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Sample records for biological damage induced

  1. Pressure pulse induced-damage in live biological samples

    NASA Astrophysics Data System (ADS)

    Bo, C.; Balzer, J.; Godfrey, S.; Francois, M.; Saffell, J. L.; Rankin, S. M.; Proud, W. G.; Brown, K. A.

    2012-08-01

    Developing a cellular and molecular understanding of the nature of traumatic and post-traumatic effects of blast on live biological samples is critical for improving clinical outcomes. To analyze the effects of blast waves upon the cellular structures and the underlying physiological and biochemical changes, we have constructed an experimental platform capable of delivering compression waves, of amplitudes relevant to blast, to cell suspensions in a contained environment. Initial characterization of the system shows that cell cultures can be subjected to high-intensity compression waves up to 15 MPa in pressure and duration of 80 ± 10μs. Studies of mouse mesenchymal stem cells subjected to two different pressure impulses were analysed by cell counting, cell viability assays and microscopic evaluation: the experiments present evidence suggestive of increased levels of damage and loss of cellular integrity compared to uncompressed cell cultures.

  2. Effects of carotenoids on damage of biological lipids induced by gamma irradiation

    NASA Astrophysics Data System (ADS)

    Saito, Takeshi; Fujii, Noriko

    2014-05-01

    Carotenoids are considered to be involved in the radioresistant mechanisms of radioresistant bacteria. In these bacterial cells, carotenoids are present in biological lipids, and therefore may be related to the radiation-induced damage of lipids. However, only limited data are available for the role of carotenoids in such damage. In this study, we irradiated an α-linolenic acid-benzene solution with gamma rays and analyzed the resulting oxidative degradation and peroxidation damage in the presence or absence of two typical carotenoids: β-carotene and astaxanthin. The analyses revealed that oxidative degradation and peroxidation of α-linolenic acid, as evaluated by the amount of malondialdehyde and conjugated diene formed, respectively, increased in a dose-dependent manner. Moreover, 8.5×10-3 M β-carotene inhibited gamma radiation-induced oxidative degradation of α-linolenic acid, whereas 5.0×10-5 and 5.0×10-6 M β-carotene, and 5.0×10-7 and 5.0×10-8 M astaxanthin promoted degradation. In contrast, neither β-carotene nor astaxanthin affected peroxidation of α-linolenic acid. These results suggest that an optimum concentration of carotenoids in radioresistant bacteria protects biological lipid structures from radiation-induced damage.

  3. Cellular characterization of compression induced-damage in live biological samples

    NASA Astrophysics Data System (ADS)

    Bo, Chiara; Balzer, Jens; Hahnel, Mark; Rankin, Sara M.; Brown, Katherine A.; Proud, William G.

    2011-06-01

    Understanding the dysfunctions that high-intensity compression waves induce in human tissues is critical to impact on acute-phase treatments and requires the development of experimental models of traumatic damage in biological samples. In this study we have developed an experimental system to directly assess the impact of dynamic loading conditions on cellular function at the molecular level. Here we present a confinement chamber designed to subject live cell cultures in liquid environment to compression waves in the range of tens of MPa using a split Hopkinson pressure bars system. Recording the loading history and collecting the samples post-impact without external contamination allow the definition of parameters such as pressure and duration of the stimulus that can be related to the cellular damage. The compression experiments are conducted on Mesenchymal Stem Cells from BALB/c mice and the damage analysis are compared to two control groups. Changes in Stem cell viability, phenotype and function are assessed flow cytometry and with in vitro bioassays at two different time points. Identifying the cellular and molecular mechanisms underlying the damage caused by dynamic loading in live biological samples could enable the development of new treatments for traumatic injuries.

  4. Biological damage induced by ionizing cosmic rays in dry Arabidopsis seeds.

    PubMed

    Kranz, A R; Bork, U; Bucker, H; Reitz, G

    1990-01-01

    In September 1987 dry seeds containing embryos of the crucifer plant Arabidopsis thaliana (L.) Heynh, were flown in orbit for 13 days on the Kosmos 1887 satellite. The seeds were fixed on CNd detectors and stored in units of Biorack type I/O. One unit was exposed inside, another one outside the satellite. The temperature profile of the flown seeds inside the satellite was simulated on earth in an identical backup control sample (BC). An additional control (SC) was studied with the original seeds sample. By use of the CNd-detector, HZE-tracks were measured with a PC-assisted microscope. The biological damages were investigated by growing the seeds under controlled climatic conditions. The following biological endpoints of the cosmic radiation damage were studied: germination, radicle length, sublethality, morphological aberrations, flower development, tumorization, embryo lethality inside the siliques. The summarized damage (D) and the mutation frequencies of embyronic lethal genes were calculated. The following results were obtained: the damages increase significantly in orbit at all biological endpoints; germination and fiowerings especially, as well as embryo lethality of fruits and lethal mutation frequency, were maximum mostly for HZE-hit seeds. Additionally, an increase of damage was observed for the seeds of the outside-exposed Biorack in comparison to the inside ones, which was probably caused by less radiation shielding and free space vacuum. The significance of the results obtained is discussed with respect to stress and risk and, thus, the quality of the RBE-factors and heavy ionizing radiation all needed for the very definition of radiation protection standards in space. PMID:11537515

  5. Role of cellular communication in the pathways of radiation-induced biological damage

    NASA Astrophysics Data System (ADS)

    Ballarini, Francesca; Facoetti, Angelica; Mariotti, Luca; Nano, Rosanna; Ottolenghi, Andrea

    During the last decade, a large number of experimental studies on the so-called "non-targeted effects", in particular bystander effects, outlined that cellular communication plays a signifi- cant role in the pathways leading to radiation-induced biological damage. This might imply a paradigm shift in (low-dose) radiobiology, according to which one has to consider the response of groups of cells behaving like a population rather than single cells behaving as individuals. Furthermore, bystander effects, which are observed both for lethal endpoints (e.g. clonogenic inactivation and apoptosis) and for non-lethal ones (e.g. mutations and neoplastic transformation), tend to show non-linear dose responses characterized by a sharp increase followed by a plateau. This might have significant consequences in terms of low-dose risk, which is generally calculated on the basis of the "Linear No Threshold" hypothesis. Although it is known that two types of cellular communication (i.e. via gap junctions and/or molecular messengers diffusing in the extra-cellular environment, such as cytokines) play a major role, it is of utmost importance to better understand the underlying mechanisms, and how such mechanisms can be modulated by ionizing radiation. Though the "final" goal is to elucidate the in vivo scenario, in the meanwhile also in vitro studies can provide useful insights. In the present paper we will discuss key issues on the mechanisms underlying non-targeted effects and, more generally, cell communication, with focus on candidate molecular signals. Theoretical models and simulation codes can be of help in elucidating such mechanisms. In this framework, we will present a model and Monte Carlo code, under development at the University of Pavia, simulating the release, diffusion and internalization of candidate signals (typically cytokines) travelling in the extra-cellular environment, both by unirradiated (i.e., control) cells and by irradiated cells. The focus will be on the

  6. Protective Effect of Selected Medicinal Plants against Hydrogen Peroxide Induced Oxidative Damage on Biological Substrates.

    PubMed

    Pai Kotebagilu, Namratha; Reddy Palvai, Vanitha; Urooj, Asna

    2014-01-01

    Oxidative stress is developed due to susceptibility of biological substrates to oxidation by generation of free radicals. In degenerative diseases, oxidative stress level can be reduced by antioxidants which neutralize free radicals. Primary objective of this work was to screen four medicinal plants, namely, Andrographis paniculata, Costus speciosus, Canthium parviflorum, and Abrus precatorius, for their antioxidant property using two biological substrates-RBC and microsomes. The antioxidative ability of three solvent extracts, methanol (100% and 80%) and aqueous leaf extracts, was studied at different concentrations by thiobarbituric acid reactive substances method using Fenton's reagent to induce oxidation in the substrates. The polyphenol and flavonoid content were analyzed to relate with the observed antioxidant effect of the extracts. The phytochemical screening indicated the presence of flavonoids, polyphenols, tannins, and β-carotene in the samples. In microsomes, 80% methanol extract of Canthium and Costus and, in RBC, 80% methanol extract of Costus showed highest inhibition of oxidation and correlated well with the polyphenol and flavonoid content. From the results it can be concluded that antioxidants from medicinal plants are capable of inhibiting oxidation in biological systems, suggesting scope for their use as nutraceuticals. PMID:25436152

  7. Protective Effect of Selected Medicinal Plants against Hydrogen Peroxide Induced Oxidative Damage on Biological Substrates

    PubMed Central

    Pai Kotebagilu, Namratha; Reddy Palvai, Vanitha

    2014-01-01

    Oxidative stress is developed due to susceptibility of biological substrates to oxidation by generation of free radicals. In degenerative diseases, oxidative stress level can be reduced by antioxidants which neutralize free radicals. Primary objective of this work was to screen four medicinal plants, namely, Andrographis paniculata, Costus speciosus, Canthium parviflorum, and Abrus precatorius, for their antioxidant property using two biological substrates—RBC and microsomes. The antioxidative ability of three solvent extracts, methanol (100% and 80%) and aqueous leaf extracts, was studied at different concentrations by thiobarbituric acid reactive substances method using Fenton's reagent to induce oxidation in the substrates. The polyphenol and flavonoid content were analyzed to relate with the observed antioxidant effect of the extracts. The phytochemical screening indicated the presence of flavonoids, polyphenols, tannins, and β-carotene in the samples. In microsomes, 80% methanol extract of Canthium and Costus and, in RBC, 80% methanol extract of Costus showed highest inhibition of oxidation and correlated well with the polyphenol and flavonoid content. From the results it can be concluded that antioxidants from medicinal plants are capable of inhibiting oxidation in biological systems, suggesting scope for their use as nutraceuticals. PMID:25436152

  8. Radiation-induced DNA damage and the relative biological effectiveness of 18F-FDG in wild-type mice

    DOE PAGESBeta

    Taylor, Kristina; Lemon, Jennifer A.; Boreham, Douglas R.

    2014-05-28

    Clinically, the most commonly used positron emission tomography (PET) radiotracer is the glucose analog 2-[18F] fluoro-2-deoxy-d-glucose (18F-FDG), however little research has been conducted on the biological effects of 18F-FDG injections. The induction and repair of DNA damage and the relative biological effectiveness (RBE) of radiation from 18F-FDG relative to 662 keV γ-rays were investigated. The study also assessed whether low-dose radiation exposure from 18F-FDG was capable of inducing an adaptive response. DNA damage to the bone marrow erythroblast population was measured using micronucleus formation and lymphocyte γH2A.X levels. To test the RBE of 18F-FDG, mice were injected with a rangemore » of activities of 18F-FDG (0–14.80 MBq) or irradiated with Cs-137 γ-rays (0–100 mGy). The adaptive response was investigated 24 h after the 18F-FDG injection by 1 Gy in vivo challenge doses for micronucleated reticulocyte (MN-RET) formation or 1, 2 and 4 Gy in vitro challenges doses for γH2A.X formation. A significant increase in MN-RET formation above controls occurred following injection activities of 3.70, 7.40 or 14.80 MBq (P < 0.001) which correspond to bone marrow doses of ~35, 75 and 150 mGy, respectively. Per unit dose, the Cs-137 radiation exposure induced significantly more damage than the 18F-FDG injections (RBE = 0.79 ± 0.04). A 20% reduction in γH2A.X fluorescence was observed in mice injected with a prior adapting low dose of 14.80 MBq 18F-FDG relative to controls (P < 0.019). A 0.74 MBq 18F-FDG injection, which gives mice a dose approximately equal to a typical human PET scan, did not cause a significant increase in DNA damage nor did it generate an adaptive response. Typical 18F-FDG injection activities used in small animal imaging (14.80 MBq) resulted in a decrease in DNA damage, as measured by γH2A.X formation, below spontaneous levels observed in control mice. Lastly, the 18F-FDG RBE was <1.0, indicating that the mixed radiation quality

  9. Laser-induced damage in biological tissue: Role of complex and dynamic optical properties of the medium

    NASA Astrophysics Data System (ADS)

    Ahmed, Elharith M.

    Since its invention in the early 1960's, the laser has been used as a tool for surgical, therapeutic, and diagnostic purposes. To achieve maximum effectiveness with the greatest margin of safety it is important to understand the mechanisms of light propagation through tissue and how that light affects living cells. Lasers with novel output characteristics for medical and military applications are too often implemented prior to proper evaluation with respect to tissue optical properties and human safety. Therefore, advances in computational models that describe light propagation and the cellular responses to laser exposure, without the use of animal models, are of considerable interest. Here, a physics-based laser-tissue interaction model was developed to predict the spatial and temporal temperature and pressure rise during laser exposure to biological tissues. Our new model also takes into account the dynamic nature of tissue optical properties and their impact on the induced temperature and pressure profiles. The laser-induced retinal damage is attributed to the formation of microbubbles formed around melanosomes in the retinal pigment epithelium (RPE) and the damage mechanism is assumed to be photo-thermal. Selective absorption by melanin creates these bubbles that expand and collapse around melanosomes, destroying cell membranes and killing cells. The Finite Element (FE) approach taken provides suitable ground for modeling localized pigment absorption which leads to a non-uniform temperature distribution within pigmented cells following laser pulse exposure. These hot-spots are sources for localized thermo-elastic stresses which lead to rapid localized expansions that manifest themselves as microbubbles and lead to microcavitations. Model predictions for the interaction of lasers at wavelengths of 193, 694, 532, 590, 1314, 1540, 2000, and 2940 nm with biological tissues were generated and comparisons were made with available experimental data for the retina

  10. Radiation-induced DNA damage and the relative biological effectiveness of 18F-FDG in wild-type mice

    SciTech Connect

    Taylor, Kristina; Lemon, Jennifer A.; Boreham, Douglas R.

    2014-05-28

    Clinically, the most commonly used positron emission tomography (PET) radiotracer is the glucose analog 2-[18F] fluoro-2-deoxy-d-glucose (18F-FDG), however little research has been conducted on the biological effects of 18F-FDG injections. The induction and repair of DNA damage and the relative biological effectiveness (RBE) of radiation from 18F-FDG relative to 662 keV γ-rays were investigated. The study also assessed whether low-dose radiation exposure from 18F-FDG was capable of inducing an adaptive response. DNA damage to the bone marrow erythroblast population was measured using micronucleus formation and lymphocyte γH2A.X levels. To test the RBE of 18F-FDG, mice were injected with a range of activities of 18F-FDG (0–14.80 MBq) or irradiated with Cs-137 γ-rays (0–100 mGy). The adaptive response was investigated 24 h after the 18F-FDG injection by 1 Gy in vivo challenge doses for micronucleated reticulocyte (MN-RET) formation or 1, 2 and 4 Gy in vitro challenges doses for γH2A.X formation. A significant increase in MN-RET formation above controls occurred following injection activities of 3.70, 7.40 or 14.80 MBq (P < 0.001) which correspond to bone marrow doses of ~35, 75 and 150 mGy, respectively. Per unit dose, the Cs-137 radiation exposure induced significantly more damage than the 18F-FDG injections (RBE = 0.79 ± 0.04). A 20% reduction in γH2A.X fluorescence was observed in mice injected with a prior adapting low dose of 14.80 MBq 18F-FDG relative to controls (P < 0.019). A 0.74 MBq 18F-FDG injection, which gives mice a dose approximately equal to a typical human PET scan, did not cause a significant increase in DNA damage nor did it generate an adaptive response. Typical 18F-FDG injection activities used in small animal imaging (14.80 MBq) resulted in a decrease in DNA damage, as measured by γH2A.X formation

  11. Design, synthesis and biological evaluation of novel chiral oxazino-indoles as potential and selective neuroprotective agents against Aβ25-35-induced neuronal damage.

    PubMed

    Chen, Jing; Tao, Ling-Xue; Xiao, Wei; Ji, Sha-Sha; Wang, Jian-Rong; Li, Xu-Wen; Zhang, Hai-Yan; Guo, Yue-Wei

    2016-08-01

    A series of chiral oxazino-indoles have been synthesized via a key intermolecular oxa-Pictet-Spengler reaction. These compounds exhibited significant and selective neuroprotective effects against Aβ25-35-induced neuronal damage. This is the first report of evaluating the influence of chiral diversity of oxazino-indoles on their neuroprotective activities, with the structure-activity relationship been analyzed. The highly active compounds 3f, 3g, 4g, 4h, and 6b all performed over 90% cell protection, providing a new direction for the development of neuroprotective agents against Alzheimer's disease. PMID:27301369

  12. Chemistry and Structural Biology of DNA Damage and Biological Consequences

    PubMed Central

    Stone, Michael P.; Huang, Hai; Brown, Kyle L.; Shanmugam, Ganesh

    2013-01-01

    The formation of adducts by the reaction of chemicals with DNA is a critical step for the initiation of carcinogenesis. The structural analysis of various DNA adducts reveals that conformational and chemical rearrangements and interconversions are a common theme. Conformational changes are modulated both by the nature of adduct and the base sequences neighboring the lesion sites. Equilibria between conformational states may modulate both DNA repair and error-prone replication past these adducts. Likewise, chemical rearrangements of initially formed DNA adducts are also modulated both by the nature of adducts and the base sequences neighboring the lesion sites. In this review, we focus on DNA damage caused by a number of environmental and endogenous agents, and biological consequences. PMID:21922653

  13. Prevention of chemotherapy-induced ovarian damage.

    PubMed

    Roness, Hadassa; Kashi, Oren; Meirow, Dror

    2016-01-01

    Recent advances in our understanding of the mechanisms underlying the impact of cytotoxic drugs on the ovary have opened up new directions for the protection of the ovary from chemotherapy-induced damage. These advances have spurred the investigation of pharmacological agents to prevent ovarian damage at the time of treatment. Prevention of ovarian damage and follicle loss would provide significant advantages over existing fertility preservation techniques. This manuscript reviews new methods for the prevention of chemotherapy-induced ovarian damage, including agents that act on the PI3K/PTEN/Akt follicle activation pathway, apoptotic pathways, the vascular system, and other potential methods of reducing chemotherapy-induced ovotoxicity. PMID:26677788

  14. The loss of ATP2C1 impairs the DNA damage response and induces altered skin homeostasis: Consequences for epidermal biology in Hailey-Hailey disease.

    PubMed

    Cialfi, Samantha; Le Pera, Loredana; De Blasio, Carlo; Mariano, Germano; Palermo, Rocco; Zonfrilli, Azzurra; Uccelletti, Daniela; Palleschi, Claudio; Biolcati, Gianfranco; Barbieri, Luca; Screpanti, Isabella; Talora, Claudio

    2016-01-01

    Mutation of the Golgi Ca(2+)-ATPase ATP2C1 is associated with deregulated calcium homeostasis and altered skin function. ATP2C1 mutations have been identified as having a causative role in Hailey-Hailey disease, an autosomal-dominant skin disorder. Here, we identified ATP2C1 as a crucial regulator of epidermal homeostasis through the regulation of oxidative stress. Upon ATP2C1 inactivation, oxidative stress and Notch1 activation were increased in cultured human keratinocytes. Using RNA-seq experiments, we found that the DNA damage response (DDR) was consistently down-regulated in keratinocytes derived from the lesions of patients with Hailey-Hailey disease. Although oxidative stress activates the DDR, ATP2C1 inactivation down-regulates DDR gene expression. We showed that the DDR response was a major target of oxidative stress-induced Notch1 activation. Here, we show that this activation is functionally important because early Notch1 activation in keratinocytes induces keratinocyte differentiation and represses the DDR. These results indicate that an ATP2C1/NOTCH1 axis might be critical for keratinocyte function and cutaneous homeostasis, suggesting a plausible model for the pathological features of Hailey-Hailey disease. PMID:27528123

  15. The loss of ATP2C1 impairs the DNA damage response and induces altered skin homeostasis: Consequences for epidermal biology in Hailey-Hailey disease

    PubMed Central

    Cialfi, Samantha; Le Pera, Loredana; De Blasio, Carlo; Mariano, Germano; Palermo, Rocco; Zonfrilli, Azzurra; Uccelletti, Daniela; Palleschi, Claudio; Biolcati, Gianfranco; Barbieri, Luca; Screpanti, Isabella; Talora, Claudio

    2016-01-01

    Mutation of the Golgi Ca2+-ATPase ATP2C1 is associated with deregulated calcium homeostasis and altered skin function. ATP2C1 mutations have been identified as having a causative role in Hailey-Hailey disease, an autosomal-dominant skin disorder. Here, we identified ATP2C1 as a crucial regulator of epidermal homeostasis through the regulation of oxidative stress. Upon ATP2C1 inactivation, oxidative stress and Notch1 activation were increased in cultured human keratinocytes. Using RNA-seq experiments, we found that the DNA damage response (DDR) was consistently down-regulated in keratinocytes derived from the lesions of patients with Hailey-Hailey disease. Although oxidative stress activates the DDR, ATP2C1 inactivation down-regulates DDR gene expression. We showed that the DDR response was a major target of oxidative stress-induced Notch1 activation. Here, we show that this activation is functionally important because early Notch1 activation in keratinocytes induces keratinocyte differentiation and represses the DDR. These results indicate that an ATP2C1/NOTCH1 axis might be critical for keratinocyte function and cutaneous homeostasis, suggesting a plausible model for the pathological features of Hailey-Hailey disease. PMID:27528123

  16. Corrosion-induced damage raises serious implications

    SciTech Connect

    Kane, R.D.; Cayard, M.S.

    1997-06-01

    One of the most difficult and often underestimated aspects of pipeline rehabilitation is the assessment of corrosion-induced damage. This question involves evaluation of damage from prior service as well as consideration of conditions which may pose additional time-dependent degradation which could affect the future serviceability of the pipeline. The present study examines the assessment of pipeline damage and rehabilitation requirements through knowledge of materials of construction, operating conditions, field inspection and service records.

  17. Quantifying pulsed laser induced damage to graphene

    SciTech Connect

    Currie, Marc; Caldwell, Joshua D.; Bezares, Francisco J.; Robinson, Jeremy; Anderson, Travis; Chun, Hayden; Tadjer, Marko

    2011-11-21

    As an emerging optical material, graphene's ultrafast dynamics are often probed using pulsed lasers yet the region in which optical damage takes place is largely uncharted. Here, femtosecond laser pulses induced localized damage in single-layer graphene on sapphire. Raman spatial mapping, SEM, and AFM microscopy quantified the damage. The resulting size of the damaged area has a linear correlation with the optical fluence. These results demonstrate local modification of sp{sup 2}-carbon bonding structures with optical pulse fluences as low as 14 mJ/cm{sup 2}, an order-of-magnitude lower than measured and theoretical ablation thresholds.

  18. BRAIN DAMAGE IN CHILDREN, THE BIOLOGICAL AND SOCIAL ASPECTS.

    ERIC Educational Resources Information Center

    BIRCH, HERBERT G., ED.

    PAPERS AND DISCUSSION SUMMARIES ARE PRESENTED FROM A CONFERENCE ON THE BIOLOGICAL AND SOCIAL PROBLEMS OF CHILDHOOD BRAIN DAMAGE, HELD AT THE CHILDREN'S HOSPITAL OF PHILADELPHIA IN NOVEMBER 1962. A VARIETY OF DISCIPLINES IS REPRESENTED, AND THE FOLLOWING TOPICS ARE CONSIDERED--(1) "THE PROBLEM OF 'BRAIN DAMAGE' IN CHILDREN" BY HERBERT G. BIRCH, (2)…

  19. Triplex-Induced DNA Damage Response

    PubMed Central

    Rogers, Faye A.; Tiwari, Meetu Kaushik

    2013-01-01

    Cellular DNA damage response is critical to preserving genomic integrity following exposure to genotoxic stress. A complex series of networks and signaling pathways become activated after DNA damage and trigger the appropriate cellular response, including cell cycle arrest, DNA repair, and apoptosis. The response elicited is dependent upon the type and extent of damage sustained, with the ultimate goal of preventing propagation of the damaged DNA. A major focus of our studies is to determine the cellular pathways involved in processing damage induced by altered helical structures, specifically triplexes. Our lab has demonstrated that the TFIIH factor XPD occupies a central role in triggering apoptosis in response to triplex-induced DNA strand breaks. We have shown that XPD co-localizes with γH2AX, and its presence is required for the phosphorylation of H2AX tyrosine142, which stimulates the signaling pathway to recruit pro-apoptotic factors to the damage site. Herein, we examine the cellular pathways activated in response to triplex formation and discuss our finding that suggests that XPD-dependent apoptosis plays a role in preserving genomic integrity in the presence of excessive structurally induced DNA damage. PMID:24348211

  20. Autophagy in light-induced retinal damage.

    PubMed

    Chen, Yu; Perusek, Lindsay; Maeda, Akiko

    2016-03-01

    Vision is reliant upon converting photon signals to electrical information which is interpreted by the brain and therefore allowing us to receive information about our surroundings. However, when exposed to excessive light, photoreceptors and other types of cells in the retina can undergo light-induced cell death, termed light-induced retinal damage. In this review, we summarize our current knowledge regarding molecular events in the retina after excessive light exposure and mechanisms of light-induced retinal damage. We also introduce works which investigate potential roles of autophagy, an essential cellular mechanism required for maintaining homeostasis under stress conditions, in the illuminated retina and animal models of light-induced retinal damage. PMID:26325327

  1. Calcium signaling in UV-induced damage

    NASA Astrophysics Data System (ADS)

    Sun, Dan; Zhang, Su-juan; Li, Yuan-yuan; Qu, Ying; Ren, Zhao-Yu

    2007-05-01

    Hepa1-6 cells were irradiated with UV and incubated for varying periods of time. [Ca 2+] i (intracellular calcium concentration) of UV-irradiated cell was measured by ratio fluorescence imaging system. The comet assay was used to determine DNA damage. During the UVB-irradiation, [Ca 2+] i had an ascending tendency from 0.88 J/m2 to 92.4J/m2. Comet assay instant test indicated that when the irradiation dosage was above 0.88J/m2, DNA damage was observed. Even after approximate 2 h of incubation, DNA damage was still not detected by 0.88J/m2 of UVB irradiation. During UVA-irradiation, the elevation of [Ca 2+] i was not dose-dependent in a range of 1200 J/m2-6000J/m2 and DNA damage was not observed by comet assay. These results suggested that several intracellular UV receptors might induce [Ca 2+] i rising by absorption of the UV energy. Just [Ca 2+] i rising can't induce DNA damage certainly, it is very likely that the breakdown of calcium steady state induces DNA damage.u

  2. Chemical genoprotection: reducing biological damage to as low as reasonably achievable levels

    PubMed Central

    Alcaraz, M; Armero, D; Martínez-Beneyto, Y; Castillo, J; Benavente-García, O; Fernandez, H; Alcaraz-Saura, M; Canteras, M

    2011-01-01

    Objectives The aim of this study was to evaluate the antioxidant substances present in the human diet with an antimutagenic protective capacity against genotoxic damage induced by exposure to X-rays in an attempt to reduce biological damage to as low a level as reasonably possible. Methods Ten compounds were assessed using the lymphocyte cytokinesis-block micronucleus (MN) cytome test. The compounds studied were added to human blood at 25 μM 5 min before exposure to irradiation by 2 Gy of X-rays. Results The protective capacity of the antioxidant substances assessed was from highest to lowest according to the frequency of the MN generated by X-ray exposure: rosmarinic acid = carnosic acid = δ-tocopherol = l-acid ascorbic = apigenin = amifostine (P < 0.001) > green tea extract = diosmine = rutin = dimetylsulfoxide (P < 0.05) > irradiated control. The reduction in genotoxic damage with the radiation doses administered reached 58%, which represents a significant reduction in X-ray-induced chromosomal damage (P < 0.001). This degree of protection is greater than that obtained with amifostine, a radioprotective compound used in radiotherapy and which is characterised by its high toxicity. Conclusion Several antioxidant substances, common components of the human diet and lacking toxicity, offer protection from the biological harm induced by ionizing radiation. Administering these protective substances to patients before radiological exploration should be considered, even in the case of small radiation doses and regardless of the biological damage expected. PMID:21697157

  3. Persistent damage induces mitochondrial DNA degradation

    PubMed Central

    Shokolenko, Inna N.; Wilson, Glenn L.; Alexeyev, Mikhail F.

    2013-01-01

    Considerable progress has been made recently toward understanding the processes of mitochondrial DNA (mtDNA) damage and repair. However, a paucity of information still exists regarding the physiological effects of persistent mtDNA damage. This is due, in part, to experimental difficulties associated with targeting mtDNA for damage, while sparing nuclear DNA. Here, we characterize two systems designed for targeted mtDNA damage based on the inducible (Tet-ON) mitochondrial expression of the bacterial enzyme, exonuclease III, and the human enzyme, uracil-N-glyosylase containing the Y147A mutation. In both systems, damage was accompanied by degradation of mtDNA, which was detectable by six hours after induction of mutant uracil-N-glycosylase and by twelve hours after induction of exoIII. Unexpectedly, increases in the steady-state levels of single-strand lesions, which led to degradation, were small in absolute terms indicating that both abasic sites and single-strand gaps may be poorly tolerated in mtDNA. mtDNA degradation was accompanied by the loss of expression of mtDNA-encoded COX2. After withdrawal of the inducer, recovery from mtDNA depletion occurred faster in the system expressing exonuclease III, but in both systems reduced mtDNA levels persisted longer than 144h after doxycycline withdrawal. mtDNA degradation was followed by reduction and loss of respiration, decreased membrane potential, reduced cell viability, reduced intrinsic reactive oxygen species production, slowed proliferation, and changes in mitochondrial morphology (fragmentation of the mitochondrial network, rounding and “foaming” of the mitochondria). The mutagenic effects of abasic sites in mtDNA were low, which indicates that damaged mtDNA molecules may be degraded if not rapidly repaired. This study establishes, for the first time, that mtDNA degradation can be a direct and immediate consequence of persistent mtDNA damage and that increased ROS production is not an invariant consequence

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

    PubMed

    Zhang, Xurui; Ye, Caiyong; Sun, Fang; Wei, Wenjun; Hu, Burong; Wang, Jufang

    2016-01-01

    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. PMID:27187621

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

    PubMed Central

    Zhang, Xurui; Ye, Caiyong; Sun, Fang; Wei, Wenjun; Hu, Burong; Wang, Jufang

    2016-01-01

    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. PMID:27187621

  6. LET analyses of biological damage during solar particle events

    NASA Technical Reports Server (NTRS)

    Cucinotta, Francis A.; Wilson, John W.; Townsend, Lawrence W.; Shinn, Judy L.; Katz, Robert

    1991-01-01

    The effects of nuclear reactions on integral low-linear-energy-transfer (LET) protons spectra are studied, behind typical levels of spacecraft and body shielding, for the historically largest flares using the high-energy transport code BRYNTRN in conjunction with several biological damage models. The cellular track model of Katz provides an accurate description of cellular damage from heavy ion exposure. The track model is applied with BRYNTRN to provide a LET decomposition of survival and transformation rates for solar proton events. In addition, a fluence-based risk coefficient formalism is used to estimate Harderian gland-tumor induction in rodents and cataractogenesis in rabbits from solar flares, and a LET analysis is used to assess the relative contribution from target fragments on these biological endpoints.

  7. Laser-Induced Damage of Calcium Fluoride

    SciTech Connect

    Espana, A.; Joly, A.G.; Hess, W.P.; Dickinson, J.T.

    2004-01-01

    As advances continue to be made in laser technology there is an increasing demand for materials that have high thresholds for laser-induced damage. Laser damage occurs when light is absorbed, creating defects in the crystal lattice. These defects can lead to the emission of atoms, ions and molecules from the sample. One specific field where laser damage is of serious concern is semiconductor lithography, which is beginning to use light at a wavelength of 157 nm. CaF2 is a candidate material for use in this new generation of lithography. In order to prevent unnecessary damage of optical components, it is necessary to understand the mechanisms for laser damage and the factors that serve to enhance it. In this research, we study various aspects of laser interactions with CaF2, including impurity absorbance and various forms of damage caused by incident laser light. Ultraviolet (UV) laser light at 266 nm with both femtosecond (fs) and nanosecond (ns) pulse widths is used to induce ion and neutral particle emission from cleaved samples of CaF2. The resulting mass spectra show significant differences suggesting that different mechanisms for desorption occur following excitation using the different pulse durations. Following irradiation by ns pulses at 266 nm, multiple single-photon absorption from defect states is likely responsible for ion emission whereas the fs case is driven by a multi-photon absorption process. This idea is further supported by the measurements made of the transmission and reflection of fs laser pulses at 266 nm, the results of which reveal a non-linear absorption process in effect at high incident intensities. In addition, the kinetic energy profiles of desorbed Ca and K contaminant atoms are different indicating that a different mechanism is responsible for their emission as well. Overall, these results show that purity plays a key role in the desorption of atoms from CaF2 when using ns pulses. On the other hand, once the irradiance reaches high

  8. Heat Stress-Induced DNA Damage

    PubMed Central

    Kantidze, O.L.; Velichko, A.K.; Luzhin, A.V.; Razin, S.V.

    2016-01-01

    Although the heat-stress response has been extensively studied for decades, very little is known about its effects on nucleic acids and nucleic acid-associated processes. This is due to the fact that the research has focused on the study of heat shock proteins and factors (HSPs and HSFs), their involvement in the regulation of transcription, protein homeostasis, etc. Recently, there has been some progress in the study of heat stress effects on DNA integrity. In this review, we summarize and discuss well-known and potential mechanisms of formation of various heat stress-induced DNA damage. PMID:27437141

  9. Laser-Induced Damage of Calcium Fluoride

    SciTech Connect

    Espana, Aubrey L.; Joly, Alan G.; Hess, Wayne P.; Dickinson, J T.

    2004-12-01

    Radiation damage of materials has long been of fundamental interest, especially since the growth of laser technology. One such source of damage comes from UV laser light. Laser systems continue to move into shorter wavelength ranges, but unfortunately are limited by the damage threshold of their optical components. For example, semiconductor lithography is making its way into the 157nm range and requires a material that can not only transmit this light (air cannot), but also withstand the highly energetic photons present at this shorter wavelength. CaF2, an alkaline earth halide, is the chosen material for vacuum UV 157 nm excimer radiation. It can transmit light down to 120 nm and is relatively inexpensive. Although it is readily available through natural and synthetic sources, it is often times difficult to find in high purity. Impurities in the crystal can result in occupied states in the band gap that induce photon absorption [2] and ultimately lead to the degradation of the material. In order to predict how well CaF2 will perform under irradiation of short wavelength laser light, one must understand the mechanisms for laser-induced damage. Laser damage is often a two-step process: initial photons create new defects in the lattice and subsequent photons excite these defects. When laser light is incident on a solid surface there is an initial production of electron-hole (e-h) pairs, a heating of free electrons and a generation of local heating around optically absorbing centers [3]. Once this initial excitation converts to the driving energy for nuclear motion, the result is an ejection of atoms, ions and molecules from the surface, known as desorption or ablation [3]. Secondary processes further driving desorption are photoabsorption, successive excitations of self-trapped excitons (STE's) and defects, and ionization of neutrals by incident laser light [3]. The combination of laser-induced desorption and the alterations to the electronic and geometrical

  10. A Mathematical Model for Estimating Biological Damage Caused by Radiation

    NASA Astrophysics Data System (ADS)

    Manabe, Yuichiro; Ichikawa, Kento; Bando, Masako

    2012-10-01

    We propose a mathematical model for estimating biological damage caused by low-dose irradiation. We understand that the linear non threshold (LNT) hypothesis is realized only in the case of no recovery effects. In order to treat the realistic living objects, our model takes into account various types of recovery as well as proliferation mechanism, which may change the resultant damage, especially for the case of lower dose rate irradiation. It turns out that the lower the radiation dose rate, the safer the irradiated system of living object (which is called symbolically ``tissue'' hereafter) can have chances to survive, which can reproduce the so-called dose and dose-rate effectiveness factor (DDREF).

  11. Correlation of polishing-induced shallow subsurface damages with laser-induced gray haze damages in fused silica optics

    NASA Astrophysics Data System (ADS)

    He, Xiang; Zhao, Heng; Wang, Gang; Zhou, Peifan; Ma, Ping

    2016-08-01

    Laser-induced damage in fused silica optics greatly restricts the performances of laser facilities. Gray haze damage, which is always initiated on ceria polished optics, is one of the most important damage morphologies in fused silica optics. In this paper, the laser-induced gray haze damages of four fused silica samples polished with CeO2, Al2O3, ZrO2, and colloidal silica slurries are investigated. Four samples all present gray haze damages with much different damage densities. Then, the polishing-induced contaminant and subsurface damages in four samples are analyzed. The results reveal that the gray haze damages could be initiated on the samples without Ce contaminant and are inclined to show a tight correlation with the shallow subsurface damages.

  12. [Galactic heavy charged particles damaging effect on biological structures].

    PubMed

    Grigor'ev, A I; Krasavin, E A; Ostrovskiĭ, M A

    2013-03-01

    A concept of the radiation risk of the manned interplanetary flights is proposed and substantiated. Heavy charged particles that are a component of the galactic cosmic rays (GCR) have a high damaging effect on the biological structures as great amount of energy is deposited in heavy particle tracks. The high biological effectiveness of heavy ions is observed in their action on cell genetic structures and the whole organism, including the brain structures. The hippocampus is the part of the central nervous system that is the most sensitive to radiation--first of all, to heavy charged particles. Irradiation of animals with accelerated iron ions at doses corresponding to the real fluxes of GCR heavy nuclei, to which Mars mission crews can be exposed, leads to marked behavioral function disorders in the post-irradiation period. To evaluate the radiation risk for the interplanetary flight crews, the concept of successful mission accomplishment is introduced. In these conditions, the central nervous system structures can be the critical target of GCR heavy nuclei. Their damage can modify the higher integrative functions of the brain and cause disorders in the crew members' operator performances. PMID:23789432

  13. Delayed chromosomal instability induced by DNA damage.

    PubMed Central

    Marder, B A; Morgan, W F

    1993-01-01

    DNA damage induced by ionizing radiation can result in gene mutation, gene amplification, chromosome rearrangements, cellular transformation, and cell death. Although many of these changes may be induced directly by the radiation, there is accumulating evidence for delayed genomic instability following X-ray exposure. We have investigated this phenomenon by studying delayed chromosomal instability in a hamster-human hybrid cell line by means of fluorescence in situ hybridization. We examined populations of metaphase cells several generations after expanding single-cell colonies that had survived 5 or 10 Gy of X rays. Delayed chromosomal instability, manifested as multiple rearrangements of human chromosome 4 in a background of hamster chromosomes, was observed in 29% of colonies surviving 5 Gy and in 62% of colonies surviving 10 Gy. A correlation of delayed chromosomal instability with delayed reproductive cell death, manifested as reduced plating efficiency in surviving clones, suggests a role for chromosome rearrangements in cytotoxicity. There were small differences in chromosome destabilization and plating efficiencies between cells irradiated with 5 or 10 Gy of X rays after a previous exposure to 10 Gy and cells irradiated only once. Cell clones showing delayed chromosomal instability had normal frequencies of sister chromatid exchange formation, indicating that at this cytogenetic endpoint the chromosomal instability was not apparent. The types of chromosomal rearrangements observed suggest that chromosome fusion, followed by bridge breakage and refusion, contributes to the observed delayed chromosomal instability. Images PMID:8413263

  14. Valsartan inhibits amylin-induced podocyte damage.

    PubMed

    Huang, Fengjuan; Wang, Qingzhu; Ma, Xiaojun; Wu, Lina; Guo, Feng; Qin, Guijun

    2016-07-01

    Previous studies have described the deposition of amylin in the kidney of patients with type 2 diabetes mellitus (T2DM). These deposits play a critical role in the pathogenesis of diabetic nephropathy (DN), although the mechanism underlying this effect is unknown. Thus, this study was undertaken to investigate whether amylin aggregation stimulates the local angiotensin II type 1 receptor (AT1R) in podocytes, and to examine its role in podocyte apoptosis. Amylin-induced apoptosis was investigated in vitro in differentiated, conditionally immortalized mouse podocytes and in vivo in KM mice. Expression of genes including nephrin, podocin, AT1R and desmin was measured through quantitative real time PCR, western blot and immunohistochemistry. Apoptosis was determined by flow cytometry, while the cellular distribution of podocin and nephrin was investigated by immunofluorescence. The ultra-structure of glomeruli was examined by transmission electron microscopy (TEM). Amylin enhanced apoptosis in a dose-dependent manner in vitro. The peptide also suppressed podocin and nephrin expression, but enhanced that of AT1R and desmin. Both effects were significantly blocked by valsartan, which inhibits angiotensin II type 1 receptor. These findings suggest that amylin activates a local intracellular RAS in podocytes and induces damage and apoptosis. PMID:27102209

  15. Opportunities for nutritional amelioration of radiation-induced cellular damage.

    PubMed

    Turner, Nancy D; Braby, Leslie A; Ford, John; Lupton, Joanne R

    2002-10-01

    The closed environment and limited evasive capabilities inherent in space flight cause astronauts to be exposed to many potential harmful agents (chemical contaminants in the environment and cosmic radiation exposure). Current power systems used to achieve space flight are prohibitively expensive for supporting the weight requirements to fully shield astronauts from cosmic radiation. Therefore, radiation poses a major, currently unresolvable risk for astronauts, especially for long-duration space flights. The major detrimental radiation effects that are of primary concern for long-duration space flights are damage to the lens of the eye, damage to the immune system, damage to the central nervous system, and cancer. In addition to the direct damage to biological molecules in cells, radiation exposure induces oxidative damage. Many natural antioxidants, whether consumed before or after radiation exposure, are able to confer some level of radioprotection. In addition to achieving beneficial effects from long-known antioxidants such as vitamins E and C and folic acid, some protection is conferred by several recently discovered antioxidant molecules, such as flavonoids, epigallocatechin, and other polyphenols. Somewhat counterintuitive is the protection provided by diets containing elevated levels of omega-3 polyunsaturated fatty acids, considering they are thought to be prone to peroxidation. Even with the information we have at our disposal, it will be difficult to predict the types of dietary modifications that can best reduce the risk of radiation exposure to astronauts, those living on Earth, or those enduring diagnostic or therapeutic radiation exposure. Much more work must be done in humans, whether on Earth or, preferably, in space, before we are able to make concrete recommendations. PMID:12361786

  16. Opportunities for nutritional amelioration of radiation-induced cellular damage

    NASA Technical Reports Server (NTRS)

    Turner, Nancy D.; Braby, Leslie A.; Ford, John; Lupton, Joanne R.

    2002-01-01

    The closed environment and limited evasive capabilities inherent in space flight cause astronauts to be exposed to many potential harmful agents (chemical contaminants in the environment and cosmic radiation exposure). Current power systems used to achieve space flight are prohibitively expensive for supporting the weight requirements to fully shield astronauts from cosmic radiation. Therefore, radiation poses a major, currently unresolvable risk for astronauts, especially for long-duration space flights. The major detrimental radiation effects that are of primary concern for long-duration space flights are damage to the lens of the eye, damage to the immune system, damage to the central nervous system, and cancer. In addition to the direct damage to biological molecules in cells, radiation exposure induces oxidative damage. Many natural antioxidants, whether consumed before or after radiation exposure, are able to confer some level of radioprotection. In addition to achieving beneficial effects from long-known antioxidants such as vitamins E and C and folic acid, some protection is conferred by several recently discovered antioxidant molecules, such as flavonoids, epigallocatechin, and other polyphenols. Somewhat counterintuitive is the protection provided by diets containing elevated levels of omega-3 polyunsaturated fatty acids, considering they are thought to be prone to peroxidation. Even with the information we have at our disposal, it will be difficult to predict the types of dietary modifications that can best reduce the risk of radiation exposure to astronauts, those living on Earth, or those enduring diagnostic or therapeutic radiation exposure. Much more work must be done in humans, whether on Earth or, preferably, in space, before we are able to make concrete recommendations.

  17. Track Structure and the Biological Effectiveness of Accelerated Particles for the Induction of Chromosome Damage

    NASA Technical Reports Server (NTRS)

    George, K.; Hada, M.; Chappell, L.; Cucinotta, F. A.

    2011-01-01

    Track structure models predict that at a fixed value of LET, particles with lower charge number, Z will have a higher biological effectiveness compared to particles with a higher Z. In this report we investigated how track structure effects induction of chromosomal aberration in human cells. Human lymphocytes were irradiated in vitro with various energies of accelerated iron, silicon, neon, or titanium ions and chromosome damage was assessed in using three color FISH chromosome painting in chemically induced PCC samples collected a first cell division post irradiation. The LET values for these ions ranged from 30 to195 keV/micron. Of the particles studied, Neon ions have the highest biological effectiveness for induction of total chromosome damage, which is consistent with track structure model predictions. For complex-type exchanges 64 MeV/ u Neon and 450 MeV/u Iron were equally effective and induced the most complex damage. In addition we present data on chromosomes exchanges induced by six different energies of protons (5 MeV/u to 2.5 GeV/u). The linear dose response term was similar for all energies of protons suggesting that the effect of the higher LET at low proton energies is balanced by the production of nuclear secondaries from the high energy protons.

  18. Ultrafine particulate pollutants induce oxidative stress and mitochondrial damage.

    PubMed Central

    Li, Ning; Sioutas, Constantinos; Cho, Arthur; Schmitz, Debra; Misra, Chandan; Sempf, Joan; Wang, Meiying; Oberley, Terry; Froines, John; Nel, Andre

    2003-01-01

    The objectives of this study were to determine whether differences in the size and composition of coarse (2.5-10 micro m), fine (< 2.5 microm), and ultrafine (< 0.1 microm) particulate matter (PM) are related to their uptake in macrophages and epithelial cells and their ability to induce oxidative stress. The premise for this study is the increasing awareness that various PM components induce pulmonary inflammation through the generation of oxidative stress. Coarse, fine, and ultrafine particles (UFPs) were collected by ambient particle concentrators in the Los Angeles basin in California and used to study their chemical composition in parallel with assays for generation of reactive oxygen species (ROS) and ability to induce oxidative stress in macrophages and epithelial cells. UFPs were most potent toward inducing cellular heme oxygenase-1 (HO-1) expression and depleting intracellular glutathione. HO-1 expression, a sensitive marker for oxidative stress, is directly correlated with the high organic carbon and polycyclic aromatic hydrocarbon (PAH) content of UFPs. The dithiothreitol (DTT) assay, a quantitative measure of in vitro ROS formation, was correlated with PAH content and HO-1 expression. UFPs also had the highest ROS activity in the DTT assay. Because the small size of UFPs allows better tissue penetration, we used electron microscopy to study subcellular localization. UFPs and, to a lesser extent, fine particles, localize in mitochondria, where they induce major structural damage. This may contribute to oxidative stress. Our studies demonstrate that the increased biological potency of UFPs is related to the content of redox cycling organic chemicals and their ability to damage mitochondria. PMID:12676598

  19. Detection of DNA damage induced by heavy ion irradiation in the individual cells with comet assay

    NASA Astrophysics Data System (ADS)

    Wada, S.; Natsuhori, M.; Ito, N.; Funayama, T.; Kobayashi, Y.

    2003-05-01

    Investigating the biological effects of high-LET heavy ion irradiation at low fluence is important to evaluate the risk of charged particles. Especially it is important to detect radiation damage induced by the precise number of heavy ions in the individual cells. Thus we studied the relationship between the number of ions traversing the cell and DNA damage produced by the ion irradiation. We applied comet assay to measure the DNA damage in the individual cells. Cells attached on the ion track detector CR-39 were irradiated with ion beams at TIARA, JAERI-Takasaki. After irradiation, the cells were stained with ethidium bromide and the opposite side of the CR-39 was etched. We observed that the heavy ions with higher LET values induced the heavier DNA damage. The result indicated that the amount of DNA damage induced by one particle increased with the LET values of the heavy ions.

  20. Hydrogen Induced Damage in Pipeline Steels

    NASA Astrophysics Data System (ADS)

    Angus, Garrett R.

    The hydrogen induced cracking (HIC) resistance of several grades of plate steels was investigated using electrolytic hydrogen charging. HIC generated by electrolytic charging was also compared to the industrial standard test for HIC, the NACE standard TM0284. The electrolytic charging (EC) apparatus was designed to optimize the reproducibility of the HIC results and the robustness of the components during long charging times. A characterization study on the EC apparatus was undertaken. Alterations to applied current density and charging time were conducted on a highly susceptible plate steel, 100XF, to assess HIC damage as a function of charging conditions. Intermediate current densities of 10 to 15 mA/cm2 produced the greatest extent of cracking without significant corrosion related surface damage. The hydrogen charging time did not greatly affect the extent and depth of cracking for test times between 24 to 48 hours. Thus, for subsequent experiments, the applied current density was set to 15 mA/cm2 and the charging time was set to 24 hours. Plate steel grades X52, X60, X70, and 100XF were prestrained in tension to various levels and then electrolytically charged with hydrogen or tested with the NACE standard TM0284 test (solution A) saturated with H2S(g) to induce HIC. Prestrain was introduced to assess its impact on HIC. Hydrogen damage was quantified with the crack ratios defined in the NACE Standard TM0284. The results from the EC and NACE methods were very comparable to one, with respect to the magnitude of cracking and the trends between alloy and pre-strain conditions observed. Both methods showed that HIC substantially increased for the high strength 100XF steel compared to the lower strength alloys. This is consistent with NACE recommendations for HIC resistance steels, which suggests that alloy strength should be less than 116 ksi (800 MPa) or 248 HV (22 HRC). The HIC results were largely independent of the pre-strain levels imposed within the

  1. Damage and failure mechanisms associated with photoablation of biological tissues

    SciTech Connect

    Antoun, T.; Seaman, L.; Curran, D.; Glinsky, M.

    1996-05-01

    This paper aims to examine the processes associated with failure of the cornea and other collagenous tissues during photoablation. Two different constitutive models are applied to simulate a series of laser deposition experiments into porcine reticular dermis (1), a biological tissue similar to the cornea in composition and photoablation characteristics. The first of our constitutive models, DFRACT, is a physically motivated, micromechanical model based on the nucleation and growth of spherical voids (2). The second is a relatively simple model that allows the material to vaporize and thermally soften. The simulation results reproduce the prominent features observed experimentally thereby shedding a new light on the operative mechanisms during photoablation. The good qualitative agreement between the simulated stress histories and the stress histories measured during the experiments also demonstrates the effectiveness of micromechanical damage and failure modeling as a viable tool for optimizing existing laser surgery procedures and designing new ones. {copyright} {ital 1996 American Institute of Physics.}

  2. Chemical and Biological Consequences of Oxidatively Damaged Guanine in DNA

    PubMed Central

    Delaney, Sarah; Jarem, Daniel A.; Volle, Catherine B.; Yennie, Craig J.

    2013-01-01

    Of the four native nucleosides, 2′-deoxyguanosine (dGuo) is most easily oxidized. Two lesions derived from dGuo are 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo) and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (Fapy)·dGuo. Furthermore, while steady-state levels of 8-oxodGuo can be detected in genomic DNA, it is also known that 8-oxodGuo is more easily oxidized than dGuo. Thus, 8-oxodGuo is susceptible to further oxidation to form several hyperoxidized dGuo products. This review addresses the structural impact, the mutagenic and genotoxic potential, and biological implications of oxidatively damaged DNA, in particular 8-oxodGuo, Fapy·dGuo, and the hyperoxidized dGuo products. PMID:22239655

  3. GUI to Facilitate Research on Biological Damage from Radiation

    NASA Technical Reports Server (NTRS)

    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.

  4. Kinetic Modeling of the X-ray-induced Damage to a Metalloprotein

    PubMed Central

    Davis, Katherine M.; Kosheleva, Irina; Henning, Robert W.; Seidler, Gerald T.; Pushkar, Yulia

    2013-01-01

    It is well known that biological samples undergo x-ray-induced degradation. One of the fastest occurring x-ray-induced processes involves redox modifications (reduction or oxidation) of redox-active cofactors in proteins. Here we analyze room temperature data on the photoreduction of Mn ions in the oxygen evolving complex (OEC) of photosystem II, one of the most radiation damage sensitive proteins and a key constituent of natural photosynthesis in plants, green algae and cyanobacteria. Time-resolved x-ray emission spectroscopy with wavelength-dispersive detection was used to collect data on the progression of x-ray-induced damage. A kinetic model was developed to fit experimental results, and the rate constant for the reduction of OEC MnIII/IV ions by solvated electrons was determined. From this model, the possible kinetics of x-ray-induced damage at variety of experimental conditions, such as different rates of dose deposition as well as different excitation wavelengths, can be inferred. We observed a trend of increasing dosage threshold prior to the onset of x-ray-induced damage with increasing rates of damage deposition. This trend suggests that experimentation with higher rates of dose deposition is beneficial for measurements of biological samples sensitive to radiation damage, particularly at pink beam and x-ray FEL sources. PMID:23815809

  5. A continuum damage model of fatigue-induced damage in laminated composites

    NASA Technical Reports Server (NTRS)

    Harris, Charles E.; Allen, David H.

    1988-01-01

    A model is presented which predicts the stress-strain behavior of continuous fiber reinforced laminated composites in the presence of microstructural damage. The model is based on the concept of continuum damage mechanics and uses internal state variables to characterize the various damage modes. The associated internal state variable growth laws are mathematical models of the loading history induced development of microstructural damage. The model is demonstrated by using it to predict the response of damaged AS-4/3502 graphite/epoxy laminate panels.

  6. Spaceflight environment induces mitochondrial oxidative damage in ocular tissue.

    PubMed

    Mao, Xiao W; Pecaut, Michael J; Stodieck, Louis S; Ferguson, Virginia L; Bateman, Ted A; Bouxsein, Mary; Jones, Tamako A; Moldovan, Maria; Cunningham, Christopher E; Chieu, Jenny; Gridley, Daila S

    2013-10-01

    A recent report shows that more than 30% of the astronauts returning from Space Shuttle missions or the International Space Station (ISS) were diagnosed with eye problems that can cause reduced visual acuity. We investigate here whether spaceflight environment-associated retinal damage might be related to oxidative stress-induced mitochondrial apoptosis. Female C57BL/6 mice were flown in the space shuttle Atlantis (STS-135), and within 3-5 h of landing, the spaceflight and ground-control mice, similarly housed in animal enclosure modules (AEMs) were euthanized and their eyes were removed for analysis. Changes in expression of genes involved in oxidative stress, mitochondrial and endothelial cell biology were examined. Apoptosis in the retina was analyzed by caspase-3 immunocytochemical analysis and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Levels of 4-hydroxynonenal (4-HNE) protein, an oxidative specific marker for lipid peroxidation were also measured. Evaluation of spaceflight mice and AEM ground-control mice showed that expression of several genes playing central roles in regulating the mitochondria-associated apoptotic pathway were significantly altered in mouse ocular tissue after spaceflight compared to AEM ground-control mice. In addition, the mRNA levels of several genes, which are responsible for regulating the production of reactive oxygen species were also significantly up-regulated in spaceflight samples compared to AEM ground-control mice. Further more, the level of HNE protein was significantly elevated in the retina after spaceflight compared to controls. Our results also revealed that spaceflight conditions induced significant apoptosis in the retina especially inner nuclear layer (INL) and ganglion cell layer (GCL) compared to AEM ground controls. The data provided the first evidence that spaceflight conditions induce oxidative damage that results in mitochondrial apoptosis in the retina. This data suggest

  7. DNA damage response induced by HZE particles in human cells

    NASA Astrophysics Data System (ADS)

    Chen, David; Aroumougame, Asaithamby

    Convincing evidences indicate that high-linear energy transfer (LET) ionizing radiation (IR) induced complex DNA lesions are more difficult to repair than isolated DNA lesions induced by low-LET IR; this has been associated with the increased RBE for cell killing, chromosomal aberrations, mutagenesis, and carcinogenesis in high energy charged-particle irradiated human cells. We have employed an in situ method to directly monitor induction and repair of clustered DNA lesions at the single-cell level. We showed, consistent with biophysical modeling, that the kinetics of loss of clustered DNA lesions was substantially compromised in human fibroblasts. The unique spatial distribution of different types of DNA lesions within the clustered damages determined the cellular ability to repair these damages. Importantly, examination of metaphase cells derived from HZE particle irradiated cells revealed that the extent of chromosome aberrations directly correlated with the levels of unrepaired clustered DNA lesions. In addition, we used a novel organotypic human lung three-dimensional (3D) model to investigate the biological significance of unrepaired DNA lesions in differentiated lung epithelial cells. We found that complex DNA lesions induced by HZE particles were even more difficult to be repaired in organotypic 3D culture, resulting enhanced cell killing and chromosome aberrations. Our data suggest that DNA repair capability in differentiated cells renders them vulnerable to DSBs, promoting genome instability that may lead to carcinogenesis. As the organotypic 3D model mimics human lung, it opens up new experimental approaches to explore the effect of radiation in vivo and will have important implications for evaluating radiation risk in human tissues.

  8. DEVELOPMENT OF RAPID TECHNIQUES FOR DETECTION OF CHEMICALLY-INDUCED DNA DAMAGE

    EPA Science Inventory

    Rapid and cost-effective indicator assays are being developed which may be used as a rapid screen to assess the potential for exposure to hazardous compounds that can be related to a biological target (e.g., DNA). Chemically-induced DNA damage will be measured using surrogate DN...

  9. DNA damage induces a meiotic arrest in mouse oocytes mediated by the spindle assembly checkpoint

    PubMed Central

    Collins, Josie K.; Lane, Simon I. R.; Merriman, Julie A.; Jones, Keith T.

    2015-01-01

    Extensive damage to maternal DNA during meiosis causes infertility, birth defects and abortions. However, it is unknown if fully grown oocytes have a mechanism to prevent the creation of DNA-damaged embryos. Here we show that DNA damage activates a pathway involving the spindle assembly checkpoint (SAC) in response to chemically induced double strand breaks, UVB and ionizing radiation. DNA damage can occur either before or after nuclear envelope breakdown, and provides an effective block to anaphase-promoting complex activity, and consequently the formation of mature eggs. This contrasts with somatic cells, where DNA damage fails to affect mitotic progression. However, it uncovers a second function for the meiotic SAC, which in the context of detecting microtubule–kinetochore errors has hitherto been labelled as weak or ineffectual in mammalian oocytes. We propose that its essential role in the detection of DNA damage sheds new light on its biological purpose in mammalian female meiosis. PMID:26522232

  10. DNA damage induces a meiotic arrest in mouse oocytes mediated by the spindle assembly checkpoint.

    PubMed

    Collins, Josie K; Lane, Simon I R; Merriman, Julie A; Jones, Keith T

    2015-01-01

    Extensive damage to maternal DNA during meiosis causes infertility, birth defects and abortions. However, it is unknown if fully grown oocytes have a mechanism to prevent the creation of DNA-damaged embryos. Here we show that DNA damage activates a pathway involving the spindle assembly checkpoint (SAC) in response to chemically induced double strand breaks, UVB and ionizing radiation. DNA damage can occur either before or after nuclear envelope breakdown, and provides an effective block to anaphase-promoting complex activity, and consequently the formation of mature eggs. This contrasts with somatic cells, where DNA damage fails to affect mitotic progression. However, it uncovers a second function for the meiotic SAC, which in the context of detecting microtubule-kinetochore errors has hitherto been labelled as weak or ineffectual in mammalian oocytes. We propose that its essential role in the detection of DNA damage sheds new light on its biological purpose in mammalian female meiosis. PMID:26522232

  11. Mechanisms of Diabetes-Induced Liver Damage

    PubMed Central

    Mohamed, Jamaludin; Nazratun Nafizah, A. H.; Zariyantey, A. H.; Budin, S. B.

    2016-01-01

    Diabetes mellitus is a non-communicable disease that occurs in both developed and developing countries. This metabolic disease affects all systems in the body, including the liver. Hyperglycaemia, mainly caused by insulin resistance, affects the metabolism of lipids, carbohydrates and proteins and can lead to non-alcoholic fatty liver disease, which can further progress to non-alcoholic steatohepatitis, cirrhosis and, finally, hepatocellular carcinomas. The underlying mechanism of diabetes that contributes to liver damage is the combination of increased oxidative stress and an aberrant inflammatory response; this activates the transcription of pro-apoptotic genes and damages hepatocytes. Significant involvement of pro-inflammatory cytokines—including interleukin (IL)-1β, IL-6 and tumour necrosis factor-α—exacerbates the accumulation of oxidative damage products in the liver, such as malondialdehyde, fluorescent pigments and conjugated dienes. This review summarises the biochemical, histological and macromolecular changes that contribute to oxidative liver damage among diabetic individuals. PMID:27226903

  12. Relationship of gonadal activity and chemotherapy-induced gonadal damage

    SciTech Connect

    Rivkees, S.A.; Crawford, J.D.

    1988-04-08

    The authors tested the hypothesis that chemotherapy-induced gonadal damage is proportional to the degree of gonadal activity during treatment. Thirty studies that evaluated gonadal function after cyclophosphamide therapy for renal disease or combination chemotherapy for Hodgkin's disease or acute lymphocytic leukemia provided data for analysis. Data were stratified according to sex, illness, chemotherapeutic regimen and dose, and pubertal stage at the time of treatment. Chemotherapy-induced damage was more likely to occur in patients who were treated when sexually mature compared with those who were treated when prepubertal. Males were significantly more frequently affected than females when treated for renal disease of Hodgkin's disease. Chemotherapy-induced damage was also more likely to occur when patients were treated with large doses of alkylating agents. These data suggest that chemotherapy-induced damage is proportional to gonadal activity. Further efforts are needed to test whether induced gonadal quiescence during chemotherapy will reduce the strikingly high incidence of gonadal failure following chemotherapy.

  13. Laser induced damage testing: Equipment and techniques

    NASA Astrophysics Data System (ADS)

    Morelli, G. L.

    1993-07-01

    A laser damage test station was designed and built at the AlliedSignal Inc., Kansas City Division (KCD). The purpose of this effort was to establish the capability for testing polished optical fibers for high energy laser transmission to support the Direct Optical Initiation (DOI), optical firing-set program. A single shot, conditioned threshold type laser damage test was implemented. A flashlamp pumped, multimode, Q-switched, Nd:YAG laser was utilized as the test source. The test laser's operational parameters were extensively characterized. The pulse width, beam divergence, and polarization state of the laser were all held constant throughout the tests. A single plano-convex lens was utilized to focus the laser beam energy into the optical fibers. A focusing geometry was utilized which avoided bulk damage and minimized damage at the fiber's core/cladding interface. A special holding fixture was fabricated, which minimized the mechanical stresses on the fiber during testing. Several uncoated, step-index, multimode, optical fibers were damage tested to verify the functionality of the test station. The fibers all had a 400 micron diameter core of pure fused silica, a 440 micron diameter fluorine doped fused silica cladding, and a 15 micron thick polyimide buffer layer. The fibers were tested up to a fluence level greater than 55.7 J/cm(exp 2) or until damage was observed. Cleaning, inspection, and testing procedures were developed and documented.

  14. Damage-induced nonassociated inelastic flow in rock salt

    SciTech Connect

    Chan, K.S.; Bodner, S.R.; Brodsky, N.S.; Fossum, A.F.

    1993-06-01

    The multi-mechanism deformation coupled fracture model recently developed by CHAN, et al. (1992), for describing time-dependent, pressure-sensitive inelastic flow and damage evolution in crystalline solids was evaluated against triaxial creep experiments on rock salt. Guided by experimental observations, the kinetic equation and the flow law for damage-induced inelastic flow in the model were modified to account for the development of damage and inelastic dilatation in the transient creep regime. The revised model was then utilized to obtain the creep response and damage evolution in rock salt as a function of confining pressure and stress difference. Comparison between model calculation and experiment revealed that damage-induced inelastic flow is nonassociated, dilatational, and contributes significantly to the macroscopic strain rate observed in rock salt deformed at low confining pressures. The inelastic strain rate and volumetric strain due to damage decrease with increasing confining pressures, and all are suppressed at sufficiently high confining pressures.

  15. DNA damage profiles induced by sunlight at different latitudes.

    PubMed

    Schuch, André Passaglia; Yagura, Teiti; Makita, Kazuo; Yamamoto, Hiromasa; Schuch, Nelson Jorge; Agnez-Lima, Lucymara Fassarella; MacMahon, Ricardo Monreal; Menck, Carlos Frederico Martins

    2012-04-01

    Despite growing knowledge on the biological effects of ultraviolet (UV) radiation on human health and ecosystems, it is still difficult to predict the negative impacts of the increasing incidence of solar UV radiation in a scenario of global warming and climate changes. Hence, the development and application of DNA-based biological sensors to monitor the solar UV radiation under different environmental conditions is of increasing importance. With a mind to rendering a molecular view-point of the genotoxic impact of sunlight, field experiments were undertaken with a DNA-dosimeter system in parallel with physical photometry of solar UVB/UVA radiation, at various latitudes in South America. On applying biochemical and immunological approaches based on specific DNA-repair enzymes and antibodies, for evaluating sunlight-induced DNA damage profiles, it became clear that the genotoxic potential of sunlight does indeed vary according to latitude. Notwithstanding, while induction of oxidized DNA bases is directly dependent on an increase in latitude, the generation of 6-4PPs is inversely so, whereby the latter can be regarded as a biomolecular marker of UVB incidence. This molecular DNA lesion-pattern largely reflects the relative incidence of UVA and UVB energy at any specific latitude. Hereby is demonstrated the applicability of this DNA-based biosensor for additional, continuous field experiments, as a means of registering variations in the genotoxic impact of solar UV radiation. PMID:22674547

  16. Lowering evaluation uncertainties in laser-induced damage testing

    NASA Astrophysics Data System (ADS)

    Jensen, Lars O.; Mrohs, Marius; Gyamfi, Mark; Mädebach, Heinrich; Ristau, Detlev

    2015-11-01

    As a consequence of the statistical nature of laser-induced damage threshold measurements in the nanosecond regime, the evaluation method plays a vital role. Within the test procedure outlined in the corresponding ISO standard, several steps of data reduction are required, and the resulting damage probability distribution as a function of laser fluence needs to be fitted either based on an empirical regression function or described by models for the respective damage mechanism.

  17. Preventing Ultraviolet Light-Induced Damage: The Benefits of Antioxidants

    ERIC Educational Resources Information Center

    Yip, Cheng-Wai

    2007-01-01

    Extracts of fruit peels contain antioxidants that protect the bacterium "Escherichia coli" against damage induced by ultraviolet light. Antioxidants neutralise free radicals, thus preventing oxidative damage to cells and deoxyribonucleic acid. A high survival rate of UV-exposed cells was observed when grapefruit or grape peel extract was added,…

  18. Effects of Ionizing Radiation on Biological Molecules—Mechanisms of Damage and Emerging Methods of Detection

    PubMed Central

    Reisz, Julie A.; Bansal, Nidhi; Qian, Jiang; Zhao, Weiling

    2014-01-01

    Abstract Significance: The detrimental effects of ionizing radiation (IR) involve a highly orchestrated series of events that are amplified by endogenous signaling and culminating in oxidative damage to DNA, lipids, proteins, and many metabolites. Despite the global impact of IR, the molecular mechanisms underlying tissue damage reveal that many biomolecules are chemoselectively modified by IR. Recent Advances: The development of high-throughput “omics” technologies for mapping DNA and protein modifications have revolutionized the study of IR effects on biological systems. Studies in cells, tissues, and biological fluids are used to identify molecular features or biomarkers of IR exposure and response and the molecular mechanisms that regulate their expression or synthesis. Critical Issues: In this review, chemical mechanisms are described for IR-induced modifications of biomolecules along with methods for their detection. Included with the detection methods are crucial experimental considerations and caveats for their use. Additional factors critical to the cellular response to radiation, including alterations in protein expression, metabolomics, and epigenetic factors, are also discussed. Future Directions: Throughout the review, the synergy of combined “omics” technologies such as genomics and epigenomics, proteomics, and metabolomics is highlighted. These are anticipated to lead to new hypotheses to understand IR effects on biological systems and improve IR-based therapies. Antioxid. Redox Signal. 21: 260–292. PMID:24382094

  19. New insights in photoaging, UVA induced damage and skin types.

    PubMed

    Battie, Claire; Jitsukawa, Setsuko; Bernerd, Françoise; Del Bino, Sandra; Marionnet, Claire; Verschoore, Michèle

    2014-10-01

    UVA radiation is the most prevalent component of solar UV radiation; it deeply penetrates into the skin and induces profound alterations of the dermal connective tissue. In recent years, the detrimental effects of UVA radiation were more precisely demonstrated at cellular and molecular levels, using adequate methods to identify biological targets of UVA radiation and the resulting cascade impairment of cell functions and tissue degradation. In particular gene expression studies recently revealed that UVA radiation induces modulation of several genes confirming the high sensitivity of dermal fibroblasts to UVA radiation. The major visible damaging effects of UVA radiation only appear after years of exposure: it has been clearly evidenced that they are responsible for more or less early signs of photoageing and photocarcinogenesis. UVA radiation appears to play a key role in pigmented changes occurring with age, the major sign of skin photoaging in Asians. Skin susceptibility to photoaging alterations also depends on constitutive pigmentation. The skin sensitivity to UV light has been demonstrated to be linked to skin color type. PMID:25234829

  20. Quercitrin protects skin from UVB-induced oxidative damage

    SciTech Connect

    Yin, Yuanqin; Li, Wenqi; Son, Young-Ok; Sun, Lijuan; Lu, Jian; Kim, Donghern; Wang, Xin; Yao, Hua; Wang, Lei; Pratheeshkumar, Poyil; Hitron, Andrew J.; Luo, Jia; Gao, Ning; Shi, Xianglin; Zhang, Zhuo

    2013-06-01

    Exposure of the skin to ultraviolet B (UVB) radiation causes oxidative damage to skin, resulting in sunburn, photoaging, and skin cancer. It is generally believed that the skin damage induced by UV irradiation is a consequence of generation of reactive oxygen species (ROS). Recently, there is an increased interest in the use of natural products as chemopreventive agents for non-melanoma skin cancer (NMSC) due to their antioxidants and anti-inflammatory properties. Quercitrin, glycosylated form of quercetin, is the most common flavonoid in nature with antioxidant properties. The present study investigated the possible beneficial effects of quercitrin to inhibit UVB irradiation-induced oxidative damage in vitro and in vivo. Our results showed that quercitrin decreased ROS generation induced by UVB irradiation in JB6 cells. Quercitrin restored catalase expression and GSH/GSSG ratio reduced by UVB exposure, two major antioxidant enzymes, leading to reductions of oxidative DNA damage and apoptosis and protection of the skin from inflammation caused by UVB exposure. The present study demonstrated that quercitrin functions as an antioxidant against UVB irradiation-induced oxidative damage to skin. - Highlights: • Oxidative stress plays a key role in UV-induced cell and tissue injuries. • Quercitrin decreases ROS generation and restores antioxidants irradiated by UVB. • Quercitrin reduces UVB-irradiated oxidative DNA damage, apoptosis, and inflammation. • Quercitrin functions as an antioxidant against UVB-induced skin injuries.

  1. DNA damage in cells exhibiting radiation-induced genomic instability

    DOE PAGESBeta

    Keszenman, Deborah J.; Kolodiuk, Lucia; Baulch, Janet E.

    2015-02-22

    Cells exhibiting radiation induced genomic instability exhibit varied spectra of genetic and chromosomal aberrations. Even so, oxidative stress remains a common theme in the initiation and/or perpetuation of this phenomenon. Isolated oxidatively modified bases, abasic sites, DNA single strand breaks and clustered DNA damage are induced in normal mammalian cultured cells and tissues due to endogenous reactive oxygen species generated during normal cellular metabolism in an aerobic environment. While sparse DNA damage may be easily repaired, clustered DNA damage may lead to persistent cytotoxic or mutagenic events that can lead to genomic instability. In this study, we tested the hypothesismore » that DNA damage signatures characterised by altered levels of endogenous, potentially mutagenic, types of DNA damage and chromosomal breakage are related to radiation-induced genomic instability and persistent oxidative stress phenotypes observed in the chromosomally unstable progeny of irradiated cells. The measurement of oxypurine, oxypyrimidine and abasic site endogenous DNA damage showed differences in non-double-strand breaks (DSB) clusters among the three of the four unstable clones evaluated as compared to genomically stable clones and the parental cell line. These three unstable clones also had increased levels of DSB clusters. The results of this study demonstrate that each unstable cell line has a unique spectrum of persistent damage and lead us to speculate that alterations in DNA damage signaling and repair may be related to the perpetuation of genomic instability.« less

  2. DNA damage in cells exhibiting radiation-induced genomic instability

    SciTech Connect

    Keszenman, Deborah J.; Kolodiuk, Lucia; Baulch, Janet E.

    2015-02-22

    Cells exhibiting radiation induced genomic instability exhibit varied spectra of genetic and chromosomal aberrations. Even so, oxidative stress remains a common theme in the initiation and/or perpetuation of this phenomenon. Isolated oxidatively modified bases, abasic sites, DNA single strand breaks and clustered DNA damage are induced in normal mammalian cultured cells and tissues due to endogenous reactive oxygen species generated during normal cellular metabolism in an aerobic environment. While sparse DNA damage may be easily repaired, clustered DNA damage may lead to persistent cytotoxic or mutagenic events that can lead to genomic instability. In this study, we tested the hypothesis that DNA damage signatures characterised by altered levels of endogenous, potentially mutagenic, types of DNA damage and chromosomal breakage are related to radiation-induced genomic instability and persistent oxidative stress phenotypes observed in the chromosomally unstable progeny of irradiated cells. The measurement of oxypurine, oxypyrimidine and abasic site endogenous DNA damage showed differences in non-double-strand breaks (DSB) clusters among the three of the four unstable clones evaluated as compared to genomically stable clones and the parental cell line. These three unstable clones also had increased levels of DSB clusters. The results of this study demonstrate that each unstable cell line has a unique spectrum of persistent damage and lead us to speculate that alterations in DNA damage signaling and repair may be related to the perpetuation of genomic instability.

  3. WILD PIGS: BIOLOGY, DAMAGE, CONTROL TECHINQUES AND MANAGEMENT

    SciTech Connect

    Mayer, John; Brisbin, I. Lehr

    2009-12-31

    about anything; and, they can live just about anywhere. On top of that, wild pigs are both very difficult to control and, with the possible exception of island ecosystems, almost impossible to eradicate (Dickson et al. 2001, Sweeney et al. 2003). The solution to the wild pig problem has not been readily apparent. The ultimate answer as to how to control these animals has not been found to date. In many ways, wild pigs are America's most successful large invasive species. All of which means that wild pigs are a veritable nightmare for land and resource managers trying to keep the numbers of these animals and the damage that they do under control. Since the more that one knows about an invasive species, the easier it is to deal with and hopefully control. For wild pigs then, it is better to 'know thy enemy' than to not, especially if one expects to be able to successfully control them. In an effort to better 'know thy enemy,' a two-day symposium was held in Augusta, Georgia, on April 21-22, 2004. This symposium was organized and sponsored by U.S.D.A. Forest Service-Savannah River (USFS-SR), U. S. Department of Energy-Savannah River Operations Office (DOE-SR), the Westinghouse Savannah River Company (WSRC), the South Carolina Chapter of the Soil & Water Conservation Society, and the Savannah River Ecology Laboratory (SREL). The goal of this symposium was to assemble researchers and land managers to first address various aspects of the biology and damage of wild pigs, and then review the control techniques and management of this invasive species. The result would then be a collected synopsis of what is known about wild pigs in the United States. Although the focus of the symposium was primarily directed toward federal agencies, presenters also included professionals from academic institutions, and private-sector control contractors and land managers. Most of the organizations associated with implementing this symposium were affiliated with the Savannah River Site (SRS), a

  4. Polymer-induced compression of biological hydrogels

    NASA Astrophysics Data System (ADS)

    Datta, Sujit; Preska Steinberg, Asher; Ismagilov, Rustem

    Hydrogels - such as mucus, blood clots, and the extracellular matrix - provide critical functions in biological systems. However, little is known about how their structure is influenced by many of the polymeric materials they come into contact with regularly. Here, we focus on one critically important biological hydrogel: colonic mucus. While several biological processes are thought to potentially regulate the mucus hydrogel structure, the polymeric composition of the gut environment has been ignored. We use Flory-Huggins solution theory to characterize polymer-mucus interactions. We find that gut polymers, including those small enough to penetrate the mucus hydrogel, can in fact alter mucus structure, changing its equilibrium degree of swelling and forcing it to compress. The extent of compression increases with increasing polymer concentration and size. We use experiments on mice to verify these predictions with common dietary and therapeutic gut polymers. Our results provide a foundation for investigating similar, previously overlooked, polymer-induced effects in other biological hydrogels.

  5. Ionization induced damage in crystalline silicon

    NASA Technical Reports Server (NTRS)

    Meulenberg, A., Jr.

    1977-01-01

    Close examination of the interaction of the energetic knock-on atoms with the local lattice environment reveals a damage mechanism which does satisfy the experimental data on proton irradiation of silicon. A proton-atom interaction with high energy transfer is considered where the proton path is delineated by a trail of ionization, and the silicon ion path is characterized by much heavier ionization terminating in a dense displacement cluster. At collision, many of the silicon electrons are stripped off, and the resulting energetic ion subsequently loses energy rapidly by Coulomb interaction with bound electrons. The rate of energy loss depends on the charge state and velocity of the knock-on ion. For ion energies in excess of 1 MeV, the intensity of ionization is sufficient to permit lattice atoms, stripped of their binding electrons, to reorient randomly before having an opportunity to recombine with electrons and re-establish the lattice. The path of a knock-on ion thus becomes a thin cylinder of amorphous material within the crystal. Amorphous silicon has a Fermi level closer to mid-band than does single crystal silicon, and a strong field therefore, results around this damaged region. The field produces a large depletion region, representing a very large capture cross section for minority carriers.

  6. Glimepiride protects neurons against amyloid-β-induced synapse damage.

    PubMed

    Osborne, Craig; West, Ewan; Nolan, William; McHale-Owen, Harriet; Williams, Alun; Bate, Clive

    2016-02-01

    Alzheimer's disease is associated with the accumulation within the brain of amyloid-β (Aβ) peptides that damage synapses and affect memory acquisition. This process can be modelled by observing the effects of Aβ on synapses in cultured neurons. The addition of picomolar concentrations of soluble Aβ derived from brain extracts triggered the loss of synaptic proteins including synaptophysin, synapsin-1 and cysteine string protein from cultured neurons. Glimepiride, a sulphonylurea used for the treatment of diabetes, protected neurons against synapse damage induced by Aβ. The protective effects of glimepiride were multi-faceted. Glimepiride treatment was associated with altered synaptic membranes including the loss of specific glycosylphosphatidylinositol (GPI)-anchored proteins including the cellular prion protein (PrP(C)) that acts as a receptor for Aβ42, increased synaptic gangliosides and altered cell signalling. More specifically, glimepiride reduced the Aβ-induced increase in cholesterol and the Aβ-induced activation of cytoplasmic phospholipase A2 (cPLA2) in synapses that occurred within cholesterol-dense membrane rafts. Aβ42 binding to glimepiride-treated neurons was not targeted to membrane rafts and less Aβ42 accumulated within synapses. These studies indicate that glimepiride modified the membrane micro-environments in which Aβ-induced signalling leads to synapse damage. In addition, soluble PrP(C), released from neurons by glimepiride, neutralised Aβ-induced synapse damage. Such observations raise the possibility that glimepiride may reduce synapse damage and hence delay the progression of cognitive decline in Alzheimer's disease. PMID:26432105

  7. [The role of the biological damaging factor in the explosive injury].

    PubMed

    Popov, V L; Kadochnikov, D S; Minaeva, P V

    2015-01-01

    This article describes the specific features of the action of the biological damaging factors on the human organism associated with the explosive injury. Both the direct action of the damaging agents contained in the biological weapons and their secondary effects in the form of systemic and local infectious complications of the inflicted wounds are considered. The criteria for the evaluation of the degree of harm to the health of the victims of explosion attributable to the action of the biological damaging factor are proposed. PMID:26856054

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

    EPA Science Inventory

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

  9. DNA damage induced by the direct effect of radiation

    NASA Astrophysics Data System (ADS)

    Yokoya, A.; Shikazono, N.; Fujii, K.; Urushibara, A.; Akamatsu, K.; Watanabe, R.

    2008-10-01

    We have studied the nature of DNA damage induced by the direct effect of radiation. The yields of single- (SSB) and double-strand breaks (DSB), base lesions and clustered damage were measured using the agarose gel electrophoresis method after exposing to various kinds of radiations to a simple model DNA molecule, fully hydrated closed-circular plasmid DNA (pUC18). The yield of SSB does not show significant dependence on linear energy transfer (LET) values. On the other hand, the yields of base lesions revealed by enzymatic probes, endonuclease III (Nth) and formamidopyrimidine DNA glycosylase (Fpg), which excise base lesions and leave a nick at the damage site, strongly depend on LET values. Soft X-ray photon (150 kVp) irradiation gives a maximum yield of the base lesions detected by the enzymatic probes as SSB and clustered damage, which is composed of one base lesion and proximate other base lesions or SSBs. The clustered damage is visualized as an enzymatically induced DSB. The yields of the enzymatically additional damages strikingly decrease with increasing levels of LET. These results suggest that in higher LET regions, the repair enzymes used as probes are compromised because of the dense damage clustering. The studies using simple plasmid DNA as a irradiation sample, however, have a technical difficulty to detect multiple SSBs in a plasmid DNA. To detect the additional SSBs induced in opposite strand of the first SSB, we have also developed a novel technique of DNA-denaturation assay. This allows us to detect multiply induced SSBs in both strand of DNA, but not induced DSB.

  10. Effects of vitamins on chromium(VI)-induced damage

    SciTech Connect

    Sugiyama, Masayasu )

    1991-05-01

    The effects of vitamin E and vitamin B{sub 2} on DNA damage and cellular reduction of chromium (VI) were investigated using Chinese hamster V-79 cells. pretreatment with {alpha}-tocopherol succinate (vitamin E) resulted in a decrease of DNA single-strand breaks produced by Na{sub 2}CrO{sub 4}, while similar treatment with riboflavin (vitamin B{sub 2}) enhanced levels of DNA breaks. Electron spin resonance (ESR) studies showed that incubation of cells with Na{sub 2}CrO{sub 4} resulted in the formation of both chromium (V) and chromium (III) complexes, and cellular pretreatment with vitamin E reduced the level of the chromium (V) complex, whereas pretreatment with vitamin B{sub 2} enhanced the level of this intermediate. ESR studies demonstrated that a chromium (V) species was formed by the reaction of Na{sub 2}CrO{sub 4} with vitamin B{sub 2} and that vitamin B{sub 2} enhanced the formation of hydroxyl radicals during the reaction of Na{sub 2}CrO{sub 4} and hydrogen peroxide. These results indicate that vitamin E and vitamin B{sub 2} are capable of altering the biological effects of carcinogenic chromium (VI) compounds, possibly through their abilities to modify levels of chromium (V) in cells. The results also suggest that chromate-induced cytotoxicity may not be directly correlated with the genotoxic effects of this metal. The importance of the role of vitamins in chromate-induced toxicity is discussed.

  11. Clustered DNA damages induced by high and low LET radiation, including heavy ions

    NASA Technical Reports Server (NTRS)

    Sutherland, B. M.; Bennett, P. V.; Schenk, H.; Sidorkina, O.; Laval, J.; Trunk, J.; Monteleone, D.; Sutherland, J.; Lowenstein, D. I. (Principal Investigator)

    2001-01-01

    Clustered DNA damages--here defined as two or more lesions (strand breaks, oxidized purines, oxidized pyrimidines or abasic sites) within a few helical turns--have been postulated as difficult to repair accurately, and thus highly significant biological lesions. Further, attempted repair of clusters may produce double strand breaks (DSBs). However, until recently, there was no way to measure ionizing radiation-induced clustered damages, except DSB. We recently described an approach for measuring classes of clustered damages (oxidized purine clusters, oxidized pyrimidine clusters, abasic clusters, along with DSB). We showed that ionizing radiation (gamma rays and Fe ions, 1 GeV/amu) does induce such clusters in genomic DNA in solution and in human cells. These studies also showed that each damage cluster results from one radiation hit (and its track), thus indicating that they can be induced by very low doses of radiation, i.e. two independent hits are not required for cluster induction. Further, among all complex damages, double strand breaks comprise--at most-- 20%, with the other clustered damages being at least 80%.

  12. Determination of the Action Spectrum of UVR-Induced Mitochondrial DNA Damage in Human Skin Cells.

    PubMed

    Latimer, Jennifer A; Lloyd, James J; Diffey, Brian L; Matts, Paul J; Birch-Machin, Mark A

    2015-10-01

    Biological responses of human skin to UVR including cancer and aging are largely wavelength-dependent, as shown by the action spectra of UVR-induced erythema and nuclear DNA (nDNA) damage. A molecular dosimeter of UVR exposure is therefore required. Although mitochondrial DNA (mtDNA) damage has been shown to be a reliable and sensitive biomarker of UVR exposure in human skin, its wavelength dependency is unknown. The current study solves this problem by determining the action spectrum of UVR-induced mtDNA damage in human skin. Human neonatal dermal fibroblasts and primary human adult keratinocyte cells were irradiated with increasing doses of UVR. Dose-response curves of mtDNA damage were produced for each of the UVR sources and cell types, and an action spectrum for each cell type was determined by mathematical induction. Similarities between these mtDNA damage action spectra and previously determined nDNA damage were observed, with the most detrimental effects occurring over the shorter UVR wavelengths. Notably, a statistically significant (P<0.0001) greater sensitivity to mtDNA damage was observed in dermal fibroblasts compared with keratinocytes at wavelengths >300 nm, possibly indicating a wider picture of depth dependence in sensitivity. This finding has implications for disease/photodamage mechanisms and interventions. PMID:26030182

  13. Clustered DNA damages induced in isolated DNA and in human cells by low doses of ionizing radiation

    NASA Technical Reports Server (NTRS)

    Sutherland, B. M.; Bennett, P. V.; Sidorkina, O.; Laval, J.; Lowenstein, D. I. (Principal Investigator)

    2000-01-01

    Clustered DNA damages-two or more closely spaced damages (strand breaks, abasic sites, or oxidized bases) on opposing strands-are suspects as critical lesions producing lethal and mutagenic effects of ionizing radiation. However, as a result of the lack of methods for measuring damage clusters induced by ionizing radiation in genomic DNA, neither the frequencies of their production by physiological doses of radiation, nor their repairability, nor their biological effects are known. On the basis of methods that we developed for quantitating damages in large DNAs, we have devised and validated a way of measuring ionizing radiation-induced clustered lesions in genomic DNA, including DNA from human cells. DNA is treated with an endonuclease that induces a single-strand cleavage at an oxidized base or abasic site. If there are two closely spaced damages on opposing strands, such cleavage will reduce the size of the DNA on a nondenaturing gel. We show that ionizing radiation does induce clustered DNA damages containing abasic sites, oxidized purines, or oxidized pyrimidines. Further, the frequency of each of these cluster classes is comparable to that of frank double-strand breaks; among all complex damages induced by ionizing radiation, double-strand breaks are only about 20%, with other clustered damage constituting some 80%. We also show that even low doses (0.1-1 Gy) of high linear energy transfer ionizing radiation induce clustered damages in human cells.

  14. Pneumococcal Pneumolysin Induces DNA Damage and Cell Cycle Arrest.

    PubMed

    Rai, Prashant; He, Fang; Kwang, Jimmy; Engelward, Bevin P; Chow, Vincent T K

    2016-01-01

    Streptococcus pneumoniae produces pneumolysin toxin as a key virulence factor against host cells. Pneumolysin is a cholesterol-dependent cytolysin (CDC) toxin that forms lytic pores in host membranes and mediates pneumococcal disease pathogenesis by modulating inflammatory responses. Here, we show that pneumolysin, which is released during bacterial lysis, induces DNA double strand breaks (DSBs), as indicated by ataxia telangiectasia mutated (ATM)-mediated H2AX phosphorylation (γH2AX). Pneumolysin-induced γH2AX foci recruit mediator of DNA damage checkpoint 1 (MDC1) and p53 binding protein 1 (53BP1), to sites of DSBs. Importantly, results show that toxin-induced DNA damage precedes cell cycle arrest and causes apoptosis when DNA-dependent protein kinase (DNA-PK)-mediated non-homologous end joining is inhibited. Further, we observe that cells that were undergoing DNA replication harbored DSBs in greater frequency during pneumolysin treatment. This observation raises the possibility that DSBs might be arising as a result of replication fork breakdown. Additionally, neutralizing the oligomerization domain of pneumolysin with monoclonal antibody suppresses DNA damage and also cell cycle arrest, indicating that pneumolysin oligomerization is important for causing DNA damage. Taken together, this study reveals a previously unidentified ability of pneumolysin to induce cytotoxicity via DNA damage, with implications in the pathophysiology of S. pneumoniae infection. PMID:27026501

  15. Modulation of irinotecan-induced genomic DNA damage by theanine.

    PubMed

    Attia, Sabry

    2012-05-01

    The possible chemoprotective activity of theanine against irinotecan-induced genomic DNA damage towards mouse bone marrow cells was investigated. Chromosomal aberrations, DNA damage, micronuclei formation and mitotic activity were studied in the current study as markers of genomic damage. Oxidative DNA stress markers such as 8-hydroxydeoxyguanosine, lipid peroxidation, reduced and oxidized glutathione levels were assessed as a possible mechanism underlying this amelioration. Theanine was neither genotoxic nor cytotoxic in mice at doses equivalent to 30 or 60 mg/kg for 12 days. Pretreatment of mice with theanine significantly reduced irinotecan-induced genomic damage in the bone marrow cells and these effects were dose dependent. Irinotecan induced marked biochemical alterations characteristic of oxidative DNA stress, including increased 8-hydroxydeoxyguanosine, enhanced lipid peroxidation and reduction in the reduced/oxidized glutathione ratio. Prior administration of theanine ahead of irinotecan challenge ameliorated these oxidative DNA stress markers. Overall, this study provides for the first time that theanine has a protective role in the abatement of irinotecan-induced genomic damage in the bone marrow cells of mice that resides, at least in part, on its ability to modulate the cellular antioxidant levels and consequently protect bone marrow from irinotecan genotoxicity. PMID:22414655

  16. Quercitrin Protects Skin from UVB-induced Oxidative Damage

    PubMed Central

    Yin, Yuanqin; Li, Wenqi; Son, Yong-Ok; Sun, Lijuan; Lu, Jian; Kim, Donghern; Wang, Xin; Yao, Hua; Wang, Lei; Pratheeshkumar, Poyil; Hitron, Andrew J; Luo, Jia; Gao, Ning; Shi, Xianglin; Zhang, Zhuo

    2013-01-01

    Exposure of the skin to ultraviolet B (UVB) radiation causes oxidative damage to skin, resulting in sunburn, photoaging, and skin cancer. It is generally believed that the skin damage induced by UV irradiation is a consequence of generation of reactive oxygen species (ROS). Recently, there is an increased interest in the use of natural products as chemopreventive agents for non-melanoma skin cancer (NMSC) due to their antioxidants and anti-inflammatory properties. Quercitrin, glycosylated form of quercetin, is the most common flavonoid in nature with antioxidant properties. The present study investigated the possible beneficial effects of quercitrin to inhibit UVB irradiation-induced oxidative damage in vitro and in vivo. Our results showed that quercitrin decreased ROS generation induced by UVB irradiation in JB6 cells. Quercitrin restored catalase expression and GSH/GSSG ratio reduced by UVB exposure, two major antioxidant enzymes, leading to reductions of oxidative DNA damage and apoptosis and protection of the skin from inflammation caused by UVB exposure. The present study demonstrated that quercitrin functions as an antioxidant against UVB irradiation-induced oxidative damage to skin. PMID:23545178

  17. Pneumococcal Pneumolysin Induces DNA Damage and Cell Cycle Arrest

    PubMed Central

    Rai, Prashant; He, Fang; Kwang, Jimmy; Engelward, Bevin P.; Chow, Vincent T.K.

    2016-01-01

    Streptococcus pneumoniae produces pneumolysin toxin as a key virulence factor against host cells. Pneumolysin is a cholesterol-dependent cytolysin (CDC) toxin that forms lytic pores in host membranes and mediates pneumococcal disease pathogenesis by modulating inflammatory responses. Here, we show that pneumolysin, which is released during bacterial lysis, induces DNA double strand breaks (DSBs), as indicated by ataxia telangiectasia mutated (ATM)-mediated H2AX phosphorylation (γH2AX). Pneumolysin-induced γH2AX foci recruit mediator of DNA damage checkpoint 1 (MDC1) and p53 binding protein 1 (53BP1), to sites of DSBs. Importantly, results show that toxin-induced DNA damage precedes cell cycle arrest and causes apoptosis when DNA-dependent protein kinase (DNA-PK)-mediated non-homologous end joining is inhibited. Further, we observe that cells that were undergoing DNA replication harbored DSBs in greater frequency during pneumolysin treatment. This observation raises the possibility that DSBs might be arising as a result of replication fork breakdown. Additionally, neutralizing the oligomerization domain of pneumolysin with monoclonal antibody suppresses DNA damage and also cell cycle arrest, indicating that pneumolysin oligomerization is important for causing DNA damage. Taken together, this study reveals a previously unidentified ability of pneumolysin to induce cytotoxicity via DNA damage, with implications in the pathophysiology of S. pneumoniae infection. PMID:27026501

  18. Modeling of Laser Induced Damage in NIF UV Optics

    SciTech Connect

    Feit, M D; Rubenchik, A M

    2001-02-21

    Controlling damage to nominally transparent optical elements such as lenses, windows and frequency conversion crystals on high power lasers is a continuing technical problem. Scientific understanding of the underlying mechanisms of laser energy absorption, material heating and vaporization and resultant mechanical damage is especially important for UV lasers with large apertures such as NIF. This LDRD project was a single year effort, in coordination with associated experimental projects, to initiate theoretical descriptions of several of the relevant processes. In understanding laser damage, we distinguish between damage initiation and the growth of existent damage upon subsequent laser irradiation. In general, the effect of damage could be ameliorated by either preventing its initiation or by mitigating its growth. The distinction comes about because initiation is generally due to extrinsic factors such as contaminants, which provide a means of local laser energy absorption. Thus, initiation tends to be local and stochastic in nature. On the other hand, the initial damaging event appears to modify the surrounding material in such a way that multiple pulse damage grows more or less regularly. More exactly, three ingredients are necessary for visible laser induced damage. These are adequate laser energy, a mechanism of laser energy absorption and mechanical weakness. For damage growth, the material surrounding a damage site is already mechanically weakened by cracks and probably chemically modified as well. The mechanical damage can also lead to electric field intensification due to interference effects, thus increasing the available laser energy density. In this project, we successfully accounted for the pulselength dependence of damage threshold in bulk DKDP crystals with the hypothesis of small absorbers with a distribution of sizes. We theoretically investigated expected scaling of damage initiation craters both to baseline detailed numerical simulations

  19. Exercise-induced oxidatively damaged DNA in humans: evaluation in plasma or urine?

    PubMed

    Karpouzi, Christina; Nikolaidis, Stefanos; Kabasakalis, Athanasios; Tsalis, George; Mougios, Vassilis

    2016-01-01

    Physical exercise can induce oxidative damage in humans. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) is a widely known biomarker of DNA oxidation, which can be determined in blood and urine. The aim of the present study was to compare these two biological fluids in terms of which is more suitable for the estimation of the oxidative damage of DNA by measuring the concentration of 8-OHdG one hour after maximal exercise by enzyme immunoassay. The concentration of 8-OHdG increased with exercise only in plasma (p < 0.001), and values differed between exercise tests in both plasma and urine (p < 0.05). In conclusion, plasma appears to be more sensitive to exercise-induced 8-OHdG changes than urine and, hence, a more appropriate medium for assessing oxidative damage of DNA, although the poor repeatability of the measurement needs to be addressed in future studies. PMID:26849281

  20. Cold-induced thermoregulation and biological aging.

    PubMed

    Florez-Duquet, M; McDonald, R B

    1998-04-01

    Aging is associated with diminished cold-induced thermoregulation (CIT). The mechanisms accounting for this phenomenon have yet to be clearly elucidated but most likely reflect a combination of increased heat loss and decreased metabolic heat production. The inability of the aged subject to reduce heat loss during cold exposure is associated with diminished reactive tone of the cutaneous vasculature and, to a lesser degree, alterations in the insulative properties of body fat. Cold-induced metabolic heat production via skeletal muscle shivering thermogenesis and brown adipose tissue nonshivering thermogenesis appears to decline with age. Few investigations have directly linked diminished skeletal muscle shivering thermogenesis with the age-related reduction in cold-induced thermoregulatory capacity. Rather, age-related declines in skeletal muscle mass and metabolic activity are cited as evidence for decreased heat production via shivering. Reduced mass, GDP binding to brown fat mitochondria, and uncoupling protein (UCP) levels are cited as evidence for attenuated brown adipose tissue cold-induced nonshivering thermogenic capacity during aging. The age-related reduction in brown fat nonshivering thermogenic capacity most likely reflects altered cellular signal transduction rather than changes in neural and hormonal signaling. The discussion in this review focuses on how alterations in CIT during the life span may offer insight into possible mechanisms of biological aging. Although the preponderance of evidence presented here demonstrates that CIT declines with chronological time, the mechanism reflecting this attenuated function remains to be elucidated. The inability to draw definitive conclusions regarding biological aging and CIT reflects the lack of a clear definition of aging. It is unlikely that the mechanisms accounting for the decline in cold-induced thermoregulation during aging will be determined until biological aging is more precisely defined. PMID

  1. Blasting-induced damage in coal

    SciTech Connect

    Kabongo, K.K.

    1995-12-31

    The paper is drawn from a project intended to explore a technique of prediction, control and optimization of fracture in coal induced by blasting. It evaluates the fines generated in coal submitted to dynamic loading stresses in an impact stamp mortar. The aim is to analyze a complex phenomenon of coal response to blast-generated stresses from a series of discrete simulations of shock and gas actions in controllable processes. It is learned that despite the nucleation of primary crushing and fractures to originate from the point of impact energy in coal, a secondary crushing appears to depart from within the burden progressing towards the free boundaries. The extension of the secondary crushing zone appears to be influenced by the magnitude of the breaking stresses generated and the coal burden distance. A strong dependence of fines on the coal`s innate discontinuities (strength) and the energy input is highlighted.

  2. Biology and damage of an undescribed baridine weevil on amryllis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The weevil subfamily Baridinae is comprised of several economically important species that cause damage to the roots and fruits of plants. In the early 1990's, a baradine weevil was observed feeding on and occasionally killing amaryllis (Hippeastrum Herb) plants in Florida. A survey was conducted to...

  3. Genetic damage induced by organic extract of coke oven emissions on human bronchial epithelial cells.

    PubMed

    Zhai, Qingfeng; Duan, Huawei; Wang, Yadong; Huang, Chuanfeng; Niu, Yong; Dai, Yufei; Bin, Ping; Liu, Qingjun; Chen, Wen; Ma, Junxiang; Zheng, Yuxin

    2012-08-01

    Coke oven emissions are known as human carcinogen, which is a complex mixture of polycyclic aromatic hydrocarbon. In this study, we aimed to clarify the mechanism of action of coke oven emissions induced carcinogenesis and to identify biomarkers of early biological effects in a human bronchial epithelial cell line with CYP1A1 activity (HBE-CYP1A1). Particulate matter was collected in the oven area on glass filter, extracted and analyzed by GC/MS. DNA breaks and oxidative damage were evaluated by alkaline and endonucleases (FPG, hOGG1 and ENDO III)-modified comet assays. Cytotoxicity and chromosomal damage were assessed by the cytokinesis-block micronucleus cytome (CBMN-Cyt) assay. The cells were treated with organic extract of coke oven emissions (OE-COE) representing 5, 10, 20, 40μg/mL extract for 24h. We found that there was a dose-effect relationship between the OE-COE and the direct DNA damage presented by tail length, tail intensity and Olive tail moment in the comet assay. The presence of lesion-specific endonucleases in the assays increased DNA migration after OE-COE treatment when compared to those without enzymes, which indicated that OE-COE produced oxidative damage at the level of pyrimidine and purine bases. The dose-dependent increase of micronuclei, nucleoplasmic bridges and nuclear buds in exposed cells was significant, indicating chromosomal and genomic damage induced by OE-COE. Based on the cytotoxic biomarkers in CBMN-Cyt assay, OE-COE may inhibit nuclear division, interfere with apoptosis, or induce cell necrosis. This study indicates that OE-COE exposure can induce DNA breaks/oxidative damage and genomic instability in HBE-CYP1A1 cells. The FPG-comet assay appears more specific for detecting oxidative DNA damage induced by complex mixtures of genotoxic substances. PMID:22522113

  4. Modification of high LET radiation-induced damage and its repair in yeast by hypoxia.

    PubMed

    Subrahmanyam, P; Rao, B S; Reddy, N M; Murthy, M S; Madhvanath, U

    1979-11-01

    The lethal response of a diploid yeast strain BZ34 to densely ionizing radiations from the reaction 10B(n, alpha)7 Li was studied. The values for relative biological effectiveness (r.b.e.) and oxygen enhancement ratio (o.e.r.) for this radiation compare favourably with the data obtained with charged particles on the same strain of yeast. Recovery from potentially lethal damage was also studied by post-irradiation holding under non-nutrient conditions. In order to understand the role of oxygen in the recovery process, the investigation covered the following treatment regimens: (a) aerobic irradiation and aerobic holding (A-A), (b) aerobic irradiation and hypoxic holding (A-H), (c) hypoxic irradiation and hypoxic holding (H-H) and (d) hypoxic irradiation and aerobic holding (H-A). It has been found that the presence of oxygen is essential for recovery from the damage induced by both gamma rays and high linear energy transfer (LET) radiations. The extent of recovery was larger for gamma-induced damage than for damage induced by high LET radiation (alpha + 7Li) for the A-A condition. In the H-H condition, while only a slight recovery was seen for gamma-induced damage, it was totally absent for high LET damage. For the modality A-H, it was found that there is not recovery from the sparsely ionising gamma radiation-induced damage. The implications of these results for the treatment of malignant tumours by radiotherapy are briefly discussed. PMID:397200

  5. Heavy ion induced damage to plasmid DNA: plateau region vs. spread out Bragg-peak

    NASA Astrophysics Data System (ADS)

    Dang, H. M.; van Goethem, M. J.; van der Graaf, E. R.; Brandenburg, S.; Hoekstra, R.; Schlathölter, T.

    2011-08-01

    We have investigated the damage of synthetic plasmid pBR322 DNA in dilute aqueous solutions induced by fast carbon ions. The relative contribution of indirect damage and direct damage to the DNA itself is expected to vary with linear energy transfer along the ion track, with the direct damage contribution increasing towards the Bragg peak. Therefore, 12C ions at the spread-out Bragg peak (dose averaged LET∞ = 189 ± 15 keV/ μm) and in the plateau region of the Bragg curve (LET = 40 keV/ μm) were employed and the radical scavenger concentration in the plasmid solution was varied to quantify the indirect effect. In order to minimize the influence of 12C break-up fragments, a relatively low initial energy of 90 MeV/nucleon was employed for the carbon ions. DNA damage has been quantified by subsequent electrophoresis on agarose gels. We find that strand breaks due to both indirect and direct effects are systematically higher in the plateau region as compared to the Bragg peak region with the difference being smallest at high scavenging capacities. In view of the fact that the relative biological effectiveness for many biological endpoints is maximum at the Bragg peak our findings imply that DNA damage at the Bragg peak is qualitatively most severe.

  6. Hardening measures for bipolar transistors against microwave-induced damage

    NASA Astrophysics Data System (ADS)

    Chai, Chang-Chun; Ma, Zhen-Yang; Ren, Xing-Rong; Yang, Yin-Tang; Zhao, Ying-Bo; Yu, Xin-Hai

    2013-06-01

    In the present paper we study the influences of the bias voltage and the external components on the damage progress of a bipolar transistor induced by high-power microwaves. The mechanism is presented by analyzing the variation in the internal distribution of the temperature in the device. The findings show that the device becomes less vulnerable to damage with an increase in bias voltage. Both the series diode at the base and the relatively low series resistance at the emitter, Re, can obviously prolong the burnout time of the device. However, Re will aid damage to the device when the value is sufficiently high due to the fact that the highest hot spot shifts from the base-emitter junction to the base region. Moreover, the series resistance at the base Rb will weaken the capability of the device to withstand microwave damage.

  7. Plasmid DNA damage induced by helium atmospheric pressure plasma jet

    NASA Astrophysics Data System (ADS)

    Han, Xu; Cantrell, William A.; Escobar, Erika E.; Ptasinska, Sylwia

    2014-03-01

    A helium atmospheric pressure plasma jet (APPJ) is applied to induce damage to aqueous plasmid DNA. The resulting fractions of the DNA conformers, which indicate intact molecules or DNA with single- or double-strand breaks, are determined using agarose gel electrophoresis. The DNA strand breaks increase with a decrease in the distance between the APPJ and DNA samples under two working conditions of the plasma source with different parameters of applied electric pulses. The damage level induced in the plasmid DNA is also enhanced with increased plasma irradiation time. The reactive species generated in the APPJ are characterized by optical emission spectra, and their roles in possible DNA damage processes occurring in an aqueous environment are also discussed.

  8. Potential role of punicalagin against oxidative stress induced testicular damage

    PubMed Central

    Rao, Faiza; Tian, Hui; Li, Wenqing; Hung, Helong; Sun, Fei

    2016-01-01

    Punicalagin is isolated from pomegranate and widely used for the treatment of different diseases in Chinese traditional medicine. This study aimed to evaluate the effect of Punicalagin (purity ≥98%) on oxidative stress induced testicular damage and its effect on fertility. We detected the antioxidant potential of punicalagin in lipopolysaccharide (LPS) induced oxidative stress damage in testes, also tried to uncover the boosting fertility effect of Punicalagin (PU) against oxidative stress-induced infertility. Results demonstrated that 9 mg kg−1 for 7 days treatment significantly decreases LPS induced oxidative damage in testes and nitric oxide production. The administration of oxidative stress resulted in a significant reduction in testes antioxidants GSH, T-SOD, and CAT raised LPO, but treatment with punicalagin for 7 days increased antioxidant defense GSH, T-SOD, and CAT by the end of the experiment and reduced LPO level as well. PU also significantly activates Nrf2, which is involved in regulation of antioxidant defense systems. Hence, the present research categorically elucidates the protective effect of punicalagin against LPS induced oxidative stress induced perturbation in the process of spermatogenesis and significantly increased sperm health and number. Moreover, fertility success significantly decreased in LPS-injected mice compared to controls. Mice injected with LPS had fertility indices of 12.5%, while others treated with a combination of PU + LPS exhibited 75% indices. By promoting fertility and eliminating oxidative stress and inflammation, PU may be a useful nutrient for the treatment of infertility. PMID:26763544

  9. Potential role of punicalagin against oxidative stress induced testicular damage.

    PubMed

    Rao, Faiza; Tian, Hui; Li, Wenqing; Hung, Helong; Sun, Fei

    2016-01-01

    Punicalagin is isolated from pomegranate and widely used for the treatment of different diseases in Chinese traditional medicine. This study aimed to evaluate the effect of Punicalagin (purity ≥98%) on oxidative stress induced testicular damage and its effect on fertility. We detected the antioxidant potential of punicalagin in lipopolysaccharide (LPS) induced oxidative stress damage in testes, also tried to uncover the boosting fertility effect of Punicalagin (PU) against oxidative stress-induced infertility. Results demonstrated that 9 mg kg-1 for 7 days treatment significantly decreases LPS induced oxidative damage in testes and nitric oxide production. The administration of oxidative stress resulted in a significant reduction in testes antioxidants GSH, T-SOD, and CAT raised LPO, but treatment with punicalagin for 7 days increased antioxidant defense GSH, T-SOD, and CAT by the end of the experiment and reduced LPO level as well. PU also significantly activates Nrf2, which is involved in regulation of antioxidant defense systems. Hence, the present research categorically elucidates the protective effect of punicalagin against LPS induced oxidative stress induced perturbation in the process of spermatogenesis and significantly increased sperm health and number. Moreover, fertility success significantly decreased in LPS-injected mice compared to controls. Mice injected with LPS had fertility indices of 12.5%, while others treated with a combination of PU + LPS exhibited 75% indices. By promoting fertility and eliminating oxidative stress and inflammation, PU may be a useful nutrient for the treatment of infertility. PMID:26763544

  10. Autophagy Induced by Calcium Phosphate Precipitates Targets Damaged Endosomes*

    PubMed Central

    Chen, Xi; Khambu, Bilon; Zhang, Hao; Gao, Wentao; Li, Min; Chen, Xiaoyun; Yoshimori, Tamotsu; Yin, Xiao-Ming

    2014-01-01

    Calcium phosphate precipitates (CPPs) form complexes with DNA, which enter cells via endocytosis. Under this condition CPPs induce autophagy via the canonic autophagy machinery. Here we showed that CPP-induced autophagy was also dependent on endocytosis as the process was significantly inhibited by methyl-β-cyclodextrin and dynasore, which suppress clathrin-dependent endocytosis. Consistently, CPP treatment triggered the formation of filipin-positive intracellular vesicles whose membranes are rich in cholesterol. Unexpectedly, these vesicles were also positive for galectin 3, suggesting that they were damaged and the membrane glycans became accessible to galectins to bind. Endosome damage was caused by endocytosis of CPPs and was reversed by calcium chelators or by endocytosis inhibitors. Notably, CPP-induced LC3-positive autophagosomes were colocalized with galectin 3, ubiquitin, and p62/SQSTM1. Inhibition of galectin 3 reduced p62 puncta and autophagosome formation. Knockdown of p62 additionally inhibited the colocalization of autophagosomes with galectins. Furthermore, most of the galectin 3-positive vesicles were colocalized with Rab7 or LAMP1. Agents that affect endosome/lysosome maturation and function, such as bafilomycin A1, also significantly affected CPP-induced tubulovesicular autophagosome formation. These findings thus indicate that endocytosed CPPs caused endosome damage and recruitment of galectins, particularly at the later endosome stage, which led to the interaction of the autophagosomal membranes with the damaged endosome in the presence of p62. PMID:24619419

  11. FURTHER EVIDENCE THAT DICHLOROMETHANE DOES NOT INDUCE CHROMOSOME DAMAGE

    EPA Science Inventory

    Dichloromethane (DCM) is a widely used industrial solvent which has been determined to be a carcinogen in rats and mice. n vitro and in vivo analyses of chromosome damage induced by this agent have provided conflicting results. n order to further investigate the clastogenic poten...

  12. NBQX and TCP prevent soman-induced hippocampal damage

    SciTech Connect

    Lallement, G.; Carpentier, P.; Pernot-Marino, I.; Baubichon, D.; Blanchet, G.

    1993-05-13

    In a previous investigation we demonstrated that the measurement of w3 (peripheral-type benzodiazepine) binding site densities could be of widespread applicability in the localization and quantification of soman-induced damage in the central nervous system. We thus used this marker to assess, in mouse hippocampus, the neuroprotective activity against soman-induced brain damage of NBQX and TCP which are respective antagonists of non-NMDA and NMDA glutamatergic receptors. Injection of NBQX at 20 or 40 mg/kg 5 min prior to soman totally prevented the neuronal damage. Comparatively, TCP had neuroprotective efficacy when administered at l mg/kg 5 min prior to soman followed by a reinjection 1 hour after. These results demonstrate that both NBQX and TCP afford a satisfactory neuroprotection against soman-induced brain damage. Since it is known that the neuropathology due to soman is closely seizure-related, it is likely that the neuroprotective activities of NBQX and TCP are related to the respective roles of non-NMDA and NMDA receptors in the onset and maintenance of soman-induced seizures.

  13. Inflammation-induced DNA damage and damage-induced inflammation: a vicious cycle.

    PubMed

    Pálmai-Pallag, Timea; Bachrati, Csanád Z

    2014-10-01

    Inflammation is the ultimate response to the constant challenges of the immune system by microbes, irritants or injury. The inflammatory cascade initiates with the recognition of microorganism-derived pathogen associated molecular patterns (PAMPs) and host cell-derived damage associated molecular patterns (DAMPs) by the pattern recognition receptors (PRRs). DNA as a molecular PAMP or DAMP is sensed directly or via specific binding proteins to instigate pro-inflammatory response. Some of these DNA binding proteins also participate in canonical DNA repair pathways and recognise damaged DNA to initiate DNA damage response. In this review we aim to capture the essence of the complex interplay between DNA damage response and the pro-inflammatory signalling through representative examples. PMID:25449753

  14. Multiscale physics of ion-induced radiation damage

    NASA Astrophysics Data System (ADS)

    Surdutovich, Eugene; Solov'yov, Andrey V.

    2013-06-01

    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 radiation damage scenario occurring on a range of temporal, spatial, and energy scales, is being reviewed. The scenario is described along with a variety of effects that take place on different temporal, spatial, and energy scales and play major roles in the scenario of interaction of ions with tissue. The understanding of these effects leads to a quantitative assessment of relative biological effectiveness that relates the physical quantities, such as dose, to the biological values, such as the probability of cell survival.

  15. Biological Therapy-Induced Systemic Vasculitis.

    PubMed

    Gutiérrez-González, Luis Arturo

    2016-07-01

    The use of biologics has been associated with the paradoxical development of biologics-induced autoimmune diseases. The purpose of this review was to describe the key immunopathogenic mechanisms involved in the development of these conditions, and to discuss the clinical and laboratory characteristics usually described in the medical literature, reviewing case reports as well as records on national biologic therapies (BIOGEAS, RABBIT, BSRBR-RA, BIOBADAVEN). More than 200 cases have so far been reported, all of them diagnosed on the basis of the histopathology or meeting the ACR/Chapel Hill criteria. Over 75 % of the cases were females with a mean age of 48 ± 5 years. More than 50 % had rheumatoid arthritis. Most of the biologics-associated vasculitis developed in 90 ± 31 days. Complete resolution in almost 75 % of the cases was observed upon treatment discontinuation; however, steroid therapy was indicated for all patients and one death was recorded. The use of cyclophosphamide, rituximab or plasma exchange was reserved for the most severe cases. PMID:27165496

  16. Analysis of alcohol-induced DNA damage in Escherichia coli by visualizing single genomic DNA molecules.

    PubMed

    Kang, Yujin; Lee, Jinyong; Kim, Jisoo; Oh, Yeeun; Kim, Dogeun; Lee, Jungyun; Lim, Sangyong; Jo, Kyubong

    2016-07-21

    Consumption of alcohol injures DNA, and such damage is considered to be a primary cause for the development of cancer and many other diseases essentially due to reactive oxygen species generated from alcohol. To sensitively detect alcohol-induced DNA lesions in a biological system, we introduced a novel analytical platform for visualization of single genomic DNA molecules using E. coli. By fluorescently labelling the DNA lesions, our approach demonstrated, with the highest sensitivity, that we could count the number of DNA lesions induced by alcohol metabolism in a single bacterial cell. Moreover, our results showed a linear relationship between ethanol concentration and the number of DNA lesions: 0.88 lesions per 1% ethanol. Using this approach, we quantitatively analysed the DNA damage induced by exposure to alcoholic beverages such as beer (5% ethanol), rice wine (13%), soju (20%), and whisky (40%). PMID:27186604

  17. Changes of color coordinates of biological tissue with superficial skin damage due to mechanical trauma

    NASA Astrophysics Data System (ADS)

    Pteruk, Vail; Mokanyuk, Olexander; Kvaternuk, Olena; Yakenina, Lesya; Kotyra, Andrzej; Romaniuk, Ryszard S.; Dussembayeva, Shynar

    2015-12-01

    Change of color coordinates of normal and pathological biological tissues is based on calculated spectral diffuse reflection. The proposed color coordinates of normal and pathological biological tissues of skin provided using standard light sources, allowing accurately diagnose skin damage due to mechanical trauma with a blunt object for forensic problems.

  18. Tissue damage negatively regulates LPS-induced macrophage necroptosis.

    PubMed

    Li, Z; Scott, M J; Fan, E K; Li, Y; Liu, J; Xiao, G; Li, S; Billiar, T R; Wilson, M A; Jiang, Y; Fan, J

    2016-09-01

    Infection is a common clinical complication following tissue damage resulting from surgery and severe trauma. Studies have suggested that cell pre-activation by antecedent trauma/tissue damage profoundly impacts the response of innate immune cells to a secondary infectious stimulus. Cell necroptosis, a form of regulated inflammatory cell death, is one of the mechanisms that control cell release of inflammatory mediators from important innate immune executive cells such as macrophages (Mφ), which critically regulate the progress of inflammation. In this study, we investigated the mechanism and role of trauma/tissue damage in the regulation of LPS-induced Mφ necroptosis using a mouse model simulating long-bone fracture. We demonstrate that LPS acting through Toll-like receptor (TLR) 4 promotes Mφ necroptosis. However, necroptosis is ameliorated by high-mobility group box 1 (HMGB1) release from damaged tissue. We show that HMGB1 acting through cell surface receptor for advanced glycation end products (RAGE) upregulates caveolin-1 expression, which in turn induces caveolae-mediated TLR4 internalization and desensitization to decrease Mφ necroptosis. We further show that RAGE-MyD88 activation of Cdc42 and subsequent activation of transcription factor Sp1 serves as a mechanism underlying caveolin-1 transcriptional upregulation. These results reveal a previous unidentified protective role of damage-associated molecular pattern (DAMP) molecules in restricting inflammation in response to exogenous pathogen-associated molecular pattern molecules. PMID:26943325

  19. Zebrafish fin regeneration after cryoinjury-induced tissue damage

    PubMed Central

    Chassot, Bérénice; Pury, David

    2016-01-01

    ABSTRACT Although fin regeneration following an amputation procedure has been well characterized, little is known about the impact of prolonged tissue damage on the execution of the regenerative programme in the zebrafish appendages. To induce histolytic processes in the caudal fin, we developed a new cryolesion model that combines the detrimental effects of freezing/thawing and ischemia. In contrast to the common transection model, the damaged part of the fin was spontaneously shed within two days after cryoinjury. The remaining stump contained a distorted margin with a mixture of dead material and healthy cells that concomitantly induced two opposing processes of tissue debris degradation and cellular proliferation, respectively. Between two and seven days after cryoinjury, this reparative/proliferative phase was morphologically featured by displaced fragments of broken bones. A blastemal marker msxB was induced in the intact mesenchyme below the damaged stump margin. Live imaging of epithelial and osteoblastic transgenic reporter lines revealed that the tissue-specific regenerative programmes were initiated after the clearance of damaged material. Despite histolytic perturbation during the first week after cryoinjury, the fin regeneration resumed and was completed without further alteration in comparison to the simple amputation model. This model reveals the powerful ability of the zebrafish to restore the original appendage architecture after the extended histolysis of the stump. PMID:27215324

  20. Zebrafish fin regeneration after cryoinjury-induced tissue damage.

    PubMed

    Chassot, Bérénice; Pury, David; Jaźwińska, Anna

    2016-01-01

    Although fin regeneration following an amputation procedure has been well characterized, little is known about the impact of prolonged tissue damage on the execution of the regenerative programme in the zebrafish appendages. To induce histolytic processes in the caudal fin, we developed a new cryolesion model that combines the detrimental effects of freezing/thawing and ischemia. In contrast to the common transection model, the damaged part of the fin was spontaneously shed within two days after cryoinjury. The remaining stump contained a distorted margin with a mixture of dead material and healthy cells that concomitantly induced two opposing processes of tissue debris degradation and cellular proliferation, respectively. Between two and seven days after cryoinjury, this reparative/proliferative phase was morphologically featured by displaced fragments of broken bones. A blastemal marker msxB was induced in the intact mesenchyme below the damaged stump margin. Live imaging of epithelial and osteoblastic transgenic reporter lines revealed that the tissue-specific regenerative programmes were initiated after the clearance of damaged material. Despite histolytic perturbation during the first week after cryoinjury, the fin regeneration resumed and was completed without further alteration in comparison to the simple amputation model. This model reveals the powerful ability of the zebrafish to restore the original appendage architecture after the extended histolysis of the stump. PMID:27215324

  1. The stochastic nature of growth of laser-induced damage

    NASA Astrophysics Data System (ADS)

    Carr, C. W.; Cross, David A.; Liao, Zhi M.; Norton, Mary A.; Negres, Raluca A.

    2015-07-01

    Laser fluence and operational tempo of ICF systems operating in the UV are typically limited by the growth of laser- induced damage on their final optics (primarily silica optics). In the early 2000 time frame, studies of laser damage growth with relevant large area beams revealed that for some laser conditions damage sites located on the exit surface of a fused silica optic grew following an exponential growth rule: D(n) = D0 exp (n α(φ)), where D is final site diameter, D0 is the initial diameter of the site, φ is the laser fluence, α(φ) is the growth coefficient, and n is the number of exposures. In general α is a linear function of φ, with a threshold of φTH. In recent years, it has been found that that growth behavior is actually considerably more complex. For example, it was found that α is not a constant for a given fluence but follows a probability distribution with a mean equal to α(φ). This is complicated by observations that these distributions are actually functions of the pulse shape, damage site size, and initial morphology of damage initiation. In addition, there is not a fixed fluence threshold for damage sites growth, which is better described by a probability of growth which depends on site size, morphology and laser fluence. Here will review these findings and discuss implications for the operation of large laser systems.

  2. Induced swelling in radiation damaged ZrSiO 4

    NASA Astrophysics Data System (ADS)

    Exarhos, G. J.

    1984-02-01

    A hydrothermal gelation method was used to prepare phase pure polycrystalline ZrSiO 4 which was sintered to 95% theoretical density. Actinide doped samples containing 10 wt% 238Pu were prepared by an analogous procedure and incurred bulk radiation damage through internal alpha-decay processes. Undoped samples were subjected to external irradiation from 5.5 MeV alpha sources, and from a 60Co gamma source. Actinide doped ZrSiO 4 exhibits dose dependent swelling caused by displacement processes leading to ingrowth of amorphous regions. Bulk density and XRD measurements, as a function of dose, showed first order exponential ingrowth behavior similar to that observed in other actinide doped materials. Results are compared with reported data for naturally damaged crystals subjected to significantly lower alpha decay rates. No significant dose rate dependence on damage ingrowth has been observed. Kinetic models for the observed dose dependent swelling are proposed and rate constants for damage ingrowth in synthetic and natural crystals are compared. To study localized damage induced by both external alpha and gamma irradiation, vibrational Raman measurements were obtained for several accumulated doses. Results indicate that the initial stage of damage ingrowth is confined to the silicate sublattice. Vibrational results will be discussed in terms of microstructural changes which result from irradiation.

  3. Pattern Learning, Damage and Repair within Biological Neural Networks

    NASA Astrophysics Data System (ADS)

    Siu, Theodore; Fitzgerald O'Neill, Kate; Shinbrot, Troy

    2015-03-01

    Traumatic brain injury (TBI) causes damage to neural networks, potentially leading to disability or even death. Nearly one in ten of these patients die, and most of the remainder suffer from symptoms ranging from headaches and nausea to convulsions and paralysis. In vitro studies to develop treatments for TBI have limited in vivo applicability, and in vitro therapies have even proven to worsen the outcome of TBI patients. We propose that this disconnect between in vitro and in vivo outcomes may be associated with the fact that in vitro tests assess indirect measures of neuronal health, but do not investigate the actual function of neuronal networks. Therefore in this talk, we examine both in vitro and in silico neuronal networks that actually perform a function: pattern identification. We allow the networks to execute genetic, Hebbian, learning, and additionally, we examine the effects of damage and subsequent repair within our networks. We show that the length of repaired connections affects the overall pattern learning performance of the network and we propose therapies that may improve function following TBI in clinical settings.

  4. Influenza infection induces host DNA damage and dynamic DNA damage responses during tissue regeneration

    PubMed Central

    Li, Na; Parrish, Marcus; Chan, Tze Khee; Yin, Lu; Rai, Prashant; Yoshiyuki, Yamada; Abolhassani, Nona; Tan, Kong Bing; Kiraly, Orsolya; Chow, Vincent TK; Engelward, Bevin P.

    2016-01-01

    Influenza viruses account for significant morbidity worldwide. Inflammatory responses, including excessive generation of reactive oxygen and nitrogen species (RONS), mediate lung injury in severe Influenza infections. However, the molecular basis of inflammation-induced lung damage is not fully understood. Here, we studied influenza H1N1 infected cells in vitro, as well as H1N1 infected mice, and we monitored molecular and cellular responses over the course of two weeks in vivo. We show that influenza induces DNA damage both when cells are directly exposed to virus in vitro (measured using the comet assay) and also when cells are exposed to virus in vivo (estimated via γH2AX foci). We show that DNA damage, as well as responses to DNA damage, persist in vivo until long after virus has been cleared, at times when there are inflammation associated RONS (measured by xanthine oxidase activity and oxidative products). The frequency of lung epithelial and immune cells with increased γH2AX foci is elevated in vivo, especially for dividing cells (Ki-67 positive) exposed to oxidative stress during tissue regeneration. Additionally, we observed a significant increase in apoptotic cells as well as increased levels of DSB repair proteins Ku70, Ku86 and Rad51 during the regenerative phase. In conclusion, results show that influenza induces DNA both in vitro and in vivo, and that DNA damage responses are activated, raising the possibility that DNA repair capacity may be a determining factor for tissue recovery and disease outcome. PMID:25809161

  5. Stress-induced DNA damage biomarkers: applications and limitations.

    PubMed

    Nikitaki, Zacharenia; Hellweg, Christine E; Georgakilas, Alexandros G; Ravanat, Jean-Luc

    2015-01-01

    A variety of environmental stresses like chemicals, UV and ionizing radiation and organism's endogenous processes such as replication stress and metabolism can lead to the generation of reactive oxygen and nitrogen species (ROS/RNS) that can attack cellular vital components like DNA, proteins and lipid membranes. Among them, much attention has been focused on DNA since DNA damage plays a role in several biological disorders and aging processes. Thus, DNA damage can be used as a biomarker in a reliable and accurate way to quantify for example radiation exposure and can indicate its possible long term effects and cancer risk. Based on the type of DNA lesions detected one can hypothesize on the most probable mechanisms involved in the formation of these lesions for example in the case of UV and ionizing radiation (e.g., X- or α-, γ-rays, energetic ions, neutrons). In this review we describe the most accepted chemical pathways for DNA damage induction and the different types of DNA lesions, i.e., single, complex DNA lesions etc. that can be used as DNA damage biomarkers. We critically compare DNA damage detection methods and their limitations. In addition, we suggest the use of DNA repair gene products as biomarkes for identification of different types of stresses i.e., radiation, oxidative, or replication stress, based on bioinformatic approaches and meta-analysis of literature data. PMID:26082923

  6. Stress-induced DNA damage biomarkers: applications and limitations

    PubMed Central

    Nikitaki, Zacharenia; Hellweg, Christine E.; Georgakilas, Alexandros G.; Ravanat, Jean-Luc

    2015-01-01

    A variety of environmental stresses like chemicals, UV and ionizing radiation and organism's endogenous processes such as replication stress and metabolism can lead to the generation of reactive oxygen and nitrogen species (ROS/RNS) that can attack cellular vital components like DNA, proteins and lipid membranes. Among them, much attention has been focused on DNA since DNA damage plays a role in several biological disorders and aging processes. Thus, DNA damage can be used as a biomarker in a reliable and accurate way to quantify for example radiation exposure and can indicate its possible long term effects and cancer risk. Based on the type of DNA lesions detected one can hypothesize on the most probable mechanisms involved in the formation of these lesions for example in the case of UV and ionizing radiation (e.g., X- or α-, γ-rays, energetic ions, neutrons). In this review we describe the most accepted chemical pathways for DNA damage induction and the different types of DNA lesions, i.e., single, complex DNA lesions etc. that can be used as DNA damage biomarkers. We critically compare DNA damage detection methods and their limitations. In addition, we suggest the use of DNA repair gene products as biomarkes for identification of different types of stresses i.e., radiation, oxidative, or replication stress, based on bioinformatic approaches and meta-analysis of literature data. PMID:26082923

  7. Stress-induced DNA Damage biomarkers: Applications and limitations

    NASA Astrophysics Data System (ADS)

    Nikitaki, Zacharenia; Hellweg, Christine; Georgakilas, Alexandros; Ravanat, Jean-Luc

    2015-06-01

    A variety of environmental stresses like chemicals, UV and ionizing radiation and organism’s endogenous processes like replication stress and metabolism can lead to the generation of reactive oxygen and nitrogen species (ROS/RNS) that can attack cellular vital components like DNA, proteins and lipid membranes. Among them, much attention has been focused on DNA since DNA damages play a role in several biological disorders and aging processes. Thus, DNA damage can be used as a biomarker in a reliable and accurate way to quantify for example radiation exposure and can indicate its possible long term effects and cancer risk. Based on the type of DNA lesions detected one can hypothesize on the most probable mechanisms involved in the formation of these lesions for example in the case of UV and ionizing radiation (e.g. X- or α-, γ-rays, energetic ions, neutrons). In this review we describe the most accepted chemical pathways for DNA damage induction and the different types of DNA lesions, i.e. single, complex DNA lesions etc. that can be used as biomarkers. We critically compare DNA damage detection methods and their limitations. In addition to such DNA damage products, we suggest possible gene inductions that can be used to characterize responses to different types of stresses i.e. radiation, oxidative and replication stress, based on bioinformatic approaches and stringent meta-analysis of literature data.

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

    SciTech Connect

    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.

  9. Radiation-induced DNA damage and chromatin structure

    NASA Technical Reports Server (NTRS)

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

    2001-01-01

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

  10. Ketamine/Xylazine-Induced Corneal Damage in Mice

    PubMed Central

    Syed, Nasreen A.; Anderson, Michael G.

    2015-01-01

    Purpose We have observed that the commonly used ketamine/xylazine anesthesia mix can induce a focally severe and permanent corneal opacity. The purpose of this study was to establish the clinical and histological features of this deleterious side effect, its sensitivity with respect to age and anesthesia protocol, and approaches for avoiding it. Methods Young C57BL/6J, C57BLKS/J, and SJL/J mice were treated with permutations of anesthesia protocols and compared using slit-lamp exams, optical coherence tomography, histologic analyses, and telemetric measurements of body temperature. Results Ketamine/xylazine induces corneal damage in mice with a variable frequency. Among 12 experimental cohorts, corneal damage associated with ketamine/xylazine was observed in 9 of them. Despite various treatments to avoid corneal dehydration during anesthesia, the frequency of corneas experiencing damage among responding cohorts was 42% (26% inclusive of all cohorts), which is significantly greater than the natural prevalence (5%). The damage was consistent with band keratopathy. It appeared as a white or gray horizontal band located proximal to the pupil and was positive for subepithelial calcium deposition with von Kossa stain. Conclusions The sum of our clinical and histological observations is consistent with ketamine/xylazine-induced band keratopathy in mice. This finding is relevant for mouse studies involving the eye and/or vision-dependent behavioral assays, which would both be prone to artifact without appreciation of the damage caused by ketamine/xylazine anesthesia. Use of yohimbine is suggested as a practical means of avoiding this complication. PMID:26222692

  11. Systems Biology of HBOC-Induced Vasoconstriction

    PubMed Central

    Hai, Chi-Ming

    2011-01-01

    Vasoconstriction is a major adverse effect of HBOCs. The use of a single drug for attenuating HBOC-induced vasoconstriction has been tried with limited success. Since HBOC causes disruptions at multiple levels of organization in the vascular system, a systems approach is helpful to explore avenues to counteract the effects of HBOC at multiple levels by targeting multiple sites in the system. A multi-target approach is especially appropriate for HBOC-induced vasoconstriction, because HBOC disrupts the cascade of amplification by NO-cGMP signaling and protein phosphorylation, ultimately resulting in vasoconstriction. Targeting multiple steps in the cascade may alter the overall gain of amplification, thereby limiting the propagation of disruptive effects through the cascade. As a result, targeting multiple sites may accomplish a relatively high overall efficacy at submaximal drug doses. Identifying targets and doses for developing a multi-target combination HBOC regimen for oxygen therapeutics requires a detailed understanding of the systems biology and phenotypic heterogeneity of the vascular system at multiple layers of organization, which can be accomplished by successive iterations between experimental studies and mathematical modeling at multiple levels of vascular systems and organ systems. Towards this goal, this article addresses the following topics: a) NO-scavenging by HBOC, b) HBOC autoxidation-induced reactive oxygen species generation and endothelial barrier dysfunction, c) NO- cGMP signaling in vascular smooth muscle cells, d) NO and cGMP-dependent regulation of contractile filaments in vascular smooth muscle cells, e) phenotypic heterogeneity of vascular systems, f) systems biology as an approach to developing a multi-target HBOC regimen. PMID:21726185

  12. Using ultra-sensitive next generation sequencing to dissect DNA damage-induced mutagenesis.

    PubMed

    Wang, Kaile; Ma, Xiaolu; Zhang, Xue; Wu, Dafei; Sun, Chenyi; Sun, Yazhou; Lu, Xuemei; Wu, Chung-I; Guo, Caixia; Ruan, Jue

    2016-01-01

    Next generation sequencing (NGS) technologies have dramatically improved studies in biology and biomedical science. However, no optimal NGS approach is available to conveniently analyze low frequency mutations caused by DNA damage treatments. Here, by developing an exquisite ultra-sensitive NGS (USNGS) platform "EasyMF" and incorporating it with a widely used supF shuttle vector-based mutagenesis system, we can conveniently dissect roles of lesion bypass polymerases in damage-induced mutagenesis. In this improved mutagenesis analysis pipeline, the initial steps are the same as in the supF mutation assay, involving damaging the pSP189 plasmid followed by its transfection into human 293T cells to allow replication to occur. Then "EasyMF" is employed to replace downstream MBM7070 bacterial transformation and other steps for analyzing damage-induced mutation frequencies and spectra. This pipeline was validated by using UV damaged plasmid after its replication in lesion bypass polymerase-deficient 293T cells. The increased throughput and reduced cost of this system will allow us to conveniently screen regulators of translesion DNA synthesis pathway and monitor environmental genotoxic substances, which can ultimately provide insight into the mechanisms of genome stability and mutagenesis. PMID:27122023

  13. Using ultra-sensitive next generation sequencing to dissect DNA damage-induced mutagenesis

    PubMed Central

    Wang, Kaile; Ma, Xiaolu; Zhang, Xue; Wu, Dafei; Sun, Chenyi; Sun, Yazhou; Lu, Xuemei; Wu, Chung-I; Guo, Caixia; Ruan, Jue

    2016-01-01

    Next generation sequencing (NGS) technologies have dramatically improved studies in biology and biomedical science. However, no optimal NGS approach is available to conveniently analyze low frequency mutations caused by DNA damage treatments. Here, by developing an exquisite ultra-sensitive NGS (USNGS) platform “EasyMF” and incorporating it with a widely used supF shuttle vector-based mutagenesis system, we can conveniently dissect roles of lesion bypass polymerases in damage-induced mutagenesis. In this improved mutagenesis analysis pipeline, the initial steps are the same as in the supF mutation assay, involving damaging the pSP189 plasmid followed by its transfection into human 293T cells to allow replication to occur. Then “EasyMF” is employed to replace downstream MBM7070 bacterial transformation and other steps for analyzing damage-induced mutation frequencies and spectra. This pipeline was validated by using UV damaged plasmid after its replication in lesion bypass polymerase-deficient 293T cells. The increased throughput and reduced cost of this system will allow us to conveniently screen regulators of translesion DNA synthesis pathway and monitor environmental genotoxic substances, which can ultimately provide insight into the mechanisms of genome stability and mutagenesis. PMID:27122023

  14. Reformulated meat products protect against ischemia-induced cardiac damage.

    PubMed

    Asensio-Lopez, M C; Lax, A; Sanchez-Mas, J; Avellaneda, A; Planes, J; Pascual-Figal, D A

    2016-02-17

    The protective effects of the antioxidants present in food are of great relevance for cardiovascular health. This study evaluates whether the extracts from reformulated meat products with a reduction in fat and/or sodium content exert a cardioprotective effect against ischemia-induced oxidative stress in cardiomyocytes, compared with non-meat foods. Ischemic damage caused loss of cell viability, increased reactive oxygen species and lipid peroxidation and decreased the antioxidant activity. Pretreatment for 24 h with digested or non-digested extracts from reformulated meat products led to protection against ischemia-induced oxidative damage: increased cell viability, reduced oxidative stress and restored the antioxidant activity. Similar results were obtained using extracts from tuna fish, but not with the extracts of green peas, salad or white beans. These results suggest that reformulated meat products have a beneficial impact in protecting cardiac cells against ischemia, and they may represent a source of natural antioxidants with benefits for cardiovascular health. PMID:26751429

  15. Mechanisms for microvascular damage induced by ultrasound-activated microbubbles

    NASA Astrophysics Data System (ADS)

    Chen, Hong; Brayman, Andrew A.; Evan, Andrew P.; Matula, Thomas J.

    2012-10-01

    To provide insight into the mechanisms of microvascular damage induced by ultrasound-activated microbubbles, experimental studies were performed to correlate microvascular damage to the dynamics of bubble-vessel interactions. High-speed photomicrography was used to record single microbubbles interacting with microvessels in ex vivo tissue, under the exposure of short ultrasound pulses with a center frequency of 1 MHz and peak negative pressures (PNP) ranging from 0.8-4 MPa. Vascular damage associated with observed bubble-vessel interactions was either indicated directly by microbubble extravasation or examined by transmission electron microscopy (TEM) analyses. As observed previously, the high-speed images revealed that ultrasound-activated microbubbles could cause distention and invagination of adjacent vessel walls, and could form liquid jets in microvessels. Vessel distention, invagination, and liquid jets were associated with the damage of microvessels whose diameters were smaller than those of maximally expanded microbubbles. However, vessel invagination appeared to be the dominant mechanism for the damage of relative large microvessels.

  16. Mechanisms for microvascular damage induced by ultrasound-activated microbubbles

    SciTech Connect

    Chen Hong; Brayman, Andrew A.; Evan, Andrew P.; Matula, Thomas J.

    2012-10-03

    To provide insight into the mechanisms of microvascular damage induced by ultrasound-activated microbubbles, experimental studies were performed to correlate microvascular damage to the dynamics of bubble-vessel interactions. High-speed photomicrography was used to record single microbubbles interacting with microvessels in ex vivo tissue, under the exposure of short ultrasound pulses with a center frequency of 1 MHz and peak negative pressures (PNP) ranging from 0.8-4 MPa. Vascular damage associated with observed bubble-vessel interactions was either indicated directly by microbubble extravasation or examined by transmission electron microscopy (TEM) analyses. As observed previously, the high-speed images revealed that ultrasound-activated microbubbles could cause distention and invagination of adjacent vessel walls, and could form liquid jets in microvessels. Vessel distention, invagination, and liquid jets were associated with the damage of microvessels whose diameters were smaller than those of maximally expanded microbubbles. However, vessel invagination appeared to be the dominant mechanism for the damage of relative large microvessels.

  17. The small molecule calactin induces DNA damage and apoptosis in human leukemia cells.

    PubMed

    Lee, Chien-Chih; Lin, Yi-Hsiung; Chang, Wen-Hsin; Wu, Yang-Chang; Chang, Jan-Gowth

    2012-09-01

    We purified calactin from the roots of the Chinese herb Asclepias curassavica L. and analyzed its biologic effects in human leukemia cells. Our results showed that calactin treatment caused DNA damage and resulted in apoptosis. Increased phosphorylation levels of Chk2 and H2AX were observed and were reversed by the DNA damage inhibitor caffeine in calactin-treated cells. In addition, calactin treatment showed that a decrease in the expression of cell cycle regulatory proteins Cyclin B1, Cdk1, and Cdc25C was consistent with a G2/M phase arrest. Furthermore, calactin induced extracellular signal-regulated kinase (ERK) phosphorylation, activation of caspase-3, caspase-8, and caspase-9, and PARP cleavage. Pretreatment with the ERK inhibitor PD98059 significantly blocked the loss of viability in calactin-treated cells. It is indicated that calactin-induced apoptosis may occur through an ERK signaling pathway. Our data suggest that calactin is a potential anticancer compound. PMID:22828439

  18. Role of paramagnetic chromium in chromium(VI)-induced damage in cultured mammalian cells.

    PubMed

    Sugiyama, M

    1994-09-01

    Chromium(VI) compounds are known to be potent toxic and carcinogenic agents. Because chromium(VI) is easily taken up by cells and is subsequently reduced to chromium(III), the formation of paramagnetic chromium such as chromium(V) and chromium(III) is believed to play a role in the adverse biological effects of chromium(VI) compounds. The present report, uses electron spin resonance (ESR) spectroscopy; the importance of the role of paramagnetic chromium in chromium(VI)-induced damage in intact cultured cells is discussed, based upon our studies with antioxidants including vitamin E (alpha-tocopherol), B2 (riboflavin), C (ascorbic acid), and so on. These studies appear to confirm the participation of paramagnetic Cr such as chromium(V) and Chromium(III) in chromium(VI)-induced cellular damage. PMID:7843124

  19. Fungicide prochloraz induces oxidative stress and DNA damage in vitro.

    PubMed

    Lundqvist, J; Hellman, B; Oskarsson, A

    2016-05-01

    Prochloraz is widely used in horticulture and agriculture, e.g. as a post-harvest anti-mold treatment. Prochloraz is a known endocrine disruptor causing developmental toxicity with multiple mechanisms of action. However, data are scarce concerning other toxic effects. Since oxidative stress response, with formation of reactive oxygen species (ROS), is a common mechanism for different toxic endpoints, e.g. genotoxicity, carcinogenicity and teratogenicity, the aim of this study was to investigate if prochloraz can induce oxidative stress and/or DNA damage in human cells. A cell culture based in vitro model was used to study oxidative stress response by prochloraz, as measured by the activity of the nuclear factor erythroid 2-related factor 2 (Nrf2), a key molecule in oxidative defense mechanisms. It was observed that prochloraz induced oxidative stress in cultured human adrenocortical H295R and hepatoma HepG2 cells at non-toxic concentrations. Further, we used Comet assay to investigate the DNA damaging potential of prochloraz, and found that non-toxic concentrations of prochloraz induced DNA damage in HepG2 cells. These are novel findings, contradicting previous studies in the field of prochloraz and genotoxicity. This study reports a new mechanism by which prochloraz may exert toxicity. Our findings suggest that prochloraz might have genotoxic properties. PMID:26945613

  20. PARP-1 modulates amyloid beta peptide-induced neuronal damage.

    PubMed

    Martire, Sara; Fuso, Andrea; Rotili, Dante; Tempera, Italo; Giordano, Cesare; De Zottis, Ivana; Muzi, Alessia; Vernole, Patrizia; Graziani, Grazia; Lococo, Emanuela; Faraldi, Martina; Maras, Bruno; Scarpa, Sigfrido; Mosca, Luciana; d'Erme, Maria

    2013-01-01

    Amyloid beta peptide (Aβ) causes neurodegeneration by several mechanisms including oxidative stress, which is known to induce DNA damage with the consequent activation of poly (ADP-ribose) polymerase (PARP-1). To elucidate the role of PARP-1 in the neurodegenerative process, SH-SY5Y neuroblastoma cells were treated with Aβ25-35 fragment in the presence or absence of MC2050, a new PARP-1 inhibitor. Aβ25-35 induces an enhancement of PARP activity which is prevented by cell pre-treatment with MC2050. These data were confirmed by measuring PARP-1 activity in CHO cells transfected with amylod precursor protein and in vivo in brains specimens of TgCRND8 transgenic mice overproducing the amyloid peptide. Following Aβ25-35 exposure a significant increase in intracellular ROS was observed. These data were supported by the finding that Aβ25-35 induces DNA damage which in turn activates PARP-1. Challenge with Aβ25-35 is also able to activate NF-kB via PARP-1, as demonstrated by NF-kB impairment upon MC2050 treatment. Moreover, Aβ25-35 via PARP-1 induces a significant increase in the p53 protein level and a parallel decrease in the anti-apoptotic Bcl-2 protein. These overall data support the hypothesis of PARP-1 involvment in cellular responses induced by Aβ and hence a possible rationale for the implication of PARP-1 in neurodegeneration is discussed. PMID:24086258

  1. PARP-1 Modulates Amyloid Beta Peptide-Induced Neuronal Damage

    PubMed Central

    Martire, Sara; Fuso, Andrea; Rotili, Dante; Tempera, Italo; Giordano, Cesare; De Zottis, Ivana; Muzi, Alessia; Vernole, Patrizia; Graziani, Grazia; Lococo, Emanuela; Faraldi, Martina; Maras, Bruno; Scarpa, Sigfrido; Mosca, Luciana; d'Erme, Maria

    2013-01-01

    Amyloid beta peptide (Aβ) causes neurodegeneration by several mechanisms including oxidative stress, which is known to induce DNA damage with the consequent activation of poly (ADP-ribose) polymerase (PARP-1). To elucidate the role of PARP-1 in the neurodegenerative process, SH-SY5Y neuroblastoma cells were treated with Aβ25–35 fragment in the presence or absence of MC2050, a new PARP-1 inhibitor. Aβ25–35 induces an enhancement of PARP activity which is prevented by cell pre-treatment with MC2050. These data were confirmed by measuring PARP-1 activity in CHO cells transfected with amylod precursor protein and in vivo in brains specimens of TgCRND8 transgenic mice overproducing the amyloid peptide. Following Aβ25–35 exposure a significant increase in intracellular ROS was observed. These data were supported by the finding that Aβ25–35 induces DNA damage which in turn activates PARP-1. Challenge with Aβ25–35 is also able to activate NF-kB via PARP-1, as demonstrated by NF-kB impairment upon MC2050 treatment. Moreover, Aβ25–35 via PARP-1 induces a significant increase in the p53 protein level and a parallel decrease in the anti-apoptotic Bcl-2 protein. These overall data support the hypothesis of PARP-1 involvment in cellular responses induced by Aβ and hence a possible rationale for the implication of PARP-1 in neurodegeneration is discussed. PMID:24086258

  2. A stochastic model of radiation-induced bone marrow damage

    SciTech Connect

    Cotlet, G.; Blue, T.E.

    2000-03-01

    A stochastic model, based on consensus principles from radiation biology, is used to estimate bone-marrow stem cell pool survival (CFU-S and stroma cells) after irradiation. The dose response model consists of three coupled first order linear differential equations which quantitatively describe time dependent cellular damage, repair, and killing of red bone marrow cells. This system of differential equations is solved analytically through the use of a matrix approach for continuous and fractionated irradiations. The analytic solutions are confirmed through the dynamical solution of the model equations using SIMULINK. Rate coefficients describing the cellular processes of radiation damage and repair, extrapolated to humans from animal data sets and adjusted for neutron-gamma mixed fields, are employed in a SIMULINK analysis of criticality accidents. The results show that, for the time structures which may occur in criticality accidents, cell survival is established mainly by the average dose and dose rate.

  3. Bacterial Genotoxins: Merging the DNA Damage Response into Infection Biology.

    PubMed

    Grasso, Francesca; Frisan, Teresa

    2015-01-01

    Bacterial genotoxins are unique among bacterial toxins as their molecular target is DNA. The consequence of intoxication or infection is induction of DNA breaks that, if not properly repaired, results in irreversible cell cycle arrest (senescence) or death of the target cells. At present, only three bacterial genotoxins have been identified. Two are protein toxins: the cytolethal distending toxin (CDT) family produced by a number of Gram-negative bacteria and the typhoid toxin produced by Salmonella enterica serovar Typhi. The third member, colibactin, is a peptide-polyketide genotoxin, produced by strains belonging to the phylogenetic group B2 of Escherichia coli. This review will present the cellular effects of acute and chronic intoxication or infection with the genotoxins-producing bacteria. The carcinogenic properties and the role of these effectors in the context of the host-microbe interaction will be discussed. We will further highlight the open questions that remain to be solved regarding the biology of this unusual family of bacterial toxins. PMID:26270677

  4. Bacterial Genotoxins: Merging the DNA Damage Response into Infection Biology

    PubMed Central

    Grasso, Francesca; Frisan, Teresa

    2015-01-01

    Bacterial genotoxins are unique among bacterial toxins as their molecular target is DNA. The consequence of intoxication or infection is induction of DNA breaks that, if not properly repaired, results in irreversible cell cycle arrest (senescence) or death of the target cells. At present, only three bacterial genotoxins have been identified. Two are protein toxins: the cytolethal distending toxin (CDT) family produced by a number of Gram-negative bacteria and the typhoid toxin produced by Salmonella enterica serovar Typhi. The third member, colibactin, is a peptide-polyketide genotoxin, produced by strains belonging to the phylogenetic group B2 of Escherichia coli. This review will present the cellular effects of acute and chronic intoxication or infection with the genotoxins-producing bacteria. The carcinogenic properties and the role of these effectors in the context of the host-microbe interaction will be discussed. We will further highlight the open questions that remain to be solved regarding the biology of this unusual family of bacterial toxins. PMID:26270677

  5. Evidence for DNA Damage as a Biological Link Between Diabetes and Cancer

    PubMed Central

    Lee, Shao Chin; Chan, Juliana CN

    2015-01-01

    Objective: This review examines the evidence that: Diabetes is a state of DNA damage; pathophysiological factors in diabetes can cause DNA damage; DNA damage can cause mutations; and DNA mutation is linked to carcinogenesis. Data Sources: We retrieved information from the PubMed database up to January, 2014, using various search terms and their combinations including DNA damage, diabetes, cancer, high glucose, hyperglycemia, free fatty acids, palmitic acid, advanced glycation end products, mutation and carcinogenesis. Study Selection: We included data from peer-reviewed journals and a textbook printed in English on relationships between DNA damage and diabetes as well as pathophysiological factors in diabetes. Publications on relationships among DNA damage, mutagenesis, and carcinogenesis, were also reviewed. We organized this information into a conceptual framework to explain the possible causal relationship between DNA damage and carcinogenesis in diabetes. Results: There are a large amount of data supporting the view that DNA mutation is a typical feature in carcinogenesis. Patients with type 2 diabetes have increased production of reactive oxygen species, reduced levels of antioxidant capacity, and increased levels of DNA damage. The pathophysiological factors and metabolic milieu in diabetes can cause DNA damage such as DNA strand break and base modification (i.e., oxidation). Emerging experimental data suggest that signal pathways (i.e., Akt/tuberin) link diabetes to DNA damage. This collective evidence indicates that diabetes is a pathophysiological state of oxidative stress and DNA damage which can lead to various types of mutation to cause aberration in cells and thereby increased cancer risk. Conclusions: This review highlights the interrelationships amongst diabetes, DNA damage, DNA mutation and carcinogenesis, which suggests that DNA damage can be a biological link between diabetes and cancer. PMID:26021514

  6. Effect of Picroliv on cadmium induced testicular damage in rat.

    PubMed

    Yadav, Neelam; Khandelwal, Shashi

    2008-02-01

    Ameliorative potential of Picroliv, a standardized extract of Picrorhiza kurroa on Cd induced early and advanced testicular damage was investigated in male rats. In the former experiment, the rats were administered Cd as CdCl(2) (0.5mg/kg, s.c.) 5days/week for 18 weeks and Picroliv at two doses (6 and 12 mg/kg, p.o.) was given for the last 4 weeks i.e. from week 15 to 18, to the Cd administered group. In the latter experiment, the Cd administration continued for 24 weeks and Picroliv was given from week 21 to 24. At 18 weeks, Cd caused alterations in oxidative stress indices like increased lipid peroxidation (MDA) and reduced levels of non protein sulphydryls (NPSH). They were found close to the control values by Picroliv treatment, suggesting its antioxidant potential. The increased levels of Zn and Ca were reduced by Picroliv, the Cd levels remained unaltered. The Cd induced testicular damage was also mitigated by Picroliv. The higher dose (12 mg/kg) being more effective than the lower dose. However, at 24 weeks of Cd exposure, the oxidative stress indicators in testis were more pronounced along with the morphological alterations. These parameters remained unaffected by Picroliv treatment. On comparative evaluation of the two studies, 18 weeks Cd exposure caused moderate testicular damage, which could be reversed significantly by Picroliv administration and correlated well with oxidative stress markers. Our results clearly demonstrate the ameliorative potential of Picroliv in Cd induced early testicular damage. PMID:17928123

  7. Enhancement of ultrasonically induced cell damage by phthalocyanines in vitro.

    PubMed

    Milowska, Katarzyna; Gabryelak, Teresa

    2008-12-01

    In this work, erythrocytes from carp were used as a nucleated cell model to test the hypothesis that the phthalocyanines (zinc--ZnPc and chloroaluminium -AlClPc) enhance ultrasonically induced damage in vitro. In order to confirm and complete our earlier investigation, the influence of ultrasound (US) and phthalocyanines (Pcs) on unresearched cellular components, was studied. Red blood cells were exposed to 1 MHz continuous ultrasound wave (0.61 and/or 2.44 W/cm(2)) in the presence or absence of phthalocyanines (3 microM). To identify target cell damage, we studied hemolysis, membrane fluidity and morphology of erythrocytes. To demonstrate the changes in the fluidity of plasma membrane we used the spectrofluorimetric methods using two fluorescence probes: 1-[4-(trimethylamino)phenyl]-6-phenyl-1,3,5,-hexatriene (TMA-DPH) and 1,6-diphenyl-1,3,5-hexatriene (DPH). The effect of US and Pcs on nucleated erythrocytes morphology was estimated on the basis of microscopic observation. The enhancement of ultrasonically induced membrane damage by both phthalocyanines was observed in case of hemolysis, and membrane surface fluidity, in comparison to ultrasound. The authors also observed changes in the morphology of erythrocytes. The obtained results support the hypothesis that the Pcs enhance ultrasonically induced cell damage in vitro. Furthermore, the influence of ultrasound on phthalocyanines (Pcs) in medium and in cells was tested. The authors observed changes in the phthalocyanines absorption spectra in the medium and the increase in the intensity of phthalocyanines fluorescence in the cells. These data can suggest changes in the structure of phthalocyanines after ultrasound action. PMID:18495194

  8. DNA damage as an indicator of pollutant-induced genotoxicity

    SciTech Connect

    Shugart, L.R.

    1989-01-01

    Biological monitoring is an approach of considerable interest to scientists in the field of environmental genotoxicity who are investigating the effects of hazardous substances on the biota. In essence the technique involves an evaluation of various types of responses in living organisms for their potential to identify exposure to dangerous substances and to define or to predict subsequent deleterious effects. The rationale for the selection of DNA damage as an indicator of exposure to genotoxic agents is based mainly on the mechanisms of action of chemicals that are known mutagens and carcinogens. An alkaline unwinding assay that detects excess strand breakage within the DNA polymer was applied to sunfish in a local stream as a biological monitor for environmental genotoxicity due to industrial pollution. The study was conducted over a period of 15 months and the temporal and spatial aspects of the data were evaluated for the effect of remedial action. 16 refs., 4 figs., 4 tabs.

  9. Microscopic studies of cellular damage induced by compression waves in different environments

    NASA Astrophysics Data System (ADS)

    Bo, Chiara; Balzer, Jens; Brown, Katherine A.; Proud, William G.

    2011-06-01

    The cellular basis of induced-damage in biological samples under dynamic loading conditions is largely uncharacterized. In this study we propose a new approach to investigate the effects of compression waves on in-vitro grown Stem cells extracted from BALB/c mice. A modified split Hopkinson pressure bar system is used to simulate damage in the biological samples: the cells are inserted in a confinement chamber either in their growing media or on a 3D scaffold, they are subjected to compression waves and finally recovered for further analysis. The difference in mechanical impedance between the cells and the hosting environments is believed to be a key point in the generation of damage. To discriminate the effects of the different mechanical supports on cell morphology pre and after compression, membrane and cytoskeletal proteins disruptions are investigated using fluorescence confocal microscopy. Understanding the underlying mechanism of damage at the microscopic scale could set the basis for the development of therapeutic applications at the cellular level.

  10. Retinal damage induced by commercial light emitting diodes (LEDs).

    PubMed

    Jaadane, Imene; Boulenguez, Pierre; Chahory, Sabine; Carré, Samuel; Savoldelli, Michèle; Jonet, Laurent; Behar-Cohen, Francine; Martinsons, Christophe; Torriglia, Alicia

    2015-07-01

    Spectra of "white LEDs" are characterized by an intense emission in the blue region of the visible spectrum, absent in daylight spectra. This blue component and the high intensity of emission are the main sources of concern about the health risks of LEDs with respect to their toxicity to the eye and the retina. The aim of our study was to elucidate the role of blue light from LEDs in retinal damage. Commercially available white LEDs and four different blue LEDs (507, 473, 467, and 449nm) were used for exposure experiments on Wistar rats. Immunohistochemical stain, transmission electron microscopy, and Western blot were used to exam the retinas. We evaluated LED-induced retinal cell damage by studying oxidative stress, stress response pathways, and the identification of cell death pathways. LED light caused a state of suffering of the retina with oxidative damage and retinal injury. We observed a loss of photoreceptors and the activation of caspase-independent apoptosis, necroptosis, and necrosis. A wavelength dependence of the effects was observed. Phototoxicity of LEDs on the retina is characterized by a strong damage of photoreceptors and by the induction of necrosis. PMID:25863264

  11. Proton-induced radiation damage in germanium detectors

    SciTech Connect

    Bruckner, J.; Korfer, M.; Wanke, H. , Mainz ); Schroeder, A.N.F. ); Figes, D.; Dragovitsch, P. ); Englert, P.A.J. ); Starr, R.; Trombka, J.I. . Goddard Space Flight Center); Taylor, I. ); Drake, D.M.; Shunk, E.R. )

    1991-04-01

    High-purity germanium (HPGe) detectors will be used in future space missions for gamma-ray measurements and will be subject to interactions with energetic particles. To simulate this process several large-volume n-type HPGe detectors were incrementally exposed to a particle fluence of up to 10{sub 8} protons cm{sup {minus}2} (proton energy: 1.5 GeV) at different operating temperatures (90 to 120 K) to induce radiation damage. Basic scientific as well as engineering data on detector performance were collected. During the incremental irradiation, the peak shape produced by the detectors showed a significant change from a Gaussian shape to a broad complex structure. After the irradiation all detectors were thoroughly characterized by measuring many parameters. To remove the accumulated radiation damage the detectors were stepwise annealed at temperatures T {le} 110{degrees}C while staying specially designed cryostats. This paper shows that n-type HPGe detectors can be used in charged particles environments as high-energy resolution devices until a certain level of radiation damage is accumulated and that the damage can be removed at moderate annealing temperatures and the detector returned to operating condition.

  12. Proton-induced radiation damage in germanium detectors

    NASA Technical Reports Server (NTRS)

    Brueckner, J.; Koerfer, M.; Waenke, H.; Schroeder, A. N. F.; Filges, D.; Dragovitsch, P.; Englert, P. A. J.; Starr, R.; Trombka, J. I.

    1991-01-01

    High-purity germanium (HPGe) detectors will be used in future space missions for gamma-ray measurements and will be subject to interactions with energetic particles. To simulate this process, several large-volume n-type HPGe detectors were incrementally exposed to a particle fluence of up to 10 to the 8th protons/sq cm (proton energy: 1.5 GeV) at different operating temperatures (90 to 120 K) to induce radiation damage. Basic scientific and engineering data on detector performance were collected. During the incremental irradiation, the peak shape produced by the detectors showed a significant change from a Gaussian shape to a broad complex structure. After the irradiation, all detectors were thoroughly characterized by measuring many parameters. To remove the accumulated radiation damage, the detectors were stepwise-annealed at temperatures below 110 C, while kept in their specially designed cryostats. This study shows that n-type HPGe detectors can be used in charged-particle environments as high-energy resolution devices until a certain level of radiation damage is accumulated and that the damage can be removed at moderate annealing temperatures and the detector returned to operating condition.

  13. Metabolic consequences of exercise-induced muscle damage.

    PubMed

    Tee, Jason C; Bosch, Andrew N; Lambert, Mike I

    2007-01-01

    Exercise-induced muscle damage (EIMD) is commonly experienced following either a bout of unaccustomed physical activity or following physical activity of greater than normal duration or intensity. The mechanistic factor responsible for the initiation of EIMD is not known; however, it is hypothesised to be either mechanical or metabolic in nature. The mechanical stress hypothesis states that EIMD is the result of physical stress upon the muscle fibre. In contrast, the metabolic stress model predicts that EIMD is the result of metabolic deficiencies, possibly through the decreased action of Ca(2+)-adenosine triphosphatase. Irrespective of the cause of the damage, EIMD has a number of profound metabolic effects. The most notable metabolic effects of EIMD are decreased insulin sensitivity, prolonged glycogen depletion and an increase in metabolic rate both at rest and during exercise. Based on current knowledge regarding the effects that various types of damaging exercise have on muscle metabolism, a new model for the initiation of EIMD is proposed. This model states that damage initiation may be either metabolic or mechanical, or a combination of both, depending on the mode, intensity and duration of exercise and the training status of the individual. PMID:17887809

  14. Nanoparticle-Mediated Mitochondrial Damage Induces Apoptosis in Cancer.

    PubMed

    Mallick, Abhik; More, Piyush; Syed, Muhammed Muazzam Kamil; Basu, Sudipta

    2016-06-01

    Detouring of conventional DNA damaging anticancer drugs into mitochondria to damage mitochondrial DNA is evolving as a promising strategy in chemotherapy. Inhibiting single target in mitochondria would eventually lead to the emergence of drug resistance. Moreover, targeting mitochondria selectively in cancer cells, keeping them intact in healthy cells, remains a major challenge. Herein, triphenylphosphine (TPP)-coated positively charged 131.6 nm spherical nanoparticles (NPs) comprised of α-tocopheryl succinate (TOS, inhibitor of complex II in electron transport chain) and obatoclax (Obt, inhibitor of Bcl-2) were engineered. The TOS-TPP-Obt-NPs entered into acidic lysosomes via macropinocytosis, followed by lysosomal escape and finally homed into mitochondria over a period of 24 h. Subsequently, these TOS-TPP-Obt-NPs triggered mitochondrial outer membrane permeabilization (MOMP) by inhibiting antiapoptotic Bcl-2, leading to Cytochrome C release. These TOS-TPP-Obt-NPs mediated mitochondrial damage induced cellular apoptosis through caspase-9 and caspase-3 cleavage to show improved efficacy in HeLa cells. Moreover, TOS-TPP-Obt-NPs induced MOMP in drug-resistant triple negative breast cancer cells (MDA-MB-231), leading to remarkable efficacy, compared to the combination of free drugs in higher drug concentrations. Results presented here clearly stimulate the usage of multiple drugs to perturb simultaneously diverse targets, selectively in mitochondria, as next-generation cancer therapeutics. PMID:27160664

  15. Viral Carcinogenesis: Factors Inducing DNA Damage and Virus Integration

    PubMed Central

    Chen, Yan; Williams, Vonetta; Filippova, Maria; Filippov, Valery; Duerksen-Hughes, Penelope

    2014-01-01

    Viruses are the causative agents of 10%–15% of human cancers worldwide. The most common outcome for virus-induced reprogramming is genomic instability, including accumulation of mutations, aberrations and DNA damage. Although each virus has its own specific mechanism for promoting carcinogenesis, the majority of DNA oncogenic viruses encode oncogenes that transform infected cells, frequently by targeting p53 and pRB. In addition, integration of viral DNA into the human genome can also play an important role in promoting tumor development for several viruses, including HBV and HPV. Because viral integration requires the breakage of both the viral and the host DNA, the integration rate is believed to be linked to the levels of DNA damage. DNA damage can be caused by both endogenous and exogenous factors, including inflammation induced by either the virus itself or by co-infections with other agents, environmental agents and other factors. Typically, cancer develops years to decades following the initial infection. A better understanding of virus-mediated carcinogenesis, the networking of pathways involved in transformation and the relevant risk factors, particularly in those cases where tumorigenesis proceeds by way of virus integration, will help to suggest prophylactic and therapeutic strategies to reduce the risk of virus-mediated cancer. PMID:25340830

  16. Morphological studies of laser-induced photoacoustic damage

    NASA Astrophysics Data System (ADS)

    Flotte, Thomas J.; Yashima, Yutaka; Watanabe, Shinichi; McAuliffe, Daniel J., Sr.; Jacques, Steven L.

    1990-06-01

    Argon-fluoride excimer laser ablation of stratum comeum causes deeper tissue damage than expected for thermal or photochemical mechanisms, suggesting thatphotoacoustic waves have arole in tissue damage. Laserirradiation (193 nm, 14 ns pulses, 1-2 Hz) attworadiantexposures, 60 and 160 mJ/cm2perpulse was usedto ablate the stratumcomeumofskin. Light and electron microscopy ofimmediate biopsies demonstrated damage to fibroblasts as deep as 88 and 220 jun, respectively, below the ablation site. Ablation throughwaterwas usedtoinertially confine the ablation zone. Partial ablationofs.c. through airproducedno damage, whereas partial ablation through water damaged skin to amean depth of 1 14.5 8.8( Full thickness ablation of s.c. through air and water produced damage zones measuring 192.2 16.2 and 293.0 71.6 rim, respectively (p <0.05). The increased depth ofdamage in the presence ofinertial confinementprovided by the layer of water strongly supports a photoacoustic mechanism ofdamage. The depths ofdamage for thelarge spot, line, and small spots were 43 1 164 urn, 269 96xni, andno damage. The spot size dependence ofthedepthofdamage is consistentwiththe geometric attenuation one would expect to be present from a pressure wave related phenomena. Sequential biopsies were taken over a 7 day period for light and transmission electron microscopy. At 24 hours, there was necrosis of the epidermis and papillary dermis subjacent to the ablation site, with neutrophils surrounding and demarcating the affected area. The necrotic zone sloughedby48 hours. Thereepithelializationwas completeby7 days. The sequenceofrepairis similartoknife wound healing which we have previously studied, and is analogous to other wound healing processes. We have used an experimental model of ArF excimer laser ablation of stratum corneum to investigate laser-induced photoacoustic damage. The evidence for the injury being due to pressure transients is indirectbutcompelling. Whether these pressuretransients are

  17. Proton-induced direct and indirect damage of plasmid DNA.

    PubMed

    Vyšín, Luděk; Pachnerová Brabcová, Kateřina; Štěpán, Václav; Moretto-Capelle, Patrick; Bugler, Beatrix; Legube, Gaelle; Cafarelli, Pierre; Casta, Romain; Champeaux, Jean Philippe; Sence, Martine; Vlk, Martin; Wagner, Richard; Štursa, Jan; Zach, Václav; Incerti, Sebastien; Juha, Libor; Davídková, Marie

    2015-08-01

    Clustered DNA damage induced by 10, 20 and 30 MeV protons in pBR322 plasmid DNA was investigated. Besides determination of strand breaks, additional lesions were detected using base excision repair enzymes. The plasmid was irradiated in dry form, where indirect radiation effects were almost fully suppressed, and in water solution containing only minimal residual radical scavenger. Simultaneous irradiation of the plasmid DNA in the dry form and in the solution demonstrated the contribution of the indirect effect as prevalent. The damage composition slightly differed when comparing the results for liquid and dry samples. The obtained data were also subjected to analysis concerning different methodological approaches, particularly the influence of irradiation geometry, models used for calculation of strand break yields and interpretation of the strand breaks detected with the enzymes. It was shown that these parameters strongly affect the results. PMID:26007308

  18. Laser pointer induced macular damage: case report and mini review.

    PubMed

    Turaka, Kiran; Bryan, J Shepard; Gordon, Alan J; Reddy, Rahul; Kwong, Henry M; Sell, Clive H

    2012-06-01

    To report laser pointer induced damage to retina and choroid and briefly review literature. A case report of a 13-year old Caucasian boy developed blurry central vision and central scotoma in right eye (OD). He was exposed for one minute to class IIIA green laser pointer of 650 nm wavelength and 5 mW power. Clinical examination showed a grayish lesion in foveal region. Ancillary testing revealed disruption of the retinal pigment epithelial (RPE) layer in foveal region and indocyanine green angiography demonstrated evidence of choroidal hypofluorescence suggestive of choroidal infarction in OD. Visual acuity improved from 20/100 to 20/60 in one day and he was treated with tapering doses of oral prednisolone (40 mg) for 3 weeks. Laser pointer with a power of >5 mW caused damage to RPE in the macula. Children should not be given laser pointers as toys especially those with label of danger instructions. PMID:22466425

  19. Antigenotoxic effect of allicin against methyl methanesulphonate induced genotoxic damage.

    PubMed

    Siddique, Yasir Hasan; Afzal, Mohammad

    2005-07-01

    Allicin, one of the sulfur compounds especially thiosulphonates of garlic (Allium sativum), possesses antioxidant and thioldisulphide exchange activity and is also shown to cause a variety of actions potentially useful for human health. In this investigation we determined its antigenotoxic potential using chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) induced by methyl methanesulphonate (MMS) as genotoxic end points both in the presence as well as absence of rat liver microsomal activation system (S9 mix) in cultured human lymphocytes. We tested the effect of 5, 10 and 20 microM of allicin on the damage exerted by 60 microM of MMS. The levels of CAs and SCEs were lowered suggesting an antigenotoxic role of allicin against genotoxic damage both in the presence as well as absence of metabolic activation. PMID:16334295

  20. Trophic Complexity and the Adaptive Value of Damage-Induced Plant Volatiles

    PubMed Central

    Kaplan, Ian

    2012-01-01

    Indirect plant defenses are those facilitating the action of carnivores in ridding plants of their herbivorous consumers, as opposed to directly poisoning or repelling them. Of the numerous and diverse indirect defensive strategies employed by plants, inducible volatile production has garnered the most fascination among plant-insect ecologists. These volatile chemicals are emitted in response to feeding by herbivorous arthropods and serve to guide predators and parasitic wasps to their prey. Implicit in virtually all discussions of plant volatile-carnivore interactions is the premise that plants “call for help” to bodyguards that serve to boost plant fitness by limiting herbivore damage. This, by necessity, assumes a three-trophic level food chain where carnivores benefit plants, a theoretical framework that is conceptually tractable and convenient, but poorly depicts the complexity of food-web dynamics occurring in real communities. Recent work suggests that hyperparasitoids, top consumers acting from the fourth trophic level, exploit the same plant volatile cues used by third trophic level carnivores. Further, hyperparasitoids shift their foraging preferences, specifically cueing in to the odor profile of a plant being damaged by a parasitized herbivore that contains their host compared with damage from an unparasitized herbivore. If this outcome is broadly representative of plant-insect food webs at large, it suggests that damage-induced volatiles may not always be beneficial to plants with major implications for the evolution of anti-herbivore defense and manipulating plant traits to improve biological control in agricultural crops. PMID:23209381

  1. The Protecting Effect of Deoxyschisandrin and Schisandrin B on HaCaT Cells against UVB-Induced Damage.

    PubMed

    Hou, Wei; Gao, Wei; Wang, Datao; Liu, Qingxiu; Zheng, Siwen; Wang, Yingping

    2015-01-01

    Schisandra chinensis is a traditional Chinese medicine that has multiple biological activities, including antioxidant, anticancer, tonic, and anti-aging effects. Deoxyschisandrin (SA) and schisandrin B (SB), the two major lignans isolated from S. chinensis, exert high antioxidant activities in vitro and in vivo by scavenging free radicals, such as reactive oxygen species (ROS). Ultraviolet B-ray (UVB) radiation induces the production of ROS and DNA damage, which eventually leads to cell death by apoptosis. However, it is unknown whether SA or SB protects cells against UVB-induced cellular DNA damage. Our study showed that both SA and SB effectively protected HaCaT cells from UVB-induced cell death by antagonizing UVB-mediated production of ROS and induction of DNA damage. Our results showed that both SA and SB significantly prevented UVB-induced loss of cell viability using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays. Dichloro-dihydro-fluorescein diacetate (DCFH-DA) assays showed that the production of ROS following UVB exposure was inhibited by treatment with SA and SB. Moreover, SA and SB decreased the UVB-induced DNA damage in HaCaT cells by comet assays. In addition, SA and SB also prevented UVB-induced cell apoptosis and the cleavage of caspase-3, caspase-8 and caspase-9. In a word, our results imply that the antioxidants SA and SB could protect cells from UVB-induced cell damage via scavenging ROS. PMID:25978330

  2. Maintenance of the DNA-Damage Checkpoint Requires DNA-Damage-Induced Mediator Protein Oligomerization

    PubMed Central

    Usui, Takehiko; Foster, Steven S.; Petrini, John H.J.

    2010-01-01

    SUMMARY Oligomeric assembly of Brca1 C-terminal (BRCT) domain-containing mediator proteins occurs at sites of DNA damage. However, the functional significance and regulation of such assemblies are not well understood. In this study, we defined the molecular mechanism of DNA-damage-induced oligomerization of the S. cerevisiae BRCT protein Rad9. Our data suggest that Rad9’s tandem BRCT domain mediates Rad9 oligomerization via its interaction with its own Mec1/Tel1-phosphorylated SQ/TQ cluster domain (SCD). Rad53 activation is unaffected by mutations that impair Rad9 oligomerization, but checkpoint maintenance is lost, indicating that oligomerization is required to sustain checkpoint signaling. Once activated, Rad53 phosphorylates the Rad9 BRCT domain, which attenuates the BRCT-SCD interaction. Failure to phosphorylate the Rad9 BRCT results in cytologically visible Rad9 foci. This suggests a feedback loop wherein Rad53 activity and Rad9 oligomerization are regulated to tune the DNA-damage response. PMID:19187758

  3. Revision of laser-induced damage threshold evaluation from damage probability data

    SciTech Connect

    Bataviciute, Gintare; Grigas, Povilas; Smalakys, Linas; Melninkaitis, Andrius

    2013-04-15

    In this study, the applicability of commonly used Damage Frequency Method (DFM) is addressed in the context of Laser-Induced Damage Threshold (LIDT) testing with pulsed lasers. A simplified computer model representing the statistical interaction between laser irradiation and randomly distributed damage precursors is applied for Monte Carlo experiments. The reproducibility of LIDT predicted from DFM is examined under both idealized and realistic laser irradiation conditions by performing numerical 1-on-1 tests. A widely accepted linear fitting resulted in systematic errors when estimating LIDT and its error bars. For the same purpose, a Bayesian approach was proposed. A novel concept of parametric regression based on varying kernel and maximum likelihood fitting technique is introduced and studied. Such approach exhibited clear advantages over conventional linear fitting and led to more reproducible LIDT evaluation. Furthermore, LIDT error bars are obtained as a natural outcome of parametric fitting which exhibit realistic values. The proposed technique has been validated on two conventionally polished fused silica samples (355 nm, 5.7 ns).

  4. Radiation-induced lung damage: dose-time-fractionation considerations.

    PubMed

    Van Dyk, J; Mah, K; Keane, T J

    1989-01-01

    The comparison of different dose-time-fractionation schedules requires the use of an isoeffect formula. In recent years, the NSD isoeffect formula has been heavily criticized. In this report, we consider an isoeffect formula which is specifically developed for radiation-induced lung damage. The formula is based on the linear-quadratic model and includes a factor for overall treatment time. The proposed procedures allow for the simultaneous derivation of an alpha/beta ratio and a gamma/beta time factor. From animal data in the literature, the derived alpha/beta and gamma/beta ratios for acute lung damage are 5.0 +/- 1.0 Gy and 2.7 +/- 1.4 Gy2/day respectively, while for late damage the suggested values are 2.0 Gy and 0.0 Gy2/day. Data from two clinical studies, one prospective and the other retrospective, were also analysed and corresponding alpha/beta and gamma/beta ratios were determined. For the prospective clinical study, with a limited range of doses per fraction, the resultant alpha/beta and gamma/beta ratios were 0.9 +/- 2.6 Gy and 2.6 +/- 2.5 Gy2/day. The combination of the retrospective and prospective data yielded alpha/beta and gamma/beta ratios of 3.3 +/- 1.5 Gy and 2.4 +/- 1.5 Gy2/day, respectively. One potential advantage of this isoeffect formalism is that it might possibly be applied to both acute and late lung damage. The results of this formulation for acute lung damage indicate that time-dependent effects such as slow repair or proliferation might be more important in determining isoeffect doses than previously predicted by the estimated single dose (ED) formula. Although we present this as an alternative approach, we would caution against its clinical use until its applicability has been confirmed by additional clinical data. PMID:2928557

  5. Damage-free vibrational spectroscopy of biological materials in the electron microscope

    NASA Astrophysics Data System (ADS)

    Rez, Peter; Aoki, Toshihiro; March, Katia; Gur, Dvir; Krivanek, Ondrej L.; Dellby, Niklas; Lovejoy, Tracy C.; Wolf, Sharon G.; Cohen, Hagai

    2016-03-01

    Vibrational spectroscopy in the electron microscope would be transformative in the study of biological samples, provided that radiation damage could be prevented. However, electron beams typically create high-energy excitations that severely accelerate sample degradation. Here this major difficulty is overcome using an `aloof' electron beam, positioned tens of nanometres away from the sample: high-energy excitations are suppressed, while vibrational modes of energies <1 eV can be `safely' investigated. To demonstrate the potential of aloof spectroscopy, we record electron energy loss spectra from biogenic guanine crystals in their native state, resolving their characteristic C-H, N-H and C=O vibrational signatures with no observable radiation damage. The technique opens up the possibility of non-damaging compositional analyses of organic functional groups, including non-crystalline biological materials, at a spatial resolution of ~10 nm, simultaneously combined with imaging in the electron microscope.

  6. Damage-free vibrational spectroscopy of biological materials in the electron microscope

    PubMed Central

    Rez, Peter; Aoki, Toshihiro; March, Katia; Gur, Dvir; Krivanek, Ondrej L.; Dellby, Niklas; Lovejoy, Tracy C.; Wolf, Sharon G.; Cohen, Hagai

    2016-01-01

    Vibrational spectroscopy in the electron microscope would be transformative in the study of biological samples, provided that radiation damage could be prevented. However, electron beams typically create high-energy excitations that severely accelerate sample degradation. Here this major difficulty is overcome using an ‘aloof' electron beam, positioned tens of nanometres away from the sample: high-energy excitations are suppressed, while vibrational modes of energies <1 eV can be ‘safely' investigated. To demonstrate the potential of aloof spectroscopy, we record electron energy loss spectra from biogenic guanine crystals in their native state, resolving their characteristic C–H, N–H and C=O vibrational signatures with no observable radiation damage. The technique opens up the possibility of non-damaging compositional analyses of organic functional groups, including non-crystalline biological materials, at a spatial resolution of ∼10 nm, simultaneously combined with imaging in the electron microscope. PMID:26961578

  7. Induction and repair of HZE induced cytogenetic damage

    NASA Technical Reports Server (NTRS)

    Brooks, A. L.; Bao, S.; Rithidech, K.; Chrisler, W. B.; Couch, L. A.; Braby, L. A.

    2001-01-01

    Wistar rats were exposed to high-mass, high energy (HZE) 56Fe particles (1000 GeV/AMU) using the Alternating Gradient Synchrotron (AGS). The animals were sacrificed at 1-5 hours or after a 30-day recovery period. The frequency of micronuclei in the tracheal and the deep lung epithelial cells were evaluated. The relative effectiveness of 56Fe, for the induction of initial chromosome damage in the form of micronuclei, was compared to damage produced in the same biological system exposed to other types of high and low-LET radiation. It was demonstrated that for animals sacrificed at short times after exposure, the tracheal and lung epithelial cells, the 56Fe particles were 3.3 and 1.3 times as effective as 60Co in production of micronuclei, respectively. The effectiveness was also compared to that for exposure to inhaled radon. With this comparison, the 56Fe exposure of the tracheal epithelial cells and the lung epithelial cells were only 0.18 and 0.20 times as effective as radon in the production of the initial cytogenetic damage. It was suggested that the low relative effectiveness was related to potential for 'wasted energy' from the core of the 56Fe particles. When the animals were sacrificed after 30 days, the slopes of the dose-response relationships, which reflect the remaining level of damage, decreased by a factor of 10 for both the tracheal and lung epithelial cells. In both cases, the slope of the dose-response lines were no longer significantly different from zero, and the r2 values were very high. Lung epithelial cells, isolated from the animals sacrificed hours after exposure, were maintained in culture, and the micronuclei frequency evaluated after 4 and 6 subcultures. These cells were harvested at 24 and 36 days after the exposure. There was no dose-response detected in these cultures and no signs of genomic instability at either sample time.

  8. Oxidative damage and neurodegeneration in manganese-induced neurotoxicity

    SciTech Connect

    Milatovic, Dejan; Yu, Yingchun

    2009-10-15

    Exposure to excessive manganese (Mn) levels results in neurotoxicity to the extrapyramidal system and the development of Parkinson's disease (PD)-like movement disorder, referred to as manganism. Although the mechanisms by which Mn induces neuronal damage are not well defined, its neurotoxicity appears to be regulated by a number of factors, including oxidative injury, mitochondrial dysfunction and neuroinflammation. To investigate the mechanisms underlying Mn neurotoxicity, we studied the effects of Mn on reactive oxygen species (ROS) formation, changes in high-energy phosphates (HEP), neuroinflammation mediators and associated neuronal dysfunctions both in vitro and in vivo. Primary cortical neuronal cultures showed concentration-dependent alterations in biomarkers of oxidative damage, F{sub 2}-isoprostanes (F{sub 2}-IsoPs) and mitochondrial dysfunction (ATP), as early as 2 h following Mn exposure. Treatment of neurons with 500 {mu}M Mn also resulted in time-dependent increases in the levels of the inflammatory biomarker, prostaglandin E{sub 2} (PGE{sub 2}). In vivo analyses corroborated these findings, establishing that either a single or three (100 mg/kg, s.c.) Mn injections (days 1, 4 and 7) induced significant increases in F{sub 2}-IsoPs and PGE{sub 2} in adult mouse brain 24 h following the last injection. Quantitative morphometric analyses of Golgi-impregnated striatal sections from mice exposed to single or three Mn injections revealed progressive spine degeneration and dendritic damage of medium spiny neurons (MSNs). These findings suggest that oxidative stress, mitochondrial dysfunction and neuroinflammation are underlying mechanisms in Mn-induced neurodegeneration.

  9. Torin2 Suppresses Ionizing Radiation-Induced DNA Damage Repair.

    PubMed

    Udayakumar, Durga; Pandita, Raj K; Horikoshi, Nobuo; Liu, Yan; Liu, Qingsong; Wong, Kwok-Kin; Hunt, Clayton R; Gray, Nathanael S; Minna, John D; Pandita, Tej K; Westover, Kenneth D

    2016-05-01

    Several classes of inhibitors of the mammalian target of rapamycin (mTOR) have been developed based on its central role in sensing growth factor and nutrient levels to regulate cellular metabolism. However, its ATP-binding site closely resembles other phosphatidylinositol 3-kinase-related kinase (PIKK) family members, resulting in reactivity with these targets that may also be therapeutically useful. The ATP-competitive mTOR inhibitor, Torin2, shows biochemical activity against the DNA repair-associated proteins ATM, ATR and DNA-PK, which raises the possibility that Torin2 and related compounds might radiosensitize cancerous tumors. In this study Torin2 was also found to enhance ionizing radiation-induced cell killing in conditions where ATM was dispensable, confirming the requirement for multiple PIKK targets. Moreover, Torin2 did not influence the initial appearance of γ-H2AX foci after irradiation but significantly delayed the disappearance of radiation-induced γ-H2AX foci, indicating a DNA repair defect. Torin2 increased the number of radiation-induced S-phase specific chromosome aberrations and reduced the frequency of radiation-induced CtIP and Rad51 foci formation, suggesting that Torin2 works by blocking homologous recombination (HR)-mediated DNA repair resulting in an S-phase specific DNA repair defect. Accordingly, Torin2 reduced HR-mediated repair of I-Sce1-induced DNA damage and contributed to replication fork stalling. We conclude that radiosensitization of tumor cells by Torin2 is associated with disrupting ATR- and ATM-dependent DNA damage responses. Our findings support the concept of developing combination cancer therapies that incorporate ionizing radiation therapy and Torin2 or compounds with similar properties. PMID:27135971

  10. Ion beam induced fluorescence imaging in biological systems

    NASA Astrophysics Data System (ADS)

    Bettiol, Andrew A.; Mi, Zhaohong; Vanga, Sudheer Kumar; Chen, Ce-belle; Tao, Ye; Watt, Frank

    2015-04-01

    Imaging fluorescence generated by MeV ions in biological systems such as cells and tissue sections requires a high resolution beam (<100 nm), a sensitive detection system and a fluorescent probe that has a high quantum efficiency and low bleaching rate. For cutting edge applications in bioimaging, the fluorescence imaging technique needs to break the optical diffraction limit allowing for sub-cellular structure to be visualized, leading to a better understanding of cellular function. In a nuclear microprobe this resolution requirement can be readily achieved utilizing low beam current techniques such as Scanning Transmission Ion Microscopy (STIM). In recent times, we have been able to extend this capability to fluorescence imaging through the development of a new high efficiency fluorescence detection system, and through the use of new novel fluorescent probes that are resistant to ion beam damage (bleaching). In this paper we demonstrate ion beam induced fluorescence imaging in several biological samples, highlighting the advantages and challenges associated with using this technique.

  11. Alleviation of cytotoxic therapy-induced normal tissue damage.

    PubMed

    Loprinzi, C L; Foote, R L; Michalak, J

    1995-04-01

    Cytotoxic chemotherapy and radiation therapy damage normal body tissues, resulting in stomatitis, conjunctivitis, esophagitis, proctitis, and dermatitis. Pursuant to this, the North Central Cancer Treatment Group has developed a series of clinical trials designed to study antidotes for these pathologic processes. These trials have demonstrated clinically helpful therapies (eg, oral cryotherapy for decreasing mucositis induced by 5-fluorouracil) and also have demonstrated lack of benefit for other proposed treatments. Results from several ongoing clinical trials should become available in the near future. PMID:7740323

  12. Proton induced radiation damage in fast crystal scintillators

    NASA Astrophysics Data System (ADS)

    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.

  13. Protective Effect of Acacia nilotica (L.) against Acetaminophen-Induced Hepatocellular Damage in Wistar Rats

    PubMed Central

    Kannan, Narayanan; Sakthivel, Kunnathur Murugesan; Guruvayoorappan, Chandrasekaran

    2013-01-01

    The potential biological functions of A. nilotica have long been described in traditional system of medicine. However, the protective effect of A. nilotica on acetaminophen-induced hepatotoxicity is still unknown. The present study attempted to investigate the protective effect of A. nilotica against acetaminophen-induced hepatic damage in Wistar rats. The biochemical liver functional tests Alanine transaminase (ALT), Aspartate transaminase (AST), Alkaline phosphatase (ALP), total bilirubin, total protein, oxidative stress test (Lipid peroxidation), antioxidant parameter glutathione (GSH), and histopathological changes were examined. Our results show that the pretreatment with A. nilotica (250 mg/kg·bw) orally revealed attenuation of serum activities of ALT, AST, ALP, liver weight, and total bilirubin levels that were enhanced by administration of acetaminophen. Further, pretreatment with extract elevated the total protein and GSH level and decreased the level of LPO. Histopathological analysis confirmed the alleviation of liver damage and reduced lesions caused by acetaminophen. The present study undoubtedly provides a proof that hepatoprotective action of A. nilotica extract may rely on its effect on reducing the oxidative stress in acetaminophen-induced hepatic damage in rat model. PMID:23864853

  14. Biological effects of pyrroloquinoline quinone on liver damage in Bmi-1 knockout mice

    PubMed Central

    HUANG, YUANQING; CHEN, NING; MIAO, DENGSHUN

    2015-01-01

    Pyrroloquinoline quinone (PQQ) has been demonstrated to function as an antioxidant by scavenging free radicals and subsequently protecting the mitochondria from oxidative stress-induced damage. The aim of the present study was to investigate whether PQQ is able to rescue premature senescence in the liver, induced by the deletion of B cell-specific Moloney MLV insertion site-1 (Bmi-1), by inhibiting oxidative stress. In vivo, the mice were allocated into three groups that underwent the following treatment protocols. WT mice received a normal diet, while BKO mice also received a normal diet. An additional group of BKO mice were fed a PQQ-supplemented diet (BKO + PQQ; 4 mg PQQ/kg in the normal diet). The results indicated that PQQ partially rescued the liver damage induced by the deletion of Bmi-1. PQQ was demonstrated to exhibit these therapeutic effects on liver damage through multiple aspects, including the promotion of proliferation, antiapoptotic effects, the inhibition of senescence, the upregulation of antioxidant ability, the downregulation of cell cycle protein expression, the scavenging of reactive oxygen species and the reduction of DNA damage. The results of these experiments indicated that treatment of BKO mice with a moderate dose of PQQ significantly protected the liver from deleterious effects by inhibiting oxidative stress and participating in DNA damage repair. Therefore, PQQ has great potential as a therapeutic agent against oxidative stress during liver damage. PMID:26622336

  15. Cellular track model of biological damage to mammalian cell cultures from galactic cosmic rays

    NASA Technical Reports Server (NTRS)

    Cucinotta, Francis A.; Katz, Robert; Wilson, John W.; Townsend, Lawrence W.; Nealy, John E.; Shinn, Judy L.

    1991-01-01

    The assessment of biological damage from the galactic cosmic rays (GCR) is a current interest for exploratory class space missions where the highly ionizing, high-energy, high-charge ions (HZE) particles are the major concern. The relative biological effectiveness (RBE) values determined by ground-based experiments with HZE particles are well described by a parametric track theory of cell inactivation. Using the track model and a deterministic GCR transport code, the biological damage to mammalian cell cultures is considered for 1 year in free space at solar minimum for typical spacecraft shielding. Included are the effects of projectile and target fragmentation. The RBE values for the GCR spectrum which are fluence-dependent in the track model are found to be more severe than the quality factors identified by the International Commission on Radiological Protection publication 26 and seem to obey a simple scaling law with the duration period in free space.

  16. Dietary Nickel Chloride Induces Oxidative Intestinal Damage in Broilers

    PubMed Central

    Wu, Bangyuan; Cui, Hengmin; Peng, Xi; Fang, Jing; Zuo, Zhicai; Deng, Junliang; Huang, Jianying

    2013-01-01

    The purpose of this study was to investigate the oxidative damage induced by dietary nickel chloride (NiCl2) in the intestinal mucosa of different parts of the intestine of broilers, including duodenum, jejunum and ileum. A total of 240 one-day-old broilers were divided into four groups and fed on a corn-soybean basal diet as control diet or the same basal diet supplemented with 300, 600 or 900 mg/kg NiCl2 during a 42-day experimental period. The results showed that the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), and the ability to inhibit hydroxy radical and glutathione (GSH) content were significantly (p < 0.05 or p < 0.01) decreased in the 300, 600 and 900 mg/kg groups in comparison with those of the control group. In contrast, malondialdehyde (MDA) content was significantly (p < 0.05 or p < 0.01) higher in the 300, 600 and 900 mg/kg groups than that in the control group. It was concluded that dietary NiCl2 in excess of 300 mg/kg could cause oxidative damage in the intestinal mucosa in broilers, which finally impaired the intestinal functions including absorptive function and mucosal immune function. The oxidative damage might be a main mechanism on the effects of NiCl2 on the intestinal health of broilers. PMID:23702803

  17. Bee Products Prevent Agrichemical-Induced Oxidative Damage in Fish

    PubMed Central

    Ferreira, Daiane; Rocha, Helio Carlos; Kreutz, Luiz Carlos; Loro, Vania Lucia; Marqueze, Alessandra; Koakoski, Gessi; Santos da Rosa, João Gabriel; Gusso, Darlan; Oliveira, Thiago Acosta; de Abreu, Murilo Sander; Barcellos, Leonardo José Gil

    2013-01-01

    In southern South America and other parts of the world, aquaculture is an activity that complements agriculture. Small amounts of agrichemicals can reach aquaculture ponds, which results in numerous problems caused by oxidative stress in non-target organisms. Substances that can prevent or reverse agrichemical-induced oxidative damage may be used to combat these effects. This study includes four experiments. In each experiment, 96 mixed-sex, 6-month-old Rhamdia quelen (118±15 g) were distributed into eight experimental groups: a control group that was not exposed to contaminated water, three groups that were exposed to various concentrations of bee products, three groups that were exposed to various concentrations of bee products plus tebuconazole (TEB; Folicur 200 CE™) and a group that was exposed to 0.88 mg L−1 of TEB alone (corresponding to 16.6% of the 96-h LC50). We show that waterborne bee products, including royal jelly (RJ), honey (H), bee pollen (BP) and propolis (P), reversed the oxidative damage caused by exposure to TEB. These effects were likely caused by the high polyphenol contents of these bee-derived compounds. The most likely mechanism of action for the protective effects of bee products against tissue oxidation and the resultant damage is that the enzymatic activities of superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST) are increased. PMID:24098336

  18. Thermally Induced Osteocyte Damage Initiates a Remodelling Signaling Cascade

    PubMed Central

    Dolan, Eimear B.; McNamara, Laoise M.

    2015-01-01

    Thermal elevations experienced by bone during orthopaedic procedures, such as cutting and drilling, exothermal reactions from bone cement, and thermal therapies such as tumor ablation, can result in thermal damage leading to death of native bone cells (osteocytes, osteoblasts, osteoclasts and mesenchymal stem cells). Osteocytes are believed to be the orchestrators of bone remodeling, which recruit nearby osteoclast and osteoblasts to control resorption and bone growth in response to mechanical stimuli and physical damage. However, whether heat-induced osteocyte damage can directly elicit bone remodelling has yet to be determined. This study establishes the link between osteocyte thermal damage and the remodeling cascade. We show that osteocytes directly exposed to thermal elevations (47°C for 1 minute) become significantly apoptotic and alter the expression of osteogenic genes (Opg and Cox2). The Rankl/Opg ratio is consistently down-regulated, at days 1, 3 and 7 in MLO-Y4s heat-treated to 47°C for 1 minute. Additionally, the pro-osteoblastogenic signaling marker Cox2 is significantly up-regulated in heat-treated MLO-Y4s by day 7. Furthermore, secreted factors from heat-treated MLO-Y4s administered to MSCs using a novel co-culture system are shown to activate pre-osteoblastic MSCs to increase production of the pro-osteoblastic differentiation marker, alkaline phosphatase (day 7, 14), and calcium deposition (day 21). Most interestingly, an initial pro-osteoclastogenic signaling response (increase Rankl and Rankl/Opg ratio at day 1) followed by later stage pro-osteoblastogenic signaling (down-regulation in Rankl and the Rankl/Opg ratio and an up-regulation in Opg and Cox2 by day 7) was observed in non-heat-treated MLO-Y4s in co-culture when these were exposed to the biochemicals produced by heat-treated MLO-Y4s. Taken together, these results elucidate the vital role of osteocytes in detecting and responding to thermal damage by means of thermally induced apoptosis

  19. Thermally induced osteocyte damage initiates a remodelling signaling cascade.

    PubMed

    Dolan, Eimear B; Haugh, Matthew G; Voisin, Muriel C; Tallon, David; McNamara, Laoise M

    2015-01-01

    Thermal elevations experienced by bone during orthopaedic procedures, such as cutting and drilling, exothermal reactions from bone cement, and thermal therapies such as tumor ablation, can result in thermal damage leading to death of native bone cells (osteocytes, osteoblasts, osteoclasts and mesenchymal stem cells). Osteocytes are believed to be the orchestrators of bone remodeling, which recruit nearby osteoclast and osteoblasts to control resorption and bone growth in response to mechanical stimuli and physical damage. However, whether heat-induced osteocyte damage can directly elicit bone remodelling has yet to be determined. This study establishes the link between osteocyte thermal damage and the remodeling cascade. We show that osteocytes directly exposed to thermal elevations (47°C for 1 minute) become significantly apoptotic and alter the expression of osteogenic genes (Opg and Cox2). The Rankl/Opg ratio is consistently down-regulated, at days 1, 3 and 7 in MLO-Y4s heat-treated to 47°C for 1 minute. Additionally, the pro-osteoblastogenic signaling marker Cox2 is significantly up-regulated in heat-treated MLO-Y4s by day 7. Furthermore, secreted factors from heat-treated MLO-Y4s administered to MSCs using a novel co-culture system are shown to activate pre-osteoblastic MSCs to increase production of the pro-osteoblastic differentiation marker, alkaline phosphatase (day 7, 14), and calcium deposition (day 21). Most interestingly, an initial pro-osteoclastogenic signaling response (increase Rankl and Rankl/Opg ratio at day 1) followed by later stage pro-osteoblastogenic signaling (down-regulation in Rankl and the Rankl/Opg ratio and an up-regulation in Opg and Cox2 by day 7) was observed in non-heat-treated MLO-Y4s in co-culture when these were exposed to the biochemicals produced by heat-treated MLO-Y4s. Taken together, these results elucidate the vital role of osteocytes in detecting and responding to thermal damage by means of thermally induced apoptosis

  20. Anchor-induced chondral damage in the hip

    PubMed Central

    Matsuda, Dean K.; Bharam, Srino; White, Brian J.; Matsuda, Nicole A.; Safran, Marc

    2015-01-01

    The purpose of this study is to investigate the outcomes from anchor-induced chondral damage of the hip, both with and without frank chondral penetration. A multicenter retrospective case series was performed of patients with chondral deformation or penetration during initial hip arthroscopic surgery. Intra-operative findings, post-surgical clinical courses, hip outcome scores and descriptions of arthroscopic treatment in cases requiring revision surgery and anchor removal are reported. Five patients (three females) of mean age 32 years (range, 16–41 years) had documented anchor-induced chondral damage with mean 3.5 years (range, 1.5–6.0 years) follow-up. The 1 o'clock position (four cases) and anterior and mid-anterior portals (two cases each) were most commonly implicated. Two cases of anchor-induced acetabular chondral deformation without frank penetration had successful clinical and radiographic outcomes, while one case progressed from deformation to chondral penetration with clinical worsening. Of the cases that underwent revision hip arthroscopy, all three had confirmed exposed hard anchors which were removed. Two patients have had clinical improvement and one patient underwent early total hip arthroplasty. Anchor-induced chondral deformation without frank chondral penetration may be treated with close clinical and radiographic monitoring with a low threshold for revision surgery and anchor removal. Chondral penetration should be treated with immediate removal of offending hard anchor implants. Preventative measures include distal-based portals, small diameter and short anchors, removable hard anchors, soft suture-based anchors, curved drill and anchor insertion instrumentation and attention to safe trajectories while visualizing the acetabular articular surface. PMID:27011815

  1. Anchor-induced chondral damage in the hip.

    PubMed

    Matsuda, Dean K; Bharam, Srino; White, Brian J; Matsuda, Nicole A; Safran, Marc

    2015-01-01

    The purpose of this study is to investigate the outcomes from anchor-induced chondral damage of the hip, both with and without frank chondral penetration. A multicenter retrospective case series was performed of patients with chondral deformation or penetration during initial hip arthroscopic surgery. Intra-operative findings, post-surgical clinical courses, hip outcome scores and descriptions of arthroscopic treatment in cases requiring revision surgery and anchor removal are reported. Five patients (three females) of mean age 32 years (range, 16-41 years) had documented anchor-induced chondral damage with mean 3.5 years (range, 1.5-6.0 years) follow-up. The 1 o'clock position (four cases) and anterior and mid-anterior portals (two cases each) were most commonly implicated. Two cases of anchor-induced acetabular chondral deformation without frank penetration had successful clinical and radiographic outcomes, while one case progressed from deformation to chondral penetration with clinical worsening. Of the cases that underwent revision hip arthroscopy, all three had confirmed exposed hard anchors which were removed. Two patients have had clinical improvement and one patient underwent early total hip arthroplasty. Anchor-induced chondral deformation without frank chondral penetration may be treated with close clinical and radiographic monitoring with a low threshold for revision surgery and anchor removal. Chondral penetration should be treated with immediate removal of offending hard anchor implants. Preventative measures include distal-based portals, small diameter and short anchors, removable hard anchors, soft suture-based anchors, curved drill and anchor insertion instrumentation and attention to safe trajectories while visualizing the acetabular articular surface. PMID:27011815

  2. Tumor necrosis factor induces glomerular damage in the rabbit.

    PubMed Central

    Bertani, T.; Abbate, M.; Zoja, C.; Corna, D.; Perico, N.; Ghezzi, P.; Remuzzi, G.

    1989-01-01

    Tumor necrosis factor (TNF) is a polypeptide hormone produced by activated macrophages detectable in the circulation of experimental animals given endotoxin. Recent evidence strongly suggests that many of the deleterious effects of endotoxin in experimental animals are mediated by TNF. Because endotoxemia in experimental animals and humans is associated with glomerular damage the present investigation was designed to establish whether TNF directly induces glomerular functional and structural changes. Twenty-three rabbits were given human recombinant TNF at the doses of 0.08, 0.8, and 8.0 micrograms/kg/h as a continuous 5-hour intravenous infusion. Animals were killed at the end of the infusion. All rabbits given 0.8 and 8.0 micrograms/kg/h TNF developed anemia (Ht value decrease at 5 hours: 0.8 microgram/kg/h, 15%; 8.0 micrograms/kg/h, 16%); leukopenia (leukocyte count decrease at 5 hours: 0.8 micrograms/kg/h, 47%; 8.0 micrograms/kg/h, 59%); thrombocytopenia (platelet count decrease at 5 hours; 0.8 micrograms/kg/h, 45%; 8.0 micrograms/kg/h, 57%). Rabbits given 8.0 micrograms/kg/h also had renal failure (serum creatinine from 1.02 +/- 0.15 to 1.64 +/- 0.34 mg/dl). By light microscopy only occasional polymorphonuclear leukocytes in the glomerular capillaries were detectable in rabbits infused with 0.08 micrograms/kg/h TNF, whereas with 0.8 micrograms/kg/h TNF the presence of inflammatory cells in the glomerular capillaries was the prominent finding. With 8.0 micrograms/kg/h TNF beside leukocyte accumulation, fibrin was detected in the glomerular capillary lumens of two of eight animals. Electron microscopy found dose-dependent glomerular endothelial cell damage in animals given TNF with fibrinlike material in the capillary lumens. Glomerular changes induced by TNF were remarkably similar to those previously found in animals given endotoxin. Thus, TNF is likely to be the mediator of endotoxin-induced glomerular damage and can be regarded as a new mediator of

  3. Laser induced damage in optical materials: tenth ASTM symposium.

    PubMed

    Glass, A J; Guenther, A H

    1979-07-01

    The tenth annual Symposium on Optical Materials for High Power Lasers (Boulder Damage Symposium) was held at the National Bureau of Standards in Boulder, Colorado, 12-14 September 1978. The symposium was held under the auspices of ASTM Committee F-1, Subcommittee on Laser Standards, with the joint sponsorship of NBS, the Defense Advanced Research Project Agency, the Department of Energy, and the Office of Naval Research. About 175 scientists attended, including representatives of the United Kingdom, France, Canada, Japan, West Germany, and the Soviet Union. The symposium was divided into sessions concerning the measurement of absorption characteristics, bulk material properties, mirrors and surfaces, thin film damage, coating materials and design, and breakdown phenomena. As in previous years, the emphasis of the papers presented was directed toward new frontiers and new developments. Particular emphasis was given to materials for use from 10.6 microm to the UV region. Highlights included surface characterization, thin film-substrate boundaries, and advances in fundamental laser-matter threshold interactions and mechanisms. The scaling of damage thresholds with pulse duration, focal area, and wavelength was also discussed. In commemoration of the tenth symposium in this series, a number of comprehensive review papers were presented to assess the state of the art in various facets of laser induced damage in optical materials. Alexander J. Glass of Lawrence Livermore Laboratory and Arthur H. Guenther of the Air Force Weapons Laboratory were co-chairpersons. The eleventh annual symposium is scheduled for 30-31 October 1979 at the National Bureau of Standards, Boulder, Colorado. PMID:20212622

  4. Investigation of possible fs-LASIK induced retinal damage

    NASA Astrophysics Data System (ADS)

    Schumacher, S.; Sander, M.; Stolte, A.; Doepke, C.; Baumgaertner, W.; Lubatschowski, H.

    2006-02-01

    Rapid development of new laser technologies enabled the application of ultra short lasers in refractive surgery. Focused ultra short laser pulses in near-infrared spectral range can generate a laser induced breakdown (LIB) in the cornea, which will disrupt the tissue. Cutting depth and position can be established by varying the laser focus. The fs-LASIK technique allows both flap and lenticule to be formed by using fs-pulses without the presence of any mechanical impact. During the cutting process not all of the pulse energy is deposited into the cornea; approximately half of the remaining energy propagates through the eye and reaches the retina. Though defocused, the transmitted energy can still induce damage to the retina due to absorption by the retinal pigment epithelium and the transfer of thermal energy to surrounding tissue. The fs-LASIK process was simulated with two laser systems; one continous-wave and one in the fs-regime. For the simulation the exposure time and focusing numerical aperature which defines the retinal spot size were varied. The Damage thresholds of the laser beam exposed eyes were determined in terms of ophthalmoscopic and histopathologic observations.

  5. Immunosuppressive treatment protects against angiotensin II-induced renal damage.

    PubMed

    Muller, Dominik N; Shagdarsuren, Erdenechimeg; Park, Joon-Keun; Dechend, Ralf; Mervaala, Eero; Hampich, Franziska; Fiebeler, Anette; Ju, Xinsheng; Finckenberg, Piet; Theuer, Jürgen; Viedt, Christiane; Kreuzer, Joerg; Heidecke, Harald; Haller, Hermann; Zenke, Martin; Luft, Friedrich C

    2002-11-01

    Angiotensin (Ang) II promotes renal infiltration by immunocompetent cells in double-transgenic rats (dTGRs) harboring both human renin and angiotensinogen genes. To elucidate disease mechanisms, we investigated whether or not dexamethasone (DEXA) immunosuppression ameliorates renal damage. Untreated dTGRs developed hypertension, renal damage, and 50% mortality at 7 weeks. DEXA reduced albuminuria, renal fibrosis, vascular reactive oxygen stress, and prevented mortality, independent of blood pressure. In dTGR kidneys, p22phox immunostaining co-localized with macrophages and partially with T cells. dTGR dendritic cells expressed major histocompatibility complex II and CD86, indicating maturation. DEXA suppressed major histocompatibility complex II+, CD86+, dendritic, and T-cell infiltration. In additional experiments, we treated dTGRs with mycophenolate mofetil to inhibit T- and B-cell proliferation. Reno-protective actions of mycophenolate mofetil and its effect on dendritic and T cells were similar to those obtained with DEXA. We next investigated whether or not Ang II directly promotes dendritic cell maturation in vitro. Ang II did not alter CD80, CD83, and MHC II expression, but increased CCR7 expression and cell migration. To explore the role of tumor necrosis factor (TNF)-alpha on dendritic cell maturation in vivo, we treated dTGRs with the soluble TNF-alpha receptor etanercept. This treatment had no effect on blood pressure, but decreased albuminuria, nuclear factor-kappaB activation, and infiltration of all immunocompetent cells. These data suggest that immunosuppression prevents dendritic cell maturation and T-cell infiltration in a nonimmune model of Ang II-induced renal damage. Ang II induces dendritic migration directly, whereas in vivo TNF-alpha is involved in dendritic cell infiltration and maturation. Thus, Ang II may initiate events leading to innate and acquired immune response. PMID:12414515

  6. Immunosuppressive Treatment Protects Against Angiotensin II-Induced Renal Damage

    PubMed Central

    Muller, Dominik N.; Shagdarsuren, Erdenechimeg; Park, Joon-Keun; Dechend, Ralf; Mervaala, Eero; Hampich, Franziska; Fiebeler, Anette; Ju, Xinsheng; Finckenberg, Piet; Theuer, Jürgen; Viedt, Christiane; Kreuzer, Joerg; Heidecke, Harald; Haller, Hermann; Zenke, Martin; Luft, Friedrich C.

    2002-01-01

    Angiotensin (Ang) II promotes renal infiltration by immunocompetent cells in double-transgenic rats (dTGRs) harboring both human renin and angiotensinogen genes. To elucidate disease mechanisms, we investigated whether or not dexamethasone (DEXA) immunosuppression ameliorates renal damage. Untreated dTGRs developed hypertension, renal damage, and 50% mortality at 7 weeks. DEXA reduced albuminuria, renal fibrosis, vascular reactive oxygen stress, and prevented mortality, independent of blood pressure. In dTGR kidneys, p22phox immunostaining co-localized with macrophages and partially with T cells. dTGR dendritic cells expressed major histocompatibility complex II and CD86, indicating maturation. DEXA suppressed major histocompatibility complex II+, CD86+, dendritic, and T-cell infiltration. In additional experiments, we treated dTGRs with mycophenolate mofetil to inhibit T- and B-cell proliferation. Reno-protective actions of mycophenolate mofetil and its effect on dendritic and T cells were similar to those obtained with DEXA. We next investigated whether or not Ang II directly promotes dendritic cell maturation in vitro. Ang II did not alter CD80, CD83, and MHC II expression, but increased CCR7 expression and cell migration. To explore the role of tumor necrosis factor (TNF)-α on dendritic cell maturation in vivo, we treated dTGRs with the soluble TNF-α receptor etanercept. This treatment had no effect on blood pressure, but decreased albuminuria, nuclear factor-κB activation, and infiltration of all immunocompetent cells. These data suggest that immunosuppression prevents dendritic cell maturation and T-cell infiltration in a nonimmune model of Ang II-induced renal damage. Ang II induces dendritic migration directly, whereas in vivo TNF-α is involved in dendritic cell infiltration and maturation. Thus, Ang II may initiate events leading to innate and acquired immune response. PMID:12414515

  7. Ligustrazine effect on lipopolysaccharide-induced pulmonary damage in rats.

    PubMed

    Wang, Huiqi; Chen, Yuanzhuo; Li, Wenjie; Li, Congye; Zhang, Xiangyu; Peng, Hu; Gao, Chengjin

    2015-09-01

    We investigated the effectiveness of ligustrazine (tetramethylpyrazine, TMP) in alleviating pulmonary damage induced by lipopolysaccharide (LPS). Twenty-four healthy male Sprague-Dawley rats were randomly divided into three groups: the blank group, LPS group, and TMP treatment group (TMP group). The LPS group was intraperitoneally injected with LPS (20mg/kg), and the TMP group was intraperitoneally injected with LPS (20mg/kg) and ligustrazine (80mg/kg). Blood gas analysis, hematoxylin-eosin staining dye extravasation and diffuse alveolar damage (DAD) score, the wet/dry lung tissue (W/D) ratios, the expression of CD31+ vascular endothelial microparticles (EMPs), tumor necrosis factor alpha (TNF-α) levels, and the protein expression of Rho-associated coiled-coil-forming protein kinase (ROCK) II and Toll-like receptor 4 (TLR4) were analyzed. Compared with the blank group, the arterial partial pressure of oxygen (PaO2) declined in both 1 and 4h (P<0.01), the W/D ratio and DAD score increased (P<0.01), and the TNF-α levels in serum, CD31+ EMPs, and protein expression of ROCK II and TLR4 were significantly increased (P<0.01) in the LPS group. Compared with the LPS group, PaO2 significantly increased in the TMP group at 4h (P<0.05), while the W/D ratio and DAD score were significantly decreased in the TMP group (P<0.01). TNF-α levels, CD31+ EMPs, and protein expression of ROCK II and TLR4 were significantly decreased in the TMP group compared with the LPS group (P<0.01). This study demonstrated that TMP can alleviate LPS-induced pulmonary damage by attenuating pulmonary vascular permeability and CD31+ EMP levels in the plasma, reducing the release of the inflammatory mediator TNF-α and inhibiting the protein expression of ROCK II and TLR4. PMID:26088147

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

    PubMed

    Lyckesvärd, Madeleine Nordén; Delle, Ulla; Kahu, Helena; Lindegren, Sture; Jensen, Holger; Bäck, Tom; Swanpalmer, John; Elmroth, Kecke

    2014-07-01

    Childhood exposure to ionizing radiation increases the risk of developing thyroid cancer later in life and this is suggested to be due to higher proliferation of the young thyroid. The interest of using high-LET alpha particles from Astatine-211 ((211)At), concentrated in the thyroid by the same 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 levels of γH2AX decreased during the first 24h in both cycling and stationary cultures and complete repair was seen in all cultures but cycling cells exposed to (211)At. Compared to stationary cells alpha particles were more harmful for cycling cultures, an effect also seen at the pChk2 levels. 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 cultures at a modest level of damage, clearly demonstrating that cell cycle status influences the relative effectiveness of alpha particles. PMID:24769180

  9. Quantitative Analysis of Clustered DNA Damages Induced by Silicon Beams of Different Kinetic Energy

    SciTech Connect

    Keszenman D. J.; Keszenman, D.J.; Bennett, P.V.; Sutherland, B.M.; Wilson, P.F.

    2013-05-14

    Humans may b exposed to highly energetic charged particle radiation as a result of medical treatments, occupational activitie or accidental events. In recent years, our increasing presence and burgeoning interest in space exploration beyond low Earth orbit has led to a large increase in the research of the biological effects ofcharged particle radiation typical of that encountered in the space radiation environment. The study of the effects of these types of radiation qualities in terms ofDNA damage induction and repair is fundamental to understand mechanisms both underlying their greater biological effectiveness as we)) as the short and long term risks of health effects such as carcinogenesis, degen rative diseases and premature aging. Charged particle radiation induces a variety of DNA alterations, notably bistranded clustered damages, defined as two or more closely-opposed strand break , oxidized bases or abasic sites within a few helical turns. The induction of such highly complex DNA damage enhances the probability of incorrect or incomplete repair and thus constitutes greater potential for genomic instability, cell death and transformation.

  10. Relative biological damage and electron fluence in and out of a 6 MV photon field

    NASA Astrophysics Data System (ADS)

    Syme, A.; Kirkby, C.; Mirzayans, R.; Mac Kenzie, M.; Field, C.; Fallone, B. G.

    2009-11-01

    Scattered radiation in the penumbra of a megavoltage radiation therapy beam can deposit a non-negligible dose in the healthy tissue around a target volume. The lower energy of the radiation in this region suggests that its biological effectiveness might not be the same as that of the open beam. In this work, we determined the relative biological damage in normal human fibroblasts after megavoltage irradiation in two geometries. The first was an open-beam irradiation and the second was a blocked configuration in which only scattered radiation could reach the target cells. The biological damage was evaluated by the γ-H2AX immunofluorescence assay, which is capable of detecting DNA double-strand breaks in individual cells. We report that the scattered radiation is more effective at producing biological damage than the open beam radiation. We found a 27% enhancement in the net mean nuclear γ-H2AX fluorescence intensity at 2 Gy and a 48% enhancement at 4 Gy. These findings are of interest due to the increased doses of penumbral radiation close to target volumes both in dose escalation studies and in IMRT treatment deliveries where high dose gradients exist for the purpose of conformal avoidance of healthy tissues.

  11. TRPM2 channels mediate acetaminophen-induced liver damage.

    PubMed

    Kheradpezhouh, Ehsan; Ma, Linlin; Morphett, Arthur; Barritt, Greg J; Rychkov, Grigori Y

    2014-02-25

    Acetaminophen (paracetamol) is the most frequently used analgesic and antipyretic drug available over the counter. At the same time, acetaminophen overdose is the most common cause of acute liver failure and the leading cause of chronic liver damage requiring liver transplantation in developed countries. Acetaminophen overdose causes a multitude of interrelated biochemical reactions in hepatocytes including the formation of reactive oxygen species, deregulation of Ca(2+) homeostasis, covalent modification and oxidation of proteins, lipid peroxidation, and DNA fragmentation. Although an increase in intracellular Ca(2+) concentration in hepatocytes is a known consequence of acetaminophen overdose, its importance in acetaminophen-induced liver toxicity is not well understood, primarily due to lack of knowledge about the source of the Ca(2+) rise. Here we report that the channel responsible for Ca(2+) entry in hepatocytes in acetaminophen overdose is the Transient Receptor Potential Melanostatine 2 (TRPM2) cation channel. We show by whole-cell patch clamping that treatment of hepatocytes with acetaminophen results in activation of a cation current similar to that activated by H2O2 or the intracellular application of ADP ribose. siRNA-mediated knockdown of TRPM2 in hepatocytes inhibits activation of the current by either acetaminophen or H2O2. In TRPM2 knockout mice, acetaminophen-induced liver damage, assessed by the blood concentration of liver enzymes and liver histology, is significantly diminished compared with wild-type mice. The presented data strongly suggest that TRPM2 channels are essential in the mechanism of acetaminophen-induced hepatocellular death. PMID:24569808

  12. DNA damage-induced translocation of S100A11 into the nucleus regulates cell proliferation

    PubMed Central

    2010-01-01

    Background Proteins are able to react in response to distinct stress stimuli by alteration of their subcellular distribution. The stress-responsive protein S100A11 belongs to the family of multifunctional S100 proteins which have been implicated in several key biological processes. Previously, we have shown that S100A11 is directly involved in DNA repair processes at damaged chromatin in the nucleus. To gain further insight into the underlying mechanism subcellular trafficking of S100A11 in response to DNA damage was analyzed. Results We show that DNA damage induces a nucleolin-mediated translocation of S100A11 from the cytoplasm into the nucleus. This translocation is impeded by inhibition of the phosphorylation activity of PKCα. Translocation of S100A11 into the nucleus correlates with an increased cellular p21 protein level. Depletion of nucleolin by siRNA severely impairs translocation of S100A11 into the nucleus resulting in a decreased p21 protein level. Additionally, cells lacking nucleolin showed a reduced colony forming capacity. Conclusions These observations suggest that regulation of the subcellular distribution of S100A11 plays an important role in the DNA damage response and p21-mediated cell cycle control. PMID:21167017

  13. Amorphous nanosilica induce endocytosis-dependent ROS generation and DNA damage in human keratinocytes

    PubMed Central

    2011-01-01

    Background Clarifying the physicochemical properties of nanomaterials is crucial for hazard assessment and the safe application of these substances. With this in mind, we analyzed the relationship between particle size and the in vitro effect of amorphous nanosilica (nSP). Specifically, we evaluated the relationship between particle size of nSP and the in vitro biological effects using human keratinocyte cells (HaCaT). Results Our results indicate that exposure to nSP of 70 nm diameter (nSP70) induced an elevated level of reactive oxygen species (ROS), leading to DNA damage. A markedly reduced response was observed using submicron-sized silica particles of 300 and 1000 nm diameter. In addition, cytochalasin D-treatment reduced nSP70-mediated ROS generation and DNA damage, suggesting that endocytosis is involved in nSP70-mediated cellular effects. Conclusions Thus, particle size affects amorphous silica-induced ROS generation and DNA damage of HaCaT cells. We believe clarification of the endocytosis pathway of nSP will provide useful information for hazard assessment as well as the design of safer forms of nSPs. PMID:21235812

  14. Effects of Lipoic Acid on Acrylamide Induced Testicular Damage

    PubMed Central

    Lebda, Mohamed; Gad, Shereen; Gaafar, Hossam

    2014-01-01

    Introduction: Acrylamide is very toxic to various organs and associated with significant increase of oxidative stress and depletion of antioxidants. Alpha-lipoic acid enhances cellular antioxidant defense capacity, thereby protecting cells from oxidative stress. Aim of the study: This study aimed to evaluate the protective role of alpha-lipoic acid on the oxidative damage induced by acrylamide in testicular and epididymal tissues. Material and methods: Forty adult male rats were divided into four groups (10 rats each). Control group; acrylamide treated group administered acrylamide 0.05% (w/v) in drinking water for 21 days; alpha-lipoic acid group received basal diet supplemented with 1% alpha-lipoic acid and forth group was exposed to acrylamide and treated with alpha-lipoic acid at the same doses and treatment regimen mentioned before. Results: The administration of acrylamide resulted in significant elevation in testicular and epididymal malondialdehyde level (MDA) and significant reduction in the level of reduced glutathione (GSH) and the activities of glutathione-S-transferase (GST), glutathione peroxidase (GPX) and glutathione reductase (GR). Also, acrylamide significantly reduced serum total testosterone and progesterone but increased estradiol (E2) levels. Treatment with alpha-lipoic acid prior to acrylamide induced protective effects and attenuated these biochemical changes. Conclusion: Alpha-lipoic acid has been shown to possess antioxidant properties offering promising efficacy against oxidative stress induced by acrylamide administration. PMID:25126019

  15. Do hyperbaric oxygen-induced seizures cause brain damage?

    PubMed

    Domachevsky, Liran; Pick, Chaim G; Arieli, Yehuda; Krinsky, Nitzan; Abramovich, Amir; Eynan, Mirit

    2012-06-01

    It is commonly accepted that hyperbaric oxygen-induced seizures, the most severe manifestation of central nervous system oxygen toxicity, are harmless. However, this hypothesis has not been investigated in depth. We used apoptotic markers to determine whether cells in the cortex and hippocampus were damaged by hyperbaric oxygen-induced seizures in mice. Experimental animals were exposed to a pressure of 6 atmospheres absolute breathing oxygen, and were randomly assigned to two groups sacrificed 1h after the appearance of seizures or 7 days later. Control groups were not exposed to hyperbaric oxygen. Caspase 9, caspase 3, and cytochrome c were used as apoptotic markers. These were measured in the cortex and the hippocampus, and compared between the groups. Levels of caspase 3, cytochrome c, and caspase 9 in the hippocampus were significantly higher in the hyperbaric oxygenexposed groups compared with the control groups 1 week after seizures (p<0.01). The levels of two fragments of caspase 9 in the cortex were higher in the control group compared with the hyperbaric oxygen-exposed group 1h after seizures (p<0.01). Hyperbaric oxygen-induced seizures activate apoptosis in the mouse hippocampus. The reason for the changes in the cortex is not understood. Further investigation is necessary to elucidate the mechanism underlying these findings and their significance. PMID:22293507

  16. Ebselen attenuates cadmium-induced testicular damage in mice.

    PubMed

    Ardais, Ana P; Santos, Francielli W; Nogueira, Cristina W

    2008-04-01

    This study was designed to examine if ebselen, an organoselenium compound with antioxidant and glutathione peroxidase-mimetic properties, attenuates testicular injury caused by intraperitoneal administration of CdCl(2). A number of toxicological parameters were evaluated in the testes of mice, such as delta-aminolevulinic acid dehydratase (delta-ALA-D) activity, lipid peroxidation, ascorbic acid levels and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Ebselen attenuated lipid peroxidation levels altered by CdCl(2). delta-ALA-D activity inhibited by the highest dose of CdCl(2) was attenuated by ebselen. A significant negative correlation between lipid peroxidation levels and delta-ALA-D activity was observed. Ebselen restored ascorbic acid levels reduced by CdCl(2). A significant negative correlation between ascorbic acid levels and delta-ALA-D activity reinforces the idea that ebselen attenuated the damage induced by CdCl(2) via its antioxidant property. The significant correlation between ALT and delta-ALA-D activity supports the assumption that ebselen prevented damage caused by CdCl(2). The results show that ebselen attenuated oxidative stress, a process important for CdCl(2) toxicity. PMID:17624921

  17. Liposomal Antioxidants for Protection against Oxidant-Induced Damage

    PubMed Central

    Suntres, Zacharias E.

    2011-01-01

    Reactive oxygen species (ROS), including superoxide anion, hydrogen peroxide, and hydroxyl radical, can be formed as normal products of aerobic metabolism and can be produced at elevated rates under pathophysiological conditions. Overproduction and/or insufficient removal of ROS result in significant damage to cell structure and functions. In vitro studies showed that antioxidants, when applied directly and at relatively high concentrations to cellular systems, are effective in conferring protection against the damaging actions of ROS, but results from animal and human studies showed that several antioxidants provide only modest benefit and even possible harm. Antioxidants have yet to be rendered into reliable and safe therapies because of their poor solubility, inability to cross membrane barriers, extensive first-pass metabolism, and rapid clearance from cells. There is considerable interest towards the development of drug-delivery systems that would result in the selective delivery of antioxidants to tissues in sufficient concentrations to ameliorate oxidant-induced tissue injuries. Liposomes are biocompatible, biodegradable, and nontoxic artificial phospholipid vesicles that offer the possibility of carrying hydrophilic, hydrophobic, and amphiphilic molecules. This paper focus on the use of liposomes for the delivery of antioxidants in the prevention or treatment of pathological conditions related to oxidative stress. PMID:21876690

  18. Laser-induced damage measurements with 266-nm pulses

    NASA Astrophysics Data System (ADS)

    Deaton, T. F.; Smith, W. L.

    1980-07-01

    Results of a survey of laser-induced damage thresholds for optical components at 266-nm are reported. The thresholds were measured at two pulse durations; 0.150 ns and 1.0 ns. The 30 samples tested include four commercial dielectric reflectors, three metallic reflectors, two anti-reflection films, a series of eight half-wave oxide and fluoride films, and twelve bare surfaces (fluoride crystals, silica, sapphire, BK-7 glass, cesium dideuterium arsenate and potassium dihydrogen phosphate). The 266-nm pulses were obtained by frequency-quadrupling a Nd:YAG, glass laser. Equivalent plane imagery and calorimetry were used to measure the peak fluence of each of the UV pulses with an accuracy of + or - of 15%; the uncertainty in the threshold determinations is typically + or - 30%.

  19. Sonic-boom-induced building structure responses including damage.

    NASA Technical Reports Server (NTRS)

    Clarkson, B. L.; Mayes, W. H.

    1972-01-01

    Concepts of sonic-boom pressure loading of building structures and the associated responses are reviewed, and results of pertinent theoretical and experimental research programs are summarized. The significance of sonic-boom load time histories, including waveshape effects, are illustrated with the aid of simple structural elements such as beams and plates. Also included are discussions of the significance of such other phenomena as three-dimensional loading effects, air cavity coupling, multimodal responses, and structural nonlinearities. Measured deflection, acceleration, and strain data from laboratory models and full-scale building tests are summarized, and these data are compared, where possible, with predicted values. Damage complaint and claim experience due both to controlled and uncontrolled supersonic flights over communities are summarized with particular reference to residential, commercial, and historic buildings. Sonic-boom-induced building responses are compared with those from other impulsive loadings due to natural and cultural events and from laboratory simulation tests.

  20. Oxidant conditioning protects cartilage from mechanically induced damage.

    PubMed

    Ramakrishnan, Prem; Hecht, Benjamin A; Pedersen, Douglas R; Lavery, Matthew R; Maynard, Jerry; Buckwalter, Joseph A; Martin, James A

    2010-07-01

    Articular cartilage degeneration in osteoarthritis has been linked to abnormal mechanical stresses that are known to cause chondrocyte apoptosis and metabolic derangement in in vitro models. Evidence implicating oxidative damage as the immediate cause of these harmful effects suggests that the antioxidant defenses of chondrocytes might influence their tolerance for mechanical injury. Based on evidence that antioxidant defenses in many cell types are stimulated by moderate oxidant exposure, we hypothesized that oxidant preconditioning would reduce acute chondrocyte death and proteoglycan depletion in cartilage explants after exposure to abnormal mechanical stresses. Porcine cartilage explants were treated every 48 h with tert-butyl hydrogen peroxide (tBHP) at nonlethal concentrations (25, 100, 250, and 500 microM) for a varying number of times (one, two, or four) prior to a bout of unconfined axial compression (5 MPa, 1 Hz, 1800 cycles). When compared with untreated controls, tBHP had significant positive effects on post-compression viability, lactate production, and proteoglycan losses. Overall, the most effective regime was 100 microM tBHP applied four times. RNA analysis revealed significant effects of 100 microM tBHP on gene expression. Catalase, hypoxia-inducible factor-1alpha (HIF-1alpha), and glyceraldehyde 6-phosphate dehydrogenase (GAPDH) were significantly increased relative to untreated controls in explants treated four times with 100 microM tBHP, a regime that also resulted in a significant decrease in matrix metalloproteinase-3 (MMP-3) expression. These findings demonstrate that repeated exposure of cartilage to sublethal concentrations of peroxide can moderate the acute effects of mechanical stress, a conclusion supported by evidence of peroxide-induced changes in gene expression that could render chondrocytes more resistant to oxidative damage. PMID:20058262

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

    NASA Technical Reports Server (NTRS)

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

    2014-01-01

    used an array of countermeasures (Antioxidant diets and injections) to prevent the radiation-induced bone loss, although these did not prevent bone loss, analysis is ongoing to determine if these countermeasure protected radiation-induced damage to other tissues.

  2. Comparison of Model Calculations of Biological Damage from Exposure to Heavy Ions with Measurements

    NASA Technical Reports Server (NTRS)

    Kim, Myung-Hee Y.; Hada, Megumi; Cucinotta, Francis A.; Wu, Honglu

    2014-01-01

    The space environment consists of a varying field of radiation particles including high-energy ions, with spacecraft shielding material providing the major protection to astronauts from harmful exposure. Unlike low-LET gamma or X rays, the presence of shielding does not always reduce the radiation risks for energetic charged-particle exposure. Dose delivered by the charged particle increases sharply at the Bragg peak. However, the Bragg curve does not necessarily represent the biological damage along the particle path since biological effects are influenced by the track structures of both primary and secondary particles. Therefore, the ''biological Bragg curve'' is dependent on the energy and the type of the primary particle and may vary for different biological end points. Measurements of the induction of micronuclei (MN) have made across the Bragg curve in human fibroblasts exposed to energetic silicon and iron ions in vitro at two different energies, 300 MeV/nucleon and 1 GeV/nucleon. Although the data did not reveal an increased yield of MN at the location of the Bragg peak, the increased inhibition of cell progression, which is related to cell death, was found at the Bragg peak location. These results are compared to the calculations of biological damage using a stochastic Monte-Carlo track structure model, Galactic Cosmic Ray Event-based Risk Model (GERM) code (Cucinotta, et al., 2011). The GERM code estimates the basic physical properties along the passage of heavy ions in tissue and shielding materials, by which the experimental set-up can be interpreted. The code can also be used to describe the biophysical events of interest in radiobiology, cancer therapy, and space exploration. The calculation has shown that the severely damaged cells at the Bragg peak are more likely to go through reproductive death, the so called "overkill".

  3. Depth position recognition-related laser-induced damage test method based on initial transient damage features.

    PubMed

    Ma, Bin; Lu, Menglei; Wang, Ke; Zhang, Li; Jiao, Hongfei; Cheng, Xinbin; Wang, Zhanshan

    2016-08-01

    Even absorptive defects or inner cracks hiding several micrometers to a few dozen micrometers beneath the top surface can induce damage to transmission elements in the ultraviolet band. The extremely small size and disordered state of such defects or cracks hinder their detection using conventional methods. Therefore, the diagnosis of factors that limit damage resistance performance is a key technique for improving the fabrication technology of optical elements. With a focus on laser damage to third-harmonic transmission elements, this study establishes a micron space-resolved and nanosecond time-resolved imaging system on the basis of the pump-probe detection technique. The changes in the properties of defect-induced laser damage in the time domain are clarified. A diagnostic method for original damage depth in micron precision is proposed according to damage behaviors. This method can retrieve initial information on damage inducement and depth position. The recognition and diagnostic capabilities of such a technique are calibrated with artificial samples and then used to analyze real samples. PMID:27505738

  4. Exposure to 50Hz-sinusoidal electromagnetic field induces DNA damage-independent autophagy.

    PubMed

    Shen, Yunyun; Xia, Ruohong; Jiang, Hengjun; Chen, Yanfeng; Hong, Ling; Yu, Yunxian; Xu, Zhengping; Zeng, Qunli

    2016-08-01

    As electromagnetic field (EMF) is commonly encountered within our daily lives, the biological effects of EMF are of great concern. Autophagy is a key process for maintaining cellular homeostasis, and it can also reveal cellular responses to environmental stimuli. In this study, we aim to investigate the biological effects of a 50Hz-sinusoidal electromagnetic field on autophagy and we identified its mechanism of action in Chinese Hamster Lung (CHL) cells. CHL cells were exposed to a 50Hz sinusoidal EMF at 0.4mT for 30min or 24h. In this study, we found that a 0.4mT EMF resulted in: (i) an increase in LC3-II expression and increased autophagosome formation; (ii) no significant difference in the incidence of γH2AX foci between the sham and exposure groups; (iii) reorganized actin filaments and increased pseudopodial extensions without promoting cell migration; and (iv) enhanced cell apoptosis when autophagy was blocked by Bafilomycin A1. These results implied that DNA damage was not directly involved in the autophagy induced by a 0.4mT 50Hz EMF. In addition, an EMF induced autophagy balanced the cellular homeostasis to protect the cells from severe adverse biological consequences. PMID:27177844

  5. Acute radiation-induced pulmonary damage: a clinical study on the response to fractionated radiation therapy.

    PubMed

    Mah, K; Van Dyk, J; Keane, T; Poon, P Y

    1987-02-01

    Acute radiation-induced pulmonary damage can be a significant cause of morbidity in radiation therapy of the thorax. A prospective, clinical study was conducted to obtain dose-response data on acute pulmonary damage caused by fractionated radiation therapy. The endpoint was a visible increase in lung density within the irradiated volume on a computed tomographic (CT) examination as observed independently by three diagnostic radiologists. Fifty-four patients with various malignancies of the thorax completed the study. CT chest scans were taken before and at preselected times following radiotherapy. To represent different fractionation schedules of equivalent biological effect, the estimated single dose (ED) model, ED = D X N-0.377 X T-0.058 was used in which D was the average lung dose within the high dose region in cGy, N was the number of fractions, and T was the overall treatment time in days. Patients were grouped according to ED and the percent incidence of pulmonary damage for each group was determined. Total average lung doses ranged from 29.8 Gy to 53.6 Gy given in 10 to 30 fractions over a range of 12 to 60 days. Five patient groups with incidence ranging from 30% (ED of 930) to 90% (ED of 1150) were obtained. The resulting dose-response curve predicted a 50% incidence level at an ED value (ED50) of 1000 +/- 40 ED units. This value represents fractionation schedules equivalent to a total average lung dose of 32.9 Gy given in 15 fractions over 19 days. Over the linear portion of the dose-response curve, a 5% increase in ED (or total dose if N and T remain constant), predicts a 12% increase in the incidence of acute radiation-induced pulmonary damage. PMID:3818385

  6. Repair and misrepair of heavy-ion-induced chromosomal damage

    NASA Astrophysics Data System (ADS)

    Goodwin, E.; Blakely, E.; Ivery, G.; Tobias, C.

    The premature chromosome condensation (PCC) technique was used to investigate chromosomal damage, repair, and misrepair in the G1 phase of a human/hamster hybrid cell line that contains a single human chromosome. Plateau-phase cell cultures were exposed to either x-rays or a 425 MeV/u beam of neon ions near the Bragg peak where the LET is 183 keV/μm. An in situ hybridization technique coupled to fluorescent staining of PCC spreads confirmed the linearity of the dose response for initial chromatin breakage in the human chromosome to high doses (1600 cGy x-ray or 1062 cGy Ne). On Giemsa-stained slides, initial chromatin breakage in the total genome and the rejoining kinetics of these breaks were determined. As a measure of chromosomal misrepair, ring PCC aberrations were also scored. Ne ions were about 1.5 x more effective per unit dose compared to x-rays at producing the initially measured chromatin breakage. 90% of the x-ray-induced breaks rejoined in cells incubated at 37°C after exposure. In contrast, only 50% of Ne-ion-induced breaks rejoined. In the irradiated G1 cells, ring PCC aberrations increased with time apparently by first order kinetics after either x-ray or Ne exposures. However, far fewer rings formed in Ne-irradiated cells after a dose giving a comparable initial number of chromatin breaks. Following x-ray exposures, the yield of rings formed after long repair times (6 to 9 hrs) fit a quadratic dose-response curve. These results indicate quantitative and qualitative differences in the chromosomal lesions induced by low- and high-LET radiations.

  7. Low Dose Iron Treatments Induce a DNA Damage Response in Human Endothelial Cells within Minutes

    PubMed Central

    Mollet, Inês G.; Giess, Adam; Paschalaki, Koralia; Periyasamy, Manikandan; Lidington, Elaine C.; Mason, Justin C.; Jones, Michael D.; Game, Laurence; Ali, Simak; Shovlin, Claire L.

    2016-01-01

    Background Spontaneous reports from patients able to report vascular sequelae in real time, and recognition that serum non transferrin bound iron may reach or exceed 10μmol/L in the blood stream after iron tablets or infusions, led us to hypothesize that conventional iron treatments may provoke acute vascular injury. This prompted us to examine whether a phenotype could be observed in normal human endothelial cells treated with low dose iron. Methodology Confluent primary human endothelial cells (EC) were treated with filter-sterilized iron (II) citrate or fresh media for RNA sequencing and validation studies. RNA transcript profiles were evaluated using directional RNA sequencing with no pre-specification of target sequences. Alignments were counted for exons and junctions of the gene strand only, blinded to treatment types. Principal Findings Rapid changes in RNA transcript profiles were observed in endothelial cells treated with 10μmol/L iron (II) citrate, compared to media-treated cells. Clustering for Gene Ontology (GO) performed on all differentially expressed genes revealed significant differences in biological process terms between iron and media-treated EC, whereas 10 sets of an equivalent number of randomly selected genes from the respective EC gene datasets showed no significant differences in any GO terms. After 1 hour, differentially expressed genes clustered to vesicle mediated transport, protein catabolism, and cell cycle (Benjamini p = 0.0016, 0.0024 and 0.0032 respectively), and by 6 hours, to cellular response to DNA damage stimulus most significantly through DNA repair genes FANCG, BLM, and H2AFX. Comet assays demonstrated that 10μM iron treatment elicited DNA damage within 1 hour. This was accompanied by a brisk DNA damage response pulse, as ascertained by the development of DNA damage response (DDR) foci, and p53 stabilization. Significance These data suggest that low dose iron treatments are sufficient to modify the vascular endothelium

  8. Zinc protects HepG2 cells against the oxidative damage and DNA damage induced by ochratoxin A

    SciTech Connect

    Zheng, Juanjuan; Zhang, Yu; Xu, Wentao; Luo, YunBo; Hao, Junran; Shen, Xiao Li; Yang, Xuan; Li, Xiaohong; Huang, Kunlun

    2013-04-15

    Oxidative stress and DNA damage are the most studied mechanisms by which ochratoxin A (OTA) induces its toxic effects, which include nephrotoxicity, hepatotoxicity, immunotoxicity and genotoxicity. Zinc, which is an essential trace element, is considered a potential antioxidant. The aim of this paper was to investigate whether zinc supplement could inhibit OTA-induced oxidative damage and DNA damage in HepG2 cells and the mechanism of inhibition. The results indicated that that exposure of OTA decreased the intracellular zinc concentration; zinc supplement significantly reduced the OTA-induced production of reactive oxygen species (ROS) and decrease in superoxide dismutase (SOD) activity but did not affect the OTA-induced decrease in the mitochondrial membrane potential (Δψ{sub m}). Meanwhile, the addition of the zinc chelator N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) strongly aggravated the OTA-induced oxidative damage. This study also demonstrated that zinc helped to maintain the integrity of DNA through the reduction of OTA-induced DNA strand breaks, 8-hydroxy-2′-deoxyguanosine (8-OHdG) formation and DNA hypomethylation. OTA increased the mRNA expression of metallothionein1-A (MT1A), metallothionein2-A (MT2A) and Cu/Zn superoxide dismutase (SOD1). Zinc supplement further enhanced the mRNA expression of MT1A and MT2A, but it had no effect on the mRNA expression of SOD1 and catalase (CAT). Zinc was for the first time proven to reduce the cytotoxicity of OTA through inhibiting the oxidative damage and DNA damage, and regulating the expression of zinc-associated genes. Thus, the addition of zinc can potentially be used to reduce the OTA toxicity of contaminated feeds. - Highlights: ► OTA decreased the intracellular zinc concentration. ► OTA induced the formation of 8-OHdG in HepG2 cells. ► It was testified for the first time that OTA induced DNA hypomethylation. ► Zinc protects against the oxidative damage and DNA damage induced by

  9. Damage-free vibrational spectroscopy of biological materials in the electron microscope

    DOE PAGESBeta

    Rez, Peter; Aoki, Toshihiro; March, Katia; Gur, Dvir; Krivanek, Ondrej L.; Dellby, Niklas; Lovejoy, Tracy C.; Wolf, Sharon G.; Cohen, Hagai

    2016-03-10

    Vibrational spectroscopy in the electron microscope would be transformative in the study of biological samples, provided that radiation damage could be prevented. However, electron beams typically create high-energy excitations that severely accelerate sample degradation. Here this major difficulty is overcome using an ‘aloof’ electron beam, positioned tens of nanometres away from the sample: high-energy excitations are suppressed, while vibrational modes of energies o1 eV can be ‘safely’ investigated. To demonstrate the potential of aloof spectroscopy, we record electron energy loss spectra from biogenic guanine crystals in their native state, resolving their characteristic C–H, N–H and C=O vibrational signatures with nomore » observable radiation damage. Furthermore, the technique opens up the possibility of non-damaging compositional analyses of organic functional groups, including non-crystalline biological materials, at a spatial resolution of ~10nm, simultaneously combined with imaging in the electron microscope.« less

  10. Molecular and sensory mechanisms to mitigate sunlight-induced DNA damage in treefrog tadpoles.

    PubMed

    Schuch, André P; Lipinski, Victor M; Santos, Mauricio B; Santos, Caroline P; Jardim, Sinara S; Cechin, Sonia Z; Loreto, Elgion L S

    2015-10-01

    The increased incidence of solar ultraviolet B (UVB) radiation has been proposed as an environmental stressor, which may help to explain the enigmatic decline of amphibian populations worldwide. Despite growing knowledge regarding the UV-induced biological effects in several amphibian models, little is known about the efficacy of DNA repair pathways. In addition, little attention has been given to the interplay between these molecular mechanisms with other physiological strategies that avoid the damage induced by sunlight. Here, DNA lesions induced by environmental doses of solar UVB and UVA radiation were detected in genomic DNA samples of treefrog tadpoles (Hypsiboas pulchellus) and their DNA repair activity was evaluated. These data were complemented by monitoring the induction of apoptosis in blood cells and tadpole survival. Furthermore, the tadpoles' ability to perceive and escape from UV wavelengths was evaluated as an additional strategy of photoprotection. The results show that tadpoles are very sensitive to UVB light, which could be explained by the slow DNA repair rates for both cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6,4) pyrimidone photoproducts (6,4PPs). However, they were resistant to UVA, probably as a result of the activation of photolyases during UVA irradiation. Surprisingly, a sensory mechanism that triggers their escape from UVB and UVA light avoids the generation of DNA damage and helps to maintain the genomic integrity. This work demonstrates the genotoxic impact of both UVB and UVA radiation on tadpoles and emphasizes the importance of the interplay between molecular and sensory mechanisms to minimize the damage caused by sunlight. PMID:26447197

  11. Mediators of Inflammation-Induced Bone Damage in Arthritis and Their Control by Herbal Products

    PubMed Central

    Nanjundaiah, Siddaraju M.; Astry, Brian; Moudgil, Kamal D.

    2013-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the synovial joints leading to bone and cartilage damage. Untreated inflammatory arthritis can result in severe deformities and disability. The use of anti-inflammatory agents and biologics has been the mainstay of treatment of RA. However, the prolonged use of such agents may lead to severe adverse reactions. In addition, many of these drugs are quite expensive. These limitations have necessitated the search for newer therapeutic agents for RA. Natural plant products offer a promising resource for potential antiarthritic agents. We describe here the cellular and soluble mediators of inflammation-induced bone damage (osteoimmunology) in arthritis. We also elaborate upon various herbal products that possess antiarthritic activity, particularly mentioning the specific target molecules. As the use of natural product supplements by RA patients is increasing, this paper presents timely and useful information about the mechanism of action of promising herbal products that can inhibit the progression of inflammation and bone damage in the course of arthritis. PMID:23476694

  12. Methylphenidate and Amphetamine Do Not Induce Cytogenetic Damage in Lymphocytes of Children with ADHD

    ERIC Educational Resources Information Center

    Witt, Kristine L.; Shelby, Michael D.; Itchon-Ramos, Nilda; Faircloth, Melissa; Kissling, Grace E.; Chrisman, Allan K.; Ravi, Hima; Murli, Hemalatha; Mattison, Donald R.; Kollins, Scott H.

    2008-01-01

    The inducement of chromosomal damage in lymphocytes among children with attention deficit hyperactivity disorder receiving treatment with methylphenidate- or amphetamine-based drugs is investigated. Findings did not reveal significant increases in cytogenetic damage related to the treatment. The risk for cytogenetic damage posed by such products…

  13. Role of creatine supplementation in exercise-induced muscle damage: A mini review.

    PubMed

    Kim, Jooyoung; Lee, Joohyung; Kim, Seungho; Yoon, Daeyoung; Kim, Jieun; Sung, Dong Jun

    2015-10-01

    Muscle damage is induced by both high-intensity resistance and endurance exercise. Creatine is a widely used dietary supplement to improve exercise performance by reducing exercise-induced muscle damage. Many researchers have suggested that taking creatine reduces muscle damage by decreasing the inflammatory response and oxidative stress, regulating calcium homeostasis, and activating satellite cells. However, the underlying mechanisms of creatine and muscle damage have not been clarified. Therefore, this review discusses the regulatory effects of creatine on muscle damage by compiling the information collected from basic science and sports science research. PMID:26535213

  14. Laser-induced damage threshold of silicon in millisecond, nanosecond, and picosecond regimes

    SciTech Connect

    Wang, X.; Shen, Z. H.; Lu, J.; Ni, X. W.

    2010-08-15

    Millisecond, nanosecond, and picosecond laser pulse induced damage thresholds on single-crystal are investigated in this study. The thresholds of laser-induced damage on silicon are calculated theoretically for three pulse widths based on the thermal damage model. An axisymmetric mathematical model is established for the transient temperature field of the silicon. Experiments are performed to test the damage thresholds of silicon at various pulse widths. The results indicate that the damage thresholds obviously increase with the increasing of laser pulse width. Additionally, the experimental results agree well with theoretical calculations and numerical simulation results.

  15. Calculation of complex DNA damage induced by ions

    NASA Astrophysics Data System (ADS)

    Surdutovich, Eugene; Gallagher, David C.; Solov'yov, Andrey V.

    2011-11-01

    This paper is devoted to the analysis of the complex damage of DNA irradiated by ions. The assessment of complex damage is important because cells in which it occurs are less likely to survive because the DNA repair mechanisms may not be sufficiently effective. We study the flux of secondary electrons through the surface of nucleosomes and calculate the radial dose and the distribution of clustered damage around the ion's path. The calculated radial dose distribution is compared to simulations. The radial distribution of the complex damage is found to be different from that of the dose. A comparison with experiments may solve the question of what is more lethal for the cell, damage complexity or absorbed energy. We suggest a way to calculate the probability of cell death based on the complexity of the damage. This work is done within the framework of the phenomenon-based multiscale approach to radiation damage by ions.

  16. Calculation of complex DNA damage induced by ions

    SciTech Connect

    Surdutovich, Eugene; Gallagher, David C.; Solov'yov, Andrey V.

    2011-11-15

    This paper is devoted to the analysis of the complex damage of DNA irradiated by ions. The assessment of complex damage is important because cells in which it occurs are less likely to survive because the DNA repair mechanisms may not be sufficiently effective. We study the flux of secondary electrons through the surface of nucleosomes and calculate the radial dose and the distribution of clustered damage around the ion's path. The calculated radial dose distribution is compared to simulations. The radial distribution of the complex damage is found to be different from that of the dose. A comparison with experiments may solve the question of what is more lethal for the cell, damage complexity or absorbed energy. We suggest a way to calculate the probability of cell death based on the complexity of the damage. This work is done within the framework of the phenomenon-based multiscale approach to radiation damage by ions.

  17. Mitochondrial DNA damage induced autophagy, cell death, and disease

    PubMed Central

    Van Houten, Bennett; Hunter, Senyene E.; Meyer, Joel N.

    2016-01-01

    Mammalian mitochondria contain multiple small genomes. While these organelles have efficient base excision removal of oxidative DNA lesions and alkylation damage, many DNA repair systems that work on nuclear DNA damage are not active in mitochondria. What is the fate of DNA damage in the mitochondria that cannot be repaired or that overwhelms the repair system? Some forms of mitochondrial DNA damage can apparently trigger mitochondrial DNA destruction, either via direct degradation or through specific forms of autophagy, such as mitophagy. However, accumulation of certain types of mitochondrial damage, in the absence of DNA ligase III (Lig3) or exonuclease G (EXOG), enzymes required for repair, can directly trigger cell death. This review examines the cellular effects of persistent damage to mitochondrial genomes and discusses the very different cell fates that occur in response to different kinds of damage. PMID:26709760

  18. Liver-specific microRNAs as biomarkers of nanomaterial-induced liver damage

    NASA Astrophysics Data System (ADS)

    Nagano, Takashi; Higashisaka, Kazuma; Kunieda, Akiyoshi; Iwahara, Yuki; Tanaka, Kota; Nagano, Kazuya; Abe, Yasuhiro; Kamada, Haruhiko; Tsunoda, Shin-ichi; Nabeshi, Hiromi; Yoshikawa, Tomoaki; Yoshioka, Yasuo; Tsutsumi, Yasuo

    2013-10-01

    Although nanomaterials are being used in various fields, their safety is not yet sufficiently understood. We have been attempting to establish a nanomaterials safety-assessment system by using biomarkers to predict nanomaterial-induced adverse biological effects. Here, we focused on microRNAs (miRNAs) because of their tissue-specific expression and high degree of stability in the blood. We previously showed that high intravenous doses of silica nanoparticles of 70 nm diameter (nSP70) induced liver damage in mice. In this study, we compared the effectiveness of serum levels of liver-specific or -enriched miRNAs (miR-122, miR-192, and miR-194) with that of conventional hepatic biomarkers (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)) as biomarkers for nSP70. After mice had been treated with nSP70, their serum miRNAs levels were measured by using quantitative RT-PCR. Serum levels of miR-122 in nSP70-treated mice were the highest among the three miRNAs. The sensitivity of miR-122 for liver damage was at least as good as those of ALT and AST. Like ALT and AST, miR-122 may be a useful biomarker of nSP70. We believe that these findings will help in the establishment of a nanomaterials safety-assessment system.

  19. Mass spectrometric analysis of HOCl- and free-radical-induced damage to lipids and proteins.

    PubMed

    Pitt, Andrew R; Spickett, Corinne M

    2008-10-01

    In inflammatory diseases, release of oxidants leads to oxidative damage to biomolecules. HOCl (hypochlorous acid), released by the myeloperoxidase/H2O2/Cl- system, can cause formation of phospholipid chlorohydrins, or alpha-chloro-fatty aldehydes from plasmalogens. It can attack several amino acid residues in proteins, causing post-translational oxidative modifications of proteins, but the formation of 3-chlorotyrosine is one of the most stable markers of HOCl-induced damage. Soft-ionization MS has proved invaluable for detecting the occurrence of oxidative modifications to both phospholipids and proteins, and characterizing the products generated by HOCl-induced attack. For both phospholipids and proteins, the application of advanced mass spectrometric methods such as product or precursor ion scanning and neutral loss analysis can yield information both about the specific nature of the oxidative modification and the biomolecule modified. The ideal is to be able to apply these methods to complex biological or clinical samples, to determine the site-specific modifications of particular cellular components. This is important for understanding disease mechanisms and offers potential for development of novel biomarkers of inflammatory diseases. In the present paper, we review some of the progress that has been made towards this goal. PMID:18793192

  20. Chemical modification of normal tissue damage induced by photodynamic therapy.

    PubMed Central

    Sigdestad, C. P.; Fingar, V. H.; Wieman, T. J.; Lindberg, R. D.

    1996-01-01

    One of the limitations of successful use of photodynamic therapy (PDT) employing porphyrins is the acute and long-term cutaneous photosensitivity. This paper describes results of experiments designed to test the effects of two radiation protective agents (WR-2721, 500 mg kg-1 or WR-3689, 700 mg kg-1) on murine skin damage induced by PDT. C3H mice were shaved and depilated three days prior to injection with the photosensitiser, Photofrin (5 or 10 mg kg-1). Twenty-four hours later, the mice were injected intraperitoneally with a protector 30 min prior to Argon dye laser (630 nm) exposure. The skin response was followed for two weeks post irradiation using an arbitrary response scale. A light dose response as well as a drug dose response was obtained. The results indicate that both protectors reduced the skin response to PDT, however WR-2721 was demonstrated to be the most effective. The effect of the protectors on vascular stasis after PDT was determined using a fluorescein dye exclusion assay. In mice treated with Photofrin (5 mg kg-1), and 630 nm light (180 J cm-2) pretreatment with either WR-2721 or WR-3689 resulted in significant protection of the vascular effects of PDT. These studies document the ability of the phosphorothioate class of radiation protective agents to reduce the effects of light on photosensitized skin. They do so in a drug dose-dependent fashion with maximum protection at the highest drug doses. PMID:8763855

  1. Retinal Damage Induced by Internal Limiting Membrane Removal

    PubMed Central

    Gelman, Rachel; Stevenson, William; Prospero Ponce, Claudia; Agarwal, Daniel; Christoforidis, John Byron

    2015-01-01

    The internal limiting membrane (ILM), the basement membrane of the Müller cells, serves as the interface between the vitreous body and the retinal nerve fiber layer. It has a fundamental role in the development, structure, and function of the retina, although it also is a pathologic component in the various vitreoretinal disorders, most notably in macular holes. It was not until understanding of the evolution of idiopathic macular holes and the advent of idiopathic macular hole surgery that the idea of adjuvant ILM peeling in the treatment of tractional maculopathies was explored. Today intentional ILM peeling is a commonly applied surgical technique among vitreoretinal surgeons as it has been found to increase the rate of successful macular hole closure and improve surgical outcomes in other vitreoretinal diseases. Though ILM peeling has refined surgery for tractional maculopathies, like all surgical procedures it is not immune to perioperative risk. The essential role of the ILM to the integrity of the retina and risk of trauma to retinal tissue spurs suspicion with regard to its routine removal. Several authors have investigated the retinal damage induced by ILM peeling and these complications have been manifested across many different diagnostic studies. PMID:26425355

  2. Incretin attenuates diabetes-induced damage in rat cardiac tissue.

    PubMed

    AbdElmonem Elbassuoni, Eman

    2014-09-01

    Glucagon-like peptide-1 (GLP-1), as a member of the incretin family, has a role in glucose homeostasis, its receptors distributed throughout the body, including the heart. The aim was to investigate cardiac lesions following diabetes induction, and the potential effect of GLP-1 on this type of lesions and the molecular mechanism driving this activity. Adult male rats were classified into: normal, diabetic, 4-week high-dose exenatide-treated diabetic rats, 4-week low-dose exenatide-treated diabetic rats, and 1-week exenatide-treated diabetic rats. The following parameters were measured: in blood: glucose, insulin, lactate dehydrogenase (LDH), total creatine kinase (CK), creatine kinase MB isoenzyme (CK-MB), and CK-MB relative index; in cardiac tissue: lipid peroxide (LPO) and some antioxidant enzymes. The untreated diabetic group displayed significant increases in blood level of glucose, LDH, and CK-MB, and cardiac tissue LPO, and a significant decrease in cardiac tissue antioxidant enzymes. GLP-1 supplementation in diabetic rats definitely decreased the hyperglycemia and abolished the detrimental effects of diabetes on the cardiac tissue. The effect of GLP-1 on blood glucose and on the heart also appeared after a short supplementation period (1 week). It can be concluded that GLP-1 has beneficial effects on diabetes-induced oxidative cardiac tissue damage, most probably via its antioxidant effect directly acting on cardiac tissue and independent of its hypoglycemic effect. PMID:25011640

  3. Laser induced damage of fused silica polished optics due to a droplet forming organic contaminant.

    PubMed

    Bien-Aimé, Karell; Néauport, Jérome; Tovena-Pecault, Isabelle; Fargin, Evelyne; Labrugère, Christine; Belin, Colette; Couzi, Michel

    2009-04-20

    We report on the effect of organic molecular contamination on single shot laser induced damage density at the wavelength of 351 nm, with a 3 ns pulse length. Specific contamination experiments were made with dioctylphthalate (DOP) in liquid or gaseous phase, on the surface of fused silica polished samples, bare or solgel coated. Systematic laser induced damage was observed only in the case of liquid phase contamination. Different chemical and morphological characterization methods were used to identify and understand the damage process. We demonstrate that the contaminant morphology, rather than its physicochemical nature, can be responsible for the decrease of laser induced damage threshold of optics. PMID:19381171

  4. Does rosmarinic acid treatment have protective role against sepsis-induced oxidative damage in Wistar Albino rats?

    PubMed

    Bacanlı, M; Aydın, S; Taner, G; Göktaş, H G; Şahin, T; Başaran, A A; Başaran, N

    2016-08-01

    Reactive oxygen species are believed to be involved in the development of sepsis. Plant-derived phenolic compounds are thought to be possible therapeutic agents against sepsis because of their antioxidant properties. Rosmarinic acid (RA) is a phenolic compound commonly found in various plants, which has many biological activities including antioxidant activity. The aim of this study was to investigate the effects of RA on sepsis-induced DNA damage in the lymphocytes and liver and kidney cells of Wistar albino rats by alkaline comet assay with and without formamidopyrimidine DNA glycosylase protein. The oxidative stress parameters such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and total glutathione (GSH) and malondialdehyde (MDA) levels in the liver and kidney tissues and an inflammatory cytokine, tumor necrosis factor α (TNF-α) level in plasma were also evaluated. It is found that DNA damage in the lymphocytes, livers, and kidneys of the RA-treated rats was significantly lower than that in the sepsis-induced rats. RA treatment also decreased the MDA levels and increased the GSH levels and SOD and GSH-Px activities in the livers and kidneys of the sepsis-induced rats. Plasma TNF-α level was found to be decreased in the RA-treated rats. It seems that RA might have a role in the attenuation of sepsis-induced oxidative damage not only by decreasing the DNA damage but also by increasing the antioxidant status and DNA repair capacity of the animals. PMID:26429925

  5. Comparison of Model Calculations of Biological Damage from Exposure to Heavy Ions with Measurements

    NASA Astrophysics Data System (ADS)

    Kim, Myung-Hee Y.; Wu, Honglu; Hada, Megumi; Cucinotta, Francis

    The space environment consists of a varying field of radiation particles including high-energy ions, with spacecraft shielding material providing the major protection to astronauts from harmful exposure. Unlike low-LET g or X rays, the presence of shielding does not always reduce the radiation risks for energetic charged-particle exposure. Dose delivered by the charged particle increases sharply at the Bragg peak. However, the Bragg curve does not necessarily represent the biological damage along the particle path since biological effects are influenced by the track structures of both primary and secondary particles. Therefore, the ‘‘biological Bragg curve’’ is dependent on the energy and the type of the primary particle and may vary for different biological end points. Measurements of the induction of micronuclei (MN) have made across the Bragg curve in human fibroblasts exposed to energetic silicon and iron ions in vitro at two different energies, 300 MeV/nucleon and 1 GeV/nucleon. Although the data did not reveal an increased yield of MN at the location of the Bragg peak, the increased inhibition of cell progression, which is related to cell death, was found at the Bragg peak location. These results are compared to the calculations of biological damage using a stochastic Monte-Carlo track structure model, Galactic Cosmic Ray Event-based Risk Model (GERM) code (Cucinotta et al., 2011). The GERM code estimates the basic physical properties along the passage of heavy ions in tissue and shielding materials, by which the experimental set-up can be interpreted. The code can also be used to describe the biophysical events of interest in radiobiology, cancer therapy, and space exploration. The calculation has shown that the severely damaged cells at the Bragg peak are more likely to go through reproductive death, the so called “overkill”. F. A. Cucinotta, I. Plante, A. L. Ponomarev, and M. Y. Kim, Nuclear Interactions in Heavy Ion Transport and Event

  6. Advances and New Concepts in Alcohol-Induced Organelle Stress, Unfolded Protein Responses and Organ Damage

    PubMed Central

    Ji, Cheng

    2015-01-01

    Alcohol is a simple and consumable biomolecule yet its excessive consumption disturbs numerous biological pathways damaging nearly all organs of the human body. One of the essential biological processes affected by the harmful effects of alcohol is proteostasis, which regulates the balance between biogenesis and turnover of proteins within and outside the cell. A significant amount of published evidence indicates that alcohol and its metabolites directly or indirectly interfere with protein homeostasis in the endoplasmic reticulum (ER) causing an accumulation of unfolded or misfolded proteins, which triggers the unfolded protein response (UPR) leading to either restoration of homeostasis or cell death, inflammation and other pathologies under severe and chronic alcohol conditions. The UPR senses the abnormal protein accumulation and activates transcription factors that regulate nuclear transcription of genes related to ER function. Similarly, this kind of protein stress response can occur in other cellular organelles, which is an evolving field of interest. Here, I review recent advances in the alcohol-induced ER stress response as well as discuss new concepts on alcohol-induced mitochondrial, Golgi and lysosomal stress responses and injuries. PMID:26047032

  7. Damage proneness induced by genomic DNA demethylation in mammalian cells cultivated in vitro.

    PubMed

    Perticone, P; Gensabella, G; Cozzi, R

    1997-07-01

    Variations in the genomic DNA methylation level have been shown to be an epigenetic inheritable modification affecting, among other targets, the sister chromatid exchange (SCE) rate in mammalian cells in vitro. The inheritable increase in SCE rate in affected cell populations appears as a puzzling phenomenon in view of the well established relation between SCE and both mutagenesis and carcinogenesis. In the present work we demonstrate that, in a treated cell population, demethylation could be responsible for the inheritable induction of damage proneness affecting both damage induction and repair. Normal and ethionine or azacytidine treated Chinese hamster ovary cells, subclone K1 (CHO-K1), were challenged with UV light (UV) or mitomycin-C (MMC) at different times from the demethylating treatment. The SCE rate was measured with two main objects in view: (i) the induction of synergism or additivity in combined treatments, where mutagen (UV or MMC) pulse is supplied from 0 to 48 h after the end of the demethylating treatment; and (ii) the pattern of damage extinction, for the duration of up to six cell cycles after the end of the combined (demethylating agent + mutagen) treatment. Results indicate both a synergism in SCE induction by mutagens in demethylated cells even if supplied up to four cell cycles after the end of the demethylation treatment and a delay in recovery of induced damage, compared with normally methylated cells. These data are discussed in the light of the supposed mechanism of SCE increase and of the possible biological significance in terms of mutagenesis and carcinogenesis. PMID:9237771

  8. High and Low LET Radiation Differentially Induce Normal Tissue Damage Signals

    SciTech Connect

    Niemantsverdriet, Maarten; Goethem, Marc-Jan van; Bron, Reinier; Hogewerf, Wytse; Brandenburg, Sytze; Langendijk, Johannes A.; Luijk, Peter van; Coppes, Robert P.

    2012-07-15

    Purpose: Radiotherapy using high linear energy transfer (LET) radiation is aimed at efficiently killing tumor cells while minimizing dose (biological effective) to normal tissues to prevent toxicity. It is well established that high LET radiation results in lower cell survival per absorbed dose than low LET radiation. However, whether various mechanisms involved in the development of normal tissue damage may be regulated differentially is not known. Therefore the aim of this study was to investigate whether two actions related to normal tissue toxicity, p53-induced apoptosis and expression of the profibrotic gene PAI-1 (plasminogen activator inhibitor 1), are differentially induced by high and low LET radiation. Methods and Materials: Cells were irradiated with high LET carbon ions or low LET photons. Cell survival assays were performed, profibrotic PAI-1 expression was monitored by quantitative polymerase chain reaction, and apoptosis was assayed by annexin V staining. Activation of p53 by phosphorylation at serine 315 and serine 37 was monitored by Western blotting. Transfections of plasmids expressing p53 mutated at serines 315 and 37 were used to test the requirement of these residues for apoptosis and expression of PAI-1. Results: As expected, cell survival was lower and induction of apoptosis was higher in high -LET irradiated cells. Interestingly, induction of the profibrotic PAI-1 gene was similar with high and low LET radiation. In agreement with this finding, phosphorylation of p53 at serine 315 involved in PAI-1 expression was similar with high and low LET radiation, whereas phosphorylation of p53 at serine 37, involved in apoptosis induction, was much higher after high LET irradiation. Conclusions: Our results indicate that diverse mechanisms involved in the development of normal tissue damage may be differentially affected by high and low LET radiation. This may have consequences for the development and manifestation of normal tissue damage.

  9. Eucalyptus globulus extract protects upon acetaminophen-induced kidney damages in male rat

    PubMed Central

    Dhibi, Sabah; Mbarki, Sakhria; Elfeki, Abdelfettah; Hfaiedh, Najla

    2014-01-01

    Plants have historically been used in treating many diseases. Eucalyptus globules, a rich source of bioactive compounds, and have been shown to possess antioxidative properties. The purpose of this study, carried out on male Wistar rats, was to evaluate the beneficial effects of Eucalyptus globulus extract upon acetaminophen-induced damages in kidney. Our study is realized in the Department of Biology, Faculty of Sciences of Sfax (Tunisia). 32 Wistar male rats; were divided into 4 batches: a control group (n=8), a group of rats treated with acetaminophen (goomg/kg) by intraperitoneal injection during 4 days (n=8), a group receiving Eucalyptus globulus extract (130 mg of dry leaves/kg/day) in drinking water during 42 days after 2 hours of acetaminophen administration (during 4 days) (n=8) and group received only Eucalyptus (n=8) during 42 days. After 6 weeks, animals from each group were rapidly sacrificed by decapitation. Blood serum was obtained by centrifugation. Under our experimental conditions, acetaminophen poisoning resulted in an oxidative stress evidenced by statistically significant losses in the activities of catalase (CAT), superoxide-dismutase (SOD), glutathione-peroxidase (GPX) activities and an increase in lipids peroxidation level in renal tissue of acetaminophen-treated group compared with the control group. Acetaminophen also caused kidney damage as evident by statistically significant (p<0.05) increase in levels of creatinine and urea and decreased levels of uric acid and proteins in blood. Histological analysis demonstrated alteration of proximal tubules, atrophy of the glomerule and dilatation of urinary space. Previous administration of plant extract is found to alleviate this acetaminophen-induced damage. PMID:24856382

  10. Eucalyptus globulus extract protects upon acetaminophen-induced kidney damages in male rat.

    PubMed

    Dhibi, Sabah; Mbarki, Sakhria; Elfeki, Abdelfettah; Hfaiedh, Najla

    2014-05-01

    Plants have historically been used in treating many diseases. Eucalyptus globules, a rich source of bioactive compounds, and have been shown to possess antioxidative properties. The purpose of this study, carried out on male Wistar rats, was to evaluate the beneficial effects of Eucalyptus globulus extract upon acetaminophen-induced damages in kidney. Our study is realized in the Department of Biology, Faculty of Sciences of Sfax (Tunisia). 32 Wistar male rats; were divided into 4 batches: a control group (n=8), a group of rats treated with acetaminophen (900 mg/kg) by intraperitoneal injection during 4 days (n=8), a group receiving Eucalyptus globulus extract (130 mg of dry leaves/kg/day) in drinking water during 42 days after 2 hours of acetaminophen administration (during 4 days) (n=8) and group received only Eucalyptus (n=8) during 42 days. After 6 weeks, animals from each group were rapidly sacrificed by decapitation. Blood serum was obtained by centrifugation. Under our experimental conditions, acetaminophen poisoning resulted in an oxidative stress evidenced by statistically significant losses in the activities of catalase (CAT), superoxide-dismutase (SOD), glutathione-peroxidase (GPX) activities and an increase in lipids peroxidation level in renal tissue of acetaminophen-treated group compared with the control group. Acetaminophen also caused kidney damage as evident by statistically significant (p<0.05) increase in levels of creatinine and urea and decreased levels of uric acid and proteins in blood. Histological analysis demonstrated alteration of proximal tubules, atrophy of the glomerule and dilatation of urinary space. Previous administration of plant extract is found to alleviate this acetaminophen-induced damage. PMID:24856382

  11. Molecular responses of radiation-induced liver damage in rats

    PubMed Central

    CHENG, WEI; XIAO, LEI; AINIWAER, AIMUDULA; WANG, YUNLIAN; WU, GE; MAO, RUI; YANG, YING; BAO, YONGXING

    2015-01-01

    The aim of the present study was to investigate the molecular responses involved in radiation-induced liver damage (RILD). Sprague-Dawley rats (6-weeks-old) were irradiated once at a dose of 20 Gy to the right upper quadrant of the abdomen. The rats were then sacrificed 3 days and 1, 2, 4, 8 and 12 weeks after irradiation and rats, which were not exposed to irradiation were used as controls. Weight measurements and blood was obtained from the rats and liver tissues were collected for histological and apoptotic analysis. Immunohistochemistry, reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis were performed to measure the expression levels of mRNAs and proteins, respectively. The serum levels of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase were increased significantly in the RILD rats. Histological investigation revealed the proliferation of collagen and the formation of fibrotic tissue 12 weeks after irradiation. Apoptotic cells were observed predominantly 2 and 4 weeks after irradiation. The immunohistochemistry, RT-qPCR and western blot analysis all revealed the same pattern of changes in the expression levels of the molecules assessed. The expression levels of transforming growth factor-β1 (TGF-β1), nuclear factor (NF)-κB65, mothers against decapentaplegic homolog 3 (Smad3) and Smad7 and connective tissue growth factor were increased during the recovery period following irradiation up to 12 weeks. The expression levels of tumor necrosis factor-α, Smad7 and Smad4 were only increased during the early phase (first 4 weeks) of recovery following irradiation. In the RILD rat model, the molecular responses indicated that the TGF-β1/Smads and NF-κB65 signaling pathways are involved in the mechanism of RILD recovery. PMID:25483171

  12. AFM CHARACTERIZATION OF LASER INDUCED DAMAGE ON CDZNTE CRYSTAL SURFACES

    SciTech Connect

    Hawkins, S; Lucile Teague, L; Martine Duff, M; Eliel Villa-Aleman, E

    2008-06-10

    Semi-conducting CdZnTe (or CZT) crystals can be used in a variety of detector-type applications. CZT shows great promise for use as a gamma radiation spectrometer. However, its performance is adversely affected by point defects, structural and compositional heterogeneities within the crystals, such as twinning, pipes, grain boundaries (polycrystallinity), secondary phases and in some cases, damage caused by external forces. One example is damage that occurs during characterization of the surface by a laser during Raman spectroscopy. Even minimal laser power can cause Te enriched areas on the surface to appear. The Raman spectra resulting from measurements at moderate intensity laser power show large increases in peak intensity that is attributed to Te. Atomic Force Microscopy (AFM) was used to characterize the extent of damage to the CZT crystal surface following exposure to the Raman laser. AFM data reveal localized surface damage in the areas exposed to the Raman laser beam. The degree of surface damage to the crystal is dependent on the laser power, with the most observable damage occurring at high laser power. Moreover, intensity increases in the Te peaks of the Raman spectra are observed even at low laser power with little to no visible damage observed by AFM. AFM results also suggest that exposure to the same amount of laser power yields different amounts of surface damage depending on whether the exposed surface is the Te terminating face or the Cd terminating face of CZT.

  13. SPATA12 and Its Possible Role in DNA Damage Induced by Ultraviolet-C

    PubMed Central

    Lin, Yiting; Rong, Zhuoxian; Liu, Xiaowen; Li, Dan

    2013-01-01

    Our previous studies indicated that SPATA12, a novel spermatogenesis-associated gene, might be an inhibitor involved in spermatogenesis and tumorigenesis. To obtain a better understanding of the functions of SPATA12, a yeast two-hybrid screening system was used to search for interacting proteins, and chromodomain helicase DNA binding protein 2 (CHD2) was successfully identified. Bimolecular fluorescence complementation (BiFC) and subcellular co-localization assays further suggested a possible interaction between SPATA12 and CHD2 in the nuclei. CHD2 is known to be involved in the later stage of the DNA damage response pathway by influencing the transcriptional activity of p53. Thus, our hypothesis is that SPATA12 might play a role in DNA damage signaling. Western blotting results showed that SPATA12 expression could be induced in ultraviolet-C (UV-C) irradiated cells. Through reporter gene assays and the activator protein-1 (AP-1) decoy oligodeoxynucleotide method, we demonstrated that SPATA12 promoter activity could be up-regulated in response to UV-C radiation exposure and an AP-1 binding site in the SPATA12 promoter may have a role in transcriptional regulation of SPATA12. Using colony formation and host cell reactivation assays, it was demonstrated that SPATA12 might lead to inhibition of cellular proliferation in UV-C-irradiated DNA damage. Furthermore, SPATA12 was transfected into H1299, MCF-7 and HeLa cells, and flow cytometry (FCM) results suggested that there are some biological association between SPATA12 and p53 in UV-C-irradiated DNA damage. In addition, we investigated whether SPATA12 could up-regulate the expression of p53. Taken together, these findings indicate that SPATA12 could be induced under UV-C stress. During DNA damage process, AP-1 involves in the transcriptional up-regulation of SPATA12 in response to UV-C radiation and p53 involves in growth inhibitory effects of SPATA12 on UV-C irradiated cells. PMID:24205157

  14. The effect of multiple wavelengths on Laser-induced damage in DKDP crystals

    SciTech Connect

    Carr, C W; Auerbach, J M

    2005-07-11

    Laser-induced damage is a key factor that constrains how optical materials are used in high-power laser systems. In this work the size and density of bulk laser-induced damage sites formed during frequency tripling in a DKDP crystal are studied. The characteristics of the damage sites formed during tripling, where 1053-nm, 526-nm, and 351-nm light is simultaneously present, are compared to damage sites formed by 351-nm light alone. The fluence of each wavelength is calculated as a function of depth with a full 4D(x,y,z,t) frequency conversion code and compared to measured damage density and size distributions. The density of damage is found be predominantly governed by 351-nm light with some lesser, though non-negligible contribution from 526-nm light. The morphology of the damage sites, however, is seen to be relatively insensitive to wavelength and depend only on total fluence of all wavelengths present.

  15. Heavy ion induced DNA transfer in biological cells

    NASA Astrophysics Data System (ADS)

    Vilaithong, T.; Yu, L. D.; Apavatjrut, P.; Phanchaisri, B.; Sangyuenyongpipat, S.; Anuntalabhochai, S.; Brown, I. G.

    2004-10-01

    Low-energy ion beam bombardment of biological materials for genetic modification purposes has experienced rapid growth in the last decade, particularly for the direct DNA transfer into living organisms including both plants and bacteria. Attempts have been made to understand the mechanisms involved in ion-bombardment-induced direct gene transfer into biological cells. Here we summarize the present status of the application of low-energy ions for genetic modification of living sample materials.

  16. Involvement of inducible nitric oxide synthase in radiation-induced vascular endothelial damage.

    PubMed

    Hong, Chang-Won; Kim, Young-Mee; Pyo, Hongryull; Lee, Joon-Ho; Kim, Suwan; Lee, Sunyoung; Noh, Jae Myoung

    2013-11-01

    The use of radiation therapy has been linked to an increased risk of cardiovascular disease. To understand the mechanisms underlying radiation-induced vascular dysfunction, we employed two models. First, we examined the effect of X-ray irradiation on vasodilation in rabbit carotid arteries. Carotid arterial rings were irradiated with 8 or 16 Gy using in vivo and ex vivo methods. We measured the effect of acetylcholine-induced relaxation after phenylephrine-induced contraction on the rings. In irradiated carotid arteries, vasodilation was significantly attenuated by both irradiation methods. The relaxation response was completely blocked by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a potent inhibitor of soluble guanylate cyclase. Residual relaxation persisted after treatment with L-N(ω)-nitroarginine (L-NA), a non-specific inhibitor of nitric oxide synthase (NOS), but disappeared following the addition of aminoguanidine (AG), a selective inhibitor of inducible NOS (iNOS). The relaxation response was also affected by tetraethylammonium, an inhibitor of endothelium-derived hyperpolarizing factor activity. In the second model, we investigated the biochemical events of nitrosative stress in human umbilical-vein endothelial cells (HUVECs). We measured iNOS and nitrotyrosine expression in HUVECs exposed to a dose of 4 Gy. The expression of iNOS and nitrotyrosine was greater in irradiated HUVECs than in untreated controls. Pretreatment with AG, L-N(6)-(1-iminoethyl) lysine hydrochloride (a selective inhibitor of iNOS), and L-NA attenuated nitrosative stress. While a selective target of radiation-induced vascular endothelial damage was not definitely determined, these results suggest that NO generated from iNOS could contribute to vasorelaxation. These studies highlight a potential role of iNOS inhibitors in ameliorating radiation-induced vascular endothelial damage. PMID:23704776

  17. Monosodium glutamate-induced oxidative kidney damage and possible mechanisms: a mini-review.

    PubMed

    Sharma, Amod

    2015-01-01

    Animal studies suggest that chronic monosodium glutamate (MSG) intake induces kidney damage by oxidative stress. However, the underlying mechanisms are still unclear, despite the growing evidence and consensus that α-ketoglutarate dehydrogenase, glutamate receptors and cystine-glutamate antiporter play an important role in up-regulation of oxidative stress in MSG-induced renal toxicity. This review summaries evidence from studies into MSG-induced renal oxidative damage, possible mechanisms and their importance from a toxicological viewpoint. PMID:26493866

  18. The Biological Effectiveness of Accelerated Particles for the Induction of Chromosome Damage: Track Structure Effects and Cytogenetic Signatures of High-LET Exposure

    NASA Technical Reports Server (NTRS)

    George, K.; Hada, M.; Chappell, L.; Cucinotta, F. A.

    2012-01-01

    Track structure models predict that at a fixed value of LET, particles with lower charge number, Z will have a higher biological effectiveness compared to particles with a higher Z. In this report we investigated how track structure effects induction of chromosomal aberration in human cells. Human lymphocytes were irradiated in vitro with various energies of accelerated iron, silicon, neon, or titanium ions and chromosome damage was assessed in using three color FISH chromosome painting in chemically induced PCC samples collected a first cell division post irradiation. The LET values for these ions ranged from 30 to 195 keV/micrometers. Of the particles studied, Neon ions have the highest biological effectiveness for induction of total chromosome damage, which is consistent with track structure model predictions. For complex-type exchanges 64 MeV/ u Neon and 450 MeV/u Iron were equally effective and induced the most complex damage. In addition we present data on chromosomes exchanges induced by six different energies of protons (5 MeV/u to 2.5 GeV/u). The linear dose response term was similar for all energies of protons suggesting that the effect of the higher LET at low proton energies is balanced by the production of nuclear secondaries from the high energy protons. All energies of protons have a much higher percentage of complex-type chromosome exchanges than gamma rays, signifying a cytogenetic signature for proton exposures.

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

    PubMed

    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. PMID:26573366

  20. Helium vs. Proton Induced Displacement Damage in Electronic Materials

    NASA Technical Reports Server (NTRS)

    Ringo, Sawnese; Barghouty, A. F.

    2010-01-01

    In this project, the specific effects of displacement damage due to the passage of protons and helium nuclei on some typical electronic materials will be evaluated and contrasted. As the electronic material absorbs the energetic proton and helium momentum, degradation of performance occurs, eventually leading to overall failure. Helium nuclei traveling at the same speed as protons are expected to impart more to the material displacement damage; due to the larger mass, and thus momentum, of helium nuclei compared to protons. Damage due to displacement of atoms in their crystalline structure can change the physical properties and hence performance of the electronic materials.

  1. Simulation of damage induced by ion implantation in Lithium Niobate

    NASA Astrophysics Data System (ADS)

    Bianconi, M.; Bentini, G. G.; Chiarini, M.; De Nicola, P.; Montanari, G. B.; Menin, A.; Nubile, A.; Sugliani, S.

    2010-11-01

    A simulation tool has been developed to engineer the damage formation in Lithium Niobate by ion irradiation with any atomic number and energy. Both nuclear and electronic processes were considered and, in particular, the dependence on the ion velocity of the electronic excitation damage efficiency has been taken into account. By using this tool it is possible both to draw damage nomograms, useful to qualitatively foresee the result of a given process, and to perform reliable simulations of the defect depth profiles, as demonstrated by the good agreement with the experimental data available in the literature.

  2. Modelling biofilm-induced formation damage and biocide treatment in subsurface geosystems

    PubMed Central

    Ezeuko, C C; Sen, A; Gates, I D

    2013-01-01

    Biofilm growth in subsurface porous media, and its treatment with biocides (antimicrobial agents), involves a complex interaction of biogeochemical processes which provide non-trivial mathematical modelling challenges. Although there are literature reports of mathematical models to evaluate biofilm tolerance to biocides, none of these models have investigated biocide treatment of biofilms growing in interconnected porous media with flow. In this paper, we present a numerical investigation using a pore network model of biofilm growth, formation damage and biocide treatment. The model includes three phases (aqueous, adsorbed biofilm, and solid matrix), a single growth-limiting nutrient and a single biocide dissolved in the water. Biofilm is assumed to contain a single species of microbe, in which each cell can be a viable persister, a viable non-persister, or non-viable (dead). Persisters describe small subpopulation of cells which are tolerant to biocide treatment. Biofilm tolerance to biocide treatment is regulated by persister cells and includes ‘innate’ and ‘biocide-induced’ factors. Simulations demonstrate that biofilm tolerance to biocides can increase with biofilm maturity, and that biocide treatment alone does not reverse biofilm-induced formation damage. Also, a successful application of biological permeability conformance treatment involving geologic layers with flow communication is more complicated than simply engineering the attachment of biofilm-forming cells at desired sites. PMID:23164434

  3. Laser-induced retinal damage thresholds for annular retinal beam profiles

    NASA Astrophysics Data System (ADS)

    Kennedy, Paul K.; Zuclich, Joseph A.; Lund, David J.; Edsall, Peter R.; Till, Stephen; Stuck, Bruce E.; Hollins, Richard C.

    2004-07-01

    The dependence of retinal damage thresholds on laser spot size, for annular retinal beam profiles, was measured in vivo for 3 μs, 590 nm pulses from a flashlamp-pumped dye laser. Minimum Visible Lesion (MVL)ED50 thresholds in rhesus were measured for annular retinal beam profiles covering 5, 10, and 20 mrad of visual field; which correspond to outer beam diameters of roughly 70, 160, and 300 μm, respectively, on the primate retina. Annular beam profiles at the retinal plane were achieved using a telescopic imaging system, with the focal properties of the eye represented as an equivalent thin lens, and all annular beam profiles had a 37% central obscuration. As a check on experimental data, theoretical MVL-ED50 thresholds for annular beam exposures were calculated using the Thompson-Gerstman granular model of laser-induced thermal damage to the retina. Threshold calculations were performed for the three experimental beam diameters and for an intermediate case with an outer beam diameter of 230 μm. Results indicate that the threshold vs. spot size trends, for annular beams, are similar to the trends for top hat beams determined in a previous study; i.e., the threshold dose varies with the retinal image area for larger image sizes. The model correctly predicts the threshold vs. spot size trends seen in the biological data, for both annular and top hat retinal beam profiles.

  4. Authigenic minerals: Biologically influenced and induced organomineralization

    NASA Astrophysics Data System (ADS)

    Dupraz, Christophe

    2016-04-01

    Organominerals are minerals precipitated by interactions with organic matter without enzymatic control. Organomineralization of authigenic carbonate minerals depends on two key components: (1) the "carbonate alkalinity engine" impacting the calcium carbonate saturation index and (2) the organic matrix comprised of extracellular organic matter (EOM), which provides a template for carbonate nucleation. The alkalinity engine can be "intrinsic" when microbial metabolisms increase supersaturation or lower the kinetic barrier of precipitation, or "extrinsic" when the physicochemical environment creates the conditions for mineral formation. The organic matrix produced by various communities within the microbial mats is known to influence nucleation, morphology and mineralogy of minerals through binding of cations. By playing with these two key components, three types of authigenic minerals can be formed: (1) a purely physicochemical precipitation on an abiotic substrate, (2) a precipitation "influenced" by the presence of an organic matrix but resulting from a physicochemical forcing (environmentally driven), or (3) a "microbially-induced" precipitation, in which both supersaturation and organic matrix are resulting from microbial activity. In this keynote, we will review important processes involved in the precipitation of authigenic carbonate minerals in modern microbial mats and open the discussion on the potential use of authigenic carbonate minerals as biosignatures in the fossil record.

  5. Femtosecond laser threshold: retinal damage versus induced breakdown mechanisms

    NASA Astrophysics Data System (ADS)

    Cain, Clarence P.; Toth, Cynthia A.; Stein, Cindy D.; Noojin, Gary D.; Stolarski, David J.; Rockwell, Benjamin A.; Boppart, Stephen A.; Roach, William P.

    1994-08-01

    Threshold measurements at 90 femtoseconds (fs) and 600 fs have been made for minimum visible lesions (MVLs) using Dutch Belted rabbit and Rhesus monkey eyes. Laser induced breakdown (LIB) thresholds on biological materials including vitreous, normal saline, tap water, and ultrapure water are reported along with irradiance calculations utilizing nonlinear transmission properties including self-focusing. At both pulsewidths the ED50 dose required for the Rhesus monkey eye was less than half the value determined for the Dutch Belted rabbit eye, all thresholds being 1 microjoule ((mu) J) or less. Measurements on the Rhesus eye at 600 fs found the ED50 dose (0.26 (mu) J) to be much lower than the ED50 dose at 90 fs (0.43 (mu) J). But for these two pulsewidths, almost the same energy level was determined for the Dutch Belted rabbit eye (0.94 (mu) J vs. 1.0 (mu) J). LIB threshold measurements at 100 fs and 300 fs using a simulated eye with isolated vitreous found the ED50 dosages to be 3.5 and 6.0 (mu) J respectively. We found in all cases that the ED50 dosages required to produce MVLs in 24 hours for rabbit and monkey eyes were less than the ED50 values measured for LIB in vitreous or saline or any other breakdown values reported. Also observed was the fact that many of the threshold lesions did not appear in the 1-hour postexposure check but clearly showed up at the 24-hour reading which provided for a much lower threshold dose after 24 hours. We discuss the energy levels and peak powers at which nonlinear effects can begin to occur.

  6. Shock induced multi-mode damage in depleted uranium

    SciTech Connect

    Koller, Darcie D; Cerreta, Ellen K; Gray, Ill, George T

    2009-01-01

    Recent dynamic damage studies on depleted uranium samples have revealed mixed mode failure mechanisms leading to incipient cracking as well as ductile failure processes. Results show that delamination of inclusions upon compression may provide nucleation sites for damage initiation in the form of crack tip production. However, under tension the material propagates cracks in a mixed shear localization and mode-I ductile tearing and cracking. Cracks tips appear to link up through regions of severe, shear dominated plastic flow. Shock recovery experiments were conducted on a 50 mm single stage light gas gun. Serial metallographic sectioning was conducted on the recovered samples to characterize the bulk response of the sample. Experiments show delaminated inclusions due to uniaxial compression without damage propagation. Further results show the propagation of the damage through tensile loading to the incipient state, illustrating ductile processes coupled with mixed mode-I tensile ductile tearing, shear localization, and mode-I cracking in depleted uranium.

  7. Electron-Induced Displacement Damage Effects in CCDs

    NASA Technical Reports Server (NTRS)

    Becker, Heidi N.; Elliott, Tom; Alexander, James W.

    2006-01-01

    We compare differences in parametric degradation for CCDs irradiated to the same displacement damage dose with 10-MeV and 50-MeV electrons. Charge transfer efficiency degradation was observed to not scale with NIEL for small signals.

  8. Genetic variation and exercise-induced muscle damage: implications for athletic performance, injury and ageing.

    PubMed

    Baumert, Philipp; Lake, Mark J; Stewart, Claire E; Drust, Barry; Erskine, Robert M

    2016-09-01

    Prolonged unaccustomed exercise involving muscle lengthening (eccentric) actions can result in ultrastructural muscle disruption, impaired excitation-contraction coupling, inflammation and muscle protein degradation. This process is associated with delayed onset muscle soreness and is referred to as exercise-induced muscle damage. Although a certain amount of muscle damage may be necessary for adaptation to occur, excessive damage or inadequate recovery from exercise-induced muscle damage can increase injury risk, particularly in older individuals, who experience more damage and require longer to recover from muscle damaging exercise than younger adults. Furthermore, it is apparent that inter-individual variation exists in the response to exercise-induced muscle damage, and there is evidence that genetic variability may play a key role. Although this area of research is in its infancy, certain gene variations, or polymorphisms have been associated with exercise-induced muscle damage (i.e. individuals with certain genotypes experience greater muscle damage, and require longer recovery, following strenuous exercise). These polymorphisms include ACTN3 (R577X, rs1815739), TNF (-308 G>A, rs1800629), IL6 (-174 G>C, rs1800795), and IGF2 (ApaI, 17200 G>A, rs680). Knowing how someone is likely to respond to a particular type of exercise could help coaches/practitioners individualise the exercise training of their athletes/patients, thus maximising recovery and adaptation, while reducing overload-associated injury risk. The purpose of this review is to provide a critical analysis of the literature concerning gene polymorphisms associated with exercise-induced muscle damage, both in young and older individuals, and to highlight the potential mechanisms underpinning these associations, thus providing a better understanding of exercise-induced muscle damage. PMID:27294501

  9. Is Allelopathic Activity of Ipomoea murucoides Induced by Xylophage Damage?

    PubMed Central

    Flores-Palacios, Alejandro; Corona-López, Angélica María; Rios, María Yolanda; Aguilar-Guadarrama, Berenice; Toledo-Hernández, Víctor Hugo; Rodríguez-López, Verónica; Valencia-Díaz, Susana

    2015-01-01

    Herbivory activates the synthesis of allelochemicals that can mediate plant-plant interactions. There is an inverse relationship between the activity of xylophages and the abundance of epiphytes on Ipomoea murucoides. Xylophagy may modify the branch chemical constitution, which also affects the liberation of allelochemicals with defense and allelopathic properties. We evaluated the bark chemical content and the effect of extracts from branches subjected to treatments of exclusion, mechanical damage and the presence/absence of epiphytes, on the seed germination of the epiphyte Tillandsia recurvata. Principal component analysis showed that branches without any treatment separate from branches subjected to treatments; damaged and excluded branches had similar chemical content but we found no evidence to relate intentional damage with allelopathy; however 1-hexadecanol, a defense volatile compound correlated positively with principal component (PC) 1. The chemical constitution of branches subject to exclusion plus damage or plus epiphytes was similar among them. PC2 indicated that palmitic acid (allelopathic compound) and squalene, a triterpene that attracts herbivore enemies, correlated positively with the inhibition of seed germination of T. recurvata. Inhibition of seed germination of T. recurvata was mainly correlated with the increment of palmitic acid and this compound reached higher concentrations in excluded branches treatments. Then, it is likely that the allelopathic response of I. murucoides would increase to the damage (shade, load) that may be caused by a high load of epiphytes than to damage caused by the xylophages. PMID:26625350

  10. Theoretical analysis for temperature dependence of laser- induced damage threshold of optical thin films

    NASA Astrophysics Data System (ADS)

    Mikami, K.; Motokoshi, S.; Somekawa, T.; Jitsuno, T.; Fujita, M.; Tanaka, KA; Azechi, H.

    2016-03-01

    The temperature dependence of the laser-induced damage threshold on optical coatings was studied in detail for laser pulses from 123 K to 473 K at different temperatures. The laser-induced damage threshold increased with decreasing temperatures when we tested long pulses (200 ps and 4 ns). The temperature dependence, however, was reversed for pulses shorter than a few picoseconds (100 fs testing). We propose a scaling model with a flowchart that includes three separate processes: free-electron generation, electron multiplication, and electron heating. Furthermore, we calculated the temperature dependence of laser-induced damage thresholds at different temperatures. Our calculation results agreed well with the experimental results.

  11. Vorinostat Induces Reactive Oxygen Species and DNA Damage in Acute Myeloid Leukemia Cells

    PubMed Central

    Pettersson, Filippa; Retrouvey, Hélène; Skoulikas, Sophia; Miller, Wilson H.

    2011-01-01

    Histone deacetylase inhibitors (HDACi) are promising anti-cancer agents, however, their mechanisms of action remain unclear. In acute myeloid leukemia (AML) cells, HDACi have been reported to arrest growth and induce apoptosis. In this study, we elucidate details of the DNA damage induced by the HDACi vorinostat in AML cells. At clinically relevant concentrations, vorinostat induces double-strand breaks and oxidative DNA damage in AML cell lines. Additionally, AML patient blasts treated with vorinostat display increased DNA damage, followed by an increase in caspase-3/7 activity and a reduction in cell viability. Vorinostat-induced DNA damage is followed by a G2-M arrest and eventually apoptosis. We found that pre-treatment with the antioxidant N-acetyl cysteine (NAC) reduces vorinostat-induced DNA double strand breaks, G2-M arrest and apoptosis. These data implicate DNA damage as an important mechanism in vorinostat-induced growth arrest and apoptosis in both AML cell lines and patient-derived blasts. This supports the continued study and development of vorinostat in AMLs that may be sensitive to DNA-damaging agents and as a combination therapy with ionizing radiation and/or other DNA damaging agents. PMID:21695163

  12. Lightning Strike Induced Damage Mechanisms of Carbon Fiber Composites

    NASA Astrophysics Data System (ADS)

    Kawakami, Hirohide

    Composite materials have a wide application in aerospace, automotive, and other transportation industries, because of the superior structural and weight performances. Since carbon fiber reinforced polymer composites possess a much lower electrical conductivity as compared to traditional metallic materials utilized for aircraft structures, serious concern about damage resistance/tolerance against lightning has been rising. Main task of this study is to clarify the lightning damage mechanism of carbon fiber reinforced epoxy polymer composites to help further development of lightning strike protection. The research on lightning damage to carbon fiber reinforced polymer composites is quite challenging, and there has been little study available until now. In order to tackle this issue, building block approach was employed. The research was started with the development of supporting technologies such as a current impulse generator to simulate a lightning strike in a laboratory. Then, fundamental electrical properties and fracture behavior of CFRPs exposed to high and low level current impulse were investigated using simple coupon specimens, followed by extensive parametric investigations in terms of different prepreg materials frequently used in aerospace industry, various stacking sequences, different lightning intensity, and lightning current waveforms. It revealed that the thermal resistance capability of polymer matrix was one of the most influential parameters on lightning damage resistance of CFRPs. Based on the experimental findings, the semi-empirical analysis model for predicting the extent of lightning damage was established. The model was fitted through experimental data to determine empirical parameters and, then, showed a good capability to provide reliable predictions for other test conditions and materials. Finally, structural element level lightning tests were performed to explore more practical situations. Specifically, filled-hole CFRP plates and patch

  13. The processes controlling damage zone propagation induced by wellbore fluid injection

    NASA Astrophysics Data System (ADS)

    Shalev, Eyal; Lyakhovsky, Vladimir

    2013-04-01

    Induced seismicity by wellbore fluid injection is an important tool for enhancing permeability in hydrocarbon and geothermal reservoirs. We model nucleation and propagation of damage zones and seismicity patterns for two-dimensional plane strain configuration at a depth of 5 km using novel numerical software developed in the course of this study. Simulations include the coupling of poro-elastic deformation and groundwater flow with damage evolution (weakening and healing) and its effect on the elastic and hydrologic parameters. Results show that the process occurring during fluid injection can be divided into four stages. The duration of each stage depends on the hydrological and mechanical parameters. Initially, fluid flows into the rock with no seismic events (5 to 20 hr). At this stage, damage increases from 0 to 1 creating two sets of conjugate zones (four narrow damage zones). Thereafter, the occurrence of seismic events and faulting begins and accelerates for the next 20 to 70 hr. At the initial part of this stage, two of the damage zones create stress shadows on the other two damage zones that stop progressing. The velocity of the advancing damage is limited only by the rock parameters controlling damage evolution. At the third stage, which lasts for the following 20-30 hr, damage acceleration decreases because fluid transport becomes a limiting factor as the damage zones are too long to efficiently transfer the pressure from the well to the tip of the damage zones. Finally, the damage decelerates and even stops in some cases. The propagation of damage is controlled and limited by fluid transport from the injection well to the tip of the damage zones because fluid transport does not keep up with the dilatancy of the damage zones. The time and distance of propagation depend on the damage-permeability coupling and the remote shear stress. Higher remote shear stress causes shorter initial periods of no seismicity; strong damage-permeability coupling causes

  14. Electron flow through biological molecules: Does hole hopping protect proteins from oxidative damage?

    PubMed Central

    Winkler, Jay R.; Gray, Harry B.

    2016-01-01

    Biological electron transfers often occur between metal-containing cofactors that are separated by very large molecular distances. Employing photosensitizer-modified iron and copper proteins, we have shown that single-step electron tunneling can occur on nanosecond to microsecond timescales at distances between 15 and 20 angstroms. We also have shown that charge transport can occur over even longer distances by hole hopping (multistep tunneling) through intervening tyrosines and tryptophans. In this Perspective, we advance the hypothesis that such hole hopping through Tyr/Trp chains could protect oxygenase, dioxygenase, and peroxidase enzymes from oxidative damage. In support of this view, by examining the structures of P450 (CYP102A) and 2OG-Fe (TauD) enzymes, we have identified candidate Tyr/Trp chains that could transfer holes from uncoupled high-potential intermediates to reductants in contact with protein surface sites. PMID:26537399

  15. DNA damage as a biological marker in aquatic organisms exposed to benzo(a)pyrene

    SciTech Connect

    Shugart, L.R.; Jimenez, B.D.; McCarthy, J.F.

    1987-01-01

    We show that minute quantities of BaPDE-DNA adducts in the liver of bluegill sunfish can be detected and quantitated using a simple analytical technique whose sensitivity depends upon the intrinsic fluorescence of the specific adduct being analyzed. These adducts represent damage to DNA of the organism, which, if left uncorrected, could trigger a sequence of events that culminate in the appearance of an overt malignancy. We believe that the data reported here demonstrate that the covalent interaction of genotoxic chemicals with cellular macromolecules such as DNA is, potentially, a sensitive biological marker which could be of early predictive value in assessing exposure and its significance. 13 refs., 1 fig., 1 tab.

  16. Modelling blast induced damage from a fully coupled explosive charge

    PubMed Central

    Onederra, Italo A.; Furtney, Jason K.; Sellers, Ewan; Iverson, Stephen

    2015-01-01

    This paper presents one of the latest developments in the blasting engineering modelling field—the Hybrid Stress Blasting Model (HSBM). HSBM includes a rock breakage engine to model detonation, wave propagation, rock fragmentation, and muck pile formation. Results from two controlled blasting experiments were used to evaluate the code’s ability to predict the extent of damage. Results indicate that the code is capable of adequately predicting both the extent and shape of the damage zone associated with the influence of point-of-initiation and free-face boundary conditions. Radial fractures extending towards a free face are apparent in the modelling output and matched those mapped after the experiment. In the stage 2 validation experiment, the maximum extent of visible damage was of the order of 1.45 m for the fully coupled 38-mm emulsion charge. Peak radial velocities were predicted within a relative difference of only 1.59% at the nearest history point at 0.3 m from the explosive charge. Discrepancies were larger further away from the charge, with relative differences of −22.4% and −42.9% at distances of 0.46 m and 0.61 m, respectively, meaning that the model overestimated particle velocities at these distances. This attenuation deficiency in the modelling produced an overestimation of the damage zone at the corner of the block due to excessive stress reflections. The extent of visible damage in the immediate vicinity of the blasthole adequately matched the measurements. PMID:26412978

  17. Long-term biological effects induced by ionizing radiation--implications for dose mediated risk.

    PubMed

    Miron, S D; Astărăstoae, V

    2014-01-01

    Ionizing radiations are considered to be risk agents that are responsible for the effects on interaction with living matter. The occurring biological effects are due to various factors such as: dose, type of radiation, exposure time, type of biological tissue, health condition and the age of the person exposed. The mechanisms involved in the direct modifications of nuclear DNA and mitochondrial DNA are reviewed. Classical target theory of energy deposition in the nucleus that causes DNA damages, in particular DNA double-strand breaks and that explanation of the biological consequences of ionizing radiation exposure is a paradigm in radiobiology. Recent experimental evidences have demonstrated the existence of a molecular mechanism that explains the non-targeted effects of ionizing radiation exposure. Among these novel data, genomic instability and a variety of bystander effects are discussed here. Those bystander effects of ionizing radiation are fulfilled by cellular communication systems that give rise to non-targeted effects in the neighboring non irradiated cells. This paper provides also a commentary on the synergistic effects induced by the co-exposures to ionizing radiation and various physical agents such as electromagnetic fields and the co-exposures to ionizing radiation and chemical environmental contaminants such as metals. The biological effects of multiple stressors on genomic instability and bystander effects are also discussed. Moreover, a brief presentation of the methods used to characterize cyto- and genotoxic damages is offered. PMID:25341291

  18. Variation of the enhanced biologically damaging solar UV due to clouds.

    PubMed

    Parisi, Alfio V; Downs, Nathan

    2004-07-01

    The variation of the biologically damaging solar UV (UVBE) enhanced by clouds above that of clear sky UVBE has been investigated. This was undertaken for summer through to winter for SZA of 5 to 60 degrees employing an integrated automatic cloud and spectral UV measurement system that recorded the solar UV spectra and the sky images at five minute intervals. The UVBE calculated with action spectra with higher relative effectiveness in the UVA produced the lower percentage of cloud enhanced cases. The DNA UVBE provided the highest percentage of cloud enhanced cases compared to the total number of UV scans with 2.2% cloud enhanced cases. As a comparison, the plant and fish melanoma UVBE provided the lowest percentage of cloud enhanced cases with 0.6 to 0.8% cloud enhanced cases. For the cases of cloud enhanced UVBE, the average ratio of the measured UVBE to calculated cloud free UVBE for the photokeratitis, cataracts, plant, generalized plant damage and fish melanoma action spectra was 1.21 to 1.25. In comparison, the highest value of 1.4 was for the DNA action spectrum. PMID:15238998

  19. Activation-induced and damage-induced cell death in aging human T cells.

    PubMed

    Sikora, Ewa

    2015-11-01

    In multicellular organisms the proper system functionality is ensured by the balance between cell division, differentiation, senescence and death. This balance is changed during aging. Immunosenescence plays a crucial role in aging and leads to the shrinkage of T cell repertoire and the propensity to apoptosis. The elimination of expanded T cells at the end of immune response is crucial to maintain homeostasis and avoid any uncontrolled inflammation. Resting mature T lymphocytes, when activated via their antigen-specific receptor (TCR) and CD28 co-receptor, start to proliferate and then undergo the so called activation induced cell death (AICD), which mechanistically is triggered by the death receptor and leads to apoptosis. T lymphocytes, like other cells, are also exposed to damage, which can trigger the so called damage-induced cell death (DICD). It was hypothesized that oxidative stress and chronic antigenic load increasing with age reduced lymphocyte susceptibility to DICD and enhanced a proinflamatory status leading to increased AICD. However, data collected so far are inconsistent and does not support this assumption. Systematic and comprehensive studies are still needed for conclusive elucidation of the role of AICD and DICD in human immunosenescence, including the role of autophagy and necroptosis in the processes. PMID:25843236

  20. Ceramide Production Mediates Aldosterone-Induced Human Umbilical Vein Endothelial Cell (HUVEC) Damages

    PubMed Central

    Zhang, Yumei; Pan, Yu; Bian, Zhixiang; Chen, Peihua; Zhu, Shijian; Gu, Huiyi; Guo, Liping; Hu, Chun

    2016-01-01

    Here, we studied the underlying mechanism of aldosterone (Aldo)-induced vascular endothelial cell damages by focusing on ceramide. We confirmed that Aldo (at nmol/L) inhibited human umbilical vein endothelial cells (HUVEC) survival, and induced considerable cell apoptosis. We propose that ceramide (mainly C18) production might be responsible for Aldo-mediated damages in HUVECs. Sphingosine-1-phosphate (S1P), an anti-ceramide lipid, attenuated Aldo-induced ceramide production and following HUVEC damages. On the other hand, the glucosylceramide synthase (GCS) inhibitor PDMP or the ceramide (C6) potentiated Aldo-induced HUVEC apoptosis. Eplerenone, a mineralocorticoid receptor (MR) antagonist, almost completely blocked Aldo-induced C18 ceramide production and HUVEC damages. Molecularly, ceramide synthase 1 (CerS-1) is required for C18 ceramide production by Aldo. Knockdown of CerS-1 by targeted-shRNA inhibited Aldo-induced C18 ceramide production, and protected HUVECs from Aldo. Reversely, CerS-1 overexpression facilitated Aldo-induced C18 ceramide production, and potentiated HUVEC damages. Together, these results suggest that C18 ceramide production mediates Aldo-mediated HUVEC damages. MR and CerS-1 could be the two signaling molecule regulating C18 ceramide production by Aldo. PMID:26788916

  1. Cryptococcus neoformans-induced macrophage lysosome damage crucially contributes to fungal virulence1

    PubMed Central

    Davis, Michael J.; Eastman, Alison J.; Qiu, Yafeng; Gregorka, Brian; Kozel, Thomas R.; Osterholzer, John J.; Curtis, Jeffrey L.; Swanson, Joel A.; Olszewski, Michal A.

    2015-01-01

    Upon ingestion by macrophages, Cryptococcus neoformans (Cn) can survive and replicate intracellularly unless the macrophages become classically activated. The mechanism enabling intracellular replication is not fully understood; neither are the mechanisms which allow classical activation to counteract replication. Cn-induced lysosome damage was observed in infected murine bone marrow-derived macrophages, increased with time and required yeast viability. To demonstrate lysosome damage in the infected host, we developed a novel flow-cytometric method for measuring lysosome damage. Increased lysosome damage was found in Cn-containing lung cells compared to Cn–free cells. Among Cn-containing myeloid cells, recently recruited cells displayed lower damage than resident cells, consistent with the protective role of recruited macrophages. The magnitude of lysosome damage correlated with increased Cn replication. Experimental induction of lysosome damage increased Cn replication. Activation of macrophages with IFN-γ abolished macrophage lysosome damage and enabled increased killing of Cn. We conclude that induction of lysosome damage is an important Cn survival strategy and that classical activation of host macrophages counters replication by preventing damage. Thus, therapeutic strategies which decrease lysosomal damage, or increase resistance to such damage, could be valuable in treating cryptococcal infections. PMID:25637026

  2. Description of particle induced damage on protected silver coatings.

    PubMed

    Schwinde, Stefan; Schürmann, Mark; Jobst, Paul Johannes; Kaiser, Norbert; Tünnermann, Andreas

    2015-06-01

    In the visible to infrared spectral range, highly-reflective silver mirrors are applied in the manufacture of optical instruments such as telescopes. However, it is still difficult to combine high reflectivity and long-term stability of the protected silver coating. We show that the deposition of impervious protective layers is necessary but often not sufficient for long-term environmental stability. Hygroscopic air borne particles absorbed by the protections surface attract water molecules and form a solution. This solution first damages the protection, subsequently permeates the protection and finally damages the silver whereby the reflectivity is reduced. We demonstrate this particular damage mechanism with different experiments and describe this mechanism in detail. PMID:26192652

  3. Properties of defect-induced multiple pulse laser damage of transmission components.

    PubMed

    Ma, Bin; Zhang, Li; Lu, Menglei; Wang, Ke; Jiao, Hongfei; Zhang, Jinlong; Cheng, Xinbin; Yang, Liming; Wang, Zhanshan

    2016-09-01

    When the number of laser pulses increases, the laser-induced damage threshold of the optical components gradually declines. The magnitude and tendency of this reduced threshold are associated with various factors. Furthermore, this reduced threshold is conclusively determined by the limiting factors or defect characteristics that trigger damage to optical components. Then, fully understanding the damage properties of different kinds of defects will contribute to the optimization of the performance and lifetime of the optical components. In this study, the statistical and deterministic characterizations of the fatigue effect are used to evaluate the properties of the multiple pulse laser damage of transmission components. First, the influence of spot sizes and polishing materials on the properties of the multiple pulse laser damage of optical components is discussed. Then, the structural, absorptive, and mixed artificial defects are fabricated, and the damage characteristics are evaluated and analyzed. Finally, the damage mechanism of different factors has been clarified. PMID:27607284

  4. Oxidative DNA damage induced by a metabolite of 2-naphthylamine, a smoking-related bladder carcinogen.

    PubMed

    Ohnishi, Shiho; Murata, Mariko; Kawanishi, Shosuke

    2002-07-01

    2-Naphthylamine (2-NA), a bladder carcinogen, is contained in cigarette smoke. DNA adduct formation is thought to be a major cause of DNA damage by carcinogenic aromatic amines. We have investigated whether a metabolite of 2-NA, 2-nitroso-1-naphthol (NO-naphthol) causes oxidative DNA damage, using (32)P-labeled DNA fragments. We compared the mechanism of DNA damage induced by NO-naphthol with that by N-hydroxy-4-aminobiphenyl (4-ABP(NHOH)), a metabolite of 4-aminobiphenyl, another smoking-related bladder carcinogen. NO-naphthol caused Cu(II)-mediated DNA damage at T > C > G residues, with non-enzymatic reduction by NADH. Catalase and bathocuproine, a Cu(I)-specific chelator, inhibited the DNA damage, suggesting the involvement of H(2)O(2) and Cu(I). Some free. OH scavengers also attenuated NO-naphthol-induced DNA damage, while free. OH scavengers had no effect on the DNA damage induced by 4-ABP(NHOH). This difference suggests that the reactive species formed by NO-naphthol has more free. OH-character than that by 4-ABP(NHOH). A high-pressure liquid chromatograph equipped with an electrochemical detector showed that NO-naphthol induced 8-oxo-7,8-dihydro-2'-deoxyguanosine formation in the presence of NADH and Cu(II). The oxidative DNA damage by these amino-aromatic compounds may participate in smoking-related bladder cancer, in addition to DNA adduct formation. PMID:12149138

  5. The Effects of Creatine Supplementation on Exercise-Induced Muscle Damage.

    ERIC Educational Resources Information Center

    Rawson, Eric S.; Gunn, Bridget; Clarkson, Priscilla M.

    2001-01-01

    Investigated the effects of oral creatine (Cr) supplementation on markers of exercise-induced muscle damage following high-force eccentric exercise in men randomly administered Cr or placebo. Results indicated that 5 days of Cr supplementation did not reduce indirect makers of muscle damage or enhance recovery from high-force eccentric exercise.…

  6. BHT blocks NfkB activation and Ethanol-Induced Brain Damage

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Binge ethanol administration causes corticolimbic brain damage that models alcoholic neurodegeneration. The mechanism of binge ethanol induced degeneration is unknown, but is not glutamate neurotoxicity. To test the hypothesis that oxidative stress and inflammation are mechanisms of binge ethanol ...

  7. Catastrophic nanosecond laser induced damage in the bulk of potassium titanyl phosphate crystals

    SciTech Connect

    Wagner, Frank R. Natoli, Jean-Yves; Akhouayri, Hassan; Commandré, Mireille; Duchateau, Guillaume

    2014-06-28

    Due to its high effective nonlinearity and the possibility to produce periodically poled crystals, potassium titanyl phosphate (KTiOPO{sub 4}, KTP) is still one of the economically important nonlinear optical materials. In this overview article, we present a large study on catastrophic nanosecond laser induced damage in this material and the very similar RbTiOPO{sub 4} (RTP). Several different systematic studies are included: multiple pulse laser damage, multi-wavelength laser damage in KTP, damage resistance anisotropy, and variations of the laser damage thresholds for RTP crystals of different qualities. All measurements were carried out in comparable experimental conditions using a 1064 nm Q-switched laser and some were repeated at 532 nm. After summarizing the experimental results, we detail the proposed model for laser damage in this material and discuss the experimental results in this context. According to the model, nanosecond laser damage is caused by light-induced generation of transient laser-damage precursors which subsequently provide free electrons that are heated by the same nanosecond pulse. We also present a stimulated Raman scattering measurement and confront slightly different models to the experimental data. Finally, the physical nature of the transient damage precursors is discussed and similarities and differences to laser damage in other crystals are pointed out.

  8. Oxidative DNA damage induced by di-(2-ethylhexyl) phthalate in HEK-293 cell line.

    PubMed

    Wang, Xuan; Jiang, Lijie; Ge, Lan; Chen, Min; Yang, Guang; Ji, Fang; Zhong, Laifu; Guan, Yingjie; Liu, Xiaofang

    2015-05-01

    Di-(2-ethylhexyl) phthalate (DEHP) is commonly employed as a plasticizer. We have found that exposure of human embryonic kidney cell line 293 (HEK-293) to DEHP resulted in a crucial dose-dependent increase of DNA strand breaks in a comet assay. To elucidate the role of glutathione (GSH) in the DNA damage, the cells were pretreated with buthionine-(S,R)-sulfoximine (BSO) and pretreated with N-acetylcysteine (NAC), a GSH precursor. Here we show that depletion of GSH in HEK-293 cells with BSO dramatically increased the susceptibility of HEK-293 cells to DEHP-induced DNA damage. Furthermore, when the intracellular GSH content was elevated by NAC, the DNA damage induced by DEHP was almost completely abolished. In addition, DEHP had effect on lysosomal or mitochondrial damage at high dose level. These results indicate that DEHP exerts genotoxic effects in HEK-293 cells, probably through DNA damage induced by oxidative stress; GSH is responsible for cellular defense against DEHP-induced DNA damage; lysosome and mitochondria may be the vital targets in DEHP-induced DNA damage. PMID:25899473

  9. Autophosphorylation and Pin1 binding coordinate DNA damage-induced HIPK2 activation and cell death.

    PubMed

    Bitomsky, Nadja; Conrad, Elisa; Moritz, Christian; Polonio-Vallon, Tilman; Sombroek, Dirk; Schultheiss, Kathrin; Glas, Carolina; Greiner, Vera; Herbel, Christoph; Mantovani, Fiamma; del Sal, Giannino; Peri, Francesca; Hofmann, Thomas G

    2013-11-01

    Excessive genome damage activates the apoptosis response. Protein kinase HIPK2 is a key regulator of DNA damage-induced apoptosis. Here, we deciphered the molecular mechanism of HIPK2 activation and show its relevance for DNA damage-induced apoptosis in cellulo and in vivo. HIPK2 autointeracts and site-specifically autophosphorylates upon DNA damage at Thr880/Ser882. Autophosphorylation regulates HIPK2 activity and mutation of the phosphorylation-acceptor sites deregulates p53 Ser46 phosphorylation and apoptosis in cellulo. Moreover, HIPK2 autophosphorylation is conserved between human and zebrafish and is important for DNA damage-induced apoptosis in vivo. Mechanistically, autophosphorylation creates a binding signal for the phospho-specific isomerase Pin1. Pin1 links HIPK2 activation to its stabilization by inhibiting HIPK2 polyubiquitination and modulating Siah-1-HIPK2 interaction. Concordantly, Pin1 is required for DNA damage-induced HIPK2 stabilization and p53 Ser46 phosphorylation and is essential for induction of apotosis both in cellulo and in zebrafish. Our results identify an evolutionary conserved mechanism regulating DNA damage-induced apoptosis. PMID:24145406

  10. Automated cell inspection systems for the determination of DNA damage and repair in the biological research

    NASA Astrophysics Data System (ADS)

    Boecker, Wilfried

    1997-10-01

    One important field of interest in medicine and biology is the evaluation of DNA repair and cellular DNA damage after physical or chemical treatment. Manual analysis has some disadvantages such as a decrease in recognition ability during the time consuming observations as well as a requirement of experts for microscopic investigations. Therefore, automatic inspection and recognition of biological structures in several applications such as fluorescence in situ hybridization (FISH), fluorescence immuno-assays, comet-assay, chromosome karyotyping and micronucleus assay have been considerably advanced in the last decade. This presentation will give an overview of the image analysis and pattern recognition methods employed in different automated cell inspection systems which have been developed in our institute during the last years. Depending on the kind of assay, different experimental setups must be used in order to extract the respective measurement quantities. For example FISH technique requires a very sensitive fluorescence microscope combined with an image intensified target or time integrating camera. The major algorithms for image preprocessing and image segmentation based on mathematical morphology are briefly introduced. Feature classification is carried out with different methods.