy, which comprises motor cortex electrical stimulation with and without concurrent trans-spinal direct current stimulation, leads to an increase in the gray matter axon length of spared CST axons in the rat spinal cord and, after a pyramidal tract lesion, restoration of skilled locomotor movements. I discuss how this approach is now being applied to a C 4 contusion rat model.

  20. Assessment by Southern blot analysis of UV-induced damage and repair in human immunoglobulin genes.

    Science.gov (United States)

    Bianchi, M S; Bianchi, N O; de la Chapelle, A

    1990-09-01

    Irradiation of DNA with UV light induces pyrimidine dimers and (6-4) photoproducts. The presence of one of these photolesions in the restriction site of a given endonuclease inhibits DNA cleavage and induces the formation of fragments by incomplete DNA digestion which appear as additional, facultative bands in Southern hybridization autoradiograms. The number and size of these fragments show a positive correlation with the UV dose. The response to UV light of immunoglobulin light-chain constant kappa and heavy-chain constant mu genes was analyzed with 2 specific probes. Constant kappa and mu genes when irradiated as part of the chromatin of living lymphocytes showed a UV sensitivity similar to that of naked DNA. The same genes from granulocytes had 50-60 times lower UV sensitivity. When cells were allowed to repair photolesions for 24 h the facultative bands from granulocytes disappeared indicating that these cells were able to remove photolesions from constant kappa and mu genes. Facultative bands from lymphocytes showed a smaller decrease of density after 24 h repair. This suggests that lymphocytes are less efficient than granulocytes in removing UV damage from constant kappa and mu genes.

  1. The Fanconi anemia pathway: Repairing the link between DNA damage and squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Romick-Rosendale, Lindsey E. [Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children' s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229 (United States); Lui, Vivian W.Y.; Grandis, Jennifer R. [Department of Otolaryngology, University of Pittsburgh School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213 (United States); Wells, Susanne I., E-mail: Susanne.Wells@cchmc.org [Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children' s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229 (United States)

    2013-03-15

    Fanconi anemia (FA) is a rare inherited recessive disease caused by mutations in one of fifteen genes known to encode FA pathway components. In response to DNA damage, nuclear FA proteins associate into high molecular weight complexes through a cascade of post-translational modifications and physical interactions, followed by the repair of damaged DNA. Hematopoietic cells are particularly sensitive to the loss of these interactions, and bone marrow failure occurs almost universally in FA patients. FA as a disease is further characterized by cancer susceptibility, which highlights the importance of the FA pathway in tumor suppression, and will be the focus of this review. Acute myeloid leukemia is the most common cancer type, often subsequent to bone marrow failure. However, FA patients are also at an extreme risk of squamous cell carcinoma (SCC) of the head and neck and gynecological tract, with an even greater incidence in those individuals who have received a bone marrow transplant and recovered from hematopoietic disease. FA tumor suppression in hematopoietic versus epithelial compartments could be mechanistically similar or distinct. Definition of compartment specific FA activities is now critical to assess the effects of today's bone marrow failure treatments on tomorrow's solid tumor development. It is our hope that current therapies can then be optimized to decrease the risk of malignant transformation in both hematopoietic and epithelial cells. Here we review our current understanding of the mechanisms of action of the Fanconi anemia pathway as it contributes to stress responses, DNA repair and squamous cell carcinoma susceptibility.

  2. Methotrexate induces DNA damage and inhibits homologous recombination repair in choriocarcinoma cells

    Directory of Open Access Journals (Sweden)

    Xie L

    2016-11-01

    Full Text Available Lisha Xie,1,* Tiancen Zhao,1,2,* Jing Cai,1 You Su,1 Zehua Wang,1 Weihong Dong1 1Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 2Department of Obstetrics and Gynecology, Central Hospital of Wuhan, Wuhan, China *These authors contributed equally to this work Objective: The objective of this study was to investigate the mechanism of sensitivity to methotrexate (MTX in human choriocarcinoma cells regarding DNA damage response. Methods: Two choriocarcinoma cancer cell lines, JAR and JEG-3, were utilized in this study. An MTX-sensitive osteosarcoma cell line MG63, an MTX-resistant epithelial ovarian cancer cell line A2780 and an MTX-resistant cervical adenocarcinoma cell line Hela served as controls. Cell viability assay was carried out to assess MTX sensitivity of cell lines. MTX-induced DNA damage was evaluated by comet assay. Quantitative reverse transcription polymerase chain reaction was used to detect the mRNA levels of BRCA1, BRCA2, RAD51 and RAD52. The protein levels of γH2AX, RAD 51 and p53 were analyzed by Western blot. Results: Remarkable DNA strand breaks were observed in MTX-sensitive cell lines (JAR, JEG-3 and MG63 but not in MTX-resistant cancer cells (A2780 and Hela after 48 h of MTX treatment. Only in the choriocarcinoma cells, the expression of homologous recombination (HR repair gene RAD51 was dramatically suppressed by MTX in a dose- and time-dependent manner, accompanied with the increase in p53. Conclusion: The MTX-induced DNA strand breaks accompanied by deficiencies in HR repair may contribute to the hypersensitivity to chemotherapy in choriocarcinoma. Keywords: choriocarcinoma, chemotherapy hypersensitivity, DNA double-strand break, RAD51, p53

  3. Calmodulin Mediates DNA Repair Pathways Involving H2AX in Response to Low-Dose Radiation Exposure of RAW 264.7 Macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Smallwood, Heather S.; Lopez Ferrer, Daniel; Eberlein, P. Elis; Watson, David J.; Squier, Thomas C.

    2009-02-05

    Understanding the molecular mechanisms that modulate macrophage radioresistance is necessary for the development of effective radiation therapies, as tumor-associated macrophages promote both angiogenesis and matrix remodeling that, in turn, enhance metastasis. In this respect, we have identified a dose-dependent increase in the abundance of the calcium regulatory protein calmodulin (CaM) in RAW 264.7 macrophages upon irradiation. CaM overexpression results in increased macrophage survival following radiation exposure, acting to diminish the sensitivity to low-dose exposures. Increases in CaM abundance also result in an increase in the number of phosphorylated histone H2AX protein complexes associated with DNA repair following macrophage irradiation, with no change in the extent of double-stranded DNA damage. In comparison, when NFκB-dependent pathways are inhibited, through the expression of a dominant-negative IκB construct, there is no significant increase in phosphorylated H2AX upon irradiation. These results indicate that the molecular basis for the up-regulation of histone H2AX mediated DNA-repair pathways is not the result of nonspecific NFκB-dependent pathways or a specific threshold of DNA damage. Rather, increases in CaM abundance act to minimize the low-dose hypersensitivity to radiation to enhance macrophage radioresistance through processes that include the upregulation of DNA repair pathways involving histone protein H2AX phosphorylation.

  4. ShaPINg cell fate upon DNA damage:role of Pin1 isomerase in DNA damage-induced cell death and repair

    Directory of Open Access Journals (Sweden)

    Thomas G Hofmann

    2014-06-01

    Full Text Available The peptidyl-prolyl cis/trans isomerase Pin1 acts as a molecular timer in proline-directed Ser/Thr kinase signaling and shapes cellular responses based on recognition of phosphorylation marks and implementing conformational changes in its substrates. Accordingly, Pin1 has been linked to numerous phosphorylation-controlled signaling pathways and cellular processes such as cell cycle progression, proliferation and differentiation. In addition, Pin1 plays a pivotal role in DNA damage-triggered cell fate decisions. Whereas moderate DNA damage is balanced by DNA repair, cells confronted with massive genotoxic stress are eliminated by the induction of programmed cell death or cellular senescence. In this review we summarize and discuss the current knowledge on how Pin1 specifies cell fate through regulating key players of the apoptotic and the repair branch of the DNA damage response.

  5. 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

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