Science.gov

Sample records for biological damage induced

  1. Early mechanisms in radiation-induced biological damage

    SciTech Connect

    Powers, E.L.

    1983-01-01

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

  2. Mechanisms of microwave-induced damage in biologic materials

    SciTech Connect

    Litovitz, T.A.; Meister, R.; Mohr, R.K.; Montrose, C.J.; Mullins, J.M.

    1990-01-01

    This report is divided into four chapters which correspond to the four main lines of research being carried out under the contract. In brief, these are (1) mathematical modeling studies, (2) experimental spectroscopic studies, (3) engineering design research, and (4) experimental biological studies. The research program is structured to attempt to discover the biological effects at the cell and molecular level that result from exposure to electromagnetic radiation. The main thrust is on the athermal effects of exposure to microwaves. Because recent work has suggested that significant cellular effects occur only when the microwaves are amplitude modulated, either with extremely low frequency (ELF) sinusoids or with pulses, we have hypothesized that the interaction of the microwave fields with cells must involve a demodulation or detection step. As a result, research designed to develop an understanding of the effects of direct ELF exposure becomes not only relevant, but vital.

  3. Mechanisms of Microwave Induced Damage in Biologic Materials

    DTIC Science & Technology

    1990-01-01

    the PhD thesis research of Babak Saif, a graduate student in our laboratory. For DNA solutions of similar DNA concentration he studied the effect of...6260 Research & Development CommanI 8C. ADDRESS (City, State, and ZIP Code) 10. SOURCE OF FUNDING NUMBERS Fort Detrick PROGRAM PROJECT TASK WORK UNIT...these are (1) mathematical model- ing studies, (2) experimental spectroscopic studies, (3) engineering design research , and (4) experimental biological

  4. The yield, processing, and biological consequences of clustered DNA damage induced by ionizing radiation.

    PubMed

    Shikazono, Naoya; Noguchi, Miho; Fujii, Kentaro; Urushibara, Ayumi; Yokoya, Akinari

    2009-01-01

    After living cells are exposed to ionizing radiation, a variety of chemical modifications of DNA are induced either directly by ionization of DNA or indirectly through interactions with water-derived radicals. The DNA lesions include single strand breaks (SSB), base lesions, sugar damage, and apurinic/apyrimidinic sites (AP sites). Clustered DNA damage, which is defined as two or more of such lesions within one to two helical turns of DNA induced by a single radiation track, is considered to be a unique feature of ionizing radiation. A double strand break (DSB) is a type of clustered DNA damage, in which single strand breaks are formed on opposite strands in close proximity. Formation and repair of DSBs have been studied in great detail over the years as they have been linked to important biological endpoints, such as cell death, loss of genetic material, chromosome aberration. Although non-DSB clustered DNA damage has received less attention, there is growing evidence of its biological significance. This review focuses on the current understanding of (1) the yield of non-DSB clustered damage induced by ionizing radiation (2) the processing, and (3) biological consequences of non-DSB clustered DNA damage.

  5. Biological consequences of radiation-induced DNA damage: relevance to radiotherapy.

    PubMed

    Lomax, M E; Folkes, L K; O'Neill, P

    2013-10-01

    DNA damage of exposed tumour tissue leading to cell death is one of the detrimental effects of ionising radiation that is exploited, with beneficial consequences, for radiotherapy. The pattern of the discrete energy depositions during passage of the ionising track of radiation defines the spatial distribution of lesions induced in DNA with a fraction of the DNA damage sites containing clusters of lesions, formed over a few nanometres, against a background of endogenously induced individual lesions. These clustered DNA damage sites, which may be considered as a signature of ionising radiation, underlie the deleterious biological consequences of ionising radiation. The concepts developed rely in part on the fact that ionising radiation creates significant levels of clustered DNA damage, including complex double-strand breaks (DSB), to kill tumour cells as clustered damage sites are difficult to repair. This reduced repairability of clustered DNA damage using specific repair pathways is exploitable in radiotherapy for the treatment of cancer. We discuss some potential strategies to enhance radiosensitivity by targeting the repair pathways of radiation-induced clustered damage and complex DNA DSB, through inhibition of specific proteins that are not required in the repair pathways for endogenous damage. The variety and severity of DNA damage from ionising radiation is also influenced by the tumour microenvironment, being especially sensitive to the oxygen status of the cells. For instance, nitric oxide is known to influence the types of damage induced by radiation under hypoxic conditions. A potential strategy based on bioreductive activation of pro-drugs to release nitric oxide is discussed as an approach to deliver nitric oxide to hypoxic tumours during radiotherapy. The ultimate aim of this review is to stimulate thinking on how knowledge of the complexity of radiation-induced DNA damage may contribute to the development of adjuncts to radiotherapy. Copyright

  6. Modeling electrical power absorption and thermally-induced biological tissue damage.

    PubMed

    Zohdi, T I

    2014-01-01

    This work develops a model for thermally induced damage from high current flow through biological tissue. Using the first law of thermodynamics, the balance of energy produced by the current and the energy absorbed by the tissue are investigated. The tissue damage is correlated with an evolution law that is activated upon exceeding a temperature threshold. As an example, the Fung material model is used. For certain parameter choices, the Fung material law has the ability to absorb relatively significant amounts of energy, due to its inherent exponential response character, thus, to some extent, mitigating possible tissue damage. Numerical examples are provided to illustrate the model's behavior.

  7. 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.

  8. Neuroglobin - a potential biological marker of retinal damage induced by LED light.

    PubMed

    Yu, Z-L; Qiu, S; Chen, X-C; Dai, Z-H; Huang, Y-C; Li, Y-N; Cai, R-H; Lei, H-T; Gu, H-Y

    2014-06-13

    Neuroglobin (NGB), a protein highly expressed in the retina, has been shown to be up-regulated to protect neurons from hypoxic and ischemic injuries. It exhibits neuroprotective functions and plays an important role in the survival of neurons. Recent studies show that light-emitting diode (LED) white light emitted significant amounts of blue light (short-wavelength), which may be harmful to retinal cells, but the studies about biomarkers for evaluating the damage from LED white light are still insufficient. In our study, we found that NGB levels in the retina showed a twofold increase and peaked at 1h after a 1-h exposure to blue light (453 nm) which did not cause damage to the retina. However, retinal damage was observed after 2h of blue-light irradiation, which induced an approximate sevenfold increase of NGB levels as confirmed by Western blot and RT-PCR analysis. Immunofluorescence study demonstrated that NGB was predominantly up-regulated in the ganglion cell layer (GCL), plexiform layer (PL) and photoreceptor layer (PRL). We also examined Ngb mRNA and protein expression in the damaged retina induced by light of other wavelengths given equal photon fluxes. The LED red light (625 nm), green light (527 nm) and blue light (453 nm) increased the expression of NGB and caused TdT-mediated dUTP nick-end labeling-positive cells, especially in the blue-light group. In addition, a negative correlation between NGB and rhodopsin was observed. These findings suggested that there was a correlation between NGB expression and the severity of the retinal damage, indicating NGB's potential function as a biological marker of retinal damage induced by LED light. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  9. 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.

  10. Shock wave induces biological renal damage by activating excessive inflammatory responses in rat model.

    PubMed

    Li, Xiang; Long, Qingzhi; Cheng, Xinfa; He, Dalin

    2014-08-01

    The study was aimed to investigate the potential mechanism of inflammatory renal damage induced by shock wave. A total of 48 rats, with the right kidney cut, are randomly assigned into control group, ESWL group and ESWL + PDTC group. Rats were treated with shock wave at the left kidney. At post-shock wave 3 and 105 days, all the animals were sacrificed for detecting the expression of tumor necrosis factor (TNF)-α, intercellular adhesion molecule (ICAM)-1, and monocyte chemoattractant protein (MCP)-1. The inflammatory responses were evaluated by detecting the level of myeloperoxidase (MPO) and ED-1. The histological renal injury was also examined. Before the animals were sacrificed, the urine samples were collected for measuring the values of malondialdehyde (MDA), β2-microglobulin, interleukin (IL)-6, and IL-18. At post-shock wave 3 days, the higher expression of ICAM-1 and TNF-α were observed in shock wave-treated kidneys. The level of urine TNF-α, IL-6, and IL-18 were also increased significantly. Using PDTC obviously decreased the expression of ICAM-1 and TNF-α. It also effectively inhibited the degree of oxidative stress and neutrophil infiltration. At post-shock wave 105 days, the expression of MCP-1 and the level of urine β2-microglobulin and IL-18 were increased significantly. The histological analysis also indicated more ED-1-positive cells and serious fibrosis in shock wave-treated kidneys. PDTC significantly suppressed MCP-1 and IL-18 expression, decreased monocyte infiltration, and alleviate the degree of interstitium fibrosis. Shock wave triggered excessive inflammatory responses and aggravated renal biological damage. Several inflammatory factors including ICAM-1, MCP-1, and TNF-α were considered to play important role in this type of renal damage.

  11. Wavelength dependence of biological damage induced by UV radiation on bacteria.

    PubMed

    Santos, Ana L; Oliveira, Vanessa; Baptista, Inês; Henriques, Isabel; Gomes, Newton C M; Almeida, Adelaide; Correia, António; Cunha, Ângela

    2013-01-01

    The biological effects of UV radiation of different wavelengths (UVA, UVB and UVC) were assessed in nine bacterial isolates displaying different UV sensitivities. Biological effects (survival and activity) and molecular markers of oxidative stress [DNA strand breakage (DSB), generation of reactive oxygen species (ROS), oxidative damage to proteins and lipids, and the activity of antioxidant enzymes catalase and superoxide dismutase] were quantified and statistically analyzed in order to identify the major determinants of cell inactivation under the different spectral regions. Survival and activity followed a clear wavelength dependence, being highest under UVA and lowest under UVC. The generation of ROS, as well as protein and lipid oxidation, followed the same pattern. DNA damage (DSB) showed the inverse trend. Multiple stepwise regression analysis revealed that survival under UVA, UVB and UVC wavelengths was best explained by DSB, oxidative damage to lipids, and intracellular ROS levels, respectively.

  12. 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.

  13. Radiation-induced damage to cellular DNA: measurement and biological role

    NASA Astrophysics Data System (ADS)

    Cadet, Jean; Douki, Thierry; Gasparutto, Didier; Ravanat, Jean-Luc

    2005-02-01

    Emphasis is placed in this short review on recent developments concerning several aspects of the chemical and biochemical effects of ionizing radiation on both isolated and cellular DNA. This includes the mechanism of formation of single and tandem DNA lesions upon one-electron oxidation and one hydroxyl radical hit only. Information is also provided on the specificity of DNA repair enzymes and the measurement of radiation-induced damage in cellular DNA.

  14. 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

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

    DOE PAGES

    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

  16. 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

  17. Biological consequences of formation and repair of complex DNA damage.

    PubMed

    Magnander, Karin; Elmroth, Kecke

    2012-12-31

    Endogenous processes or genotoxic agents can induce many types of single DNA damage (single-strand breaks, oxidized bases and abasic sites). In addition, ionizing radiation induces complex lesions such as double-strand breaks and clustered damage. To preserve the genomic stability and prevent carcinogenesis, distinct repair pathways have evolved. Despite this, complex DNA damage can cause severe problems and is believed to contribute to the biological consequences observed in cells exposed to genotoxic stress. In this review, the current knowledge of formation and repair of complex DNA damage is summarized and the risks and biological consequences associated with their repair are discussed. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  18. DNA Damage Induced Neuronal Death

    DTIC Science & Technology

    1999-10-01

    Experiments are proposed to examine the molecular mechanism by which mustard chemical warfare agents induce neuronal cell death . DNA damage is the...proposed underlying mechanism of mustard-induced neuronal cell death . We propose a novel research strategy to test this hypothesis by using mice with...perturbed DNA repair to explore the relationship between mustard-induced DNA damage and neuronal cell death . Initial in vitro studies (Years 1, 2 & 3

  19. Relative biological effectiveness of carbon ions for tumor control, acute skin damage and late radiation-induced fibrosis in a mouse model.

    PubMed

    Sørensen, Brita S; Horsman, Michael R; Alsner, Jan; Overgaard, Jens; Durante, Marco; Scholz, Michael; Friedrich, Thomas; Bassler, Niels

    2015-01-01

    The aim of the present study was to compare the biological effectiveness of carbon ions relative to x-rays between tumor control, acute skin reaction and late RIF of CDF1 mice. CDF1 mice with a C3H mouse mammary carcinoma implanted subcutaneously on the foot of the right hind limb were irradiated with single fractions of either photons, or (12)C ions using a 30-mm spread-out Bragg peak. The endpoint of the study was local control (no tumor recurrence within 90 days). For the acute skin reaction, non-tumor bearing CDF1 mice were irradiated with a comparable radiation scheme, and monitored for acute skin damage between Day 7 and 40. Late RIF was assessed in the irradiated mice. The TCD50 (dose producing tumor control in 50% of mice) values with 95% confidence interval were 29.7 (25.4-34.8) Gy for C ions and 43.9 (39.2-49.2) Gy for photons, with a corresponding Relative biological effectiveness (RBE) value of 1.48 (1.28-1.72). For acute skin damage the MDD50 (dose to produce moist desquamation in 50% of mice) values with 95% confidence interval were 26.3 (23.0-30.1) Gy for C ions and 35.8 (32.9-39.0) Gy for photons, resulting in a RBE of 1.36 (1.20-1.54). For late radiation-induced fibrosis the FD50 (dose to produce severe fibrosis in 50% of mice) values with 95% confidence interval were 26.5 (23.1-30.3) Gy for carbon ions and 39.8 (37.8-41.8) Gy for photons, with a RBE of 1.50 (1.33-1.69). The observed RBE values were very similar for tumor response, acute skin damage and late RIF when irradiated with large doses of high- linear energy transfer (LET) carbon ions. This study adds information to the variation in biological effectiveness in different tumor and normal tissue models.

  20. 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

  1. DNA damage as a biological sensor for environmental sunlight.

    PubMed

    Schuch, André Passaglia; Garcia, Camila Carrião Machado; Makita, Kazuo; Menck, Carlos Frederico Martins

    2013-08-01

    Solar ultraviolet (UV) radiation is widely known as an environmental genotoxic agent that affects ecosystems and the human population, generating concerns and motivating worldwide scientific efforts to better understand the role of sunlight in the induction of DNA damage, cell death, mutagenesis, and ultimately, carcinogenesis. In this review, general aspects of UV radiation at the Earth's surface are reported, considering measurements by physical and biological sensors that monitor solar UV radiation under different environmental conditions. The formation of DNA photoproducts and other types of DNA damage by different UV wavelengths are compared with the present information on their roles in inducing biological effects. Moreover, the use of DNA-based biological dosimeters is presented as a feasible molecular and cellular tool that is focused on the evaluation of DNA lesions induced by natural sunlight. Clearly, direct environmental measurements demonstrate the biological impact of sunlight in different locations worldwide and reveal how this affects the DNA damage profile at different latitudes. These tools are also valuable for the quantification of photoprotection provided by commercial sunscreens against the induction of DNA damage and cell death, employing DNA repair-deficient cells that are hypersensitive to sunlight. Collectively, the data demonstrate the applicability of DNA-based biosensors as alternative, complementary, and reliable methods for registering variations in the genotoxic impact of solar UV radiation and for determining the level of photoprotection sunscreens provided at the level of DNA damage and cell death.

  2. Damage to biological tissues induced by radical initiator 2,2'-azobis(2-amidinopropane) dihydrochloride and its inhibition by chain-breaking antioxidants.

    PubMed

    Terao, K; Niki, E

    1986-01-01

    A water-soluble azo compound, 2,2'-azobis(2-amidinopropane) dihydrochloride, a well-known free radical initiator, was administered intraperitoneally to mice to study the toxicological effects on biological tissues in vivo and their inhibition by chain-breaking antioxidants. It caused damage to biological tissues without biotransformation. No specific target organ was observed. The most striking fine structural changes were the degeneration, swelling, and disruption of the endothelium lining cells of the capillaries in various organs. Furthermore, the death of lymphocytes in the lymphoid tissues and the fatty degeneration of the liver and kidneys have also been observed. Water-soluble chain-breaking antioxidants, such as 2-carboxy-2,5,7,8-tetramethyl-6-chromanol (a vitamin E analogue), uric acid, cysteine, and glutathione suppressed the above damage, whereas vitamin C was ineffective.

  3. 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

  4. Effect of polishing induced subsurface damages on laser induced damage in fused silica optics

    NASA Astrophysics Data System (ADS)

    He, Xiang; Zhao, Heng; Huang, Ying; Cai, Chao; Hu, JiangChuan; Ma, Ping

    2016-10-01

    Conventional used ceria polishing would induce both of Ce contaminants and subsurface damages, which mainly restricts the laser induced damage resistance of fused silica optics. To control the near surface defects, nanometer sized colloidal silica are used to polish fused silica optics after the normal ceria polishing process. Then the contaminant elements and subsurface damages of the polished samples were analyzed by secondary ion mass spectrometry and Nomarski microscopy. It reveals that ceria polishing would introduce lots of subsurface damages whereas colloidal silica polishing induces much fewer subsurface damages especially no fracture induced severe subsurface damages. The laser damage tests reveal that subsequent colloidal silica polishing of the ceria pre-polished samples could gradually eliminate the ceria polishing induced subsurface damages and lower the laser induced damage density accordingly with the increased polishing time. But unlike the damage density, only the severe subsurface damages are totally eliminated could the damage threshold be substantially improved. These results incline to indicate that the subsurface damages have great influence on the laser induced damage density and the fracture related severe subsurface damages will greatly restrict the damage threshold in polished optics.

  5. 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

  6. DNA damage and biological effects induced by photosensitization with new N(1)-unsubstituted furo[2,3-h]quinolin-2(1H)-ones.

    PubMed

    Marzano, Cristina; Chilin, Adriana; Bordin, Franco; Baccichetti, Francarosa; Guiotto, Adriano

    2002-09-01

    New furoquinolinones unsubstituted at the N(1) position were prepared and their photobiological activities were studied in comparison with 4,6,8,9-tetramethylfuro[2,3-h]quinolin-2(1H)-one (HFQ) and 8-MOP. The anti-proliferative activity of furoquinolinones 3a-f was tested upon UVA irradiation in mammalian cells, studying DNA synthesis and clonal growth capacity, and in micro-organisms, evaluating T2 infectivity. Almost all compounds appeared to be more active than 8-MOP, and free of any mutagenic activity and skin phototoxicity. Among them, compound 3b was the most effective one. Similarly to HFQ, compound 3b appeared to be very active also in DNA damaging, forming monoadducts and DPC(L=0), but no ISC and DPC(L>0), both responsible for furocoumarin genotoxicity and phototoxicity. Moreover, Ehrlich ascites cells, photoinactivated by the new furoquinolinone 3b and injected into recipient mice, proved to be capable of inducing protection against a successive challenge performed with the same tumor cells. For all these features, 3b seemed to be a new promising potential drug for PUVA therapy and photopheresis.

  7. Muscle damage induced by electrical stimulation.

    PubMed

    Nosaka, Kazunori; Aldayel, Abdulaziz; Jubeau, Marc; Chen, Trevor C

    2011-10-01

    Electrical stimulation (ES) induces muscle damage that is characterised by histological alterations of muscle fibres and connective tissue, increases in circulating creatine kinase (CK) activity, decreases in muscle strength and development of delayed onset muscle soreness (DOMS). Muscle damage is induced not only by eccentric contractions with ES but also by isometric contractions evoked by ES. Muscle damage profile following 40 isometric contractions of the knee extensors is similar between pulsed current (75 Hz, 400 μs) and alternating current (2.5 kHz delivered at 75 Hz, 400 μs) ES for similar force output. When comparing maximal voluntary and ES-evoked (75 Hz, 200 μs) 50 isometric contractions of the elbow flexors, ES results in greater decreases in maximal voluntary contraction strength, increases in plasma CK activity and DOMS. It appears that the magnitude of muscle damage induced by ES-evoked isometric contractions is comparable to that induced by maximal voluntary eccentric contractions, although the volume of affected muscles in ES is not as large as that of eccentric exercise-induced muscle damage. It seems likely that the muscle damage in ES is associated with high mechanical stress on the activated muscle fibres due to the specificity of motor unit recruitment (i.e., non-selective, synchronous and spatially fixed manner). The magnitude of muscle damage induced by ES is significantly reduced when the second ES bout is performed 2-4 weeks later. It is possible to attenuate the magnitude of muscle damage by "pre-conditioning" muscles, so that muscle damage should not limit the use of ES in training and rehabilitation.

  8. 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.

  9. Blood-Induced Joint Damage

    PubMed Central

    Roosendaal, Goris; Jansen, Nathalie W.D.; Lafeber, Floris P.J.G.; Mastbergen, Simon C.

    2013-01-01

    Objective. Four days of blood exposure leads to irreversible cartilage damage in vitro. In contrast, intermittent intra-articular blood injections twice a week during 4 weeks (mimicking micro-bleeds) in a canine model resulted in transient damage only. In this study, it was evaluated whether acute joint bleeds are more harmful than micro-bleeds in a canine model of knee arthropathy. Design. Seven dogs received 4 sequential daily intra-articular blood injections twice in 2 weeks (mimicking 2 acute 4-day joint bleeds). Seven other dogs received the same blood load but in a total of 8 injections intermittently over the 4-week period with at least 1 day in between (mimicking micro-bleeds over the same timespan). Contralateral knees served as controls. Ten weeks after the last injection cartilage matrix turnover and synovial inflammation were evaluated. Results. Only after the acute joint bleeds the release of newly formed and total (resident) cartilage matrix glycosaminoglycans were increased (P = 0.04 and P = 0.01, respectively). Furthermore, in animals with the acute joint bleeds cartilage glycosaminoglycan content was decreased (P = 0.01) and not in animals with micro-bleeds. Mild synovial inflammation was observed in both groups (both P < 0.0001) but was not different between groups. Conclusions. In contrast to micro-bleeds, 2 acute joint bleeds lead to prolonged cartilage damage independent of the level of synovial inflammation. This model suggests that micro-bleeds are less devastating than acute joint bleeds with respect to joint damage, which might be of relevance to treatment of joint bleeds in clinical practice. PMID:26069675

  10. 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)…

  11. 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)…

  12. Triplex-induced DNA damage response.

    PubMed

    Rogers, Faye A; Tiwari, Meetu Kaushik

    2013-12-13

    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.

  13. 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.

  14. Autophagy in light-induced retinal damage

    PubMed Central

    Chen, Yu; Perusek, Lindsay; Maeda, Akiko

    2015-01-01

    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

  15. Multiomic Analysis of the UV-Induced DNA Damage Response.

    PubMed

    Boeing, Stefan; Williamson, Laura; Encheva, Vesela; Gori, Ilaria; Saunders, Rebecca E; Instrell, Rachael; Aygün, Ozan; Rodriguez-Martinez, Marta; Weems, Juston C; Kelly, Gavin P; Conaway, Joan W; Conaway, Ronald C; Stewart, Aengus; Howell, Michael; Snijders, Ambrosius P; Svejstrup, Jesper Q

    2016-05-11

    In order to facilitate the identification of factors and pathways in the cellular response to UV-induced DNA damage, several descriptive proteomic screens and a functional genomics screen were performed in parallel. Numerous factors could be identified with high confidence when the screen results were superimposed and interpreted together, incorporating biological knowledge. A searchable database, bioLOGIC, which provides access to relevant information about a protein or process of interest, was established to host the results and facilitate data mining. Besides uncovering roles in the DNA damage response for numerous proteins and complexes, including Integrator, Cohesin, PHF3, ASC-1, SCAF4, SCAF8, and SCAF11, we uncovered a role for the poorly studied, melanoma-associated serine/threonine kinase 19 (STK19). Besides effectively uncovering relevant factors, the multiomic approach also provides a systems-wide overview of the diverse cellular processes connected to the transcription-related DNA damage response.

  16. Comparative DNA damage and repair induced by misonidazole, CB 1954 and RSU 1069.

    PubMed

    Dale, L D; Widdick, D A; Edwards, D I; Biol, G I

    1989-04-01

    We have studied the ability of CB 1954, misonidazole, and RSU 1069 to induce biologically relevant DNA damage in single- and double-stranded phi X174 DNA under oxic, anoxic, and anoxic reductive conditions using a double transfection technique. In addition, the ability of the three drugs to induce the SOS repair response in E. coli under the same conditions was measured. Whereas the relative order of DNA damage was RSU 1069 greater than CB 1954 greater than misonidazole the order in inducing SOS repair was RSU 1069 greater than misonidazole greater than CB 1954. Drug-induced damage by RSU 1069 involves enhanced damage by endonuclease III suggesting drug-induced pyrimidine damage. There appears to be no correlation between drug-induced damage and the degree of SOS repair induction. Thus it appears that enzymes other than, or in addition to, those of the SOS repair system are involved in the repair of DNA damage induced by these drugs.

  17. Femtosecond Laser-Induced Damage of Dielectrics

    NASA Astrophysics Data System (ADS)

    Lenzner, M.

    Optical damage in non-metals (dielectrics) may severely affect the performance of high-power laser systems as well as the efficiency of optical systems based on nonlinear processes and has therefore been subject to extensive research for some 30 years. The current knowledge of laser-induced optical damage in these materials is reviewed. Emphasis is placed on the recent extension of available experimental data into the femtosecond range. Recent results are presented achieved with a sub-10 fs laser system which explores the limits of time resolution as well as the limit of intensities that a solid can sustain without irreversible damage. It is concluded that sub-10fs laser pulses open up the way to reversible nonperturbative nonlinear optics at intensities greater than 1014 W/cm2 (slightly below damage threshold) and to nanometer-precision laser ablation (slightly above threshold) in dielectric materials.

  18. Laser-Induced Damage with Femtosecond Pulses

    NASA Astrophysics Data System (ADS)

    Kafka, Kyle R. P.

    The strong electric fields of focused femtosecond laser pulses lead to non-equilibrium dynamics in materials, which, beyond a threshold intensity, causes laser-induced damage (LID). Such a strongly non-linear and non-perturbative process renders important LID observables like fluence and intensity thresholds and damage morphology (crater) extremely difficult to predict quantitatively. However, femtosecond LID carries a high degree of precision, which has been exploited in various micro/nano-machining and surface engineering applications, such as human eye surgery and super-hydrophobic surfaces. This dissertation presents an array of experimental studies which have measured the damage behavior of various materials under femtosecond irradiation. Precision experiments were performed to produce extreme spatio-temporal confinement of the femtosecond laser-solid damage interaction on monocrystalline Cu, which made possible the first successful direct-benchmarking of LID simulation with realistic damage craters. A technique was developed to produce laser-induced periodic surface structures (LIPSS) in a single pulse (typically a multi-pulse phenomenon), and was used to perform a pump-probe study which revealed asynchronous LIPSS formation on copper. Combined with 1-D calculations, this new experimental result suggests more drastic electron heating than expected. Few-cycle pulses were used to study the LID performance and morphology of commercial ultra-broadband optics, which had not been systematically studied before. With extensive surface analysis, various morphologies were observed, including LIPSS, swelling (blisters), simple craters, and even ring-shaped structures, which varied depending on the coating design, number of pulses, and air/vacuum test environment. Mechanisms leading to these morphologies are discussed, many of which are ultrafast in nature. The applied damage behavior of multi-layer dielectric mirrors was measured and compared between long pulse (150 ps

  19. DNA damage induced by 4,6,8,9-tetramethyl-2H-furo[2,3-h]quinolin-2-one, a new furocoumarin analog: biological consequences.

    PubMed

    Marzano, C; Baccichetti, F; Carlassare, F; Chilin, A; Lora, S; Bordin, F

    2000-03-01

    4,6,8,9-Tetramethyl-2H-furo[2,3-h]quinolin-2-one (HFQ) and its isomer FQ (1,4,6,8-tetramethyl-2H-furo[2,3-h]quinolin-2-one) showed very strong antiproliferative activity in mammalian cells, about two times greater than 8-methoxypsoralen (8-MOP). Both compounds induced DNA-protein cross-links (DPC) but not interstrand cross-links. The FQ generated DPC in a biphotonic process, yielding a new kind of diadduct, whereas HFQ induced DPC by a monophotonic one, probably without its physical participation in the covalent bridge. These lesions gave different toxic responses. Sensitization of FQ led to extensive DNA fragmentation and to a number of chromosomal aberrations. Conversely, HFQ seemed to be completely inactive and 8-MOP gave intermediate results. A strict relationship between DPC formation and induction of chromosomal aberrations was observed. The HFQ did not induce light skin erythemas, whereas FQ was more phototoxic than 8-MOP, thus suggesting that FQ lesions, DPC in particular, may be implicated in skin phototoxicity. Ehrlich ascites cells, a transplantable mouse tumor, inactivated by furoquinolinone sensitization and injected into healthy mice, protected them from a successive challenge by viable tumor cells. This response appeared to be based on an immune mechanism. Comparable amounts of base substitution revertants were scored when testing furoquinolinones and 8-MOP in bacteria but no DPC were detected. This suggests that classic mutagenesis tests on bacteria are insufficient to give adequate information on furocoumarin genotoxicity. Given its features, HFQ can be regarded as an interesting new agent for psoralen plus UVA photochemotherapy and photopheresis.

  20. 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

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

    PubMed

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

    2011-07-01

    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. 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. 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. 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.

  2. Oxygen radical induced fluorescence in proteins; identification of the fluorescent tryptophan metabolite, N-formyl kynurenine, as a biological index of radical damage.

    PubMed

    Griffiths, H R; Lunec, J; Blake, D R

    1992-06-01

    , not tyrosine products. In addition, this work has demonstrated that the measurement of a specific product of an oxidised amino acid can be applied to biological macromolecules, and may be important in implicating free radical reactions in certain disease processes.

  3. Non-Problematic Risks from Low-Dose Radiation-Induced DNA Damage Clusters

    PubMed Central

    Hayes, Daniel P.

    2008-01-01

    Radiation-induced DNA damage clusters have been proposed and are usually considered to pose the threat of serious biological damage. This has been attributed to DNA repair debilitation or cessation arising from the complexity of cluster damage. It will be shown here, contrary to both previous suggestions and perceived wisdom, that radiation induced damage clusters contribute to non-problematic risks in the low-dose, low-LET regime. The very complexity of cluster damage which inhibits and/or compromises DNA repair will ultimately be responsible for the elimination and/or diminution of precancer-ous and cancerous cells. PMID:18648573

  4. 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.

  5. 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.

  6. Mechanisms of bleomycin-induced lung damage.

    PubMed

    Hay, J; Shahzeidi, S; Laurent, G

    1991-01-01

    Bleomycins are a family of compounds produced by Streptomyces verticillis. They have potent tumour killing properties which have given them an important place in cancer chemotherapy. They cause little marrow suppression, but pulmonary toxicity is a major adverse effect. The mechanisms of cell toxicity are well described based on in vitro experiments on DNA. The bleomycin molecule has two main structural components: a bithiazole component which partially intercalates into the DNA helix, parting the strands, as well as pyrimidine and imidazole structures, which bind iron and oxygen forming an activated complex capable of releasing damaging oxidants in close proximity to the polynucleotide chains of DNA. This may lead to chain scission or structural modifications leading to release of free bases or their propenal derivatives. The mechanisms are well described based on in vitro experiments on DNA, but how they relate to intact cells in whole animals is more tenuous. Bleomycin is able to cause cell damage independent from its effect on DNA by induction lipid peroxidation. This may be particularly important in the lung and in part account for its ability to cause alveolar cell damage and subsequent pulmonary inflammation. The lung injury seen following bleomycin comprises an interstitial oedema with an influx of inflammatory and immune cells. This may lead to the development of pulmonary fibrosis, characterized by enhanced production and deposition of collagen and other matrix components. Several polypeptide mediators capable of stimulating fibroblasts replication or excessive collagen deposition have been implicated in this, but the precise role of these in bleomycin-induced fibrosis is yet to be demonstrated. Current therapy for bleomycin-induced lung damage is inadequate, with corticosteroids most often used. Given the mechanism of action described above, antioxidants and iron chelators might be beneficial. Although, studies to date are equivocal and there is

  7. 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

  8. 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.

  9. 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

  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. Initial Biological Damage from Space Radiation: Implications for Development of Biological Countermeasures

    NASA Technical Reports Server (NTRS)

    Cucinotta, Francis A.; Paloski, William H. (Technical Monitor)

    1999-01-01

    Astronauts are exposed to high-energy nuclear particles originating from the galactic cosmic rays, high-energy protons trapped in the Earth's magnetic field or solar particle events, and secondary radiation produced by nuclear reactions. Important differences between conventional radiation including X-rays or gamma-rays, and high-energy nuclei occur at the level of initial damage to DNA and other potential biological target molecules, and to tissues. Such differences include a large fraction of the initial damage from high charge and energy (HZE) nuclear particles manifested as irreparable lesions including small- and large-scale DNA deletions. Also, low dose-rate exposures in space result in a heterogeneous population of damaged cells distinct from energetic photon irradiation of tissue. We present an overview of the initial biological damage and dose and dose-rate effects produced by ionizing radiation using track structure and nuclear reaction models. Implications of the differences in cellular and tissue damage between conventional radiation and space radiation for the development of biological countermeasures are discussed.

  12. Initial Biological Damage from Space Radiation: Implications for Development of Biological Countermeasures

    NASA Technical Reports Server (NTRS)

    Cucinotta, Francis A.; Paloski, William H. (Technical Monitor)

    1999-01-01

    Astronauts are exposed to high-energy nuclear particles originating from the galactic cosmic rays, high-energy protons trapped in the Earth's magnetic field or solar particle events, and secondary radiation produced by nuclear reactions. Important differences between conventional radiation including X-rays or gamma-rays, and high-energy nuclei occur at the level of initial damage to DNA and other potential biological target molecules, and to tissues. Such differences include a large fraction of the initial damage from high charge and energy (HZE) nuclear particles manifested as irreparable lesions including small- and large-scale DNA deletions. Also, low dose-rate exposures in space result in a heterogeneous population of damaged cells distinct from energetic photon irradiation of tissue. We present an overview of the initial biological damage and dose and dose-rate effects produced by ionizing radiation using track structure and nuclear reaction models. Implications of the differences in cellular and tissue damage between conventional radiation and space radiation for the development of biological countermeasures are discussed.

  13. [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.

  14. Selenomethionine protects against adverse biological effects induced by space radiation.

    PubMed

    Kennedy, Ann R; Ware, Jeffrey H; Guan, Jun; Donahue, Jeremiah J; Biaglow, John E; Zhou, Zhaozong; Stewart, Jelena; Vazquez, Marcelo; Wan, X Steven

    2004-01-15

    Ionizing radiation-induced adverse biological effects impose serious challenges to astronauts during extended space travel. Of particular concern is the radiation from highly energetic, heavy, charged particles known as HZE particles. The objective of the present study was to characterize HZE particle radiation-induced adverse biological effects and evaluate the effect of D-selenomethionine (SeM) on the HZE particle radiation-induced adverse biological effects. The results showed that HZE particle radiation can increase oxidative stress, cytotoxicity, and cell transformation in vitro, and decrease the total antioxidant status in irradiated Sprague-Dawley rats. These adverse biological effects were all preventable by treatment with SeM, suggesting that SeM is potentially useful as a countermeasure against space radiation-induced adverse effects. Treatment with SeM was shown to enhance ATR and CHK2 gene expression in cultured human thyroid epithelial cells. As ionizing radiation is known to result in DNA damage and both ATR and CHK2 gene products are involved in DNA damage, it is possible that SeM may prevent HZE particle radiation-induced adverse biological effects by enhancing the DNA repair machinery in irradiated cells.

  15. WE-DE-202-03: Modeling of Biological Processes - What Happens After Early Molecular Damage?

    PubMed

    McMahon, S

    2016-06-01

    Radiation therapy for the treatment of cancer has been established as a highly precise and effective way to eradicate a localized region of diseased tissue. To achieve further significant gains in the therapeutic ratio, we need to move towards biologically optimized treatment planning. To achieve this goal, we need to understand how the radiation-type dependent patterns of induced energy depositions within the cell (physics) connect via molecular, cellular and tissue reactions to treatment outcome such as tumor control and undesirable effects on normal tissue. Several computational biology approaches have been developed connecting physics to biology. Monte Carlo simulations are the most accurate method to calculate physical dose distributions at the nanometer scale, however simulations at the DNA scale are slow and repair processes are generally not simulated. Alternative models that rely on the random formation of individual DNA lesions within one or two turns of the DNA have been shown to reproduce the clusters of DNA lesions, including single strand breaks (SSBs), double strand breaks (DSBs) without the need for detailed track structure simulations. Efficient computational simulations of initial DNA damage induction facilitate computational modeling of DNA repair and other molecular and cellular processes. Mechanistic, multiscale models provide a useful conceptual framework to test biological hypotheses and help connect fundamental information about track structure and dosimetry at the sub-cellular level to dose-response effects on larger scales. In this symposium we will learn about the current state of the art of computational approaches estimating radiation damage at the cellular and sub-cellular scale. How can understanding the physics interactions at the DNA level be used to predict biological outcome? We will discuss if and how such calculations are relevant to advance our understanding of radiation damage and its repair, or, if the underlying biological

  16. MECHANISTIC AND BIOLOGICAL ASPECTS OF HELICASE ACTION ON DAMAGED DNA

    PubMed Central

    Suhasini, Avvaru N.; Brosh, Robert M.

    2010-01-01

    Helicases catalytically unwind structured nucleic acids in a nucleoside-triphosphate-dependent and directionally specific manner, and are essential for virtually all aspects of nucleic acid metabolism. ATPase-driven helicases which translocate along nucleic acids play a role in damage recognition or unwinding of a DNA tract containing the lesion. Although classical biochemical experiments provided evidence that bulky covalent adducts inhibit DNA unwinding catalyzed by certain DNA helicases in a strand-specific manner (i.e. , block to DNA unwinding restricted to adduct residence in the strand the helicase translocates), recent studies suggest more complex arrangements that may depend on the helicase under study, its assembly in a protein complex, and the type of structural DNA perturbation. Moreover, base and sugar phosphate backbone modifications exert effects on DNA helicases that suggest specialized tracking mechanisms. As a component of the replication stress response, the single-stranded DNA binding protein Replication Protein A (RPA) may serve to enable eukaryotic DNA helicases to overcome certain base lesions. Helicases play important roles in DNA damage signaling which also involve their partnership with RPA. In this review, we will discuss our current understanding of mechanistic and biological aspects of helicase action on damaged DNA. PMID:20574162

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. Renal tissue damage induced by focused shock waves

    NASA Astrophysics Data System (ADS)

    Ioritani, N.; Kuwahara, M.; Kambe, K.; Taguchi, K.; Saitoh, T.; Shirai, S.; Orikasa, S.; Takayama, K.; Lush, P. A.

    1990-07-01

    Biological evidence of renal arterial wall damage induced by the microjet due to shock wave-cavitation bubble interaction was demonstrated in living dog kidneys. We also intended to clarify the mechanism of renal tissue damage and the effects of different conditions of shock wave exposure (peak pressure of focused area, number of shots, exposure rate) on the renal tissue damage in comparison to stone disintegration. Disruption of arterial wall was the most remarkable histological change in the focused area of the kidneys. This lesion appeared as if the wall had been punctured by a needle. Large hematoma formation in the renal parenchym, and interstitial hemorrhage seemed to be the results of the arterial lesion. This arterial disorder also led to ischemic necrosis of the tubules surrounding the hematoma. Micro-angiographic examination of extracted kidneys also proved such arterial puncture lesions and ischemic lesions. The number of shots required for model stone disintegration was not inversely proportional to peak pressure. It decreased markedly when peak pressure was above 700 bar. Similarly thenumber of shots for hematoma formation was not inversely proportional to peak pressure, however, this decreased markedly above 500 bar. These results suggested that a hematoma could be formed under a lower peak pressure than that required for stone disintegration.

  3. Silica radical-induced DNA damage and lipid peroxidation.

    PubMed Central

    Shi, X; Mao, Y; Daniel, L N; Saffiotti, U; Dalal, N S; Vallyathan, V

    1994-01-01

    In recent years, more attention has been given to the mechanism of disease induction caused by the surface properties of minerals. In this respect, specific research needs to be focused on the biologic interactions of oxygen radicals generated by mineral particles resulting in cell injury and DNA damage leading to fibrogenesis and carcinogenesis. In this investigation, we used electron spin resonance (ESR) and spin trapping to study oxygen radical generation from aqueous suspensions of freshly fractured crystalline silica. Hydroxyl radical (.OH), superoxide radical (O2.-) and singlet oxygen (1O2) were all detected. Superoxide dismutase (SOD) partially inhibited .OH yield, whereas catalase abolished .OH generation. H2O2 enhanced .OH generation while deferoxamine inhibited it, indicating that .OH is generated via a Haber-Weiss type reaction. These spin trapping measurements provide the first evidence that aqueous suspensions of silica particles generate O2.- and 1O2. Oxygen consumption measurements indicate that freshly fractured silica uses molecular oxygen to generate O2.- and 1O2. Electrophoretic assays of in vitro DNA strand breakages showed that freshly fractured silica induced DNA strand breakage, which was inhibited by catalase and enhanced by H2O2. In an argon atmosphere, DNA damage was suppressed, showing that molecular oxygen is required for the silica-induced DNA damage. Incubation of freshly fractured silica with linoleic acid generated linoleic acid-derived free radicals and caused dose-dependent lipid peroxidation as measured by ESR spin trapping and malondialdehyde formation. SOD, catalase, and sodium benzoate inhibited lipid peroxidation by 49, 52, and 75%, respectively, again showing the role of oxygen radicals in silica-induced lipid peroxidation.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 7. PMID:7705289

  4. 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

  5. Copper deficiency potentiates ethanol induced liver damage

    SciTech Connect

    Zidenberg-Cherr, S.; Han, B.; Graham, T.W.; Keen, C.L. )

    1992-02-26

    Copper sufficient (+Cu) and deficient ({minus}Cu) rats were fed liquid diets with EtOH or dextrose at 36% of kcals for 2 mo. Consumption of either the {minus}Cu diet or EtOH resulted in lower liver CuZn superoxide dismutase (CuZnSOD) and glutathione peroxidase (GPx) activities were lowest in EtOH/{minus}Cu rats; being 20% and 50% of control values, respectively. Ethanol resulted in higher MnSOD activity in +Cu and {minus}Cu rats. Low Cu intake as well as EtOH resulted in lower mitochondrial (Mit) TBARS relative to controls. TBARS were lowest in Mit from EtOH/{minus}Cu rats. Microsomal (Micro) TBARS were lower in {minus}Cu and EtOH-fed rats than in controls. The peroxidizability index (PI) was calculated as an index of substrate availability for lipid peroxidation. Ethanol feeding resulted in lower PI's in Mit and Micro than measured in non-EtOH rats. There was a positive correlation between Micro PI's and TBARS. These results show that despite reductions in components of antioxidant defense, compensatory mechanism arise resulting in reduction in peroxidation targets and/or an increase in alternate free radical quenching factors. Histological examination demonstrated increased portal and intralobular connective tissue and cell necrosis in EtOH/{minus}Cu rats, suggesting that Cu may be a critical modulator of EtOH induced tissue damage.

  6. 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.

  7. Radiation-induced chromosome damage in astronauts' lymphocytes.

    PubMed

    Testard, I; Ricoul, M; Hoffschir, F; Flury-Herard, A; Dutrillaux, B; Fedorenko, B; Gerasimenko, V; Sabatier, L

    1996-10-01

    The increased number of manned space missions has made it important to estimate the biological risks encountered by astronauts. As they are exposed to cosmic rays, especially ions with high linear energy transfer (LET), it is necessary to estimate the doses they receive. The most sensitive biological dosimetry used is based on the quantification of radiation-induced chromosome damage to human lymphocytes. After the space missions ANTARES (1992) and ALTAIR (1993), we performed cytogenetic analysis of blood samples from seven astronauts who had spent from 2 weeks to 6 months in space. After 2 or 3 weeks, the X-ray equivalent dose was found to be below the cytogenetic detection level of 20 mGy. After 6 months, the biological dose greatly varied among the astronauts, from 95 to 455 mGy equivalent dose. These doses are in the same range as those estimated by physical dosimetry (90 mGy absorbed dose and 180 mSv equivalent dose). Some blood cells exhibited the same cytogenetic pattern as the 'rogue cells' occasionally observed in controls, but with a higher frequency. We suggest that rogue cells might result from irradiation with high-LET particles of cosmic origin. However, the responsibility of such cells for the long-term effects of cosmic irradiation remains unknown and must be investigated.

  8. Acrylonitrile-induced oxidative DNA damage in rat astrocytes.

    PubMed

    Pu, Xinzhu; Kamendulis, Lisa M; Klaunig, James E

    2006-10-01

    Chronic administration of acrylonitrile results in a dose-related increase in astrocytomas in rat brain, but the mechanism of acrylonitrile carcinogenicity is not fully understood. The potential of acrylonitrile or its metabolites to induce direct DNA damage as a mechanism for acrylonitrile carcinogenicity has been questioned, and recent studies indicate that the mechanism involves the induction of oxidative stress in rat brain. The present study examined the ability of acrylonitrile to induce DNA damage in the DI TNC1 rat astrocyte cell line using the alkaline Comet assay. Oxidized DNA damage also was evaluated using formamidopyrimidine DNA glycosylase treatment in the modified Comet assay. No increase in direct DNA damage was seen in astrocytes exposed to sublethal concentrations of acrylonitrile (0-1.0 mM) for 24 hr. However, acrylonitrile treatment resulted in a concentration-related increase in oxidative DNA damage after 24 hr. Antioxidant supplementation in the culture media (alpha-tocopherol, (-)-epigallocathechin-3 gallate, or trolox) reduced acrylonitrile-induced oxidative DNA damage. Depletion of glutathione using 0.1 mM DL-buthionine-[S,R]-sulfoximine increased acrylonitrile-induced oxidative DNA damage (22-46%), while cotreatment of acrylonitrile with 2.5 mM L-2-oxothiazolidine-4-carboxylic acid, a precursor for glutathione biosynthesis, significantly reduced acrylonitrile-induced oxidative DNA damage (7-47%). Cotreatment of acrylonitrile with 0.5 mM 1-aminobenzotriazole, a suicidal inhibitor of cytochrome P450, prevented the oxidative DNA damage produced by acrylonitrile. Cyanide (0.1-0.5 mM) increased oxidative DNA damage (44-160%) in astrocytes. These studies demonstrate that while acrylonitrile does not directly damage astrocyte DNA, it does increase oxidative DNA damage. The oxidative DNA damage following acrylonitrile exposure appears to arise mainly through the P450 metabolic pathway; moreover, glutathione depletion may contribute to the

  9. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

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

  11. 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.

  12. 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

  13. 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.

  14. Biological oxidative damage by carbon nanotubes: fingerprint or footprint?

    PubMed

    Hsieh, Shu-Feng; Bello, Dhimiter; Schmidt, Daniel F; Pal, Anoop K; Rogers, Eugene J

    2012-02-01

    Carbon nanotubes (CNTs) have received much attention for performance and toxicity, but vary substantially in terms of impurity type and content, morphology, and surface activity. This study determined the decrease of antioxidant capacity, defined as biological oxidative damage (BOD), of CNTs-exposed serum. The variability in several physicochemical properties of CNTs and their links to BOD elicited in human serum were explored. Tremendous variation in transition metal type and content (104-fold), specific surface area (SSA, nine-fold), and BOD were observed. Mass specific BOD (mBOD) varied from 0.006-0.187 μmol TEU mg(-1), whereas surface area specific BOD (sBOD) varied from 0.068-0.42 μmol TEU m(-2). The sBOD increased in a stepwise fashion from ∼0.1-0.32 μmol TEU m(-2) for tubes with outer diameter less than 10 nm. The mBOD and sBOD may be useful denominators of surface activity and impurity content and assist in designing safer CNTs.

  15. An inducible long noncoding RNA amplifies DNA damage signaling.

    PubMed

    Schmitt, Adam M; Garcia, Julia T; Hung, Tiffany; Flynn, Ryan A; Shen, Ying; Qu, Kun; Payumo, Alexander Y; Peres-da-Silva, Ashwin; Broz, Daniela Kenzelmann; Baum, Rachel; Guo, Shuling; Chen, James K; Attardi, Laura D; Chang, Howard Y

    2016-11-01

    Long noncoding RNAs (lncRNAs) are prevalent genes with frequently precise regulation but mostly unknown functions. Here we demonstrate that lncRNAs guide the organismal DNA damage response. DNA damage activated transcription of the DINO (Damage Induced Noncoding) lncRNA via p53. DINO was required for p53-dependent gene expression, cell cycle arrest and apoptosis in response to DNA damage, and DINO expression was sufficient to activate damage signaling and cell cycle arrest in the absence of DNA damage. DINO bound to p53 protein and promoted its stabilization, mediating a p53 auto-amplification loop. Dino knockout or promoter inactivation in mice dampened p53 signaling and ameliorated acute radiation syndrome in vivo. Thus, inducible lncRNA can create a feedback loop with its cognate transcription factor to amplify cellular signaling networks.

  16. 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.

  17. An inducible long noncoding RNA amplifies DNA damage signaling

    PubMed Central

    Schmitt, Adam M.; Garcia, Julia T.; Hung, Tiffany; Flynn, Ryan A.; Shen, Ying; Qu, Kun; Payumo, Alexander Y.; Peres-da-Silva, Ashwin; Broz, Daniela Kenzelmann; Baum, Rachel; Guo, Shuling; Chen, James K.; Attardi, Laura D.; Chang, Howard Y.

    2016-01-01

    Long noncoding RNAs (lncRNAs) are prevalent genes with frequently exquisite regulation but mostly unknown functions. Here we demonstrate a role of lncRNAs in guiding organismal DNA damage response. DNA damage activates transcription of DINO (Damage Induced NOncoding) via p53. DINO is required for p53-dependent gene expression, cell cycle arrest, and apoptosis in response to DNA damage, and DINO expression suffice to activate damage signaling and cell cycle arrest in the absence of DNA damage. DINO binds to and promotes p53 protein stabilization, mediating a p53 auto-amplification loop. Dino knockout or promoter inactivation in mice dampens p53 signaling and ameliorates acute radiation syndrome in vivo. Thus, inducible lncRNA can create a feedback loop with its cognate transcription factor to amplify cellular signaling networks. PMID:27668660

  18. 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. © 2012 Wiley Periodicals, Inc.

  19. Characterization of UVC-induced DNA damage in bloodstains: forensic implications.

    PubMed

    Hall, Ashley; Ballantyne, Jack

    2004-09-01

    The ability to detect DNA polymorphisms using molecular genetic techniques has revolutionized the forensic analysis of biological evidence. DNA typing now plays a critical role within the criminal justice system, but one of the limiting factors with the technology is that DNA isolated from biological stains recovered from the crime scene is sometimes so damaged as to be intractable to analysis. Potential remedies for damaged DNA are likely to be dependent upon the precise nature of the DNA damage present in any particular sample but, unfortunately, current knowledge of the biochemical nature, and the extent, of such DNA damage in dried biological stains is rudimentary. As a model for DNA damage assessment in biological stains recovered from crime scenes, we have subjected human bloodstains and naked DNA in the hydrated and dehydrated states to varying doses of UVC radiation. It was possible to damage the DNA sufficiently in a bloodstain to cause a standard autosomal short tandem repeat (STR) profile to be lost. However, a detailed analysis of the process, based upon assays developed to detect bipyrimidine photoproducts (BPPPs), single- and double-strand breaks, and DNA-DNA crosslinks, produced some unexpected findings. Contrary to the situation with living tissues or cells in culture, the predominant UVC-induced damage to DNA in bloodstains appears not to be pyrimidine dimers. Although some evidence for the presence of BPPPs and DNA crosslinks was obtained, the major form of UVC damage causing genetic profile loss appeared to be single-strand breaks. It was not possible, however, to preclude the possibility that a combination of damage types was responsible for the profile loss observed. We demonstrate here that a significant measure of protection against UVC-mediated genetic profile loss in dried biological stain material is afforded by the dehydrated state of the DNA and, to a lesser extent, the DNA cellular milieu.

  20. RNF111-dependent neddylation activates DNA damage-induced ubiquitination

    PubMed Central

    Ma, Teng; Chen, Yibin; Zhang, Feng; Yang, Chao-Yie; Wang, Shaomeng; Yu, Xiaochun

    2013-01-01

    Summary Ubiquitin-like proteins have been shown to be covalently conjugated to targets. However, the functions of these ubiquitin-like proteins are largely unknown. Here, we have screened most known ubiquitin-like proteins after DNA damage and found that NEDD8 is involved in the DNA damage response. Following various DNA damage stimuli, NEDD8 accumulated at DNA damage sites, and this accumulation was dependent on an E2 enzyme UBE2M and an E3 ubiquitin ligase RNF111. We further found that histone H4 was polyneddylated in response to DNA damage, and NEDD8 was conjugated to the N-terminal lysine residues of H4. Interestingly, the DNA damage-induced polyneddylation chain could be recognized by the MIU (Motif Interacting with Ubiquitin) domain of RNF168. Loss of DNA damage-induced neddylation negatively regulated DNA damage-induced foci formation of RNF168 and its downstream functional partners, such as 53BP1 and BRCA1, thus affecting the normal DNA damage repair process. PMID:23394999

  1. Roles of oxidative stress in synchrotron radiation X-ray-induced testicular damage of rodents

    PubMed Central

    Ma, Yingxin; Nie, Hui; Sheng, Caibin; Chen, Heyu; Wang, Ban; Liu, Tengyuan; Shao, Jiaxiang; He, Xin; Zhang, Tingting; Zheng, Chaobo; Xia, Weiliang; Ying, Weihai

    2012-01-01

    Synchrotron radiation (SR) X-ray has characteristic properties such as coherence and high photon flux, which has excellent potential for its applications in medical imaging and cancer treatment. However, there is little information regarding the mechanisms underlying the damaging effects of SR X-ray on biological tissues. Oxidative stress plays an important role in the tissue damage induced by conventional X-ray, while the role of oxidative stress in the tissue injury induced by SR X-ray remains unknown. In this study we used the male gonads of rats as a model to study the roles of oxidative stress in SR X-ray-induced tissue damage. Exposures of the testes to SR X-ray at various radiation doses did not significantly increase the lipid peroxidation of the tissues, assessed at one day after the irradiation. No significant decreases in the levels of GSH or total antioxidation capacity were found in the SR X-ray-irradiated testes. However, the SR X-ray at 40 Gy induced a marked increase in phosphorylated H2AX – a marker of double-strand DNA damage, which was significantly decreased by the antioxidant N-acetyl cysteine (NAC). NAC also attenuated the SR X-ray-induced decreases in the cell layer number of seminiferous tubules. Collectively, our observations have provided the first characterization of SR X-ray-induced oxidative damage of biological tissues: SR X-ray at high doses can induce DNA damage and certain tissue damage during the acute phase of the irradiation, at least partially by generating oxidative stress. However, SR X-ray of various radiation doses did not increase lipid peroxidation. PMID:22837810

  2. Mitochondrial DNA damage by bleomycin induces AML cell death.

    PubMed

    Yeung, ManTek; Hurren, Rose; Nemr, Carine; Wang, Xiaoming; Hershenfeld, Samantha; Gronda, Marcela; Liyanage, Sanduni; Wu, Yan; Augustine, Jeevan; Lee, Eric A; Spagnuolo, Paul A; Southall, Noel; Chen, Catherine; Zheng, Wei; Jeyaraju, Danny V; Minden, Mark D; Laposa, Rebecca; Schimmer, Aaron D

    2015-06-01

    Mitochondria contain multiple copies of their own 16.6 kb circular genome. To explore the impact of mitochondrial DNA (mtDNA) damage on mitochondrial (mt) function and viability of AML cells, we screened a panel of DNA damaging chemotherapeutic agents to identify drugs that could damage mtDNA. We identified bleomycin as an agent that damaged mtDNA in AML cells at concentrations that induced cell death. Bleomycin also induced mtDNA damage in primary AML samples. Consistent with the observed mtDNA damage, bleomycin reduced mt mass and basal oxygen consumption in AML cells. We also demonstrated that the observed mtDNA damage was functionally important for bleomycin-induced cell death. Finally, bleomycin delayed tumor growth in xenograft mouse models of AML and anti-leukemic concentrations of the drug induced mtDNA damage in AML cells preferentially over normal lung tissue. Taken together, mtDNA-targeted therapy may be an effective strategy to target AML cells and bleomycin could be useful in the treatment of this disease.

  3. 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…

  4. 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…

  5. Protection by estrogens of biological damage by 2,2'-azobis(2-amidinopropane) dihydrochloride.

    PubMed

    Muraoka, Sanae; Miura, Toshiaki

    2002-11-01

    We examined by using 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) as a radical generator the ability of estrogens to scavenge carbon-centered and peroxyl radicals. Electron spin resonance signals of carbon-centered radicals from AAPH were diminished by catecholestrogens but not by phenolic estrogens, showing that catecholestrogens efficiently scavenged carbon-centered radicals. However, fluorescent decomposition of R-phycoerythrin by AAPH-derived peroxyl radicals was inhibited by catecholestrogens and phenolic estrogens. Evidently, peroxyl radicals were scavenged by catecholestrogens and by phenolic estrogens. However, the scavenging ability of 4-hydroxyestradiol was less than 2-hydroxyestradiol. Strand break of DNA induced by AAPH was inhibited by catecholestrogens, but not by phenolic estrogens under aerobic and anaerobic conditions. Inactivation of lysozyme induced by AAPH was completely blocked by 2-hydroxyestradiol under aerobic and anaerobic conditions, and by 4-hyroxyestradiol only under anaerobic conditions. Peroxidation of arachidonic acid by AAPH was strongly inhibited by catecholestrogens at low concentrations. Only large amounts of phenolic estrogens markedly inhibited lipid peroxidation. These results show that catecholestrogens were antioxidant against AAPH-induced damage to biological molecules through scavenging both carbon-centered and peroxyl radicals, but phenolic estrogens partially inhibited AAPH-induced damage because they scavenged only peroxyl radicals.

  6. 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

  7. Single-cell analysis challenges the connection between autophagy and senescence induced by DNA damage.

    PubMed

    Filippi-Chiela, Eduardo Cremonese; Bueno e Silva, Mardja Manssur; Thomé, Marcos Paulo; Lenz, Guido

    2015-01-01

    Autophagy and senescence have been described as central features of cell biology, but the interplay between these mechanisms remains obscure. Using a therapeutically relevant model of DNA damage-induced senescence in human glioma cells, we demonstrated that acute treatment with temozolomide induces DNA damage, a transitory activation of PRKAA/AMPK-ULK1 and MAPK14/p38 and the sustained inhibition of AKT-MTOR. This produced a transient induction of autophagy, which was followed by senescence. However, at the single cell level, this coordinated transition was not observed, and autophagy and senescence were triggered in a very heterogeneous manner. Indeed, at a population level, autophagy was highly negatively correlated with senescence markers, while in single cells this correlation did not exist. The inhibition of autophagy triggered apoptosis and decreased senescence, while its activation increased temozolomide-induced senescence, showing that DNA damage-induced autophagy acts by suppressing apoptosis.

  8. 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.

  9. 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.

  10. Photoexcited riboflavin induces oxidative damage to human serum albumin

    NASA Astrophysics Data System (ADS)

    Hirakawa, Kazutaka; Yoshioka, Takuto

    2015-08-01

    Photoexcited riboflavin induced damage of human serum albumin (HSA), a water soluble protein, resulting in the diminishment of fluorescence from the tryptophan residue. Because riboflavin hardly photosensitized singlet oxygen generation and sodium azide, a singlet oxygen quencher, did not inhibit protein damage, electron transfer-mediated oxidation of HSA was speculated. Fluorescence lifetime of riboflavin was not affected by HSA, suggesting that the excited triplet state of riboflavin is responsible for protein damage through electron transfer. In addition, the preventive effect of xanthone derivatives, triplet quenchers, on photosensitized protein damage could be evaluated using this photosensitized reaction system of riboflavin and HSA.

  11. PWR fuel features to preclude externally induced damage

    SciTech Connect

    Shallenberger, J.M.; Wilson, J.F.; Knott, R.P.

    1987-01-01

    Over the past several years there have been instances of pressurized water reactor (PWR) fuel damage attributed to factors external to the fuel. These externally induced causes include debris in the reactor coolant and baffle jetting. These causes of PWR fuel damage account for --50% of the total number of damaged rods. This paper discusses two features that significantly reduce the potential for fuel damage due to debris and baffle jetting. These two features are the debris filter bottom nozzle (DFBN) and the antivibration clip.

  12. 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

  13. 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.

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

    DOE PAGES

    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

  15. Modelling low velocity impact induced damage in composite laminates

    NASA Astrophysics Data System (ADS)

    Shi, Yu; Soutis, Constantinos

    2017-12-01

    The paper presents recent progress on modelling low velocity impact induced damage in fibre reinforced composite laminates. It is important to understand the mechanisms of barely visible impact damage (BVID) and how it affects structural performance. To reduce labour intensive testing, the development of finite element (FE) techniques for simulating impact damage becomes essential and recent effort by the composites research community is reviewed in this work. The FE predicted damage initiation and propagation can be validated by Non Destructive Techniques (NDT) that gives confidence to the developed numerical damage models. A reliable damage simulation can assist the design process to optimise laminate configurations, reduce weight and improve performance of components and structures used in aircraft construction.

  16. Femtosecond laser induced damage of pulse compression gratings

    NASA Astrophysics Data System (ADS)

    Kong, Fanyu; Huang, Haopeng; Wang, Leilei; Shao, Jianda; Jin, Yunxia; Xia, Zhilin; Chen, Junming; Li, Linxin

    2017-12-01

    Laser induced damage of Au-coated gratings (ACG) and metal multilayer dielectric gratings (MMDG) for pulse compression were measured using 800 ± 35 nm femto-laser with pulse width of 30.2 fs. The -1st order diffraction efficiency of the ACG is over 90% in wavelength range from 700 to 1000 nm. The MMDG has a 148 nm bandwidth (750-897 nm) with -1st order diffraction efficiency greater than 90%. The laser damage experiment on grating samples was performed in air for single-shot damage. The single-shot damage threshold of the ACG and MMDG was determined to be 0.32 ± 0.02 J/cm2 and 0.31 ± 0.02 J/cm2, respectively. The damage morphologies of the ACG revealed that the damage was attributed to the pinholes at the base of the grating pillars and the weak adhesion between metal layer and photoresist gratings layer. The damage feature combined with near field distribution of MMDG indicated that the damage was due to the nonlinear ionization process of the valence electrons in HfO2 film. According to analysis results, the laser damage resistance of the ACG can be enhanced through avoiding the appearance of pinholes and increasing adhesion between metal layer and photoresist layer. And for the MMDG, good performance of HfO2 film, low near field enhancement and single HfO2 grating structures may increase its laser damage resistance.

  17. Laser-Induced Thermal Damage of Skin

    DTIC Science & Technology

    1977-12-01

    Negro Skin . 17 7 Transmission Spectrum of Human Epidermis , . 18 8 Radial and Axial Grid Poinkts and Increments 29 9 CO2 Laser Setup and Resulcant Burns...of -•y of Chicago. Two-thirds of the predicted del ir- reversible damage were within one ) f the histological measurements of dama e 13 ro- duced by... NEGRO 1 0 - i - .-- - - --10VI SIBLE il L li . 0.2 0.4 0.6 0.8 1.0 2.0 4.C 6.0 8.0 10.0 20.0 40.0 WAVELENGTH, Um Figure 6. Spectral reflectance of white

  18. New Treatment Strategies for Alcohol-Induced Heart Damage

    PubMed Central

    Fernández-Solà, Joaquim; Planavila Porta, Ana

    2016-01-01

    High-dose alcohol misuse induces multiple noxious cardiac effects, including myocyte hypertrophy and necrosis, interstitial fibrosis, decreased ventricular contraction and ventricle enlargement. These effects produce diastolic and systolic ventricular dysfunction leading to congestive heart failure, arrhythmias and an increased death rate. There are multiple, dose-dependent, synchronic and synergistic mechanisms of alcohol-induced cardiac damage. Ethanol alters membrane permeability and composition, interferes with receptors and intracellular transients, induces oxidative, metabolic and energy damage, decreases protein synthesis, excitation-contraction coupling and increases cell apoptosis. In addition, ethanol decreases myocyte protective and repair mechanisms and their regeneration. Although there are diverse different strategies to directly target alcohol-induced heart damage, they are partially effective, and can only be used as support medication in a multidisciplinary approach. Alcohol abstinence is the preferred goal, but control drinking is useful in alcohol-addicted subjects not able to abstain. Correction of nutrition, ionic and vitamin deficiencies and control of alcohol-related systemic organ damage are compulsory. Recently, several growth factors (myostatin, IGF-1, leptin, ghrelin, miRNA, and ROCK inhibitors) and new cardiomyokines such as FGF21 have been described to regulate cardiac plasticity and decrease cardiac damage, improving cardiac repair mechanisms, and they are promising agents in this field. New potential therapeutic targets aim to control oxidative damage, myocyte hypertrophy, interstitial fibrosis and persistent apoptosis In addition, stem-cell therapy may improve myocyte regeneration. However, these strategies are not yet approved for clinical use. PMID:27690014

  19. Physics associated with cavitation induced material damage

    NASA Technical Reports Server (NTRS)

    Peterson, F. B.

    1974-01-01

    The role of cavitation in mechanical failure is discussed. Some of the most common types of material damage associated with the presence of cavitation are surface material removal, delamination and structural vibration. This occurs in external flows such as on propellers, hydrofoils, and high speed non-lifting surfaces. In internal flows, pipe bends, inlets, constructions, pumps and turbines are typical. Nominally nonflowing liquids are also susceptible in, for example, strong acoustic fields and high energy particle detectors. For flowing systems, Bernoulli's equation shows how a local pressure is reduced as the fluid's velocity is increased. At sufficiently high velocities, a tension can actually develop and this has, in fact, been demonstrated experimentally. Once the pressure is reduced below the fluid vapor pressure a vapor cavity can be nucleated. Various aspects of this process are simply shown by considering the flow over a lifting surface.

  20. Hydroxyl radical Thymine adduct induced DNA damages

    NASA Astrophysics Data System (ADS)

    Schyman, Patric; Eriksson, Leif A.; Zhang, Ru bo; Laaksonen, Aatto

    2008-06-01

    DNA damages caused by a 5-hydroxy-5,6-dihydrothymine-6-yl radical (5-OHT-6yl) abstracting a C2‧ hydrogen from a neighboring sugar (inter-H abstraction) have been theoretically investigated using hybrid DFT in gas phase and in water solution. The inter-H abstraction was here shown to be comparable in energy (24 kcal mol-1) with the intra-H abstraction in which the 5-OHT-6yl abstracts a C2‧ hydrogen from its own sugar. The effect of a neutrally or a negatively charged phosphate group was also studied and the results show no significant impact on the activation energy of the hydrogen abstraction whereas base release and strand break reactions are affected.

  1. Physics associated with cavitation induced material damage

    NASA Technical Reports Server (NTRS)

    Peterson, F. B.

    1974-01-01

    The role of cavitation in mechanical failure is discussed. Some of the most common types of material damage associated with the presence of cavitation are surface material removal, delamination and structural vibration. This occurs in external flows such as on propellers, hydrofoils, and high speed non-lifting surfaces. In internal flows, pipe bends, inlets, constructions, pumps and turbines are typical. Nominally nonflowing liquids are also susceptible in, for example, strong acoustic fields and high energy particle detectors. For flowing systems, Bernoulli's equation shows how a local pressure is reduced as the fluid's velocity is increased. At sufficiently high velocities, a tension can actually develop and this has, in fact, been demonstrated experimentally. Once the pressure is reduced below the fluid vapor pressure a vapor cavity can be nucleated. Various aspects of this process are simply shown by considering the flow over a lifting surface.

  2. Heavy ion induced permanent damage in MNOS gate insulators

    NASA Astrophysics Data System (ADS)

    Pickel, J. C.; Blandford, J. T., Jr.; Waskiewicz, A. E.; Strahan, V. H., Jr.

    1985-12-01

    Heavy-ion-induced permanent damage in MNOS gate insulators has been investigated using a Cf252 fission source. The electric field and ion LET thresholds for onset of the damage has been characterized. The results are consistent with a thermal runaway mechanism in the silicon nitride layer initiated by a single heavy ion and leading to a permanent high conductivity path through the dielectric layers.

  3. Tyrosine-dependent oxidative DNA damage induced by carcinogenic tetranitromethane.

    PubMed

    Murata, Mariko; Kurimoto, Saori; Kawanishi, Shosuke

    2006-10-01

    Tetranitromethane (TNM) is used as an oxidizer in rocket propellants and explosives and as an additive to increase the cetane number of diesel fuel. TNM was reported to induce pulmonary adenocarcinomas and squamous cell carcinomas in mice and rats. However, the mechanisms underlying carcinogenesis induced by TNM has not yet been clarified. We previously revealed that nitroTyr and nitroTyr-containing peptides caused Cu(II)-dependent DNA damage in the presence of P450 reductase, which is considered to yield nitroreduction. Since TNM is a reagent for nitration of Tyr in proteins and peptides, we have hypothesized that TNM-treated Tyr and Tyr-containing peptides induce DNA damage by the modification of Tyr. We examined DNA damage induced by TNM-treated amino acids or peptides using (32)P-5'-end-labeled DNA fragments obtained from the human p53 tumor suppressor gene and the c-Ha-ras-1 protooncogene. TNM-treated Tyr and Lys-Tyr-Lys induced DNA damage including the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine in the presence of Cu(II) and NADH. DNA damage was inhibited by catalase and bathocuproine, indicating the involvement of H(2)O(2) and Cu(I). The cytosine residue of the ACG sequence complementary to codon 273, well-known hotspots of the p53 gene, was cleaved with piperidine and Fpg treatments. On the other hand, nitroTyr and Lys-nitroTyr-Lys did not induce DNA damage in the presence of Cu(II) and NADH. Time-of-flight mass spectrometry confirmed that reactions between Lys-Tyr-Lys and TNM yielded not only Lys-nitroTyr-Lys but also Lys-nitrosoTyr-Lys. Therefore, it is speculated that the nitrosotyrosine residue can induce oxidative DNA damage in the presence of Cu(II) and NADH. It is concluded that Tyr-dependent DNA damage may play an important role in the carcinogenicity of TNM. TNM is a new type of carcinogen that induces DNA damage not by itself but via Tyr modification.

  4. Molecular biology of doxorubicin-induced cardiomyopathy

    PubMed Central

    Umlauf, J; Horký, M

    2002-01-01

    The anthracycline doxorubicin is an antineoplastic agent, eliciting chronic cardiac toxicity. It occurs in patients after prolonged administration of doxorubicin, leading to congestive heart failure. The pathogenesis of the doxorubicin-induced car-diomyopathy is not well understood. The present article summarizes the unique effect of doxorubicin on cardiac-specific gene expression. In addition to binding to DNA, doxorubicin directly affects the function of a variety of proteins. Free radical generation, damage to mitochondria and active cell death are also critical in the development of doxorubicin-induced cardiac toxicity. Agents providing effective cardioprotection are also reviewed. PMID:19644577

  5. Pathology and biology of radiation-induced cardiac disease

    PubMed Central

    Tapio, Soile

    2016-01-01

    Heart disease is the leading global cause of death. The risk for this disease is significantly increased in populations exposed to ionizing radiation, but the mechanisms are not fully elucidated yet. This review aims to gather and discuss the latest data about pathological and biological consequences in the radiation-exposed heart in a comprehensive manner. A better understanding of the molecular and cellular mechanisms underlying radiation-induced damage in heart tissue and cardiac vasculature will provide novel targets for therapeutic interventions. These may be valuable for individuals clinically or occupationally exposed to varying doses of ionizing radiation. PMID:27422929

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

    PubMed

    Demple, B; Halbrook, J

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

  7. 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.

  8. 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.

  9. 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

  10. Laser Induced Damage in Optical Materials: 1979.

    DTIC Science & Technology

    1980-07-01

    an oscillator in laser fusion systems [8, 9]. Tm:YLF, pumped by an XeF laser , and emitting at 453 nm [10], is an efficient storage laser and is being...Chicklis, [4] Wilson, R., Varian Associates (private E.P. and Jenssen, H.P., XeF pumped communication). Tm:YLF an excimer excited storage laser , Technical...caused by pulsed laser -induced thermal stress were not signifi- cantly influenced by transverse heat conduction. However, the fluence levels were above

  11. 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.

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

    PubMed

    Mavragani, Ifigeneia V; Nikitaki, Zacharenia; Souli, Maria P; Aziz, Asef; Nowsheen, Somaira; Aziz, Khaled; Rogakou, Emmy; Georgakilas, Alexandros G

    2017-07-18

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

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

    PubMed Central

    Mavragani, Ifigeneia V.; Nikitaki, Zacharenia; Souli, Maria P.; Aziz, Asef; Nowsheen, Somaira; Aziz, Khaled; Rogakou, Emmy

    2017-01-01

    Cellular effects of ionizing radiation (IR) are of great variety and level, but they are mainly damaging since radiation can perturb all important components of the cell, from the membrane to the nucleus, due to alteration of different biological molecules ranging from lipids to proteins or DNA. Regarding DNA damage, which is the main focus of this review, as well as its repair, all current knowledge indicates that IR-induced DNA damage is always more complex than the corresponding endogenous damage resulting from endogenous oxidative stress. Specifically, it is expected that IR will create clusters of damage comprised of a diversity of DNA lesions like double strand breaks (DSBs), single strand breaks (SSBs) and base lesions within a short DNA region of up to 15–20 bp. Recent data from our groups and others support two main notions, that these damaged clusters are: (1) repair resistant, increasing genomic instability (GI) and malignant transformation and (2) can be considered as persistent “danger” signals promoting chronic inflammation and immune response, causing detrimental effects to the organism (like radiation toxicity). Last but not least, the paradigm shift for the role of radiation-induced systemic effects is also incorporated in this picture of IR-effects and consequences of complex DNA damage induction and its erroneous repair. PMID:28718816

  14. 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.

  15. Quercitrin protects skin from UVB-induced oxidative damage.

    PubMed

    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. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. 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%.

  17. Protective effect of an aminothiazole compound against γ-radiation induced oxidative damage.

    PubMed

    De, Strayo; Devasagayam, Thomas P A

    2011-11-01

    Ionizing radiation causes its biological effects mainly through oxidative damage induced by reactive oxygen species. During radiotherapy of cancer, one of the undesirable side-effects is toxicity to normal cells. Compounds with antioxidant activities are being tried as 'prophylactic radioprotectants' to overcome this problem. We evaluated the protective effect of an aminothiazole compound, in the form of dendrodoine analogue (DA) originally derived from a marine tunicate, against γ-radiation-induced damage to lipid, protein, and DNA besides its cytotoxicity. Oxidative damage was examined by different biochemcial assays. Our studies reveal that DA gave significant protection, in fairly low concentrations, against damage induced by γ-radiation to rat liver mitochondria, plasmid pBR322 DNA, and mouse splenic lymphocytes in vitro. It also protected against oxidative damage in whole-body irradiated mice exposed to therapeutic dose of radiation (2 Gy) in vivo. Spleen, a major target organ for radiation damage, of the irradiated mice showed significant protection when treated with DA, as examined by histopathology. In conclusion, due to the possible protective effects against normal cells/tissues both in vitro and in vivo, DA shows potential to be a radioprotector for possible use during radiotherapy.

  18. 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%.

  19. 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...

  20. 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...

  1. 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.

  2. 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.

  3. Transesophageal Echocardiography and Radiation-induced Damages

    PubMed Central

    Cottini, Marzia; Polizzi, Vincenzo; Pino, Paolo Giuseppe; Buffa, Vitaliano; Musumeci, Francesco

    2016-01-01

    The long-term sequelae of mantle therapy include, especially lung and cardiac disease but also involve the vessels and the organs in the neck and thorax (such as thyroid, aorta, and esophagus). We presented the case of 66-year-old female admitted for congestive heart failure in radiation-induced heart disease. The patient had undergone to massive radiotherapy 42 years ago for Hodgkin's disease (type 1A). Transesophageal echocardiography was performed unsuccessfully with difficulty because of the rigidity and impedance of esophageal walls. Our case is an extraordinary report of radiotherapy's latency effect as a result of dramatic changes in the structure of mediastinum, in particular in the esophagus, causing unavailability of a transesophageal echocardiogram. PMID:27867461

  4. 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.

  5. Photoprotective Effect of Carpomitra costata Extract against Ultraviolet B-Induced Oxidative Damage in Human Keratinocytes.

    PubMed

    Zheng, J; Hewage, S R K Madduma; Piao, Mei Jing; Kang, Kyoung Ah; Han, X; Kang, H K; Yoo, E S; Koh, Y S; Lee, N H; Ko, C S; Lee, J C; Ko, Mi Hee; Hyuna, Jin Won

    2016-01-01

    Natural marine products show various biological properties such as antiphotoaging, antioxidant, anticancer, and anti-inflammation. This study evaluated the protective effects of the brown alga Carpomitra costata (Stackhouse) Batters (Sporochnaceae) against ultraviolet B (UVB)-provoked damage in human HaCaT keratinocytes. C. costata extract (CCE) effectively reduced superoxide anion, hydroxyl radical, and UVB-stimulated intracellular reactive oxygen species (ROS) levels. CCE also restored the expression and activity of UVB-suppressed antioxidant enzymes. Furthermore, CCE decreased UVB-triggered oxidative damage to cellular components including DNA, protein, and lipid and defended the cells against mitochondrial membrane depolarization-medicated apoptosis. The results of this study indicate that CCE can safeguard human keratinocytes against UVB-induced cellular damage via a potent antioxidant mechanism. CCE may find utility as part of a therapeutic arsenal against the damaging effects of UVB radiation on the skin.

  6. 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.

  7. UV and ionizing radiations induced DNA damage, differences and similarities

    NASA Astrophysics Data System (ADS)

    Ravanat, Jean-Luc; Douki, Thierry

    2016-11-01

    Both UV and ionizing radiations damage DNA. Two main mechanisms, so-called direct and indirect pathways, are involved in the degradation of DNA induced by ionizing radiations. The direct effect of radiation corresponds to direct ionization of DNA (one electron ejection) whereas indirect effects are produced by reactive oxygen species generated through water radiolysis, including the highly reactive hydroxyl radicals, which damage DNA. UV (and visible) light damages DNA by again two distinct mechanisms. UVC and to a lesser extend UVB photons are directly absorbed by DNA bases, generating their excited states that are at the origin of the formation of pyrimidine dimers. UVA (and visible) light by interaction with endogenous or exogenous photosensitizers induce the formation of DNA damage through photosensitization reactions. The excited photosensitizer is able to induce either a one-electron oxidation of DNA (type I) or to produce singlet oxygen (type II) that reacts with DNA. In addition, through an energy transfer from the excited photosensitizer to DNA bases (sometime called type III mechanism) formation of pyrimidine dimers could be produced. Interestingly it has been shown recently that pyrimidine dimers are also produced by direct absorption of UVA light by DNA, even if absorption of DNA bases at these wavelengths is very low. It should be stressed that some excited photosensitizers (such as psoralens) could add directly to DNA bases to generate adducts. The review will described the differences and similarities in terms of damage formation (structure and mechanisms) between these two physical genotoxic agents.

  8. 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.

  9. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2011-06-01

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

  11. Mitochondrial and nuclear DNA damage induced by 5-aminolevulinic acid.

    PubMed

    Onuki, Janice; Chen, Yiming; Teixeira, Priscila C; Schumacher, Robert I; Medeiros, Marisa H G; Van Houten, Bennett; Di Mascio, Paolo

    2004-12-15

    5-Aminolevulinic acid (ALA) is a heme precursor accumulated in plasma and in organs in acute intermittent porphyria (AIP), a disease associated with neuromuscular dysfunction and increased incidence of hepatocellular carcinoma (HCC). Liver biopsies of AIP patients showed odd-shaped mitochondria and autophagic vacuoles containing well-preserved mitochondria. ALA yields reactive oxygen species upon metal-catalyzed oxidation and causes in vivo and in vitro impairment of rat liver mitochondria and DNA damage. Using a quantitative polymerase chain reaction assay, we demonstrated that ALA induces a dose-dependent damage in nuclear and mitochondrial DNA in human SVNF fibroblasts and rat PC12 cells. CHO cells treated with ALA also show nuclear DNA damage and human HepG2 cells entered in apoptosis and necrosis induced by ALA and its dimerization product, DHPY. The present data provide additional information on the genotoxicity of ALA, reinforcing the hypothesis that it may be involved in the development of HCC in AIP patients.

  12. 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.

  13. Shock-induced damage in rocks: Application to impact cratering

    NASA Astrophysics Data System (ADS)

    Ai, Huirong

    Shock-induced damage beneath impact craters is studied in this work. Two representative terrestrial rocks, San Marcos granite and Bedford limestone, are chosen as test target. Impacts into the rock targets with different combinations of projectile material, size, impact angle, and impact velocity are carried out at cm scale in the laboratory. Shock-induced damage and fracturing would cause large-scale compressional wave velocity reduction in the recovered target beneath the impact crater. The shock-induced damage is measured by mapping the compressional wave velocity reduction in the recovered target. A cm scale nondestructive tomography technique is developed for this purpose. This technique is proved to be effective in mapping the damage in San Marcos granite, and the inverted velocity profile is in very good agreement with the result from dicing method and cut open directly. Both compressional velocity and attenuation are measured in three orthogonal directions on cubes prepared from one granite target impacted by a lead bullet at 1200 m/s. Anisotropy is observed from both results, but the attenuation seems to be a more useful parameter than acoustic velocity in studying orientation of cracks. Our experiments indicate that the shock-induced damage is a function of impact conditions including projectile type and size, impact velocity, and target properties. Combined with other crater phenomena such as crater diameter, depth, ejecta, etc., shock-induced damage would be used as an important yet not well recognized constraint for impact history. The shock-induced damage is also calculated numerically to be compared with the experiments for a few representative shots. The Johnson-Holmquist strength and failure model, initially developed for ceramics, is applied to geological materials. Strength is a complicated function of pressure, strain, strain rate, and damage. The JH model, coupled with a crack softening model, is used to describe both the inelastic response of

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. Multiscale physics of ion-induced radiation damage.

    PubMed

    Surdutovich, Eugene; Solov'yov, A V

    2014-01-01

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

  19. 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.

  20. The basic chemistry of exercise-induced DNA oxidation: oxidative damage, redox signaling, and their interplay.

    PubMed

    Cobley, James N; Margaritelis, Nikos V; Morton, James P; Close, Graeme L; Nikolaidis, Michalis G; Malone, John K

    2015-01-01

    Acute exercise increases reactive oxygen and nitrogen species generation. This phenomenon is associated with two major outcomes: (1) redox signaling and (2) macromolecule damage. Mechanistic knowledge of how exercise-induced redox signaling and macromolecule damage are interlinked is limited. This review focuses on the interplay between exercise-induced redox signaling and DNA damage, using hydroxyl radical ((·)OH) and hydrogen peroxide (H2O2) as exemplars. It is postulated that the biological fate of H2O2 links the two processes and thus represents a bifurcation point between redox signaling and damage. Indeed, H2O2 can participate in two electron signaling reactions but its diffusion and chemical properties permit DNA oxidation following reaction with transition metals and (·)OH generation. It is also considered that the sensing of DNA oxidation by repair proteins constitutes a non-canonical redox signaling mechanism. Further layers of interaction are provided by the redox regulation of DNA repair proteins and their capacity to modulate intracellular H2O2 levels. Overall, exercise-induced redox signaling and DNA damage may be interlinked to a greater extent than was previously thought but this requires further investigation.

  1. 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.

  2. Avermectin induced inflammation damage in king pigeon brain.

    PubMed

    Chen, Li-Jie; Sun, Bao-Hong; Qu, Jian Ping; Xu, Shiwen; Li, Shu

    2013-11-01

    To determine the effect of Avermectin (AVM) on inflammation damage in king pigeon brain, eighty two-month-old American king pigeons were randomly divided into four groups, and were fed with either commercial diet or AVM-supplemented diet containing 20 mg kg(-1)diet, 40 mg kg(-1)diet, and 60 mg kg(-1)diet AVM for 30, 60 and 90 d, respectively. Then, the expression level of inflammatory factors (iNOS, PTGEs, NF-κB), histological damage, and ultra-structural damage were examined. It showed that AVM caused higher expressions (P<0.05) of iNOS, PTGEs, NF-κB with disorganized histological and ultra-structural structures in cerebrum, cerebellum, and optic lobe. Meanwhile, inflammatory and histopathological damage were induced by AVM in king pigeon brains. In addition, the main targeted organelle in nervous system was mitochondria, which indicated that mitochondria may be relevant to the process of inflammation induced by AVM. To our best knowledge, this is the first report to study the toxic effect of AVM on inflammatory damage in king pigeon. Thus, the information presented in this study is believed to be helpful in supplementing data for further AVM toxicity study.

  3. Overloaded training increases exercise-induced oxidative stress and damage.

    PubMed

    Palazzetti, Stephane; Richard, Marie-Jeanne; Favier, Alain; Margaritis, Irene

    2003-08-01

    We hypothesized that overloaded training (OT) in triathlon would induce oxidative stress and damage on muscle and DNA. Nine male triathletes and 6 male sedentary subjects participated in this study. Before and after a 4-week OT, triathletes exercised for a duathlon. Blood ratio of reduced vs. oxidized glutathione (GSH/GSSG), plasma thiobarbituric acid reactive substances (TBARS), leukocyte DNA damage, creatine kinase (CK), and CK-MB mass in plasma, erythrocyte superoxide dismutase (SOD) activity, erythrocyte and plasma glutathione peroxidase (GSH-Px) activities, and plasma total antioxidant status (TAS) were measured before and after OT in pre- and postexercise situations. Triathletes were overloaded in response to OT. In rest conditions, OT induced plasma GSH-Px activity increase and plasma TAS decrease (both p < 0.05). In exercise conditions, OT resulted in higher exercise-induced variations of blood GSH/GSSG ratio, TBARS level (both p < 0.05), and CK-MB mass (p < 0.01) in plasma; and decreased TAS response (p < 0.05). OT could compromise the antioxidant defense mechanism with respect to exercise-induced response. The resulting increased exercise-induced oxidative stress and further cellular susceptibility to damage needs more study.

  4. Obesity Exacerbates Sepsis-Induced Oxidative Damage in Organs.

    PubMed

    Petronilho, Fabricia; Giustina, Amanda Della; Nascimento, Diego Zapelini; Zarbato, Graciela Freitas; Vieira, Andriele Aparecida; Florentino, Drielly; Danielski, Lucinéia Gainski; Goldim, Mariana Pereira; Rezin, Gislaine Tezza; Barichello, Tatiana

    2016-12-01

    Sepsis progression is linked to the imbalance between reactive oxygen species and antioxidant enzymes. Sepsis affects multiple organs, but when associated with a chronic inflammatory disease, such as obesity, it may be exacerbated. We hypothesized that obesity could aggravate the oxidative damage to peripheral organs of rats submitted to an animal model of sepsis. Male Wistar rats aged 8 weeks received hypercaloric nutrition for 2 months to induce obesity. Sepsis was induced by cecal ligation and puncture (CLP) procedure, and sham-operated rats were considered as control group. The experimental groups were divided into sham + eutrophic, sham + obese, CLP + eutrophic, and CLP + obese. Twelve and 24 h after surgery, oxidative damage to lipids and proteins and superoxide dismutase (SOD) and catalase (CAT) activities were evaluated in the liver, lung, kidney, and heart. The data indicate that obese rats subjected to sepsis present oxidative stress mainly in the lung and liver. This alteration reflected an oxidative damage to lipids and proteins and an imbalance of SOD and CAT levels, especially 24 h after sepsis. It follows that obesity due to its pro-inflammatory phenotype can aggravate sepsis-induced damage in peripheral organs.

  5. Mitochondrial DNA damage induces apoptosis in senescent cells

    PubMed Central

    Laberge, R-M; Adler, D; DeMaria, M; Mechtouf, N; Teachenor, R; Cardin, G B; Desprez, P-Y; Campisi, J; Rodier, F

    2013-01-01

    Senescence is a cellular response to damage and stress. The senescence response prevents cancer by suppressing the proliferation of cells with a compromised genome and contributes to optimal wound healing in normal tissues. Persistent senescent cells are also thought to drive aging and age-associated pathologies through their secretion of inflammatory factors that modify the tissue microenvironment and alter the function of nearby normal or transformed cells. Understanding how senescent cells alter the microenvironment would be aided by the ability to induce or eliminate senescent cells at will in vivo. Here, we combine the use of the synthetic nucleoside analog ganciclovir (GCV) with herpes simplex virus thymidine kinase (HSVtk) activity to create or eliminate senescent human cells. We show that low concentrations of GCV induce senescence through the accumulation of nuclear DNA damage while higher concentrations of GCV, similar to those used in vivo, kill non-dividing senescent cells via mitochondrial DNA (mtDNA) damage and caspase-dependent apoptosis. Using this system, we effectively eliminated xenografted normal human senescent fibroblasts or induced senescence in human breast cancer cells in vivo. Thus, cellular senescence and mtDNA damage are outcomes of synthetic nucleoside analog treatment, indicating that the GCV–HSVtk combination can be used effectively to promote the targeted formation or eradication of senescent cells. PMID:23868060

  6. Mitochondrial DNA damage induces apoptosis in senescent cells.

    PubMed

    Laberge, R-M; Adler, D; DeMaria, M; Mechtouf, N; Teachenor, R; Cardin, G B; Desprez, P-Y; Campisi, J; Rodier, F

    2013-07-18

    Senescence is a cellular response to damage and stress. The senescence response prevents cancer by suppressing the proliferation of cells with a compromised genome and contributes to optimal wound healing in normal tissues. Persistent senescent cells are also thought to drive aging and age-associated pathologies through their secretion of inflammatory factors that modify the tissue microenvironment and alter the function of nearby normal or transformed cells. Understanding how senescent cells alter the microenvironment would be aided by the ability to induce or eliminate senescent cells at will in vivo. Here, we combine the use of the synthetic nucleoside analog ganciclovir (GCV) with herpes simplex virus thymidine kinase (HSVtk) activity to create or eliminate senescent human cells. We show that low concentrations of GCV induce senescence through the accumulation of nuclear DNA damage while higher concentrations of GCV, similar to those used in vivo, kill non-dividing senescent cells via mitochondrial DNA (mtDNA) damage and caspase-dependent apoptosis. Using this system, we effectively eliminated xenografted normal human senescent fibroblasts or induced senescence in human breast cancer cells in vivo. Thus, cellular senescence and mtDNA damage are outcomes of synthetic nucleoside analog treatment, indicating that the GCV-HSVtk combination can be used effectively to promote the targeted formation or eradication of senescent cells.

  7. 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

  8. Computational modeling of process induced damage during plasma clean

    NASA Astrophysics Data System (ADS)

    Rauf, S.; Haggag, A.; Moosa, M.; Ventzek, P. L. G.

    2006-07-01

    When partially completed circuits come in contact with plasmas during integrated circuit fabrication, current from the plasma can potentially damage active devices on the wafer. A suite of computational models is used in this article to investigate damage to ultrathin (1.0-5.5nm) transistor gate dielectric (SiO2) during Ar /O2 based plasma cleaning in a capacitively coupled plasma reactor. This modeling infrastructure includes a two-dimensional plasma equipment model for relating process control parameters to ion and electron currents, a three-dimensional model for flux density calculation within a circular via, an electrostatic model for computing potential across the gate dielectric, and a percolation model to investigate dielectric damage characteristics. Computational results show that when the plasma current comes in contact with the gate dielectric, the gate dielectric rapidly charges up and the potential difference across the dielectric saturates at the level necessary to support the plasma induced current. The steady-state voltage across the dielectric determines the propensity of irreversible damage that can occur under this electrical stress. Gate dielectric damage was found to be most sensitively linked to dielectric thickness. As thin dielectrics (<2.0nm) are leaky, direct tunneling current flow ensures that the potential drop across the gate dielectric remains small. As a consequence, the dielectric is able to withstand the plasma current and the probability of damage is small. However, for thicker dielectrics where Fowler-Nordheim tunneling is dominant, a large voltage builds up across the gate dielectric due to the plasma induced current. The probability of thicker dielectrics getting damaged during the plasma process is therefore high. For given plasma conditions and gate dielectric thickness, current collection area (i.e., antenna size) determines the voltage buildup across the gate dielectric. Damage probability increases with the size of the

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. Evaluation of DNA damage induced by Auger electrons from (137)Cs.

    PubMed

    Watanabe, Ritsuko; Hattori, Yuya; Kai, Takeshi

    2016-11-01

    To understand the biological effect of external and internal exposure from (137)Cs, DNA damage spectrum induced by directly emitted electrons (γ-rays, internal conversion electrons, Auger electrons) from (137)Cs was compared with that induced by (137)Cs γ-rays. Monte Carlo track simulation method was used to calculate the microscopic energy deposition pattern in liquid water. Simulation was performed for the two simple target systems in microscale. Radiation sources were placed inside for one system and outside for another system. To simulate the energy deposition by directly emitted electrons from (137)Cs placed inside the system, the multiple ejections of electrons after internal conversion were considered. In the target systems, induction process of DNA damage was modeled and simulated for both direct energy deposition and the water radical reaction on the DNA. The yield and spatial distribution of simple and complex DNA damage including strand breaks and base lesions were calculated for irradiation by electrons and γ-rays from (137)Cs. The simulation showed that the significant difference in DNA damage spectrum was not caused by directly ejected electrons and γ-rays from (137)Cs. The result supports the existing perception that the biological effects by internal and external exposure by (137)Cs are equivalent.

  14. Cellular senescence determines endothelial cell damage induced by uremia.

    PubMed

    Carracedo, Julia; Buendía, Paula; Merino, Ana; Soriano, Sagrario; Esquivias, Elvira; Martín-Malo, Alejandro; Aljama, Pedro; Ramírez, Rafael

    2013-08-01

    Renal dysfunction is closely associated with endothelial damage leading to cardiovascular disease. However, the extent to which endothelial damage induced by uremia is modulated by aging is poorly known. Aging can render endothelial cells more susceptible to apoptosis through an oxidative stress-dependent pathway. We examined whether senescence-associated to oxidative stress determines the injury induced by the uremia in endothelial cells. Human umbilical vein endothelial cells (HUVEC) was incubated with human uremic serum and, in the animal model, endothelial cells were obtained from aortas of uremic and no uremic rats. Vitamin C was used to prevent oxidative stress. Senescence, assessed by telomere length and enzyme-betagalactosidase (β-gal), reactive oxygen species (ROS), mitochondrial depolarization (JC-1 probe), caspase 3, and apoptosis were determined by flow cytometry. NF-κB activity was determined by Western blot. Uremic serum increased ROS and NF-κB in young and aging HUVEC. However only in aging cells, uremic serum induced apoptosis (vs young HUVEC, p<0.01). The endothelial damage induced by uremia seems to be related with the increased oxidative stress, since in both HUVEC and in the experimental model of renal disease in rats, vitamin C prevents endothelial apoptosis. However, vitamin C did not decrease the oxidative stress associated to senescence. These results showed that as compared with young cells, senescent cells have high sensitivity to damage associated to the oxidative stress induced by the uremia. Consequently, protecting senescent endothelial cells from increased oxidative stress might be an effective therapeutic approach in the treatment of vascular disorders in chronic kidney diseases. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. 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.

  16. Investigation of the laser-induced damage of dispersive coatings

    NASA Astrophysics Data System (ADS)

    Angelov, Ivan B.; von Conta, Aaron; Trushin, Sergei A.; Major, Zsuzsanna; Karsch, Stefan; Krausz, Ferenc; Pervak, Vladimir

    2011-12-01

    Different dispersive coatings were tested in terms of laser-induced damage threshold by using a Ti:Sapphire laser yielding 1 mJ, 30 fs pulses at 500 Hz repetition rate at 790 nm central wavelength. The beam was focused down to 140 μm. Single layer coatings of Au, Ag, Nb2O5, SiO2, Ta2O5 and mixtures of Ta2O5 and silica were examined as well as different dispersive coatings. We observed a direct dependence of the damage threshold on the band gap of the materials used to produce the different samples. The damage threshold values for the dispersive coatings employing the same high index material lay within a range of 30% of each other.

  17. 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.

  18. Stellate Cells Orchestrate Concanavalin A-Induced Acute Liver Damage.

    PubMed

    Rani, Richa; Tandon, Ashish; Wang, Jiang; Kumar, Sudhir; Gandhi, Chandrashekhar R

    2017-09-01

    Concanavalin A (ConA) causes immune cell-mediated liver damage, but the contribution of resident nonparenchymal cells (NPCs) is also evident. Hepatic stellate cells (HSCs) induce hepatic inflammation and immunological reactions; we therefore investigated their role in ConA-induced liver injury. ConA was administered i.v. to control or HSC-depleted mice; hepatic histopathology and cytokines/chemokines were determined after 6 hours. In vitro, effects of ConA-conditioned HSC medium on hepatocytes were determined. ConA induced inflammation, sinusoidal congestion, and extensive midzonal hepatocyte death in control mice, which were strongly minimized in HSC-depleted mice. CD4 and natural killer T cells and neutrophils were markedly reduced in ConA-treated HSC-depleted mice compared with control mice. The increase in cytokines/chemokines of hepatic injury was much higher in ConA-treated control mice than in HSC-depleted mice. ConA-treated HSCs showed increased expression of interferon-β, tumor necrosis factor-α, and CXCL1, induced oxidative stress in hepatocytes, and caused hepatocyte apoptosis. ConA induced nuclear translocation of interferon-regulatory factor-1 (IRF1) in hepatocytes in vivo, and ConA/HSC induced a similar effect in cultured hepatocytes. IRF1-knockout mice were resistant to ConA-induced liver damage, and anti-interferon β antibody mitigated ConA/HSC-induced injury. In HSC-NPC co-culture, ConA-induced expression of inflammatory cytokines/chemokines was significantly augmented compared with NPCs alone. HSCs play an essential role in ConA-induced liver injury directly via the interferon-β/IRF1 axis, and by modulating properties of NPCs. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  19. Statistical analysis of vibration-induced bone and joint damages.

    PubMed

    Schenk, T

    1995-01-01

    Vibration-induced damages to bones and joints are still occupational diseases with insufficient knowledge about causing and moderating factors and resulting damages. For a better understanding of these relationships also retrospective analyses of already acknowledged occupational diseases may be used. Already recorded detailed data for 203 in 1970 to 1979 acknowledged occupational diseases in the building industry and the building material industry of the GDR are the basis for the here described investigations. The data were gathered from the original documents of the occupational diseases and scaled in cooperation of an industrial engineer and an industrial physician. For the purposes of this investigations the data are to distinguish between data which describe the conditions of the work place (e.g. material, tools and posture), the exposure parameters (e.g. beginning of exposure and latency period) and the disease (e.g. anamnestical and radiological data). These data are treated for the use with sophisticated computerized statistical methods. The following analyses were carried out. Investigation of the connections between the several characteristics, which describe the occupational disease (health damages), including the comparison of the severity of the damages at the individual joints. Investigation of the side dependence of the damages. Investigation of the influence of the age at the beginning of the exposure and the age at the acknowledgement of the occupational disease and herewith of the exposure duration. Investigation of the effect of different occupational and exposure conditions.

  20. 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.

  1. 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

    2016-02-01

    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.

  2. Measurement of oxidatively induced DNA damage and its repair, by mass spectrometric techniques.

    PubMed

    Dizdaroglu, M; Coskun, E; Jaruga, P

    2015-05-01

    Oxidatively induced damage caused by free radicals and other DNA-damaging agents generate a plethora of products in the DNA of living organisms. There is mounting evidence for the involvement of this type of damage in the etiology of numerous diseases including carcinogenesis. For a thorough understanding of the mechanisms, cellular repair, and biological consequences of DNA damage, accurate measurement of resulting products must be achieved. There are various analytical techniques, with their own advantages and drawbacks, which can be used for this purpose. Mass spectrometric techniques with isotope dilution, which include gas chromatography (GC) and liquid chromatography (LC), provide structural elucidation of products and ascertain accurate quantification, which are absolutely necessary for reliable measurement. Both gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-mass spectrometry (LC-MS), in single or tandem versions, have been used for the measurement of numerous DNA products such as sugar and base lesions, 8,5'-cyclopurine-2'-deoxynucleosides, base-base tandem lesions, and DNA-protein crosslinks, in vitro and in vivo. This article reviews these techniques and their applications in the measurement of oxidatively induced DNA damage and its repair.

  3. 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

  4. Laser Induced Retinal Damage Thresholds for Annular Retinal Beam Profiles

    DTIC Science & Technology

    2004-01-01

    Thompson-Gerstman granular model of laser-induced thermal damage to the retina ."°20 The study documented in this paper is a continuation of our earlier...Retinal Beam Profiles DISTRIBUTION: Approved for public release, distribution unlimited This paper is part of the following report: TITLE: Laser Interaction...mrad of visual field; which correspond to outer beam diameters of roughly 70, 160, and 300 tin, respectively, on the primate retina . Annular beam

  5. 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

  6. Chemistry and biology of DNA damage by malondialdehyde.

    PubMed

    Marnett, L J

    1999-01-01

    Malondialdehyde is a naturally occurring product of lipid peroxidation and prostaglandin biosynthesis which is mutagenic and carcinogenic. It reacts with DNA to form adducts to deoxyguanosine and deoxyadenosine. The major adduct to DNA is a pyrimidopurinone called pyrimido[1,2-a]purin-10(3H)-one (M1G). Studies of site-specific mutagenesis indicate that M1G is mutagenic in bacteria and is repaired by the nucleotide excision repair pathway. M1G has been detected in liver, leukocytes, pancreas and breast from healthy human beings at levels ranging from 1 to 120 per 10(8) nucleotides. Several assays for M1G have been described which are based on mass spectrometry, 32P-postlabelling or immunochemical techniques. M1G appears to be a major endogenous DNA adduct in human beings that may contribute significantly to cancer linked to lifestyle and dietary factors. Recent advances in the chemistry and biology of M1G are reviewed.

  7. Methylmalonic acid administration induces DNA damage in rat brain and kidney.

    PubMed

    Andrade, Vanessa M; Dal Pont, Hugo S; Leffa, Daniela D; Damiani, Adriani P; Scaini, Giselli; Hainzenreder, Giana; Streck, Emilio L; Ferreira, Gustavo C; Schuck, Patrícia F

    2014-06-01

    Accumulation of methylmalonic acid (MMA) in tissues and biological fluids is the biochemical hallmark of methylmalonic aciduria. Affected patients present renal failure and severe neurological findings. Considering that the underlying pathomechanisms of tissue damage are not yet understood, in the present work we assessed the in vivo e in vitro effects of MMA on DNA damage in brain and kidney, as well as on p53 and caspase 3 levels, in the presence or absence of gentamicin (acute renal failure model). For in vitro studies, tissue prisms were incubated in the presence of different concentrations of MMA and/or gentamicin for one hour. For in vivo studies, animals received a single injection of gentamicin (70 mg/kg) and/or three injections of MMA (1.67 μmol/g; 11 h interval between injections). The animals were killed 1 h after the last MMA injection. Controls received saline in the same volumes. DNA damage was analyzed by the comet assay. We found that MMA and gentamicin alone or combined in vitro increased DNA damage in cerebral cortex and kidney of rats. Furthermore, MMA administration increased DNA damage in both brain and kidney. Gentamicin per se induced DNA damage only in kidney, and the association of MMA plus gentamicin also caused DNA damage in cerebral cortex and kidney. On the other hand, p53 and caspase 3 levels were not altered by the administration of MMA and/or gentamicin. Our findings provide evidence that DNA damage may contribute to the neurological and renal damage found in patients affected by methylmalonic aciduria.

  8. Stochastics of diffusion induced damage in intercalation materials

    NASA Astrophysics Data System (ADS)

    Barai, Pallab; Mukherjee, Partha P.

    2016-10-01

    Fundamental understanding of the underlying diffusion-mechanics interplay in the intercalation electrode materials is critical toward improved life and performance of lithium-ion batteries for electric vehicles. Especially, diffusion induced microcrack formation in brittle, intercalation active materials, with emphasis on the grain/grain-boundary (GB) level implications, has been fundamentally investigated based on a stochastic modeling approach. Quasistatic damage evolution has been analyzed under lithium concentration gradient induced stress. Scaling of total amount of microcrack formation shows a power law variation with respect to the system size. Difference between the global and local roughness exponent indicates the existence of anomalous scaling. The deterioration of stiffness with respect to microcrack density displays two distinct regions of damage propagation; namely, diffused damage evolution and stress concentration driven localized crack propagation. Polycrystalline material microstructures with different grain sizes have been considered to study the diffusion-induced fracture in grain and GB regions. Intergranular crack paths are observed within microstructures containing softer GB region, whereas, transgranular crack paths have been observed in microstructures with relatively strong GB region. Increased tortuosity of the spanning crack has been attributed as the reason behind attaining increased fracture strength in polycrystalline materials with smaller grain sizes.

  9. Phosphoinositide 3-kinase inhibitors induce DNA damage through nucleoside depletion

    PubMed Central

    Juvekar, Ashish; Hu, Hai; Yadegarynia, Sina; Lyssiotis, Costas A.; Ullas, Soumya; Lien, Evan C.; Bellinger, Gary; Son, Jaekyoung; Hok, Rosanna C.; Seth, Pankaj; Daly, Michele B.; Kim, Baek; Scully, Ralph; Asara, John M.; Cantley, Lewis C.; Wulf, Gerburg M.

    2016-01-01

    We previously reported that combining a phosphoinositide 3-kinase (PI3K) inhibitor with a poly-ADP Rib polymerase (PARP)-inhibitor enhanced DNA damage and cell death in breast cancers that have genetic aberrations in BRCA1 and TP53. Here, we show that enhanced DNA damage induced by PI3K inhibitors in this mutational background is a consequence of impaired production of nucleotides needed for DNA synthesis and DNA repair. Inhibition of PI3K causes a reduction in all four nucleotide triphosphates, whereas inhibition of the protein kinase AKT is less effective than inhibition of PI3K in suppressing nucleotide synthesis and inducing DNA damage. Carbon flux studies reveal that PI3K inhibition disproportionately affects the nonoxidative pentose phosphate pathway that delivers Rib-5-phosphate required for base ribosylation. In vivo in a mouse model of BRCA1-linked triple-negative breast cancer (K14-Cre BRCA1f/fp53f/f), the PI3K inhibitor BKM120 led to a precipitous drop in DNA synthesis within 8 h of drug treatment, whereas DNA synthesis in normal tissues was less affected. In this mouse model, combined PI3K and PARP inhibition was superior to either agent alone to induce durable remissions of established tumors. PMID:27402769

  10. Inflammation-Induced Cell Proliferation Potentiates DNA Damage-Induced Mutations In Vivo

    PubMed Central

    Kiraly, Orsolya; Gong, Guanyu; Olipitz, Werner; Muthupalani, Sureshkumar; Engelward, Bevin P.

    2015-01-01

    Mutations are a critical driver of cancer initiation. While extensive studies have focused on exposure-induced mutations, few studies have explored the importance of tissue physiology as a modulator of mutation susceptibility in vivo. Of particular interest is inflammation, a known cancer risk factor relevant to chronic inflammatory diseases and pathogen-induced inflammation. Here, we used the fluorescent yellow direct repeat (FYDR) mice that harbor a reporter to detect misalignments during homologous recombination (HR), an important class of mutations. FYDR mice were exposed to cerulein, a potent inducer of pancreatic inflammation. We show that inflammation induces DSBs (γH2AX foci) and that several days later there is an increase in cell proliferation. While isolated bouts of inflammation did not induce HR, overlap between inflammation-induced DNA damage and inflammation-induced cell proliferation induced HR significantly. To study exogenously-induced DNA damage, animals were exposed to methylnitrosourea, a model alkylating agent that creates DNA lesions relevant to both environmental exposures and cancer chemotherapy. We found that exposure to alkylation damage induces HR, and importantly, that inflammation-induced cell proliferation and alkylation induce HR in a synergistic fashion. Taken together, these results show that, during an acute bout of inflammation, there is a kinetic barrier separating DNA damage from cell proliferation that protects against mutations, and that inflammation-induced cell proliferation greatly potentiates exposure-induced mutations. These studies demonstrate a fundamental mechanism by which inflammation can act synergistically with DNA damage to induce mutations that drive cancer and cancer recurrence. PMID:25647331

  11. 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.

  12. Comparison of biologically damaging spectral solar ultraviolet radiation at a southern hemisphere sub-tropical site.

    PubMed

    Parisi, A V; Sabburg, J; Kimlin, M G

    2003-04-21

    The first dataset of a complete year of biologically damaging spectral UV at a sub-tropical latitude in the southern hemisphere has been presented. The new data provides a baseline dataset against which comparisons can be made in the future to establish if there have been any long term trends in the biologically damaging UV. The general shape of the variation of the daily biologically damaging exposures through the year depends on the relative response of the various action spectra at the different wavelengths. The ratio of the daily erythemal to actinic exposures drops by approximately 20 to 25% from winter to summer. The ratio of the erythemal to DNA exposures drops by approximately 50% over the same period. In contrast, the ratio of the erythemal to plant damage exposures is higher in summer compared to winter. This is due to the changes in the relative proportion of UVA to UVB wavebands and relative responses of the different action spectra. The relative changes for the different action spectra show that the erythemal action spectrum cannot be used as a proxy for other biologically damaging responses.

  13. 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.

  14. 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.

  15. 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.

  16. Prevention of downhill walking-induced muscle damage by non-damaging downhill walking

    PubMed Central

    Yamamoto, Masayoshi; Kanehisa, Hiroaki; Nosaka, Kazunori

    2017-01-01

    Purpose Mountain trekking involves level, uphill, and downhill walking (DW). Prolonged DW induces damage to leg muscles, reducing force generating ability and muscle coordination. These increase risks for more serious injuries and accidents in mountain trekking, thus a strategy to minimize muscle damage is warranted. It has been shown that low-intensity eccentric contractions confer protective effect on muscle damage induced by high-intensity eccentric contractions. This study tested the hypothesis that 5-min non-damaging DW would attenuate muscle damage induced by 40-min DW, but 5-min level walking (LW) would not. Methods Untrained young men were allocated (n = 12/group) to either a control or one of the two preconditioning groups (PRE-DW or PRE-LW). The PRE-DW and PRE-LW groups performed 5-min DW (-28%) and 5-min LW, respectively, at 5 km/h with a load of 10% body mass, 1 week before 40-min DW (-28%, 5 km/h, 10% load). The control group performed 40-min DW only. Maximal knee extension strength, plasma creatine kinase (CK) activity, and muscle soreness (0–100 mm visual analogue scale) were measured before and 24 h after 5-min DW and 5-min LW, and before and 24, 48, and 72 h after 40-min DW. Results No significant changes in any variables were evident after 5-min DW and 5-min LW. After 40-min DW, the control and PRE-LW groups showed significant (P<0.05) changes in the variables without significant differences between groups (control vs. PRE-LW; peak strength reduction: -19.2 ± 6.9% vs. -18.7 ± 11.0%, peak CK: 635.5 ± 306.0 vs. 639.6 ± 405.4 U/L, peak soreness: 81.4 ± 14.8 vs. 72.0 ± 29.2 mm). These changes were significantly (P<0.05) attenuated (47–64%) for the PRE-DW group (-9.9 ± 9.6%, 339.3 ± 148.4 U/L, 27.8 ± 16.8 mm). Conclusions The results supported the hypothesis and suggest that performing small volume of downhill walking is crucial in preparation for trekking. PMID:28288187

  17. Quantitative analysis of isolated and clustered DNA damage induced by gamma-rays, carbon ion beams, and iron ion beams.

    PubMed

    Terato, Hiroaki; Tanaka, Ruri; Nakaarai, Yusuke; Nohara, Tomonori; Doi, Yusuke; Iwai, Shigenori; Hirayama, Ryoichi; Furusawa, Yoshiya; Ide, Hiroshi

    2008-03-01

    Ionizing radiation induces multiple damaged sites (clustered damage) together with isolated lesions in DNA. Clustered damage consists of closely spaced lesions within a few helical turns of DNA and is considered to be crucial for understanding the biological consequences of ionizing radiation. In the present study, two types of DNA, supercoiled plasmid DNA and linear lambda DNA, were irradiated with gamma-rays, carbon ion beams, and iron ion beams, and the spectra and yield of isolated DNA damage and bistranded clustered DNA damage were fully analyzed. Despite using different methods for damage analysis, the experiments with plasmid and lambda DNA gave largely consistent results. The spectra of both isolated and clustered damage were essentially independent of the quality of the ionizing radiation used for irradiation. The yields of clustered damage as well as of isolated damage decreased with the different radiation beams in the order gamma> C > Fe, thus exhibiting an inverse correlation with LET [gamma (0.2 keV/microm) < C (13 keV/microm) < Fe (200 keV/microm)]. Consistent with in vitro data, the yield of chromosomal DNA DSBs decreased with increasing LET in Chinese hamster cells irradiated with carbon ion beams with different LETs, suggesting that the decrease in the yield of clustered damage with increasing LET is not peculiar to in vitro irradiation of DNA, but is common for both in vitro and in vivo irradiation. These results suggest that the adverse biological effect of the ionizing radiation is not simply accounted for by the yield of clustered DNA damage, and that the complexity of the clustered damage needs to be considered to understand the biological consequences of ionizing radiation.

  18. 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

  19. Mechanism of site-specific DNA damage induced by ozone.

    PubMed

    Ito, Kimiko; Inoue, Sumiko; Hiraku, Yusuke; Kawanishi, Shosuke

    2005-08-01

    Ozone has been shown to induce lung tumors in mice. The reactivity of ozone with DNA in an aqueous solution was investigated by a DNA sequencing technique using 32P-labeled DNA fragments. Ozone induced cleavages in the deoxyribose-phosphate backbone of double-stranded DNA, which were reduced by hydroxyl radical scavengers, suggesting the participation of hydroxyl radicals in the cleavages. The ozone-induced DNA cleavages were enhanced with piperidine treatment, which induces cleavages at sites of base modification, but the inhibitory effect of hydroxyl radical scavengers on the piperidine-induced cleavages was limited. Main piperidine-labile sites were guanine and thymine residues. Cleavages at some guanine and thymine residues after piperidine treatment became more predominant with denatured single-stranded DNA. Exposure of calf thymus DNA to ozone resulted in a dose-dependent increase of the 8-oxo-7,8-dihydro-2'-deoxyguanosine formation, which was partially inhibited by hydroxyl radical scavengers. ESR studies using 5,5-dimethylpyrroline-N-oxide (DMPO) showed that aqueous ozone produced the hydroxyl radical adduct of DMPO. In addition, the fluorescein-dependent chemiluminescence was detected during the decomposition of ozone in a buffer solution and the enhancing effect of D2O was observed, suggesting the formation of singlet oxygen. However, no or little enhancing effect of D2O on the ozone-induced DNA damage was observed. These results suggest that DNA backbone cleavages were caused by ozone via the production of hydroxyl radicals, while DNA base modifications were mainly caused by ozone itself and the participation of hydroxyl radicals and/or singlet oxygen in base modifications is small, if any. A possible link of ozone-induced DNA damage to inflammation-associated carcinogenesis as well as air pollution-related carcinogenesis is discussed.

  20. Oxidant-induced DNA damage of target cells.

    PubMed Central

    Schraufstätter, I; Hyslop, P A; Jackson, J H; Cochrane, C G

    1988-01-01

    In this study we examined the leukocytic oxidant species that induce oxidant damage of DNA in whole cells. H2O2 added extracellularly in micromolar concentrations (10-100 microM) induced DNA strand breaks in various target cells. The sensitivity of a specific target cell was inversely correlated to its catalase content and the rate of removal of H2O2 by the target cell. Oxidant species produced by xanthine oxidase/purine or phorbol myristate acetate-stimulated monocytes induced DNA breakage of target cells in proportion to the amount of H2O2 generated. These DNA strand breaks were prevented by extracellular catalase, but not by superoxide dismutase. Cytotoxic doses of HOCl, added to target cells, did not induce DNA strand breakage, and myeloperoxidase added extracellularly in the presence of an H2O2-generating system, prevented the formation of DNA strand breaks in proportion to its H2O2 degrading capacity. The studies also indicated that H2O2 formed hydroxyl radical (.OH) intracellularly, which appeared to be the most likely free radical responsible for DNA damage: .OH was detected in cells exposed to H2O2; the DNA base, deoxyguanosine, was hydroxylated in cells exposed to H2O2; and intracellular iron was essential for induction of DNA strand breaks. PMID:2843565

  1. Acetaldehyde-induced mitochondrial dysfunction sensitizes hepatocytes to oxidative damage.

    PubMed

    Farfán Labonne, Blanca Eugenia; Gutiérrez, Mario; Gómez-Quiroz, Luis Enrique; Konigsberg Fainstein, Mina; Bucio, Leticia; Souza, Verónica; Flores, Oscar; Ortíz, Victor; Hernández, Elizabeth; Kershenobich, David; Gutiérrez-Ruíz, María Concepción

    2009-12-01

    Acetaldehyde (Ac), the main metabolite of ethanol oxidation, is a very reactive compound involved in alcohol-induced liver damage. In the present work, we studied the effect of Ac in mitochondria functionality. Mitochondria from Wistar rats were isolated and treated with Ac. Ac decreased respiratory control by 50% which was associated with a decrease in adenosine triphosphate content (28.5%). These results suggested that Ac could be inducing changes in cell redox status. We determined protein oxidation, superoxide dismutase (SOD) activity, and glutathione ratio, indicating that Ac induced an enhanced oxidation of proteins and a decrease in SOD activity (90%) and glutathione/oxidized GSH ratio (36%). The data suggested that Ac-induced oxidative stress mediated by mitochondria dysfunction can lead to cell sensitization and to a second oxidative challenge. We pretreated hepatocytes with Ac followed by treatment with antimycin A, and this experiment revealed a noticeable decrease in cell viability, determined by neutral red assay, in comparison with cells treated with Ac alone. Our data demonstrate that Ac impairs mitochondria functionality generating oxidative stress that sensitizes cells to a second damaging signal contributing to the development of alcoholic liver disease.

  2. Sunscreens promote repair of ultraviolet radiation-induced dermal damage.

    PubMed

    Kligman, L H; Akin, F J; Kligman, A M

    1983-08-01

    Chronic UV irradiation profoundly damages the dermis of human and animal skin. These alterations were thought to be irreversible. Recently, we showed that substantial repair occurred in hairless mice after stopping UV exposure. A band of new connective tissue was laid down subepidermally. The present study focussed on whether repair would occur if animals were protected by sunscreens after dermal damage was induced and irradiation was continued. Albino hairless mice were exposed to Westinghouse FS20 sunlamps thrice weekly for 30 weeks. The daily dose of UV (UVB + UVA) was 0.17 J/cm2. Sunscreens of sun protection factors (SPF) 6 and 15 were applied after 10 and 20 weeks of irradiation. Biopsies were taken at 10, 20, 30, and 45 weeks of the experiment. With both sunscreens, especially SPF-15, previously damaged dermis was repaired during continued irradiation. Repair occurred in situ and, in severely damaged skin, in the novel form of subepidermal reconstruction zones of new connective tissue with parallel collagen bundles and a network of fine elastic fibers.

  3. Leukocyte involvement in renal reperfusion-induced liver damage.

    PubMed

    Khastar, Hossein; Kadkhodaee, Mehri; Sadeghipour, Hamid Reza; Seifi, Behjat; Hadjati, Jamshid; Delavari, Fatemeh; Soleimani, Manoocher

    2011-01-01

    Renal ischemia-reperfusion (IR) induces organ damage in remote organs. The aim of this study was to assess the role of leukocytes in the induction of liver damage after renal IR injury. Inbred mice were subjected to either sham operation or bilateral renal IR injury (60 min ischemia followed by 3 h reperfusion). Mice were then anesthetized for collection of leukocytes by heart puncture. Isolated leukocytes were transferred to two other groups: intact recipient mice that received leukocytes from IR mice and intact recipient mice that received leukocytes from sham-operated control mice. After 24 h, recipient mice were anesthetized and samples were collected. Alanine aminotransferase, aspartate aminotransferase, and hepatic malondialdehyde increased significantly, and hepatic glutathione decreased significantly in intact recipient mice that received leukocytes from IR mice in comparison with intact recipient mice that received leukocytes from sham-operated control mice. Loss of normal liver architecture, cytoplasmic vacuolization, and focal infiltration of leukocytes were seen. These results suggest that leukocytes are one of the possible factors that contribute to liver damage after renal IR injury and this damage is partly due to the induction of oxidative stress.

  4. 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.

  5. 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.

  6. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. 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.

  8. Mitochondrial injury and dysfunction in hypertension-induced cardiac damage

    PubMed Central

    Eirin, Alfonso; Lerman, Amir; Lerman, Lilach O.

    2014-01-01

    Hypertension remains an important modifiable risk factor for cardiovascular disease, associated with increased morbidity and mortality. Deciphering the mechanisms involved in the pathogenesis of hypertension is critical, as its prevalence continues increasing worldwide. Mitochondria, the primary cellular energy producers, are numerous in parenchymal cells of the heart, kidney, and brain, major target organs in hypertension. These membrane-bound organelles not only maintain cellular respiration but also modulate several functions of the cell including proliferation, apoptosis, generation of reactive oxygen species, and intracellular calcium homeostasis. Therefore, mitochondrial damage and dysfunction compromise overall cell functioning. In recent years, significant advances increased our understanding of mitochondrial morphology, bioenergetics, and homeostasis, and in turn of their role in several diseases, so that mitochondrial abnormalities and dysfunction have been identified in experimental models of hypertension. In this review, we summarize current knowledge of the contribution of dysfunctional mitochondria to the pathophysiology of hypertension-induced cardiac damage, as well as available evidence of mitochondrial injury-induced damage in other organs. Finally, we discuss the capability of antihypertensive therapy to ameliorate hypertensive mitochondrial injury, and the potential position of mitochondria as therapeutic targets in patients with hypertension. PMID:25385092

  9. Exercise-Induced Muscle Damage and Running Economy in Humans

    PubMed Central

    Assumpção, Cláudio de Oliveira; Lima, Leonardo Coelho Rabello; Oliveira, Felipe Bruno Dias; Greco, Camila Coelho; Denadai, Benedito Sérgio

    2013-01-01

    Running economy (RE), defined as the energy demand for a given velocity of submaximal running, has been identified as a critical factor of overall distance running performance. Plyometric and resistance trainings, performed during a relatively short period of time (~15–30 days), have been successfully used to improve RE in trained athletes. However, these exercise types, particularly when they are unaccustomed activities for the individuals, may cause delayed onset muscle soreness, swelling, and reduced muscle strength. Some studies have demonstrated that exercise-induced muscle damage has a negative impact on endurance running performance. Specifically, the muscular damage induced by an acute bout of downhill running has been shown to reduce RE during subsequent moderate and high-intensity exercise (>65% VO2max). However, strength exercise (i.e., jumps, isoinertial and isokinetic eccentric exercises) seems to impair RE only for subsequent high-intensity exercise (~90% VO2max). Finally, a single session of resistance exercise or downhill running (i.e., repeated bout effect) attenuates changes in indirect markers of muscle damage and blunts changes in RE. PMID:23431253

  10. 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

  11. Radiation-induced thymine base damage in replicating chromatin

    SciTech Connect

    Warters, R.L.; Childers, T.J.

    1982-06-01

    The efficiency of radiation-induced production of 5',6'-dihydroxydihydrothymine (t/sup ..gamma../)-type damage was determined in nascent and mature chromatin DNA for the dose range of 50 to 150 krad. These large doses affected neither the total fraction of nuclear DNA in chromatin subunits nor the nucleosome subunit repeat length. The DNA in nascent chromatin, however, was found to be 3.3 times more sensitive than mature chromatin DNA to ..gamma..-ray (/sup 137/Cs)-induced t/sup ..gamma../-type damage, while thymine damage of this type was uniformly distributed in the nucleosomal DNA of mature chromatin (i.e., in the nucleosome core and spacer DNA). The half-time for the transition of nascent DNA sensitivity to mature chromatin DNA sensitivity levels was the same as the half-time at 37/sup 0/C for the maturation of nascent into mature chromatin structure. The rate at which nascent chromatin matured was unaffected by radiation doses as large as 150 krad. The most logical explanation for the greater sensitivity of nascent DNA to radiation is the decreased concentration of histone chromosomal proteins in nascent chromatin.

  12. NLRP3 Inflammasome Mediates Aldosterone-Induced Vascular Damage.

    PubMed

    Bruder-Nascimento, Thiago; Ferreira, Nathanne S; Zanotto, Camila Z; Ramalho, Fernanda; Pequeno, Isabela O; Olivon, Vania C; Neves, Karla B; Alves-Lopes, Rheure; Campos, Eduardo; Silva, Carlos Alberto A; Fazan, Rubens; Carlos, Daniela; Mestriner, Fabiola L; Prado, Douglas; Pereira, Felipe V; Braga, Tarcio; Luiz, Joao Paulo M; Cau, Stefany B; Elias, Paula C; Moreira, Ayrton C; Câmara, Niels O; Zamboni, Dario S; Alves-Filho, Jose Carlos; Tostes, Rita C

    2016-12-06

    Inflammation is a key feature of aldosterone-induced vascular damage and dysfunction, but molecular mechanisms by which aldosterone triggers inflammation remain unclear. The NLRP3 inflammasome is a pivotal immune sensor that recognizes endogenous danger signals triggering sterile inflammation. We analyzed vascular function and inflammatory profile of wild-type (WT), NLRP3 knockout (NLRP3(-/-)), caspase-1 knockout (Casp-1(-/-)), and interleukin-1 receptor knockout (IL-1R(-/-)) mice treated with vehicle or aldosterone (600 µg·kg(-1)·d(-1) for 14 days through osmotic mini-pump) while receiving 1% saline to drink. Here, we show that NLRP3 inflammasome plays a central role in aldosterone-induced vascular dysfunction. Long-term infusion of aldosterone in mice resulted in elevation of plasma interleukin-1β levels and vascular abnormalities. Mice lacking the IL-1R or the inflammasome components NLRP3 and caspase-1 were protected from aldosterone-induced vascular damage. In vitro, aldosterone stimulated NLRP3-dependent interleukin-1β secretion by bone marrow-derived macrophages by activating nuclear factor-κB signaling and reactive oxygen species generation. Moreover, chimeric mice reconstituted with NLRP3-deficient hematopoietic cells showed that NLRP3 in immune cells mediates aldosterone-induced vascular damage. In addition, aldosterone increased the expression of NLRP3, active caspase-1, and mature interleukin-1β in human peripheral blood mononuclear cells. Hypertensive patients with hyperaldosteronism or normal levels of aldosterone exhibited increased activity of NLRP3 inflammasome, suggesting that the effect of hyperaldosteronism on the inflammasome may be mediated through high blood pressure. Together, these data demonstrate that NLRP3 inflammasome, through activation of IL-1R, is critically involved in the deleterious vascular effects of aldosterone, placing NLRP3 as a potential target for therapeutic interventions in conditions with high aldosterone levels

  13. 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).

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

    NASA Astrophysics Data System (ADS)

    BatavičiutÄ--, GintarÄ--; Grigas, Povilas; Smalakys, Linas; Melninkaitis, Andrius

    2013-04-01

    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).

  15. Chlorambucil induced chromosome damage in juvenile chronic arthritis.

    PubMed Central

    Palmer, R G; Varonos, S; Doré, C J; Denman, A M; Ansell, B M

    1985-01-01

    Sister chromatid exchanges, a sensitive measure of chromosome damage, were counted in peripheral blood lymphocytes from 23 patients with juvenile chronic arthritis receiving long term, low dose chlorambucil treatment. Thirty five patients with juvenile chronic arthritis who had not been treated with cytotoxic drugs served as controls. All of the treated patients have cells with abnormal sister chromatid exchange frequencies. Damage is related to the daily dose and may, in part, be determined by the duration of treatment. Sister chromatid exchanges from nine patients who had received chlorambucil at some time in the past remained high for at least five months after stopping the drug. Long term follow up will determine whether sister chromatid exchange analysis can help predict those most at risk of drug induced malignancies. Images Fig. 1 PMID:4073932

  16. 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.

  17. Damage induced by paracetamol compared with N-acetylcysteine.

    PubMed

    Kisaoglu, Abdullah; Ozogul, Bunyami; Turan, Mehmet Ibrahim; Yilmaz, Ismayil; Demiryilmaz, Ismail; Atamanalp, Sabri Selcuk; Bakan, Ebubekir; Suleyman, Halis

    2014-09-01

    This study investigated the effect of thiamine pyrophosphate (TPP) on oxidative liver damage induced in rats with high-dose paracetamol. Rats for this experiment were divided into the following groups: healthy control, paracetamol control, thiamine + paracetamol, TPP + paracetamol, and N-acetylcysteine + paracetamol. Oxidant and antioxidant parameters and liver function test levels were compared between the groups. The results show that TPP and N-acetylcysteine with paracetamol equally prevented a rise in oxidants such as malondialdehyde and nitric oxide. They also prevented a decrease in enzymatic and nonenzymatic antioxidants such as glutathione, glutathione peroxidase, glutaredoxin, glutathione S-transferase, superoxide dismutase, and catalase in the rat liver. Thiamine pyrophosphate and N-acetylcysteine had a similar positive effect on oxidative damage caused by paracetamol hepatotoxicity. These findings show that TPP may be beneficial in paracetamol hepatotoxicity. Copyright © 2014. Published by Elsevier B.V.

  18. Dietary strategies to recover from exercise-induced muscle damage.

    PubMed

    Sousa, Mónica; Teixeira, Vítor H; Soares, José

    2014-03-01

    Exhaustive or unaccustomed intense exercise can cause exercise-induced muscle damage (EIMD) and its undesirable consequences may decrease the ability to exercise and to adhere to a training programme. This review briefly summarises the muscle damage process, focusing predominantly on oxidative stress and inflammation as contributing factors, and describes how nutrition may be positively used to recover from EIMD. The combined intake of carbohydrates and proteins and the use of antioxidants and/or anti-inflammatory nutrients within physiological ranges are interventions that may assist the recovery process. Although the works studying food instead of nutritional supplements are very scarce, their results seem to indicate that food might be a favourable option as a recovery strategy. To date, the only tested foods were milk, cherries, blueberries and pomegranate with promising results. Other potential solutions are foods rich in protein, carbohydrates, antioxidants and/or anti-inflammatory nutrients.

  19. Protective effect of curcumin against heavy metals-induced liver damage.

    PubMed

    García-Niño, Wylly Ramsés; Pedraza-Chaverrí, José

    2014-07-01

    Occupational or environmental exposures to heavy metals produce several adverse health effects. The common mechanism determining their toxicity and carcinogenicity is the generation of oxidative stress that leads to hepatic damage. In addition, oxidative stress induced by metal exposure leads to the activation of the nuclear factor (erythroid-derived 2)-like 2/Kelch-like ECH-associated protein 1/antioxidant response elements (Nrf2/Keap1/ARE) pathway. Since antioxidant and chelating agents are generally used for the treatment of heavy metals poisoning, this review is focused on the protective role of curcumin against liver injury induced by heavy metals. Curcumin has shown, in clinical and preclinical studies, numerous biological activities including therapeutic efficacy against various human diseases and anti-hepatotoxic effects against environmental or occupational toxins. Curcumin reduces the hepatotoxicity induced by arsenic, cadmium, chromium, copper, lead and mercury, prevents histological injury, lipid peroxidation and glutathione (GSH) depletion, maintains the liver antioxidant enzyme status and protects against mitochondrial dysfunction. The preventive effect of curcumin on the noxious effects induced by heavy metals has been attributed to its scavenging and chelating properties, and/or to the ability to induce the Nrf2/Keap1/ARE pathway. However, additional research is needed in order to propose curcumin as a potential protective agent against liver damage induced by heavy metals. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    SciTech Connect

    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 no 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.

  1. 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

  2. Protective effects of honokiol against methylglyoxal-induced osteoblast damage.

    PubMed

    Suh, Kwang Sik; Chon, Suk; Choi, Eun Mi

    2016-01-25

    Honokiol is an active compound isolated from Magnolia officinalis that has been used without notable side effects in traditional medicine. We investigated the effects of honokiol against methylglyoxal (MG)-induced cytotoxicity in MC3T3-E1 osteoblast cells and the possible molecular mechanism(s) involved. The results showed that honokiol alleviated MG-induced cell death and the production of intracellular ROS, mitochondrial superoxide, cardiolipin peroxidation, and inflammatory cytokines. MG induction of the soluble receptor for advanced glycation end product (AGE) was reduced by pretreatment with honokiol. Furthermore, honokiol increased the levels of Nrf2 and increased the levels of glutathione and the activity of glyoxalase I. Pretreatment with honokiol prior to MG exposure reduced MG-induced mitochondrial dysfunction and alleviated MG-induced reduction of nitric oxide and PGC1α levels, suggesting that honokiol may induce mitochondrial biogenesis. It was concluded that honokiol could be useful in the attenuation of MG-induced cell damage. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. 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

  4. Role of neutrophils in acrylonitrile-induced gastric mucosal damage.

    PubMed

    Hamdy, Nadia M; Al-Abbasi, Fahad A; Alghamdi, Hassan A; Tolba, Mai F; Esmat, Ahmed; Abdel-Naim, Ashraf B

    2012-01-25

    Acrylonitrile (ACN) is a widely used intermediate in the manufacture of plastics, acrylic fibers, synthetic rubbers and resins that are used in a variety of products including food containers and medical devices. ACN is a possible human carcinogen and a documented animal carcinogen, with the stomach being an important target of its toxicity. ACN has been previously reported to require metabolic activation to reactive intermediates and finally to cyanide (CN⁻). The current study aimed at exploring the potential role of neutrophils in ACN-induced gastric damage in rats. Experimental neutropenia was attained by injecting rats with methotrexate. This significantly ameliorated gastric mucosal injury induced by ACN. This is evidenced by protection against the increase in gastric ulcer index, myeloperoxidase (MPO) activity and CN⁻ level. Also, neutropenia guarded against the decrease in prostaglandin E2 (PGE2), induction of oxidative stress and reduction of total nitrites and alleviated histopathological alterations in rat stomachs. These data indicate that neutrophil infiltration is, at least partly, involved in ACN-induced gastric damage in rats.

  5. DNA damage induces the accumulation of Tiam1 by blocking β-TrCP-dependent degradation.

    PubMed

    Zhu, Guixin; Fan, Zhongyun; Ding, Miao; Mu, Libing; Liang, Juan; Ding, Yajie; Fu, Yu; Huang, Binlu; Wu, Wei

    2014-05-30

    The Rac1/JNK cascade plays important roles in DNA damage-induced apoptosis. However, how this cascade is activated upon DNA damage remains to be fully understood. We show here that, in untreated cells, Tiam1, a Rac1-specific guanine nucleotide exchange factor, is phosphorylated by casein kinase 1 (CK1) at its C terminus, leading to Skp, Cullin, F-box-containing(β-TrCP) recognition, ubiquitination, and proteasome-mediated degradation. Upon DNA-damaging anticancer drug treatment, CK1/β-TrCP-mediated Tiam1 degradation is abolished, and the accumulated Tiam1 contributes to downstream activation of Rac1/JNK. Consistently, tumor cells overexpressing Tiam1 are hypersensitive to DNA-damaging drug treatment. In xenograft mice, Tiam1-high cells are more susceptible to doxorubicin treatment. Thus, our results uncover that inhibition of proteasome-mediated Tiam1 degradation is an upstream event leading to Rac1/JNK activation and cell apoptosis in response to DNA-damaging drug treatment. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. 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.

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

    PubMed Central

    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

  9. 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.

  10. 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.

  11. Gender differences in alcohol-induced neurotoxicity and brain damage.

    PubMed

    Alfonso-Loeches, Silvia; Pascual, María; Guerri, Consuelo

    2013-09-06

    Considerable evidence has demonstrated that women are more vulnerable than men to the toxic effects of alcohol, although the results as to whether gender differences exist in ethanol-induced brain damage are contradictory. We have reported that ethanol, by activating the neuroimmune system and Toll-like receptors 4 (TLR4), can cause neuroinflammation and brain injury. However, whether there are gender differences in alcohol-induced neuroinflammation and brain injury are currently controversial. Using the brains of TLR4(+/+) and TLR4(-/-) (TLR4-KO) mice, we report that chronic ethanol treatment induces inflammatory mediators (iNOS and COX-2), cytokines (IL-1β, TNF-α), gliosis processes, caspase-3 activation and neuronal loss in the cerebral cortex of both female and male mice. Conversely, the levels of these parameters tend to be higher in female than in male mice. Using an in vivo imaging technique, our results further evidence that ethanol treatment triggers higher GFAP levels and lower MAP-2 levels in female than in male mice, suggesting a greater effect of ethanol-induced astrogliosis and less MAP-2(+) neurons in female than in male mice. Our results further confirm the pivotal role of TLR4 in alcohol-induced neuroinflammation and brain damage since the elimination of TLR4 protects the brain of males and females against the deleterious effects of ethanol. In short, the present findings demonstrate that, during the same period of ethanol treatment, females are more vulnerable than males to the neurotoxic/neuroinflammatory effects of ethanol, thus supporting the view that women are more susceptible than men to the medical consequences of alcohol abuse.

  12. 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

  13. 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.

  14. 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

  15. 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

  16. Bile-Induced DNA Damage in Salmonella enterica

    PubMed Central

    Prieto, Ana I.; Ramos-Morales, Francisco; Casadesús, Josep

    2004-01-01

    In the absence of DNA adenine methylase, growth of Salmonella enterica serovar Typhimurium is inhibited by bile. Mutations in any of the mutH, mutL, and mutS genes suppress bile sensitivity in a Dam− background, indicating that an active MutHLS system renders Dam− mutants bile sensitive. However, inactivation of the MutHLS system does not cause bile sensitivity. An analogy with Escherichia coli, in which the MutHLS system sensitizes Dam− mutants to DNA-injuring agents, suggested that bile might cause DNA damage. In support of this hypothesis, we show that bile induces the SOS response in S. enterica and increases the frequency of point mutations and chromosomal rearrangements. Mutations in mutH, mutL, or mutS cause partial relief of virulence attenuation in a Dam− background (50- to 100-fold by the oral route and 10-fold intraperitoneally), suggesting that an active MutHLS system reduces the ability of Salmonella Dam− mutants to cope with DNA-damaging agents (bile and others) encountered during the infection process. The DNA-damaging ability of bile under laboratory conditions raises the possibility that the phenomenon may be relevant in vivo, since high bile concentrations are found in the gallbladder, the niche for chronic Salmonella infections. PMID:15611156

  17. Quercetin protection against ciprofloxacin induced liver damage in rats.

    PubMed

    Taslidere, E; Dogan, Z; Elbe, H; Vardi, N; Cetin, A; Turkoz, Y

    2016-01-01

    Ciprofloxacin is a common, broad spectrum antibacterial agent; however, evidence is accumulating that ciprofloxacin may cause liver damage. Quercetin is a free radical scavenger and antioxidant. We investigated histological changes in hepatic tissue of rats caused by ciprofloxacin and the effects of quercetin on these changes using histochemical and biochemical methods. We divided 28 adult female Wistar albino rats into four equal groups: control, quercetin treated, ciprofloxacin treated, and ciprofloxacin + quercetin treated. At the end of the experiment, liver samples were processed for light microscopic examination and biochemical measurements. Sections were prepared and stained with hematoxylin and eosin, and a histopathologic damage score was calculated. The sections from the control group appeared normal. Hemorrhage, inflammatory cell infiltration and intracellular vacuolization were observed in the ciprofloxacin group. The histopathological findings were reduced in the group treated with quercetin. Significant differences were found between the control and ciprofloxacin groups, and between the ciprofloxacin and ciprofloxacin + quercetin groups. Quercetin administration reduced liver injury caused by ciprofloxacin in rats. We suggest that quercetin may be useful for preventing ciprofloxacin induced liver damage.

  18. Photodynamic therapy induced vascular damage: an overview of experimental PDT

    NASA Astrophysics Data System (ADS)

    Wang, W.; Moriyama, L. T.; Bagnato, V. S.

    2013-02-01

    Photodynamic therapy (PDT) has been developed as one of the most important therapeutic options in the treatment of cancer and other diseases. By resorting to the photosensitizer and light, which convert oxygen into cytotoxic reactive oxygen species (ROS), PDT will induce vascular damage and direct tumor cell killing. Another consequence of PDT is the microvascular stasis, which results in hypoxia and further produces tumor regression. To improve the treatment with PDT, three promising strategies are currently attracting much interest: (1) the combination of PDT and anti-angiogenesis agents, which more effectively prevent the proliferation of endothelial cells and the formation of new blood vessels; (2) the nanoparticle-assisted delivery of photosensitizer, which makes the photosensitizer more localized in tumor sites and thus renders minimal damage to the normal tissues; (3) the application of intravascular PDT, which can avoid the loss of energy during the transmission and expose the target area directly. Here we aim to review the important findings on vascular damage by PDT on mice. The combination of PDT with other approaches as well as its effect on cancer photomedicine are also reviewed.

  19. Simulation of ion induced radiation damage in cells

    NASA Astrophysics Data System (ADS)

    Friedland, W.; Jacob, P.; Paretzke, H. G.; Ottolenghi, A.; Ballarini, F.; Dingfelder, M.

    The biophysical simulation code PARTRAC has been used in several studies of DNA damage induced by various radiation qualities including photons electrons protons alphas and ions heavier than alpha particles Ion-electron interaction cross sections are taken from isotachic protons scaled by Z eff 2 with the effective charge calculated according to the Barkas formula Recently ion type dependent angular distributions were introduced for intermediate secondary electron energies taking into account the different kinematic scaling of the constituents of the electron spectra Calculated stopping powers radial dose distributions and secondary electron spectra were found in good agreement with available experimental and theoretical results Radiation damage to DNA is determined in PARTRAC by superposition of the calculated track structures with a DNA target model taking into account direct effects from coincidences of ionisations and atoms within the DNA helix as well as indirect effects due to interactions of OH radicals produced in water surrounding the DNA For a simulation of radiation effects in human cells this target model comprises several genomic structure levels from the DNA double-helix up to chromosomes Calculated DNA damage due to irradiation of human fibroblast cells by ions of boron nitrogen and neon was compared to corresponding experimental data The calculated total yield of DSB per dose showed saturation behaviour with an RBE of about 2 whereas experimental data had a decreasing tendency with increasing LET to RBE values

  20. Bee products prevent agrichemical-induced oxidative damage in fish.

    PubMed

    Ferreira, Daiane; Rocha, Helio Carlos; Kreutz, Luiz Carlos; Loro, Vania Lucia; Marqueze, Alessandra; Koakoski, Gessi; da Rosa, João Gabriel Santos; 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.

  1. Solvent effect induced solute damage in an organic inner salt.

    PubMed

    Shui, Min; Jin, Xiao; Li, Zhongguo; Yang, Junyi; Shi, Guang; Zhang, Xueru; Wang, Yuxiao; Yang, Kun; Wei, Tai-huei; Song, Yinglin

    2010-12-20

    Nonlinear absorption of a newly synthesized organic inner salt Ge-150 dissolved in four different solvents (DMF, DMSO, acetonitrile and acetone) is investigated by the Z-scan technique with both nanosecond and picosecond pulses. When pulse energy surpasses a threshold and pulse-to-pulse separation is shorter than a characteristic time, all the four solutions show absorption weakening induced by cross-pulse effects in the picosecond regime. However, only two of them (Ge-150 dissolved in DMF and DMSO) show this weakening in the nanosecond regime. By conducting a simple verification experiment, we verify this absorption weakening is induced by solute damage related to solvent effect rather than solute migration. A simple theoretical model is proposed to interpret the experimental phenomenon.

  2. Pulsed light induced damages in Listeria innocua and Escherichia coli.

    PubMed

    Kramer, B; Wunderlich, J; Muranyi, P

    2015-10-01

    Pulsed light (PL) is an upcoming nonthermal decontamination technology mainly used for surface sterilization. The objective of this study was to investigate the extent of cellular damage caused by PL treatments of Listeria innocua and Escherichia coli on a polysaccharide surface in order to gain knowledge about the main inactivation pathways. The impact of PL on the cellular ATP level was investigated as well as the bacterial ability to take up fluorescently labelled glucose (2-NBDG). Furthermore, the extent of DNA damages was assessed by qPCR. The ability of L. innocua and E. coli to photorepair under artificial daylight exposure was quantified. Finally, the induction of reactive oxygen species (ROS) and lipid peroxidation were studied by fluorometric detection of ROS and thiobarbituric acid reactive substances (TBARS). It is shown that intracellular ATP levels and glucose uptake ability do not correlate with the immediate loss of bacterial reproducibility, which indicates that cellular activity and energy may remain on a relatively high level, although growth on tryptic soy agar is not observable. Sequence specific investigation of PL induced DNA damages by qPCR revealed distinct differences between L. innocua and E. coli although the observed inactivation efficacy of PL by the culture based method was similar. Photoreactivation has been observed for both bacteria, a higher recovery rate of up to 2 log was seen in case of E. coli. Intracellular ROS and lipid peroxides were both detectable at relatively high fluencies with E. coli so the contribution of oxidative damage to microbial inactivation of PL cannot be excluded. Escherichia coli as well as L. innocua cells have proven to maintain residual cellular activity after having been exposed to PL even when they are not able to reproduce any more. High proportions of sublethal damages were also obvious with regard to occurring photoreactivation. The destruction of bacterial DNA seems to be the primary

  3. 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.

  4. 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.

  5. Damages of Biological Components in Bacteria and Bacteriophages Exposed to Atmospheric Non-thermal Plasma

    NASA Astrophysics Data System (ADS)

    Mizuno, Akira; Yasuda, Hachiro

    Mechanism of inactivation of bio-particles exposed to dielectric barrier discharge, DBD, has been studied using E. coli and bacteriophages. States of different biological components were monitored during the course of inactivation. Analysis of green fluorescent protein, GFP, introduced into E.coli cells proved that Non-thermal Plasma, NTP causes a prominent protein damages without cutting peptide bonds. We have developed a biological assay which evaluates in vitro DNA damage of the bacteriophages. Bacteriophage λ having double stranded DNA was exposed to DBD, then DNA was purified and subjected to in vitro DNA packaging reactions. The re-packaged phages consist of the DNA from discharged phages and brand-new coat proteins. Survival curves of the re-packaged phages showed extremely large D value (D = 25 s) compared to the previous D value (D = 3 s) from the discharged phages. The results indicate that DNA damage hardly contributed to the inactivation, and the damage in coat proteins is responsible for inactivation of the phages. M13 phages having single stranded DNA were also examined with the same manner. In this case, damage to DNA was as severe as that of the coat proteins.

  6. Scaling Relations for Intercalation Induced Damage in Electrodes

    SciTech Connect

    Chen, Chien-Fan; Barai, Pallab; Smith, Kandler; Mukherjee, Partha P.

    2016-04-02

    Mechanical degradation, owing to intercalation induced stress and microcrack formation, is a key contributor to the electrode performance decay in lithium-ion batteries (LIBs). The stress generation and formation of microcracks are caused by the solid state diffusion of lithium in the active particles. Here in this work, scaling relations are constructed for diffusion induced damage in intercalation electrodes based on an extensive set of numerical experiments with a particle-level description of microcrack formation under disparate operating and cycling conditions, such as temperature, particle size, C-rate, and drive cycle. The microcrack formation and evolution in active particles is simulated based on a stochastic methodology. A reduced order scaling law is constructed based on an extensive set of data from the numerical experiments. The scaling relations include combinatorial constructs of concentration gradient, cumulative strain energy, and microcrack formation. Lastly, the reduced order relations are further employed to study the influence of mechanical degradation on cell performance and validated against the high order model for the case of damage evolution during variable current vehicle drive cycle profiles.

  7. Scaling Relations for Intercalation Induced Damage in Electrodes

    DOE PAGES

    Chen, Chien-Fan; Barai, Pallab; Smith, Kandler; ...

    2016-04-02

    Mechanical degradation, owing to intercalation induced stress and microcrack formation, is a key contributor to the electrode performance decay in lithium-ion batteries (LIBs). The stress generation and formation of microcracks are caused by the solid state diffusion of lithium in the active particles. Here in this work, scaling relations are constructed for diffusion induced damage in intercalation electrodes based on an extensive set of numerical experiments with a particle-level description of microcrack formation under disparate operating and cycling conditions, such as temperature, particle size, C-rate, and drive cycle. The microcrack formation and evolution in active particles is simulated based onmore » a stochastic methodology. A reduced order scaling law is constructed based on an extensive set of data from the numerical experiments. The scaling relations include combinatorial constructs of concentration gradient, cumulative strain energy, and microcrack formation. Lastly, the reduced order relations are further employed to study the influence of mechanical degradation on cell performance and validated against the high order model for the case of damage evolution during variable current vehicle drive cycle profiles.« less

  8. Scaling Relations for Intercalation Induced Damage in Electrodes

    SciTech Connect

    Chen, Chien-Fan; Barai, Pallab; Smith, Kandler; Mukherjee, Partha P.

    2016-06-01

    Mechanical degradation, owing to intercalation induced stress and microcrack formation, is a key contributor to the electrode performance decay in lithium-ion batteries (LIBs). The stress generation and formation of microcracks are caused by the solid state diffusion of lithium in the active particles. In this work, scaling relations are constructed for diffusion induced damage in intercalation electrodes based on an extensive set of numerical experiments with a particle-level description of microcrack formation under disparate operating and cycling conditions, such as temperature, particle size, C-rate, and drive cycle. The microcrack formation and evolution in active particles is simulated based on a stochastic methodology. A reduced order scaling law is constructed based on an extensive set of data from the numerical experiments. The scaling relations include combinatorial constructs of concentration gradient, cumulative strain energy, and microcrack formation. The reduced order relations are further employed to study the influence of mechanical degradation on cell performance and validated against the high order model for the case of damage evolution during variable current vehicle drive cycle profiles.

  9. Risk of Eye Damage from the Wavelength-Dependent Biologically Effective UVB Spectrum Irradiances

    PubMed Central

    Wang, Fang; Gao, Qian; Hu, Liwen; Gao, Na; Ge, Tiantian; Yu, Jiaming; Liu, Yang

    2012-01-01

    A number of previous studies have discussed the risk of eye damage from broadband ultraviolet (UV) radiation. As the biologically damaging effectiveness of UV irradiation on the human body is known to be wavelength-dependent, it is necessary to study the distribution of the UV spectral irradiance. In order to quantify the ocular biologically effective UV (UVBE) irradiance exposure of different wavelengths and assess the risk of eye damage, UV exposure values were measured at Sanya, China (18.4° N, 109.7°E, altitude 18 m), using a manikin and a dual-detector spectrometer to measure simultaneously the ocular exposure and ambient UV spectral irradiance data and solar elevation angle (SEA) range (approximately 7°–85°). The present study uses the ocular UV spectral irradiance exposure weighted with the action spectra for photokeratitis, photoconjunctivitis and cataracts to calculate the ocular UVBE irradiance exposure for photokeratitis (UVBEpker), photoconjunctivitis (UVBEpcon) and cataracts (UVBEcat). We found that the ocular exposure to UV irradiance is strongest in the 30°–60° SEA range when ∼50% of ocular exposure to UV irradiance on a summer’s day is received. In the 7°–30° SEA range, all the biologically highly effective wavelengths of UVBEpker, UVBEpcon and UVBEcat irradiances are at 300 nm. However, in other SEA ranges the biologically highly effective wavelengths of UVBEpker, UVBEpcon and UVBEcat irradiances are different, corresponding to 311 nm, 300 nm and 307 nm, respectively. PMID:23284960

  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. 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. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Diethylstilbestrol induces oxidative DNA damage, resulting in apoptosis of spermatogonial stem cells in vitro.

    PubMed

    Habas, Khaled; Brinkworth, Martin H; Anderson, Diana

    2017-03-14

    The spermatogonial stem cells (SSCs) are the only germline stem cells in adults that are responsible for the transmission of genetic information from mammals to the next generation. SSCs play a very important role in the maintenance of progression of spermatogenesis and help provide an understanding of the reproductive biology of future gametes and a strategy for diagnosis and treatment of infertility and male reproductive toxicity. Androgens/oestrogens are very important for the suitable maintenance of male germ cells. There is also evidence confirming the damaging effects of oestrogen-like compounds on male reproductive health. We investigated the effects in vitro, of diethylstilbestrol (DES) on mouse spermatogonial stem cells separated using Staput unit-gravity velocity sedimentation, evaluating any DNA damage using the Comet assay and apoptotic cells in the TUNEL assay. Immunocytochemistry assays showed that the purity of isolated mouse spermatogonial cells was 90%, and the viability of these isolated cells was over 96%. Intracellular superoxide anion production (O2(-)) in SSCs was detected using p-Nitro Blue Tetrazolium (NBT) assay. The viability of cells after DES treatment was examined in the CCK8 (cell counting kit-8) cytotoxicity assay. The results showed that DES-induced DNA damage causes an increase in intracellular superoxide anions which are reduced by the flavonoid, quercetin. Investigating the molecular mechanisms and biology of SSCs provides a better understanding of spermatogonial stem cell regulation in the testis.

  13. 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.

  14. TRPM2 channels mediate acetaminophen-induced liver damage

    PubMed Central

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

    2014-01-01

    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 Ca2+ homeostasis, covalent modification and oxidation of proteins, lipid peroxidation, and DNA fragmentation. Although an increase in intracellular Ca2+ 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 Ca2+ rise. Here we report that the channel responsible for Ca2+ 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

  15. CDP-choline circumvents mercury-induced mitochondrial damage and renal dysfunction.

    PubMed

    Buelna-Chontal, Mabel; Franco, Martha; Hernández-Esquivel, Luz; Pavón, Natalia; Rodríguez-Zavala, José S; Correa, Francisco; Jasso, Ricardo; Pichardo-Ramos, Gregorio; Santamaría, José; González-Pacheco, Héctor; Soto, Virgilia; Díaz-Ruíz, Jorge L; Chávez, Edmundo

    2017-09-08

    Heavy metal ions are known to produce harmful alterations on kidney function. Specifically, the accumulation of Hg(2+) in kidney tissue may induce renal failure. In this work, the protective effect of CDP-choline against the deleterious effects induced by Hg(2+) on renal function was studied. CDP-choline administered ip at a dose of 125 mg/kg body weight prevented the damage induced by Hg(2+) administration at a dose of 3 mg/kg body weight. The findings indicate that CDP-choline guards mitochondria against Hg(2+) -toxicity by preserving their ability to retain matrix content, such as accumulated Ca(2+) . This nucleotide also protected mitochondria from Hg(2+) -induced loss of the transmembrane electric gradient and from the generation of hydrogen peroxide and membrane TBARS. In addition, CDP-choline avoided the oxidative damage of mtDNA and inhibited the release of the interleukins IL-1 and IL6, recognized as markers of acute inflammatory reaction. After the administration of Hg(2+) and CDP, CDP-choline maintained nearly normal levels of renal function and creatinine clearance, as well as blood urea nitrogen (BUN) and serum creatinine. © 2017 International Federation for Cell Biology.

  16. 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

  17. DNA damage induced by low energy electron collision and new experimental setup for further studying DNA damage by plasma

    NASA Astrophysics Data System (ADS)

    Park, Yeunsoo; Sanche, Leon; Wagner, Richard

    2013-09-01

    Low energy electrons (LEEs; below 10 eV) are the most abundant among the radiolytic species generated along the high energy radiation track in living cell. And these electrons are also one of major components with ions and photon in plasma. Interestingly, it has turned out that LEEs can create DNA damages such as base release, single- and double- strand breaks (SSB and DSB) via indirect action named dissociative electron attachment (DEA). The purposes of this study are to further find out exact mechanisms of DNA damage by LEEs at the molecular level and to verify new DNA damage like structural alteration on DNA subunits. And we will expand our study to DNA damage by plasma source to develop plasma-based new medical and biological applications. We are currently setting new experimental system for reaching our goals. We will show some recent results about new finding DNA modification damage and some experimental designs and working principles.

  18. Earthquake-induced Landslidingand Ground Damage In New Zealand

    NASA Astrophysics Data System (ADS)

    Hancox, G. T.; Perrin, N. D.; Dellow, G. D.

    A study of landsliding caused by 22 historical earthquakes in New Zealand was completed at the end of 1997 (Hancox et al., 1997). The main aims of that study were to determine: (a) the nature and extent of landsliding and other ground damage (sand boils, subsidence and lateral spreading due to soil liquefaction) caused by historical earthquakes; (b) relationships between landsliding and earthquake magnitude, epicentre, faulting, geology and topography; (c) improved environmental criteria and ground classes for assigning MM intensities and seismic hazard assessments in N.Z. The data and results of the 1997 study have recently been summarised and expanded (Hancox et al., in press), and are described in this paper. Relationships developed from these studies indicate that the minimum magnitude for earthquake-induced landsliding (EIL) in N.Z. is about M 5, with significant landsliding occurring at M 6 or greater. The minimum MM intensity for landsliding is MM6, while the most common intensities for significant landsliding are MM7-8. The intensity threshold for soil liquefaction in New Zealand was found to be MM7 for sand boils, and MM8 for lateral spreading, although such effects may also occur at one intensity level lower in highly susceptible materials. The minimum magnitude for liquefaction phenomena in N.Z. is about M 6, compared to M 5 overseas where highly susceptible soils are probably more widespread. Revised environmental response criteria (landsliding, subsidence, liquefaction-induced sand boils and lateral spreading) have also been established for the New Zealand MM Intensity Scale, and provisional landslide susceptibility Ground Classes developed for assigning MM intensities in areas where there are few buildings. Other new data presented include a size/frequency distribution model for earthquake-induced landslides over the last 150 years and a preliminary EIL Opportunity model for N.Z. The application of EIL data and relationships for seismic hazard

  19. [The role of free radicals in the UV-induced skin damage. Photo-aging].

    PubMed

    Emri, Gabriella; Horkay, Irén; Remenyik, Eva

    2006-04-23

    The natural (intrinsic) ageing of the skin is enhanced by environmental factors (extrinsic ageing). One of the most important exogenous factors is the solar UV exposure, which results in photo-aging. Besides this, epidemiological and experimental data show a rapid increase in the incidence of human skin cancers, which is also in relation to the increased sunlight exposure of the skin. In the background of these processes there are cell biological effects, photochemical reactions, membrane receptor changes, lipid- and protein modifications, DNA-damage induced by UV. The qualities and quantities of them are wavelength dependent. The UVB photons are absorbed mostly by the DNA of the epidermal keratinocytes, therefore this spectrum is more relevant for photocarcinogenesis. The effect of UVA-irradiation is mainly manifested in the induction of free radicals, which have not only DNA-damaging, but also immunomodulating effect, which also can influence on tumour development. Furthermore, the free radicals cause dermal connective tissue damage as well via activating transcription factors, inducing matrix metalloproteinases, diminishing the procollagen I and fibrillin-1 synthesis. These processes are augmented by mitochondrial DNA mutations, protein oxidation, apoptosis induction. Therefore the enzymes neutralising free radicals and antioxidant molecules, respectively, have an important role in the defence mechanisms. In the therapy of photo-aging the local retinoids lived up to expectations, but the clinical effectiveness of antioxidant vitamins is lower than expected. The most important factor in the prevention of the photo-aging and photocarcinogenesis is the sun protection at present.

  20. Mechanisms of Microwave Induced Damage in Biologic Materials

    DTIC Science & Technology

    1991-01-01

    transcription from exposure to electromagnetic fields. Bioelectro - magnetics, 11:297-312. Maffeo, S., A. A. Brayman, M. W. Miler, E. L. Carstensen, V...613-618. Martin, A. H. (1988) Magnetic fields and time dependent effects on development. Bioelectro - magnetics, 9:393-396. Martin, A. H. (1990) ELF...under isothermal conditions. Bioelectro - magnetics, 11:47-56. Cossarizza, A., D. Miti, F. Bersani, M. Cantini, R. Cadossi, A. Sacchi and C. Franceschi

  1. Mechanisms of Microwave Induced Damage in Biologic Materials.

    DTIC Science & Technology

    1992-01-01

    Radiat. Biol. 52,1 787-793 (1987). 7. A. H. Martin, Magnetic fields and time dependent effects on development, Bioelectro - magnetics 9, 393-396 (1988...of the effect of ELF on oncogene expression in normal and transformed human cells, presented at the Thirteenth Annual Meeting of the Bioelectro

  2. Mechanisms of Microwave Induced Damage in Biologic Materials

    DTIC Science & Technology

    1992-10-01

    Logarithmically growing cultures of murine L929 cells were maintained in Eagle’s minimum essential culture medium with 5 % fetal bovine serum. Daudi cells were...grown in RPMI 1640 medium supplemented with 20% fetal bovine serum. Cells were plated 24 h prior to microwave exposure. To avoid serum stimulation of ODC...growing cultures of murine L929 cells, maintained in Eagle’s minimum essential culture medium with 5% fetal bovine serum, were plated 24 h prior to

  3. Mechanisms of Microwave Induced Damage in Biologic Materials

    DTIC Science & Technology

    1989-01-01

    been advanced are independent of developments in the theory of polyelectrolytes, the fundamen - tals of which were proposed by Manning6,1 7 . Of... Spectroscopy , Volume 4, ed. R. J. H. Clark and R. E. Hester (Heyden and Sons, Ltd., London, 1978) Chapter 5. 41 I 3. Design and Evaluation of Microwave...the UV . The kinetics of the reaction were 52 Ii observed for 3 to 6 minutes by monitoring with a spectrophotometer the increase in the absorption peak

  4. Mechanisms of Microwave Induced Damage in Biologic Materials

    DTIC Science & Technology

    1988-01-25

    assess the effects of micro- wave exposure on mammalian cultured cells. Three cell lines were chosen for use. The murine fibroblast line L-929 was...eIVqr% . Watts 53 30 .9 - - - -------- . - - ----- ... 58d -- - - -- - - -- - - - --- 47o stm 0.pih oe rzotlpe 44 / . 43 41 40 . - 39 0 0.4 0.8 1.2 1.6...Mullins, R. Nardone, and L. Shonk Experiments were conducted to assess the effects of microwave exposure on mammalian cultured cells. Three cell lines

  5. DNA damage and mutations induced by arachidonic acid peroxidation.

    PubMed

    Lim, Punnajit; Sadre-Bazzaz, Kianoush; Shurter, Jesse; Sarasin, Alain; Termini, John

    2003-12-30

    Endogenous cellular oxidation of omega6-polyunsaturated fatty acids (PUFAs) has long been recognized as a contributing factor in the development of various cancers. The accrual of DNA damage as a result of reaction with free radical and electrophilic aldehyde products of lipid peroxidation is believed to be involved; however, the genotoxic and mutation-inducing potential of specific membrane PUFAs remains poorly defined. In the present study we have examined the ability of peroxidizing arachidonic acid (AA, 20:4omega6) to induce DNA strand breaks, base modifications, and mutations. The time-dependent induction of single-strand breaks and oxidative base modifications by AA in genomic DNA was quantified using denaturing glyoxal gel electrophoresis. Mutation spectra were determined in XP-G fibroblasts and a repair-proficient line corrected for this defect by c-DNA complementation (XP-G(+)). Mutation frequencies were elevated from approximately 5- to 30-fold over the background following reaction of DNA with AA for various times. The XPG gene product was found to be involved in the suppression of mutations after extended reaction of DNA with AA. Arachidonic acid-induced base substitutions were consistent with the presence of both oxidized and aldehyde base adducts in DNA. The frequency of multiple-base substitutions induced by AA was significantly reduced upon correction for the XPG defect (14% vs 2%, P = 0.0015). Evidence is also presented which suggests that the induced frequency of multiple mutations is lesion dependent. These results are compared to published data for mutations stimulated by alpha,beta-unsaturated aldehydes identified as products of lipid peroxidation.

  6. Chemical-induced DNA damage and human cancer risk.

    PubMed

    Poirier, Miriam C

    2012-10-01

    For more than 200 years human cancer induction has been known to be associated with a large variety of chemical exposures. Most exposures to chemical carcinogens occur as a result of occupation, pollution in the ambient environment, lifestyle choices, or pharmaceutical use. Scientific investigations have revealed that the majority of cancer causing chemicals, or chemical carcinogens, act through "genotoxic" or DNA damaging mechanisms, which involve covalent binding of the chemical to DNA (DNA adduct formation). Cancer-inducing exposures are typically frequent and/or chronic over years, and the accumulation of DNA damage or DNA adduct formation is considered to be a necessary requirement for tumor induction. Studies in animal models have indicated that the ability to reduce DNA damage will also result in reduction of tumor risk, leading to the hypothesis that individuals having the highest levels of DNA adducts may have an increased cancer risk, compared to individuals with the lowest levels of DNA adducts. Here we have reviewed twelve investigations showing 2- to 9-fold increased Relative Risks (RR) or Odds Ratios (OR) for cancer in (the 25% of) individuals having the highest DNA adduct levels, compared to (the 25% of) matched individuals with the lowest DNA adducts. These studies also provided preliminary evidence that multiple types of DNA adducts combined, or DNA adducts combined with other risk factors (such as infection or inflammation), may be associated with more than 10-fold higher cancer risks (RR = 34-60), compared to those found with a single carcinogen. Taken together the data suggest that a reduction in human DNA adduct level is likely to produce a reduction in human cancer risk.

  7. Knee proprioception after exercise-induced muscle damage.

    PubMed

    Torres, R; Vasques, J; Duarte, J A; Cabri, J M H

    2010-06-01

    The purpose of the present study was to investigate whether exercise-induced quadriceps muscle damage affects knee proprioception such as joint position sense (JPS), force sense and the threshold to detect passive movement (TTDPM). Fourteen young men performed sets of eccentric quadriceps contractions at a target of 60% of the maximal concentric peak torque until exhaustion; the exercise was interrupted whenever the subject could not complete two sets. Muscle soreness, JPS, the TTDPM and force sense were examined before the exercise as well as one, 24, 48, 72 and 96 h after exercise. The results were compared using one-way repeated-measure ANOVA. Plasma CK activity, collected at the same times, was analyzed by the Friedman's test to discriminate differences between baseline values and each of the other assessment moments (p<0.05). Relative to the proprioception assessment, JPS at 30 and 70 degrees of knee flexion and force sense were significantly decreased up to 48 h, whereas TTDPM decreased significantly at only one hour and 24 h after exercise, at 30 and 70 degrees of the knee flexion, respectively. The results allow the conclusion that eccentric exercise leading to muscle damage alters joint proprioception, suggesting that there might be impairment in the intrafusal fibres of spindle muscles and in the tendon organs.

  8. 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

  9. Oxidatively induced DNA damage and its repair in cancer.

    PubMed

    Dizdaroglu, Miral

    2015-01-01

    Oxidatively induced DNA damage is caused in living organisms by endogenous and exogenous reactive species. DNA lesions resulting from this type of damage are mutagenic and cytotoxic and, if not repaired, can cause genetic instability that may lead to disease processes including carcinogenesis. Living organisms possess DNA repair mechanisms that include a variety of pathways to repair multiple DNA lesions. Mutations and polymorphisms also occur in DNA repair genes adversely affecting DNA repair systems. Cancer tissues overexpress DNA repair proteins and thus develop greater DNA repair capacity than normal tissues. Increased DNA repair in tumors that removes DNA lesions before they become toxic is a major mechanism for development of resistance to therapy, affecting patient survival. Accumulated evidence suggests that DNA repair capacity may be a predictive biomarker for patient response to therapy. Thus, knowledge of DNA protein expressions in normal and cancerous tissues may help predict and guide development of treatments and yield the best therapeutic response. DNA repair proteins constitute targets for inhibitors to overcome the resistance of tumors to therapy. Inhibitors of DNA repair for combination therapy or as single agents for monotherapy may help selectively kill tumors, potentially leading to personalized therapy. Numerous inhibitors have been developed and are being tested in clinical trials. The efficacy of some inhibitors in therapy has been demonstrated in patients. Further development of inhibitors of DNA repair proteins is globally underway to help eradicate cancer.

  10. Laser induced damage and fracture in fused silica vacuum windows

    SciTech Connect

    Campbell, J.H.; Hurst, P.A.; Heggins, D.D.; Steele, W.A.; Bumpas, S.E.

    1996-11-01

    Laser-induced damage, that initiates catastrophic fracture, has been observed in large ({le}61 cm dia) fused silica lenses that also serve as vacuum barriers in Nova and Beamlet lasers. If the elastic stored energy in the lens is high enough, the lens will fracture into many pieces (implosion). Three parameters control the degree of fracture in the vacuum barrier window: elastic stored energy (tensile stress), ratio of window thickness to flaw depth, and secondary crack propagation. Fracture experiments were conducted on 15-cm dia fused silica windows that contain surface flaws caused by laser damage. Results, combined with window failure data on Beamlet and Nova, were used to develop design criteria for a ``fail-safe`` lens (that may catastrophically fracture but not implode). Specifically, the window must be made thick enough so that the peak tensile stress is less than 500 psi (3.4 MPa) and the thickness/critical flaw size is less than 6. The air leak through the window fracture and into the vacuum must be rapid enough to reduce the load on the window before secondary crack growth occurs. Finite element stress calculations of a window before and immediately following fracture into two pieces show that the elastic stored energy is redistributed if the fragments ``lock`` in place and thereby bridge the opening. In such cases, the peak stresses at the flaw site can increase, leading to further (i.e. secondary) crack growth.

  11. Prevention of chloride-induced corrosion damage to bridges

    SciTech Connect

    Cramer, Stephen D.; Covino, Bernard S., Jr.; Bullard, Sophie J.; Holcomb, Gordon R.; Russell, James H.; Ziomek-Moroz, Margaret; Virmani, Y.P. | Butler, J.T.; Nelson, F.J. | Thompson, N.G.

    2002-01-01

    The annual direct cost of bridge infrastructure corrosion to the U.S. economy is estimated at $8.3 billion, with indirect costs approximately 10 times higher. Of the approximately 600000 bridges in the U.S., between 15% and 20% are listed as ?structurally deficient,? frequently due to corrosion damage. Five technologies are presented for reducing the cost of chloride-induced corrosion damage: (1) conductive coating anodes for cathodic protection of existing reinforce concrete bridges, (2) epoxy-coated rebar (ECR), (3) stainless steel rebar, and (4) high-performance concrete for extending the service life of new structures, and (5) metalizing to provide economical, long-term corrosion protection of steel bridges. Conductive coating anodes and stainless steel rebar represent ongoing work by the Oregon Department of Transportation with final verdicts not expected for years. The ECR and metalizing technology have longer track records and are better established in the bridge construction and protection industry. Application of these technologies is guided by a thorough understanding of their performance, of characteristics of the bridge and its environment, and of the results that are sought.

  12. Tamoxifen inhibits mitochondrial oxidative stress damage induced by copper orthophenanthroline.

    PubMed

    Buelna-Chontal, Mabel; Hernández-Esquivel, Luz; Correa, Francisco; Díaz-Ruiz, Jorge Luis; Chávez, Edmundo

    2016-12-01

    In this work, we studied the effect of tamoxifen and cyclosporin A on mitochondrial permeability transition caused by addition of the thiol-oxidizing pair Cu(2+) -orthophenanthroline. The findings indicate that tamoxifen and cyclosporin A circumvent the oxidative membrane damage manifested by matrix Ca(2+) release, mitochondrial swelling, and transmembrane electrical gradient collapse. Furthermore, it was found that tamoxifen and cyclosporin A prevent the generation of TBARs promoted by Cu(2+) -orthophenanthroline, as well as the inactivation of the mitochondrial enzyme aconitase and disruption of mDNA. Electrophoretic analysis was unable to demonstrate a cross-linking reaction between membrane proteins. Yet, it was found that Cu(2+) -orthophenanthroline induced the generation of reactive oxygen species. It is thus plausible that membrane leakiness is due to an oxidative stress injury.

  13. 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.

  14. 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.

  15. OXIDANT CONDITIONING PROTECTS CARTILAGE FROM MECHANICALLY-INDUCED DAMAGE

    PubMed Central

    Ramakrishnan, Prem; Hecht, Benjamin; Pedersen, Doug; Lavery, Matthew; Maynard, Jerry; Buckwalter, Joseph; Martin, James

    2013-01-01

    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 anti-oxidant defenses of chondrocytes might influence their tolerance for mechanical injury. Based on evidence that anti-oxidant defenses in many cell types are stimulated by moderate oxidant exposure, we hypothesized that oxidant pre-conditioning would reduce acute chondrocyte death and proteoglycan depletion in cartilage explants after exposure to abnormal mechanical stresses. Porcine cartilage explants were treated every 48 hours with tert-butyl hydrogen peroxide (tBHP) at non-lethal concentrations (25, 100, 250, 500 µM) for a varying number of times (1, 2 or 4) 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 µM tBHP applied 4 times. RNA analysis revealed significant effects of 100 µM tBHP on gene expression. Catalase, hypoxia-inducible factor-1alpha (HIF-1α), and glyceraldehyde 6-phosphate dehydrogenase (GAPDH) were significantly increased relative to untreated controls in explants treated 4 times with 100 µM 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 sub-lethal 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

  16. Pyrosequencing: Applicability for Studying DNA Damage-induced Mutagenesis

    PubMed Central

    Minko, Irina G.; Earley, Lauriel F.; Larlee, Kimberly E.; Lin, Ying-Chih; Lloyd, R. Stephen

    2014-01-01

    Site-specifically modified DNAs are routinely used in the study of DNA damage-induced mutagenesis. These analyses involve the creation of DNA vectors containing a lesion at a predetermined position, DNA replication, and detection of mutations at the target site. The final step has previously required the isolation of individual DNA clones, hybridization with radioactively-labeled probes, and verification of mutations by Sanger sequencing. In search for an alternative procedure that would allow direct quantification of sequence variants in a mixed population of DNA molecules, we evaluated the applicability of pyrosequencing to site-specific mutagenesis assays. The progeny DNAs were analyzed that originated from replication of N6-(deoxy-D-erythro-pentofuranosyl)-2,6-diamino-3,4-dihydro-4-oxo-5-N-methylformamidopyrimidine (MeFapy-dG)-containing vectors in primate cells, with the lesion being positioned in the 5′-GCNGG-3′ sequence context. Pyrosequencing detected ~8% G to T transversions and ~3.5% G to A transitions, a result that was in excellent agreement with frequencies previously measured by the standard procedure [Earley et al., 2013]. However, ~3.5% G to C transversions and ~2.0% deletions could not be detected by pyrosequencing. Consistent with these observations, the sensitivity of pyrosequencing for measuring the single deoxynucleotide variants differed depending on the deoxynucleotide identity, and in the given sequence contexts, was determined to be ~1-2% for A and T and ~5% for C. Pyrosequencing of other DNA isolates that were obtained following replication of MeFapy-dG-containing vectors in primate cells or Escherichia coli, identified several additional limitations. Collectively, our data demonstrated that pyrosequencing can be used for studying DNA damage-induced mutagenesis as an effective complementary experimental approach to current protocols. PMID:24962778

  17. 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".

  18. Role of TRPM2 and TRPV1 cation channels in cellular responses to radiation-induced DNA damage.

    PubMed

    Masumoto, Kanako; Tsukimoto, Mitsutoshi; Kojima, Shuji

    2013-06-01

    Radiation exposure causes DNA damage, and DNA repair systems are essential to rescue damaged cells. Although DNA damage or oxidative stress activates transient receptor potential melastatin 2 (TRPM2) and vanilloid 1 (TRPV1) cation channels, it has not been established whether these TRP channels are involved in cellular responses to radiation-induced DNA damage. Here, we investigated the contribution of TRPM2 and TRPV1 channels to γ-irradiation- and UVB-induced DNA damage responses in human lung cancer A549 cells. A549 cells were irradiated with γ-rays (2.0Gy) or UVB (5-10mJ/cm(2)). γH2AX foci, ATM activation, 53BP1 accumulation and EGFR expression were evaluated by immunofluorescence staining. Extracellular ATP concentration was measured by luciferin-luciferase assay. Knockdown of TRPM2 and TRPV1 expression was done by siRNA transfection. γ-Irradiation-induced γH2AX focus formation, ATM activation, 53BP1 accumulation and EGFR nuclear translocation, which are all associated with DNA repair, were suppressed by knockdown of TRPM2 and TRPV1 channels in A549 cells. Release of ATP, which mediates DNA damage response-associated activation of P2Y receptors, was suppressed by pre-treatment with catalase or knockdown of TRPM2 channel, but not TRPV1 channel. Similarly, UVB-induced γH2AX focus formation was suppressed in TRPM2- and TRPV1-knockdown cells, while UVB-induced ATP release was blocked in TRPM2- but not TRPV1-knockdown cells. Our results suggest that the activation of TRPM2 channel, which mediates ATP release, and TRPV1 channel plays significant roles in the cellular responses to DNA damage induced by γ-irradiation and UVB irradiation. Our results provide a new insight into the function of TRP channels from the viewpoint of radiation biology. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Topical Application of Liposomal Antioxidants for Protection Against CEES Induced Skin Damage

    DTIC Science & Technology

    2007-07-01

    keratinocytes. Task 2: Similar to HD, CEES induces oxidative stress in the skin cells resulting in ROS generation, DNA damaging, protein and lipid oxidation...W81XWH-05-2-0034 TITLE: Topical Application of Liposomal Antioxidants for Protection Against CEES Induced Skin Damage PRINCIPAL...NUMBER Topical Application of Liposomal Antioxidants for Protection Against CEES Induced Skin Damage 5b. GRANT NUMBER W81XWH-05-2-0034 5c. PROGRAM

  20. Exenatide Induces Impairment of Autophagy Flux to Damage Rat Pancreas.

    PubMed

    Li, Zhiqiang; Huang, Lihua; Yu, Xiao; Yu, Can; Zhu, Hongwei; Li, Xia; Han, Duo; Huang, Hui

    2017-01-01

    The study aimed to explore the alteration of autophagy in rat pancreas treated with exenatide. Normal Sprague-Dawley rats and diabetes-model rats induced by 2-month high-sugar and high-fat diet and streptozotocin injection were subcutaneously injected with exenatide, respectively, for 10 weeks, with homologous rats treated with saline as control. Meanwhile, AR42J cells, pancreatic acinar cell line, were cultured with exenatide at doses of 5 pM for 3 days. The pancreas was disposed, and several sections were stained with hematoxylin-eosin. Immunohistochemistry was used to measure the expressions of glucagon-like peptide 1 receptor (GLP-1R) and cysteine-aspartic acid protease-3 in rat pancreas, and Western blot was used to test the expressions of GLP-1R, light chain 3B-I and -II, and p62 in rat pancreas and AR42J cells. The data were expressed as mean (standard deviation) and analyzed by unpaired Student's t-test. Exenatide can induce pathological changes in rat pancreas. The GLP-1R, p62, light chain 3B-II, and cysteine-aspartic acid protease-3 in rat pancreas and AR42J cells treated with exenatide were significantly overexpressed. Exenatide can activate and upregulate its receptor, GLP-1R, then impair autophagy flux and activate apoptosis in the pancreatic acinar cell, thus damaging rat pancreas.

  1. Nitrous acid induced damage in T7 DNA and phage

    SciTech Connect

    Scearce, L.M.; Masker, W.E.

    1986-05-01

    The response of bacteriophage T7 to nitrous acid damage was investigated. The T7 system allows in vitro mimicry of most aspects of in vivo DNA metabolism. Nitrous acid is of special interest since it has been previously shown to induce deletions and point mutations as well as novel adducts in DNA. T7 phage was exposed to 56 mM nitrous acid at pH 4.6 in vivo, causing a time dependent 98% decrease in survival for each 10 min duration of exposure to nitrous acid. These studies were extended to include examination of pure T7 DNA exposed in vitro to nitrous acid conditions identical to those used in the in vivo survival studies. The treated DNA was dialyzed to remove the nitrous acid and the DNA was encapsulated into empty phage heads. These in vitro packaged phage showed a survival curve analogous to the in vivo system. There was no change in survival when either in vitro or in vivo exposed phage were grown on wild type E. coli or on E. coli strains deficient in DNA repair due to mutations in DNA polymerase I, exonuclease III or a uvrA mutation. Survival was not increased when nitrous acid treated T7 were grown on E. coli induced for SOS repair. In vitro replication of nitrous acid treated DNA showed a time dependent decrease in the total amount of DNA synthesized.

  2. Ischemic Preconditioning Blunts Muscle Damage Responses Induced by Eccentric Exercise.

    PubMed

    Franz, Alexander; Behringer, Michael; Harmsen, Jan-Frieder; Mayer, Constantin; Krauspe, Rüdiger; Zilkens, Christoph; Schumann, Moritz

    2017-08-22

    Ischemic preconditioning (IPC) is known to reduce muscle damage induced by ischemia and reperfusion-injury (I/R-Injury) during surgery. Due to similarities between the pathophysiological formation of I/R-injury and eccentric exercise-induced muscle damage (EIMD), as characterized by an intracellular accumulation of Ca, an increased production of reactive oxygen species and increased pro-inflammatory signaling, the purpose of the present study was to investigate whether IPC performed prior to eccentric exercise may also protect against EIMD. Nineteen healthy men were matched to an eccentric only (ECC) (n=9) or eccentric proceeded by IPC group (IPC+ECC) (n=10). The exercise protocol consisted of bilateral biceps curls (3x10 repetitions at 80% of the concentric 1RM). In IPC+ECC, IPC was applied bilaterally at the upper arms by a tourniquet (200 mmHg) immediately prior to the exercise (3x5 minutes of occlusion, separated by 5 minutes of reperfusion). Creatine Kinase (CK), arm circumference, subjective pain (VAS score) and radial displacement (Tensiomyography, Dm) were assessed before IPC, pre-exercise, post-exercise, 20 minutes-, 2 hours-, 24 hours-, 48 hours- and 72 hours post-exercise. CK differed from baseline only in ECC at 48h (p<0.001) and 72h (p<0.001) post-exercise. After 24h, 48h and 72h, CK was increased in ECC compared to IPC+ECC (between groups: 24h: p=0.004, 48h: p<0.001, 72h: p<0.001). VAS was significantly higher in ECC at 24-72 h post-exercise, when compared to IPC+ECC (between groups: all p<0.001). Dm was decreased on all post-exercise days in ECC (all p<0.001) but remained statistically unchanged in IPC+ECC (between-groups p<0.01). These findings indicate that IPC performed prior to a bout of eccentric exercise of the elbow flexors blunts EIMD and exercise-induced pain, while maintaining the contractile properties of the muscle.

  3. Characteristics of high-peak pulsed laser induced damage to fibers

    NASA Astrophysics Data System (ADS)

    Zhao, Xinghai; Gao, Yang; Xu, Meijian; Duan, Wentao; Yu, Haiwu

    2008-03-01

    The properties of high peak pulsed laser induced damage to fused-silica fibers are investigated using damage experiments. The laser source is Q-switched Nd:YAG pumped dye laser system, the pulse width is 15.2 ns, and the wavelength is 1064 nm. The experimental results show that all the damaging scenes are fiber entry faces. Damaging patterns can be classified as three types: pit damage, fusion damage and sputtering damage. Pit damage occurs most frequently. Scaffolding defects come into being pits when the laser irradiation is lower. Fusion damage is related to the laser energy, but sputtering damage occurs frequently when the laser energy or power density is very high (>10 7W/cm2~109W/cm2, ns pulse). The damage photos illustrate that fiber end damage is mainly due to laser ablation and gasification. Impurities of fiber material or contaminant particles adhere to fiber end are stress-raisers, which absorbed enough laser energy, make local temperature rises up quickly, ulterior fusion or gasification, and finally strong tensile stress. When stress goes beyond the tensile strength of fused-silica, damage occurs. The main damage mechanisms appear to be thermal effect and plasma ionization. The origin for the decline of laser induced-damage to fibers threshold appears to be extrinsic defect. The damage criterion and damage threshold test method are presented. The zero probability damage threshold is calculated by linear fitting, that is 58.6J/cm2. The damage process of fiber end faces could be divided into six steps. The origin for the decline of laser induced-damage to fibers threshold appears to be extrinsic defects which are closely related to the end-face quality.

  4. DNA damage induces nuclear actin filament assembly by Formin -2 and Spire-½ that promotes efficient DNA repair. [corrected].

    PubMed

    Belin, Brittany J; Lee, Terri; Mullins, R Dyche

    2015-08-19

    Actin filaments assemble inside the nucleus in response to multiple cellular perturbations, including heat shock, protein misfolding, integrin engagement, and serum stimulation. We find that DNA damage also generates nuclear actin filaments-detectable by phalloidin and live-cell actin probes-with three characteristic morphologies: (i) long, nucleoplasmic filaments; (ii) short, nucleolus-associated filaments; and (iii) dense, nucleoplasmic clusters. This DNA damage-induced nuclear actin assembly requires two biologically and physically linked nucleation factors: Formin-2 and Spire-1/Spire-2. Formin-2 accumulates in the nucleus after DNA damage, and depletion of either Formin-2 or actin's nuclear import factor, importin-9, increases the number of DNA double-strand breaks (DSBs), linking nuclear actin filaments to efficient DSB clearance. Nuclear actin filaments are also required for nuclear oxidation induced by acute genotoxic stress. Our results reveal a previously unknown role for nuclear actin filaments in DNA repair and identify the molecular mechanisms creating these nuclear filaments.

  5. Biological effects of DNA damage in the hyperthermophilic archaeon Sulfolobus acidocaldarius.

    PubMed

    Reilly, Michelle S; Grogan, Dennis W

    2002-02-19

    To investigate the generality of efficient double-strand break repair and damage-induced mutagenesis in hyperthermophilic archaea, we systematically measured the effects of five DNA-damaging agents on Sulfolobus acidocaldarius and compared the results to those obtained for Escherichia coli under corresponding conditions. The observed lethality of gamma-radiation was very similar for S. acidocaldarius and E. coli, arguing against unusually efficient double-strand break repair in S. acidocaldarius. In addition, DNA-strand-breaking agents (gamma-radiation or bleomycin), as well as DNA-cross-linking agents (mechlorethamine, butadiene diepoxide or cisplatin) stimulated forward mutation, reverse mutation, and formation of recombinants via conjugation in Sulfolobus cells. Although two of the five DNA-damaging agents failed to revert the E. coli auxotrophs under these conditions, all five reverted S. acidocaldarius auxotrophs.

  6. A tissue phantom for visualization and measurement of ultrasound-induced cavitation damage.

    PubMed

    Maxwell, Adam D; Wang, Tzu-Yin; Yuan, Lingqian; Duryea, Alexander P; Xu, Zhen; Cain, Charles A

    2010-12-01

    Many ultrasound studies involve the use of tissue-mimicking materials to research phenomena in vitro and predict in vivo bioeffects. We have developed a tissue phantom to study cavitation-induced damage to tissue. The phantom consists of red blood cells suspended in an agarose hydrogel. The acoustic and mechanical properties of the gel phantom were found to be similar to soft tissue properties. The phantom's response to cavitation was evaluated using histotripsy. Histotripsy causes breakdown of tissue structures by the generation of controlled cavitation using short, focused, high-intensity ultrasound pulses. Histotripsy lesions were generated in the phantom and kidney tissue using a spherically focused 1-MHz transducer generating 15 cycle pulses, at a pulse repetition frequency of 100 Hz with a peak negative pressure of 14 MPa. Damage appeared clearly as increased optical transparency of the phantom due to rupture of individual red blood cells. The morphology of lesions generated in the phantom was very similar to that generated in kidney tissue at both macroscopic and cellular levels. Additionally, lesions in the phantom could be visualized as hypoechoic regions on a B-mode ultrasound image, similar to histotripsy lesions in tissue. High-speed imaging of the optically transparent phantom was used to show that damage coincides with the presence of cavitation. These results indicate that the phantom can accurately mimic the response of soft tissue to cavitation and provide a useful tool for studying damage induced by acoustic cavitation. Copyright © 2010 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  7. 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.

  8. 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

  9. 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

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

    DOE PAGES

    Rez, Peter; Aoki, Toshihiro; March, Katia; ...

    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

  11. On the relationship between indentation hardness and modulus, and the damage resistance of biological materials.

    PubMed

    Labonte, David; Lenz, Anne-Kristin; Oyen, Michelle L

    2017-07-15

    The remarkable mechanical performance of biological materials is based on intricate structure-function relationships. Nanoindentation has become the primary tool for characterising biological materials, as it allows to relate structural changes to variations in mechanical properties on small scales. However, the respective theoretical background and associated interpretation of the parameters measured via indentation derives largely from research on 'traditional' engineering materials such as metals or ceramics. Here, we discuss the functional relevance of indentation hardness in biological materials by presenting a meta-analysis of its relationship with indentation modulus. Across seven orders of magnitude, indentation hardness was directly proportional to indentation modulus. Using a lumped parameter model to deconvolute indentation hardness into components arising from reversible and irreversible deformation, we establish criteria which allow to interpret differences in indentation hardness across or within biological materials. The ratio between hardness and modulus arises as a key parameter, which is related to the ratio between irreversible and reversible deformation during indentation, the material's yield strength, and the resistance to irreversible deformation, a material property which represents the energy required to create a unit volume of purely irreversible deformation. Indentation hardness generally increases upon material dehydration, however to a larger extent than expected from accompanying changes in indentation modulus, indicating that water acts as a 'plasticiser'. A detailed discussion of the role of indentation hardness, modulus and toughness in damage control during sharp or blunt indentation yields comprehensive guidelines for a performance-based ranking of biological materials, and suggests that quasi-plastic deformation is a frequent yet poorly understood damage mode, highlighting an important area of future research. Instrumented

  12. Radiation-Induced Damage to Nucleic Acid Constituents

    NASA Astrophysics Data System (ADS)

    Kim, Heasook

    The objective of this research was to identify the primary free radical species produced by ionizing radiation in DNA. The ultimate goal would be to use these data obtained from model compounds to analyze radiation-induced damage in DNA itself. The different single crystals were studied in detail. The first was the sodium salt of guanosine-3 ^':5^' -cyclic monophosphate (cyclic GMP). The results of studies on crystals irradiated at 4.2^ circK distinguished two species. One of these species exhibited a non-exchangeable proton coupling that was characterized by ENDOR spectroscopy and shown to be sigma proton. The spin density on C8 was deduced from the ENDOR hyperfine coupling tensor and found to be 0.15. The second species also exhibited a non-exchangeable sigma proton coupling and a beta proton coupling. The spin densities on C8 and N9 were deduced from ENDOR measurements to be 0.09 and 0.36. The former is attributed to the oxidation product and the latter to the primary reduction product. These products are respectively the guanine cation and anion. The second single crystal studied was a sodium salt of 2^'-deoxyguanosine -5^'-monophosphate tetrahydrate. The ESR and ENDOR spectra obtained from this crystal after x-irradiation at 4.2^circK were complex and the paramagnetic species were tentatively identified as ionic species. The third DNA model compound studied was thymidine. Single crystal of thymidine were irradiated at 1.6^ circK and at 4.2^circ K. The lower temperature preserved a more primitive stage of the radiation damage process. ENDOR measurements distinguished three paramagnetic species. The most interesting component of the paramagnetic absorption in crystals irradiated at 1.6^circK is attributed to trapped electron. These electrons are stabilized by the electrostatic fields generated by hydroxy dipoles. The hyperfine couplings between the trapped electron and the proton of these polar groups were deduced from ENDOR measurements. The ESR and ENDOR

  13. The effects of pre-exercise vibration stimulation on the exercise-induced muscle damage

    PubMed Central

    Kim, Ji-Yun; Kang, Da-Haeng; Lee, Joon-Hee; O, Se-Min; Jeon, Jae-Keun

    2017-01-01

    [Purpose] To investigate the effects of pre-induced muscle damage vibration stimulation on the pressure-pain threshold and muscle-fatigue-related metabolites of exercise-induced muscle damage. [Subjects and Methods] Thirty healthy, adult male subjects were randomly assigned to the pre-induced muscle damage vibration stimulation group, post-induced muscle damage vibration stimulation group, or control group (n=10 per group). To investigate the effects of pre-induced muscle damage vibration stimulation, changes in the pressure-pain threshold (lb), creatine kinase level (U/L), and lactate dehydrogenase level (U/L) were measured and analyzed at baseline and at 24 hours, 48 hours, and 72 hours after exercise. [Results] The pressure-pain thresholds and concentrations of creatine kinase and lactate dehydrogenase varied significantly in each group and during each measurement period. There were interactions between the measurement periods and groups, and results of the post-hoc test showed that the pre-induced muscle damage vibration stimulation group had the highest efficacy among the groups. [Conclusion] Pre-induced muscle damage vibration stimulation is more effective than post-induced muscle damage vibration stimulation for preventing muscle damage. PMID:28210056

  14. Nonthermal Atmospheric Plasma Rapidly Disinfects Multidrug-Resistant Microbes by Inducing Cell Surface Damage

    PubMed Central

    Davis, Brian; Mondello, Frank; Garner, Allen L.

    2012-01-01

    Plasma, a unique state of matter with properties similar to those of ionized gas, is an effective biological disinfectant. However, the mechanism through which nonthermal or “cold” plasma inactivates microbes on surfaces is poorly understood, due in part to challenges associated with processing and analyzing live cells on surfaces rather than in aqueous solution. Here, we employ membrane adsorption techniques to visualize the cellular effects of plasma on representative clinical isolates of drug-resistant microbes. Through direct fluorescent imaging, we demonstrate that plasma rapidly inactivates planktonic cultures, with >5 log10 kill in 30 s by damaging the cell surface in a time-dependent manner, resulting in a loss of membrane integrity, leakage of intracellular components (nucleic acid, protein, ATP), and ultimately focal dissolution of the cell surface with longer exposure time. This occurred with similar kinetic rates among methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and Candida albicans. We observed no correlative evidence that plasma induced widespread genomic damage or oxidative protein modification prior to the onset of membrane damage. Consistent with the notion that plasma is superficial, plasma-mediated sterilization was dramatically reduced when microbial cells were enveloped in aqueous buffer prior to treatment. These results support the use of nonthermal plasmas for disinfecting multidrug-resistant microbes in environmental settings and substantiate ongoing clinical applications for plasma devices. PMID:22232292

  15. Male-killing symbiont damages host's dosage-compensated sex chromosome to induce embryonic apoptosis

    PubMed Central

    Harumoto, Toshiyuki; Anbutsu, Hisashi; Lemaitre, Bruno; Fukatsu, Takema

    2016-01-01

    Some symbiotic bacteria are capable of interfering with host reproduction in selfish ways. How such bacteria can manipulate host's sex-related mechanisms is of fundamental interest encompassing cell, developmental and evolutionary biology. Here, we uncover the molecular and cellular mechanisms underlying Spiroplasma-induced embryonic male lethality in Drosophila melanogaster. Transcriptomic analysis reveals that many genes related to DNA damage and apoptosis are up-regulated specifically in infected male embryos. Detailed genetic and cytological analyses demonstrate that male-killing Spiroplasma causes DNA damage on the male X chromosome interacting with the male-specific lethal (MSL) complex. The damaged male X chromosome exhibits a chromatin bridge during mitosis, and bridge breakage triggers sex-specific abnormal apoptosis via p53-dependent pathways. Notably, the MSL complex is not only necessary but also sufficient for this cytotoxic process. These results highlight symbiont's sophisticated strategy to target host's sex chromosome and recruit host's molecular cascades toward massive apoptosis in a sex-specific manner. PMID:27650264

  16. 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

  17. Nonthermal atmospheric plasma rapidly disinfects multidrug-resistant microbes by inducing cell surface damage.

    PubMed

    Kvam, Erik; Davis, Brian; Mondello, Frank; Garner, Allen L

    2012-04-01

    Plasma, a unique state of matter with properties similar to those of ionized gas, is an effective biological disinfectant. However, the mechanism through which nonthermal or "cold" plasma inactivates microbes on surfaces is poorly understood, due in part to challenges associated with processing and analyzing live cells on surfaces rather than in aqueous solution. Here, we employ membrane adsorption techniques to visualize the cellular effects of plasma on representative clinical isolates of drug-resistant microbes. Through direct fluorescent imaging, we demonstrate that plasma rapidly inactivates planktonic cultures, with >5 log(10) kill in 30 s by damaging the cell surface in a time-dependent manner, resulting in a loss of membrane integrity, leakage of intracellular components (nucleic acid, protein, ATP), and ultimately focal dissolution of the cell surface with longer exposure time. This occurred with similar kinetic rates among methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and Candida albicans. We observed no correlative evidence that plasma induced widespread genomic damage or oxidative protein modification prior to the onset of membrane damage. Consistent with the notion that plasma is superficial, plasma-mediated sterilization was dramatically reduced when microbial cells were enveloped in aqueous buffer prior to treatment. These results support the use of nonthermal plasmas for disinfecting multidrug-resistant microbes in environmental settings and substantiate ongoing clinical applications for plasma devices.

  18. 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. © 2015. Published by The Company of Biologists Ltd.

  19. 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…

  20. 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…

  1. From chemistry of DNA damage to repair and biological significance. Comprehending the future.

    PubMed

    Georgakilas, Alexandros G

    2011-06-03

    Knowledge of the chemistry behind induction of DNA damage and processing mechanisms is considered very important not only for the understanding of the biological significance but also for clinical applications. In this Special Issue, we have compiled a number of succinct reviews and original research articles, by top experts in their fields. The articles discuss and/or explore the current status of knowledge and new advances in the chemical and molecular pathways related to the induction of high oxidative stress, DNA damage and its repair in human cells and tissues. Experimental and theoretical insights are provided of how the DNA repair processes maybe modulated by gene mutations and other factors like temperature and radiation quality. 2011 Elsevier B.V. All rights reserved.

  2. 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.

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

    PubMed

    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), 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.

  4. Relative biological damage in and out of field of 6, 10 and 18 MV clinical photon beams

    NASA Astrophysics Data System (ADS)

    Ezzati, A. O.

    2016-08-01

    The lower energy of scattered radiation in and out of a megavoltage (MV) photon beam suggests that relative biological damage (RBD) may change from in- to out-of-field regions for unit absorbed dose. Because of high linear energy transfer (LET) and potential of causing severe damage to the DNA, low-energy (10 eV-1 keV) slowing down electrons should be included in radiation biological damage calculations. In this study RBD was calculated in and out of field of 6, 10 and 18 MV clinical photon beams including low-energy slowing down electrons in the track length estimated method. Electron spectra at energies higher than 2 keV were collected in a water phantom at different depths and off-axis points by using the MCNP code. A new extrapolation method was used to estimate the electron spectra at energies lower than 2 keV. The obtained spectra at energies lower than 2 keV merged with spectra at energies higher than 2 keV by using continuity of the spectra. These spectra were used as an input to a validated microdosimetric Monte Carlo (MC) code, MC damage simulation (MCDS), to calculate the RBD of induced DSB in DNA at points in and out of the primary radiation field under fully aerobic (100% O2 and anoxic (0% O2 conditions. There was an observable difference in the energy spectra for electrons for points in the primary radiation field and those points out of field. RBD had maximum variation, 11% in 6 MV photons at field size of 20×20 cm2. This variation was less than 11% for 10 and 18 MV photons and field sizes smaller than 20×20 cm2. Our simulations also showed that under the anoxic condition, RBD increases up to 6% for 6 and 10 MV photons and the 20×20 cm2 field size. This work supports the hypothesis that in megavoltage treatments out-of-field radiation quality can vary enough to have an impact on RBD per unit dose and that this may play a role as the radiation therapy community explores biological optimization as a tool to assist treatment planning.

  5. Subsurface defects of fused silica optics and laser induced damage at 351 nm.

    PubMed

    Hongjie, Liu; Jin, Huang; Fengrui, Wang; Xinda, Zhou; Xin, Ye; Xiaoyan, Zhou; Laixi, Sun; Xiaodong, Jiang; Zhan, Sui; Wanguo, Zheng

    2013-05-20

    Many kinds of subsurface defects are always present together in the subsurface of fused silica optics. It is imperfect that only one kind of defects is isolated to investigate its impact on laser damage. Therefore it is necessary to investigate the impact of subsurface defects on laser induced damage of fused silica optics with a comprehensive vision. In this work, we choose the fused silica samples manufactured by different vendors to characterize subsurface defects and measure laser induced damage. Contamination defects, subsurface damage (SSD), optical-thermal absorption and hardness of fused silica surface are characterized with time-of-flight secondary ion mass spectrometry (TOF-SIMS), fluorescence microscopy, photo-thermal common-path interferometer and fully automatic micro-hardness tester respectively. Laser induced damage threshold and damage density are measured by 351 nm nanosecond pulse laser. The correlations existing between defects and laser induced damage are analyzed. The results show that Cerium element and SSD both have a good correlation with laser-induced damage thresholds and damage density. Research results evaluate process technology of fused silica optics in China at present. Furthermore, the results can provide technique support for improving laser induced damage performance of fused silica.

  6. Apigenin inhibits oxidative stress-induced macromolecular damage in N-nitrosodiethylamine (NDEA)-induced hepatocellular carcinogenesis in Wistar albino rats.

    PubMed

    Jeyabal, Prince Vijeya Singh; Syed, Mumtaz Banu; Venkataraman, Magesh; Sambandham, Jamuna Kumari; Sakthisekaran, Dhanapal

    2005-09-01

    Apigenin (4',5,7-trihydroxyflavone), a flavone subclass of flavonoid widely distributed in many herbs, fruits, and vegetables is a substantial component of the human diet and has been shown to possess a variety of biological activities including tumor growth inhibition and chemoprevention. Recent studies in several biological systems have shown that apigenin induces tumor growth inhibition, cell cycle arrest, and apoptosis. Free radical-induced degradation of polyunsaturated fatty acid results in electrophilic products and causes severe oxidative stress. Oxidative stress induced by free radicals, nonoxidizing species, electrophiles, and associated DNA damages have been frequently coupled with carcinogenesis. In the present study, the protective role of apigenin was examined against the oxidative stress caused by N-nitrosodiethylamine (NDEA) and phenobarbital (PB) in Wistar albino rats. Oxidative stress was measured in terms of lipid peroxidation (LPO) and protein carbonyl formation. Oxidative stress-induced DNA damage was measured by single cell gel electrophoresis (comet assay). Apigenin exhibited its antioxidant defense against NDEA-induced oxidative stress. We have observed minimal levels of LPO and DNA damage in apigenin-treated hepatoma bearing animals. Based on the results, we suggest that apigenin may be developed as a promising chemotherapeutic agent against the development of chemical carcinogenesis.

  7. Examination of naturally occurring polyacetylenes and alpha-terthienyl for their ability to induce cytogenetic damage.

    PubMed

    MacRae, W D; Chan, G F; Wat, C K; Towers, G H; Lam, J

    1980-09-15

    alpha-Terthienyl and 5 polyacetylenes were examined for chromosome damaging activity using Syrian hamster cells. None of these naturally occurring compounds induced sister chromatid exchanges and neither alpha-terthienyl nor phenylheptatriyne induced chromosome aberrations.

  8. Physical analysis on laser-induced cerebral damage

    NASA Astrophysics Data System (ADS)

    Luo, Xiaosen; Liu, Jiangang; Tao, Chunkan; Lan, Xiufeng; Cao, Lingyan; Pan, Weimin; Shen, Zhonghua; Lu, Jian; Ni, Xiaowu

    2005-01-01

    Experimental investigation on cerebral damage of adult SD rats induced by 532nm CW laser was performed. Tissue heat conductive equation was set up based on two-layered structure model. Finite difference algorithm was utilized to numerically simulate the temperature distribution in the brain tissue. Allowing for tissue response to temperature variation, free boundary model was used to discuss tissue thermal coagulation formation in brain. Experimental observations show that thermal coagulation and necrosis can be caused due to laser light absorption. The result of the calculation shows that the process of the thermal coagulation of the given mode comprises two stages: fast and slow. At the first stage, necrosis domain grows fast. Then necrosis domain growth becomes slower because of the competition between the heat diffusion into the surrounding undamaged tissue and the heat dissipation caused by blood perfusion. At the center of coagulation area no neuron was observed and at the transitional zone few nervous cells were seen by microscope. The research can provide reference data for developing clinical therapy of some kind of encephalic diseases by using 532nm laser, and for making cerebral infarction models in animal experiment.

  9. SHI induced damage in electrical properties of silicon NPN BJTs

    NASA Astrophysics Data System (ADS)

    Kumar, M. Vinay; Kumar, Santhosh; Yashoda, T.; Krishnaveni, S.

    2016-05-01

    The investigation of radiation damage in Si microelectronic circuitry and devices are being carried out by various research groups globally. In particular the Si Bipolar junction transistors are very sensitive to high energetic radiation. In the present study, radiation response of NPN Bipolar junction transistor (2N3773) has been examined for 60 MeV B4+ ion. Key electrical properties like Gummel, dc current gain and capacitance - voltage (C-V) characteristics of 60 MeV B4+ ion irradiated transistor were studied before and after irradiation. Ion irradiation and subsequent electrical characterizations were performed at room temperature. Current voltage (I-V) measurements showed the increase in collector current for VBE ≤ 0.4 V as a function of fluence, which is due to B4+ ion induced surface leakage currents. Base current is observed to be more sensitive than collector current and gain appears to be degraded with ion fluence. Also, C-V measurements shows that both built in potential and doping concentration increased significantly after irradiation.

  10. 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

  11. Calculation of radiation damage induced by neutrons in compound materials

    NASA Astrophysics Data System (ADS)

    Lunéville, L.; Simeone, D.; Jouanne, C.

    2006-07-01

    Many years have been devoted to study the behaviour of solids submitted to impinging particles like ions or neutrons. The nuclear evaluations describe more and more accurately the various neutron-atom interactions. Anisotropic neutron-atom cross-sections are now available for many elements. Moreover, clear mathematical formalism now allows to calculate the number of displacements per atom in polyatomic targets in a realistic way using the binary collision approximation (BCA) framework. Even if these calculations do not take into account relaxation processes at the end of the displacement spike, they can be used to compare damages induced by different facilities like pressurized water reactors (PWR), fast breeder reactors (FBR), high temperature reactors (HTR) and fusion facilities like the European Spallation Source (ESS) and the International Fusion Material Irradiation Facility (IFMIF) on a defined material. In this paper, a formalism is presented to describe the neutron-atom cross-section and primary recoil spectra taking into account the anisotropy of nuclear reactions extracted from nuclear evaluations. Such a formalism permitted to compute displacement per atom production rate, primary and weighted recoil spectra within the BCA. The multigroup approximation has been used to calculate displacement per atom production rate and recoil spectra for a define nuclear reactor. All these informations are useful to compare recoil spectra and displacement per atom production rate produced by particle accelerator and nuclear reactor.

  12. 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

  13. SHI induced damage in electrical properties of silicon NPN BJTs

    SciTech Connect

    Kumar, M. Vinay Krishnaveni, S.; Kumar, Santhosh; Yashoda, T.

    2016-05-23

    The investigation of radiation damage in Si microelectronic circuitry and devices are being carried out by various research groups globally. In particular the Si Bipolar junction transistors are very sensitive to high energetic radiation. In the present study, radiation response of NPN Bipolar junction transistor (2N3773) has been examined for 60 MeV B{sup 4+} ion. Key electrical properties like Gummel, dc current gain and capacitance – voltage (C-V) characteristics of 60 MeV B{sup 4+} ion irradiated transistor were studied before and after irradiation. Ion irradiation and subsequent electrical characterizations were performed at room temperature. Current voltage (I-V) measurements showed the increase in collector current for V{sub BE} ≤ 0.4 V as a function of fluence, which is due to B{sup 4+} ion induced surface leakage currents. Base current is observed to be more sensitive than collector current and gain appears to be degraded with ion fluence. Also, C-V measurements shows that both built in potential and doping concentration increased significantly after irradiation.

  14. Novel DNA damage checkpoint in mitosis: Mitotic DNA damage induces re-replication without cell division in various cancer cells.

    PubMed

    Hyun, Sun-Yi; Rosen, Eliot M; Jang, Young-Joo

    2012-07-06

    DNA damage induces multiple checkpoint pathways to arrest cell cycle progression until damage is repaired. In our previous reports, when DNA damage occurred in prometaphase, cells were accumulated in 4 N-DNA G1 phase, and mitosis-specific kinases were inactivated in dependent on ATM/Chk1 after a short incubation for repair. We investigated whether or not mitotic DNA damage causes cells to skip-over late mitotic periods under prolonged incubation in a time-lapse study. 4 N-DNA-damaged cells re-replicated without cell division and accumulated in 8 N-DNA content, and the activities of apoptotic factors were increased. The inhibition of DNA replication reduced the 8 N-DNA cell population dramatically. Induction of replication without cell division was not observed upon depletion of Chk1 or ATM. Finally, mitotic DNA damage induces mitotic slippage and that cells enter G1 phase with 4 N-DNA content and then DNA replication is occurred to 8 N-DNA content before completion of mitosis in the ATM/Chk1-dependent manner, followed by caspase-dependent apoptosis during long-term repair.

  15. Partial IGF-1 deficiency induces brain oxidative damage and edema, which are ameliorated by replacement therapy.

    PubMed

    Puche, Juan E; Muñoz, Úrsula; García-Magariño, Mariano; Sádaba, María C; Castilla-Cortázar, Inma

    2016-01-01

    Insulin-like growth factor 1 (IGF-1) induces multiple cytoprotective effects on every tissue, including the brain. Since the mechanisms by which IGF-1 produces neuroprotection are not fully understood, the aim of this work was to delve into the underlying mechanisms. IGF-1 deficient mice (Hz) were compared with wild type (WT) and Hz mice treated with low doses of IGF-1 (2 µg/100 g body weight/day) for 10 days (Hz + IGF). Gene expression, quantitative PCR, histology, and magnetic resonance imaging were performed in the three groups. IGF-1 deficiency induced increased oxidative damage determined by markers of lipid peroxidation and hypoxia, as well as gene expression of heat shock proteins, antioxidant enzymes, and molecules involved in inflammation, apoptosis, and mitochondrial protection. These changes correlated with edema and learning impairment in Hz mice. IGF-1 therapy improved all these alterations. In conclusion, IGF-1 deficiency is responsible for increased brain oxidative damage, edema, and impaired learning and memory capabilities which are rescued by IGF-1 replacement therapy. © 2016 International Union of Biochemistry and Molecular Biology.

  16. Acid pump antagonist-provoked HSP27 dephosphorylation and accentuation rescues stomach from indomethacin-induced damages.

    PubMed

    Ock, Chan Young; Lim, Yun Jeong; Kim, Yoon Jae; Chung, Jun Won; Kwon, Kwang An; Kim, Ju Hyun; Hahm, Ki Baik

    2011-04-01

    Heat shock proteins (HSPs) are crucial for the maintenance of cellular integrity during normal cell growth as well as pathophysiological conditions. While acting as molecular chaperones with their folding activities, HSPs play a cytoprotective role to rescue epithelial cells from several gastric damages including non-steroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori. Since the exact relationship between HSP27 phosphorylation and biological function remains unknown in NSAID-induced gastropathy, we hypothesized that revaprazan, a novel acid pump antagonist, can secure significant cytoprotection from NSAID damages through HSP27 accentuation. We evaluated protective actions of revaprazan against either in vivo animal model of indomethacin induced gastropathy or in vitro cell model focused on HSP27 expression and activation. Indomethacin induced significant cytotoxicities accompanied with phosphorylated HSP27 and attenuated levels of HSP27 in the in vitro cell experiment and revaprazan administration protected stomach from indomethacin-induced gastric damages in accordance with HSP27 dephosphorylation in the in vivo animal experiment. HSP27 siRNA abolished these cytoprotective privileges of revaprazan. Indomethacin, 40 mg/kg, po, administration provoked significant levels of gastric damages accompanied with decrement in HSP27, while rats administrated with revaprazan prior to indomethacin imposed the accentuation of HSP27, of which levels were significantly correlated with the prevention of the indomethacin-induced gastric damages. HSP27 phosphorylation with resultant decrease in HSP27 level was one of the mechanisms of indomethacin-induced cytotoxicity, of which post-translational modifications were prevented with revaprazan administration in the presence of indomethacin. Therefore, acid pump antagonist could be a choice for the prevention of NSAID-induced gastropathy backed up with distinctive cytoprotective action beyond acid suppressor. © 2011 The

  17. The biology of gall-inducing arthropods.

    Treesearch

    Gyuri Csoka; William J. Mattson; Graham N. Stone; Peter W. Price

    1998-01-01

    This proceedings explores many facets of the ever intriguing and enigmatic relationships between plants and their gall-forming herbivores. The research reported herein ranges from studies on classical biology and systematics of galling to molecular phylogeny, population genetics, and ecological and evolutionary theory. Human kind has much to learn and gain from...

  18. 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

  19. Topical Application of Liposomal Antioxidants for Protection Against CEES Induced Skin Damage

    DTIC Science & Technology

    2008-06-01

    W81XWH-05-2-0034 TITLE: Topical Application of Liposomal Antioxidants for Protection Against CEES Induced Skin Damage PRINCIPAL...Topical Application of Liposomal Antioxidants for Protection Against CEES Induced Skin Damage 5b. GRANT NUMBER W81XWH-05-2-0034 5c. PROGRAM...effective prophylactic therapy against skin damage caused by an analog of mustard gas, 2-chloroethylethyl sulfide (CEES) using in vitro model systems

  20. Blood Flow After Exercise-Induced Muscle Damage

    PubMed Central

    Selkow, Noelle M.; Herman, Daniel C.; Liu, Zhenqi; Hertel, Jay; Hart, Joseph M.; Saliba, Susan A.

    2015-01-01

    Context: The most common modality used to address acute inflammation is cryotherapy. Whereas pain decreases with cryotherapy, evidence that changes occur in perfusion of skeletal muscle is limited. We do not know whether ice attenuates the increases in perfusion associated with acute inflammation. Objective: To examine the effects of repeated applications of ice bags on perfusion of the gastrocnemius muscle after an eccentric exercise protocol. Design: Controlled laboratory study. Setting: Laboratory. Patients or Other Participants: Eighteen healthy participants (3 men, 15 women; age = 22.2 ± 2.2 years, height = 166.0 ± 11.9 cm, mass = 69.4 ± 25.0 kg). Intervention(s): To induce eccentric muscle damage, participants performed 100 unilateral heel-lowering exercises off a step to the beat of a metronome. A randomized intervention (cryotherapy, sham, control) was applied to the exercised lower extremity immediately after the protocol and again at 10, 24, and 34 hours after the protocol. Main Outcome Measure(s): Baseline perfusion measurements (blood volume, blood flow, and blood flow velocity) were taken using contrast-enhanced ultrasound of the exercised leg. Perfusion was reassessed after the first intervention and 48 hours after the protocol as percentage change scores. Pain was measured with a visual analog scale at baseline and at 10, 24, 34, and 48 hours after the protocol. Separate repeated-measures analyses of variance were used to assess each dependent variable. Results: We found no interactions among interventions for microvascular perfusion. Blood volume and blood flow, however, increased in all conditions at 48 hours after exercise (P < .001), and blood flow velocity decreased postintervention from baseline (P = .041). We found a time-by-intervention interaction for pain (P = .009). Visual analog scale scores were lower for the cryotherapy group than for the control group at 34 and 48 hours after exercise. Conclusions: Whereas eccentric muscle damage

  1. The protective effect of grape seed procyanidin extract against cadmium-induced renal oxidative damage in mice.

    PubMed

    Chen, Qing; Zhang, Rong; Li, Wei-min; Niu, Yu-jie; Guo, Hui-cai; Liu, Xue-hui; Hou, Yu-chun; Zhao, Li-juan

    2013-11-01

    As an important environmental pollutant, cadmium (Cd) can lead to serious renal damage. Grape seed procyanidins extract (GSPE), a biological active component of grape seed, has been shown to possess antioxidative effects. Here, we assessed the protective effect of GSPE on Cd-induced renal damage using animal experiment. After 30 days, the oxidative damage of kidney was evaluated through measurement of superoxide dismutase (SOD), glutathione peroxidation (GSH-Px) and malondialdehyde (MDA). Since, oxidative stress could lead to apoptosis, the renal apoptosis was measured using flow cytometer. Moreover, the expression of apoptosis-related protein Bax and Bcl-2 was analyzed by immunohistochemistry and Western blot. The results showed that Cd led to the decrease of SOD and GSH-Px activities, and the increase of MDA level, induced renal apoptosis. However, the coadministration of GSPE attenuated Cd-induced lipid peroxidation, and antagonized renal apoptosis, probably associated with the expression of Bax and Bcl-2. These data suggested that GSPE has protective effect against renal oxidative damage induced by Cd, which provide a potential natural chemopreventive agent against Cd-poisoning. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. 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

  3. Local opioid-sensitive afferent sensory neurones in the modulation of gastric damage induced by Paf.

    PubMed Central

    Esplugues, J. V.; Whittle, B. J.; Moncada, S.

    1989-01-01

    1. The role of local sensory neurones in modulating the extent of gastric mucosal damage induced by close-arterial infusion of platelet-activating factor (Paf 50 ng kg-1 min-1 for 10 min) has been investigated in the anaesthetized rat. 2. Local intra-arterial infusion of the neurotoxin, tetrodotoxin (TTX), substantially augmented the mucosal damage induced by Paf, as assessed by both macroscopic and histological techniques. 3. In rats pretreated with capsaicin 2 weeks prior to study, to induce a functional ablation of primary afferent neurones, gastric damage induced by Paf was significantly augmented. 4. Administration of morphine (0.75-3 mg kg-1 i.v.) or its peripherally acting quaternary analogue, N-methyl morphine (15 mg kg-1 i.v.), also significantly enhanced the gastric damage induced by Paf. 5. The potentiation by morphine of Paf-induced gastric damage was inhibited by administration of the opioid antagonists, naloxone (1 mg kg-1 i.v.) or the peripherally acting N-methyl nalorphine (3 mg kg-1 i.v.). 6. Administration of TTX or morphine alone, or pretreatment with capsaicin did not induce any detectable mucosal damage, suggesting that interference with local sensory neuronal activity itself does not directly induce mucosal disruption. 7. These results indicate that peripheral opiate-sensitive afferent sensory neurones play a physiological defensive role in the mucosa, attenuating the extent of gastric damage induced by Paf. PMID:2758231

  4. Origin and temperature dependence of radiation damage in biological samples at cryogenic temperatures.

    PubMed

    Meents, Alke; Gutmann, Sascha; Wagner, Armin; Schulze-Briese, Clemens

    2010-01-19

    Radiation damage is the major impediment for obtaining structural information from biological samples by using ionizing radiation such as x-rays or electrons. The knowledge of underlying processes especially at cryogenic temperatures is still fragmentary, and a consistent mechanism has not been found yet. By using a combination of single-crystal x-ray diffraction, small-angle scattering, and qualitative and quantitative radiolysis experiments, we show that hydrogen gas, formed inside the sample during irradiation, rather than intramolecular bond cleavage between non-hydrogen atoms, is mainly responsible for the loss of high-resolution information and contrast in diffraction experiments and microscopy. The experiments that are presented in this paper cover a temperature range between 5 and 160 K and reveal that the commonly used temperature in x-ray crystallography of 100 K is not optimal in terms of minimizing radiation damage and thereby increasing the structural information obtainable in a single experiment. At 50 K, specific radiation damage to disulfide bridges is reduced by a factor of 4 compared to 100 K, and samples can tolerate a factor of 2.6 and 3.9 higher dose, as judged by the increase of R(free) values of elastase and cubic insulin crystals, respectively.

  5. Photo-induced DNA damage, DNA repair and cell lethality

    SciTech Connect

    Cool, B.L.

    1982-01-01

    DNA lesion induction and repair was measured in DNA repair proficient and deficient cells after exposures to far-UV, mid-UV, near-UV and visible light and an attempt was made to relate these molecular phenomena to the biological endpoint of cell lethality. Pyrimidine dimer and strand break induction, DNA repair and cell killing were measured after cell exposure to polychromatic but narrow bandwidth light sources with peak emissions at 254, 305, 353, 369, and 445 nm. Pyrimidine dimers were detected using specific endonuclease that nicks DNA adjacent to dimers, while strand breaks were measured using an alkaline unwinding assay. The induction efficiencies of both lesions declined with increasing wavelength; however, the decrease in strand break induction was not as rapid as that of dimer induction. The ratio of strand breaks to dimers following cell exposure to 254 or 369 nm radiation was, respectively, 1.8 x 10/sup -4/ or 0.19. The kinetics of dimer repair as well as the size of repair synthesized patches remained constant with increasing wavelength, indicating a similar repair mechanism for dimers induced by all wavelengths tested. However, consistent with the detected decline in dimer induction with increasing wavelength the proportion of dimer repair to total DNA repair decreased with increasing wavelength. The efficiency of cell killing, determined using chlonagenic survival assays, dropped rapidly, but not as rapidly as that of dimer induction, with increasing wavelength. In addition, dimer repair deficient xeroderma pigmentosum cells became less lethally hypersensitive with increasing wavelength. These data suggest a decline in dimer induced cell lethality and the existence of non-dimer lethal lesions at longer wavelengths.

  6. 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

  7. Quantitative Evaluation of Hard X-ray Damage to Biological Samples using EUV Ptychography

    NASA Astrophysics Data System (ADS)

    Baksh, Peter; Odstrcil, Michal; Parsons, Aaron; Bailey, Jo; Deinhardt, Katrin; Chad, John E.; Brocklesby, William S.; Frey, Jeremy G.

    2017-06-01

    Coherent diffractive imaging (CDI) has become a standard method on a variety of synchrotron beam lines. The high brilliance short wavelength radiation from these sources can be used to reconstruct attenuation and relative phase of a sample with nanometre resolution via CDI methods. However, the interaction between the sample and high energy ionising radiation can cause degradation to sample structure. We demonstrate, using a laboratory based high harmonic generation (HHG) based extreme ultraviolet (EUV) source, imaging a sample of hippocampal neurons using the ptychography method. The significant increase in contrast of the sample in the EUV light allows identification of damage induced from exposure to 7.3 keV photons, without causing any damage to the sample itself.

  8. Cosmic ray induced permanent damage in MNOS EAROMs

    NASA Astrophysics Data System (ADS)

    Blandford, J. T., Jr.; Pickel, J. C.; Waskiewicz, A. E.

    1984-12-01

    Permanent damage to the memory cells in Metal Nitride Oxide Semiconductor (MNOS) Electrically Alterable Read Only Memories (EAROM) has been observed after exposure to a heavy ion beam from a cyclotron under high field (Erase/Write Mode) conditions. The probability of permanent damage depends on the system application.

  9. Cosmic ray induced permanent damage in MNOS EAROMs

    SciTech Connect

    Blandford, J.T.; Pickel, J.C.; Waskiewicz, A.E.

    1984-12-01

    Permanent damage to the memory cells in Metal Nitride Oxide Semiconductor (MNOS) Electrically Alterable Read Only Memories (EAROM) has been observed after exposure to a heavy ion beam from a cyclotron under high field (Erase/Write Mode) conditions. The probability, of permanent damage depends on the system application.

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

    PubMed

    Cheng, Wei; Xiao, Lei; Ainiwaer, Aimudula; Wang, Yunlian; Wu, Ge; Mao, Rui; Yang, Ying; Bao, Yongxing

    2015-04-01

    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.

  11. DNA damage induced by red food dyes orally administered to pregnant and male mice.

    PubMed

    Tsuda, S; Murakami, M; Matsusaka, N; Kano, K; Taniguchi, K; Sasaki, Y F

    2001-05-01

    We determined the genotoxicity of synthetic red tar dyes currently used as food color additives in many countries, including JAPAN: For the preliminary assessment, we treated groups of 4 pregnant mice (gestational day 11) once orally at the limit dose (2000 mg/kg) of amaranth (food red No. 2), allura red (food red No. 40), or acid red (food red No. 106), and we sampled brain, lung, liver, kidney, glandular stomach, colon, urinary bladder, and embryo 3, 6, and 24 h after treatment. We used the comet (alkaline single cell gel electrophoresis) assay to measure DNA damage. The assay was positive in the colon 3 h after the administration of amaranth and allura red and weakly positive in the lung 6 h after the administration of amaranth. Acid red did not induce DNA damage in any sample at any sampling time. None of the dyes damaged DNA in other organs or the embryo. We then tested male mice with amaranth, allura red, and a related color additive, new coccine (food red No. 18). The 3 dyes induced DNA damage in the colon starting at 10 mg/kg. Twenty ml/kg of soaking liquid from commercial red ginger pickles, which contained 6.5 mg/10 ml of new coccine, induced DNA damage in colon, glandular stomach, and bladder. The potencies were compared to those of other rodent carcinogens. The rodent hepatocarcinogen p-dimethylaminoazobenzene induced colon DNA damage at 1 mg/kg, whereas it damaged liver DNA only at 500 mg/kg. Although 1 mg/kg of N-nitrosodimethylamine induced DNA damage in liver and bladder, it did not induce colon DNA damage. N-nitrosodiethylamine at 14 mg/kg did not induce DNA damage in any organs examined. Because the 3 azo additives we examined induced colon DNA damage at a very low dose, more extensive assessment of azo additives is warranted.

  12. Induced plant defences in biological control of arthropod pests: a double-edged sword.

    PubMed

    Pappas, Maria L; Broekgaarden, Colette; Broufas, George D; Kant, Merijn R; Messelink, Gerben J; Steppuhn, Anke; Wäckers, Felix; van Dam, Nicole M

    2017-09-01

    Biological control is an important ecosystem service delivered by natural enemies. Together with breeding for plant defence, it constitutes one of the most promising alternatives to pesticides for controlling herbivores in sustainable crop production. Especially induced plant defences may be promising targets in plant breeding for resistance against arthropod pests. Because they are activated upon herbivore damage, costs are only incurred when defence is needed. Moreover, they can be more specific than constitutive defences. Nevertheless, inducible defence traits that are harming plant pest organisms may interfere with biological control agents, such as predators and parasitoids. Despite the vast fundamental knowledge on plant defence mechanisms and their effects on natural enemies, our understanding of the feasibility of combining biological control with induced plant defence in practice is relatively poor. In this review, we focus on arthropod pest control and present the most important features of biological control with natural enemies and of induced plant defence. Furthermore, we show potential synergies and conflicts among them and, finally, identify gaps and list opportunities for their combined use in crop protection. We suggest that breeders should focus on inducible resistance traits that are compatible with the natural enemies of arthropod pests, specifically traits that help communities of natural enemies to build up. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

  13. Chromium-induced skin damage among Taiwanese cement workers.

    PubMed

    Chou, Tzu-Chieh; Wang, Po-Chih; Wu, Jyun-De; Sheu, Shiann-Cherng

    2016-10-01

    Little research has been done on the relationships between chromium exposure, skin barrier function, and other hygienic habits in cement workers. Our purpose was to investigate chromium-induced skin barrier disruption due to cement exposure among cement workers. One hundred and eight cement workers were recruited in this study. Urinary chromium concentration was used to characterize exposure levels. The biological exposure index was used to separate high and low chromium exposure. Transepidermal water loss (TEWL) was used to assess the skin barrier function. TEWL was significantly increased in workers with high chromium exposure levels than those with low chromium exposure levels (p = 0.048). A positive correlation was also found between urinary chromium concentration and TEWL (R = 0.28, p = 0.004). After adjusting for smoking status and glove use, a significant correlation between urinary chromium concentrations and TEWL remained. Moreover, workers who smoked and had a high chromium exposure had significantly increased TEWL compared to nonsmokers with low chromium exposure (p = 0.01). Skin barrier function of cement workers may have been disrupted by chromium in cement, and smoking might significantly enhance such skin barrier perturbation with chromium exposure. Decreased chromium skin exposure and smoking cessation should be encouraged at work. © The Author(s) 2015.

  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. Impact of organic contamination on the laser-induced damage in vacuum

    NASA Astrophysics Data System (ADS)

    Ling, Xiulan; Zhao, Yuanan; Li, Dawei; Li, Shuhong; zhou, Ming; Shao, Jianda; Fan, Zhengxiu

    2009-08-01

    The impact of two organic contaminations on the damage characteristics of anti-reflector (AR) at 1064 nm is investigated. Contamination experiments were made with toluene and acetone in liquid phase on the surface of AR coatings. Chemical and morphological characterization methods were used to identify and understand the damage process. The possible damage process is analyzed and discussed. It is found that toluene decreases laser-induced damage threshold and acetone seems to be benign and has little influence on laser-induced damage threshold due to its quickly spreading into the coating. Adsorption and droplet micro-lensing effect mechanism are the main cause of enhanced laser-induced damage of toluene.

  16. Ellagic and ferulic acids alleviate gamma radiation and aluminium chloride-induced oxidative damage.

    PubMed

    Salem, Ahmed M; Mohammaden, Tarek F; Ali, Mohamed A M; Mohamed, Enas A; Hassan, Hesham F

    2016-09-01

    Ionizing radiation interacts with biological systems through the generation of free radicals, which induce oxidative stress. Aluminium (Al) can negatively impact human health by direct interaction with antioxidant enzymes. Ellagic acid (EA) and Ferulic acid (FA) are plant polyphenolic compounds, have gained attention due to their multiple biological activities. To date, no studies investigating the antioxidant effect of EA/FA in a model involving both γ radiation and aluminium chloride (AlCl3) have been reported. Herein, we investigated the protective effect of EA and FA against oxidative stress induced by γ radiation and AlCl3 in rats. Rats were divided into thirteen groups: a negative control group, 3 positive control groups (γ-irradiated, AlCl3-treated and γ-irradiated+AlCl3-treated) and 9 groups (3 γ-irradiated, 3 AlCl3-treated and 3 γ-irradiated+AlCl3-treated) treated with EA and/or FA. Liver function and lipid profile were assessed. Levels of lipid peroxidation, protein oxidation and endogenous antioxidants as well as the concentrations of copper, iron and zinc were estimated in liver tissue homogenate. Furthermore, liver tissue sections were histologically examined. Oral administration of EA and/or FA resulted in 1) amelioration of AlCl3 and/or γ-radiation-induced hepatic function impairment, dyslipidemia and hepatic histological alterations; 2) reduction in liver MDA and PCC levels; 3) elevation of liver CAT, GPx and SOD activity as well as GSH level; 4) elevation in liver Cu concentrations which was accompanied by a reduction in Fe and Zn concentrations. Oral administration of EA and/or FA may be useful for ameliorating γ radiation and/or AlCl3-induced oxidative damage. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. DNA damage-induced cell death: from specific DNA lesions to the DNA damage response and apoptosis.

    PubMed

    Roos, Wynand P; Kaina, Bernd

    2013-05-28

    DNA damaging agents are potent inducers of cell death triggered by apoptosis. Since these agents induce a plethora of different DNA lesions, it is firstly important to identify the specific lesions responsible for initiating apoptosis before the apoptotic executing pathways can be elucidated. Here, we describe specific DNA lesions that have been identified as apoptosis triggers, their repair and the signaling provoked by them. We discuss methylating agents such as temozolomide, ionizing radiation and cisplatin, all of them are important in cancer therapy. We show that the potentially lethal events for the cell are O(6)-methylguanine adducts that are converted by mismatch repair into DNA double-strand breaks (DSBs), non-repaired N-methylpurines and abasic sites as well as bulky adducts that block DNA replication leading to DSBs that are also directly induced following ionizing radiation. Transcriptional inhibition may also contribute to apoptosis. Cells are equipped with sensors that detect DNA damage and relay the signal via kinases to executors, who on their turn evoke a process that inhibits cell cycle progression and provokes DNA repair or, if this fails, activate the receptor and/or mitochondrial apoptotic cascade. The main DNA damage recognition factors MRN and the PI3 kinases ATM, ATR and DNA-PK, which phosphorylate a multitude of proteins and thus induce the DNA damage response (DDR), will be discussed as well as the downstream players p53, NF-κB, Akt and survivin. We review data and models describing the signaling from DNA damage to the apoptosis executing machinery and discuss the complex interplay between cell survival and death. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  18. 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.

  19. [Attenuation of chronic stress-induced hippocampal damages following physical exercise].

    PubMed

    Ma, Qiang; Wang, Jing; Liu, Hong-Tao; Chao, Fu-Huan

    2002-10-25

    The long-term potentiation (LTP) in the hippocampal dentate gyrus and the plasma glucocorticoids level were observed in rats to study the effects of physical exercise on chronic stress-induced hippocampal damages. Eight-week spontaneous wheel running exercise could attenuate the suppression of LTP induced by 21-day restraint stress, and maintain the normal plasma glucocorticoids levels. It is suggested that long-term physical exercise may protect the hippocampus from stress-induced damages.

  20. Poly(ADP-ribose) polymerase activation mediates synchrotron radiation X-ray-induced damage of rodent testes by exacerbating DNA damage and apoptotic changes.

    PubMed

    Sheng, Caibin; Chen, Heyu; Wang, Ban; Wang, Caixia; Lin, Li; Li, Yexin; Ying, Weihai

    2014-07-01

    Synchrotron radiation (SR) X-ray has great potential for cancer treatment and medical imaging. It is of significance to investigate the mechanisms underlying the effects of SR X-ray irradiation on biological tissues, and search for the strategies for preventing the damaging effects of SR X-ray irradiation on normal tissues. The major aim of our current study is to test our hypothesis that poly(ADP-ribose) polymerase (PARP) plays a significant role in SR X-ray-induced tissue damage. The testes of rodents were pre-treated with PARP inhibitor 3-aminobenzamide (3-AB) or antioxidant N-acetyl-acetylcysteine (NAC), followed by SR X-ray irradiation. PARP activation, double-strand DNA breaks (DSB), Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) signals, caspase-3 activity and weight of the testes were determined. SR X-ray irradiation produced dose-dependent increases in poly(ADP-ribose) (PAR) formation - an index of PARP activation, which can be prevented by NAC administration. Administration of 10 or 20 mg/kg 3-AB attenuated a variety of tissue injury induced by SR X-ray, including caspase-3 activation, increases in TUNEL signals and loss of testical weight. The PARP inhibitor also significantly decreased SR X-ray-induced γ-H2AX signal - a marker of DSB. Our study has provided the first evidence suggesting that SR X-ray can induce PARP activation by generating oxidative stress, which leads to various tissue injuries at least partially by exacerbating DNA damage and apoptotic changes.

  1. 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.

  2. 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.

  3. Laser-induced damage on fused silica with photo-acoustic method

    NASA Astrophysics Data System (ADS)

    Yi, Muyu; Ke, Kai; Zhao, Jianjun; Yuan, Xiao; Zhang, Xiang

    2016-11-01

    The surface damage processes of fused silica are studied by a new photo-acoustic probe with Anti-Emi (Electron-Magnetic Interference), easy-adjusted and non-damage for the samples, and the damage thresholds is detected according to the rapid increase of the acoustic signals. Experimental results show that the damage threshold of fused silica samples is 13.86 J/cm2 at the wavelength of 1064 nm and the pulse width of 10 ns. This work may provide an effective technical support for the laser-induced damage detection.

  4. Short and longer-term effects of creatine supplementation on exercise induced muscle damage.

    PubMed

    Rosene, John; Matthews, Tracey; Ryan, Christine; Belmore, Keith; Bergsten, Alisa; Blaisdell, Jill; Gaylord, James; Love, Rebecca; Marrone, Michael; Ward, Kristine; Wilson, Eric

    2009-01-01

    The purpose of this investigation was to determine if creatine supplementation assisted with reducing the amount of exercise induced muscle damage and if creatine supplementation aided in recovery from exercise induced muscle damage. Two groups of subjects (group 1 = creatine; group 2 = placebo) participated in an eccentric exercise protocol following 7 and 30 days of creatine or placebo supplementation (20 g.d(-1) for 7 d followed by 6g.d(-1) for 23 d = 30 d). Prior to the supplementation period, measurements were obtained for maximal dynamic strength, maximal isometric force, knee range of motion, muscle soreness, and serum levels of creatine kinase (CK) and lactate dehydrogenase (LDH). Following 7 days of creatine supplementation, on day 8, subjects began consuming 6 g.d(-1) of creatine for 23 days. Additionally on days 8 and 31, subjects performed an eccentric exercise protocol using the knee extensors to induce muscle damage. Indirect markers of muscle damage, including maximal isometric force, knee range of motion, muscle soreness, and serum levels of CK and LDH, were collected at 12, 24, and 48 hours following each exercise bout. The results indicated that acute bouts of creatine have no effect on indirect markers of muscle damage for the acute (7 days) bout. However, maximal isometric force was greater for the creatine group versus placebo for the chronic (30 days) bout. This suggests that the ergogenic effect of creatine following 30 days of supplementation may have a positive impact on exercise induced muscle damage. Key pointsEccentric muscle actions highly associated with exercise induced muscle damage.Creatine supplementation has ergogenic effect to increase protein synthesis.Creatine supplementation does not attenuate exercise induced muscle damage with short term supplementation (7 days).Increased maximal isometric force seen with creatine supplementation after 30 days following exercise induced muscle damage.Ergogenic effect of creatine

  5. Influence of Subsurface Cracks on Laser Induced Surface Damage

    SciTech Connect

    Feit, M D; Rubenchik, A M

    2003-11-07

    Cracks can affect laser damage susceptibility in three ways. These are field intensification due to interference, enhanced absorption due to trapped material in the cracks, and increased mechanical weakness. Enhanced absorption is the most important effect.

  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. 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.

  9. Hepatoprotective effect of bis(4-methylbenzoyl) diselenide against CCl(4)-induced oxidative damage in mice.

    PubMed

    Filho, Carlos Borges; Del Fabbro, Lucian; Boeira, Silvana P; Furian, Ana Flávia; Savegnago, Lucielli; Soares, Letiére Cabreira; Braga, Antonio Luiz; Jesse, Cristiano R

    2013-03-01

    From a pharmacological point of view, organoseleniums are compounds with important and interesting antioxidant and biological activities. The aim of this study was to evaluate the hepatoprotective effect of bis(4-methylbenzoyl) diselenide (BMD) against carbon tetrachloride (CCl4 )-induced oxidative damage in mice. The animals received BMD (25 mg/kg p.o., for 3 days), and after 1 day, CCl4 (1 mg/kg body weight) was administered by intraperitoneal route. One day after the CCl4 exposure, the animals were euthanized for biochemical and histological analysis. Treatment with BMD (25 mg/kg p.o.) protected against aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase and lactate dehydrogenase activity increases induced by CCl4 plasma exposure. Treatment with BMD (25 mg/kg) protected against increases in thiobarbituric reactive species and decreasing non-protein thiols and ascorbic acid levels in liver of mice. Catalase and superoxide dismutase activity inhibition in the liver caused by CCl4 were protected by treatment with BMD (25 mg/kg). Glutathione S-transferase activity was inhibited by CCl4 and remained unaltered even after treatment with BMD. Sections of liver from CCl4 -exposed mice presented an intense infiltration of inflammatory cells and loss of the cellular architecture. BMD (25 mg/kg) attenuated CCl4 -induced hepatic histological alterations. The results demonstrated the hepatoprotective effects of BMD in the mouse liver, possibly by modulating the antioxidant status. Copyright © 2012 John Wiley & Sons, Ltd.

  10. Repair Machinery for Radiation-Induced DNA Damage

    DTIC Science & Technology

    2000-07-01

    significant defect in the repair of certain DNA damages, but of which damages needs to be determined. We have selected Chinese Hamster Ovary ( CHO ) as...chromosome (BAC) genomic fragment, which we isolated from a CHO BAC library, revealed that APE1 exists as a single copy gene in AA8 (see Appendix, Figure... cells , we first determined the APE1 gene copy number in the CHO AA8 cell line. Fluorescence in situ hybridization with an APE1 bacterial artificial

  11. Investigation of Friction-induced Damage to the Pig Cornea.

    PubMed

    Barros, Raquel C; Van Kooten, Theo G; Veeregowda, Deepak Halenahally

    2015-10-01

    Mechanical friction causes damage to the cornea. A friction measurement device with minimal intervention with the pig cornea tear film revealed a low friction coefficient of 0.011 in glycerine solution. Glycerine molecules presumably bind to water, mucins, and epithelial cells and therewith improve both squeeze film and boundary lubrication. Using confocal microscopy, we determined that glycerine solution reduced damage to epithelial cells by 50% compared with the phosphate buffer saline.

  12. 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

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

    PubMed

    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.

  14. NAD(+) administration decreases doxorubicin-induced liver damage of mice by enhancing antioxidation capacity and decreasing DNA damage.

    PubMed

    Wang, Ban; Ma, Yingxin; Kong, Xiaoni; Ding, Xianting; Gu, Hongchen; Chu, Tianqing; Ying, Weihai

    2014-04-05

    One of the major obstacles for cancer treatment is the toxic side effects of anti-cancer drugs. Doxorubicin (DOX) is one of the most widely used anti-cancer drugs, which produces significant toxic side effects on the heart and such organs as the liver. Because NAD(+) can decrease cellular or tissue damage under multiple conditions, we hypothesized that NAD(+) administration may decrease DOX-induced hepatotoxicity. In this study we tested this hypothesis by using a mouse model, showing that NAD(+) administration can significantly attenuate DOX-induced increase in serum glutamate oxaloacetate transaminase activity and decrease in liver weight. The NAD(+) administration also attenuated the DOX-induced increases in the levels of double-strand DNA (dsDNA) damage, TUNEL signals, and active caspase-3. Furthermore, our data has suggested that the NAD(+) administration could produce protective effects at least partially by restoring the antioxidation capacity of the liver, because NAD(+) administration can attenuate the decreases in both the GSH levels and the glutathione reductase activity of the DOX-treated liver, which could play a significant role in the DOX-induced hepatotoxicity. This finding has provided the first evidence indicating that NAD(+) is capable of increasing the antioxidation capacity of tissues. Collectively, our study has found that NAD(+) can significantly decrease DOX-induced liver damage at least partially by enhancing antioxidation capacity and decreasing dsDNA damage. Because it can also selectively decrease tumor cell survival, NAD(+) may have significant merits over antioxidants for applying jointly with DOX to decrease the toxic side effects of DOX.

  15. 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

  16. Contribution of reactive oxygen species to UV-B-induced damage in bacteria.

    PubMed

    Santos, Ana L; Gomes, Newton C M; Henriques, Isabel; Almeida, Adelaide; Correia, António; Cunha, Ângela

    2012-12-05

    The present work aimed to identify the reactive oxygen species (ROS) produced during UV-B exposure and their biochemical targets, in a set of bacterial isolates displaying different UV susceptibilities. For that, specific exogenous ROS scavengers (catalase/CAT, superoxide dismutase/SOD, sodium azide and mannitol) were used. Biological effects were assessed from total bacterial number, colony counts and heterotrophic activity (glucose uptake and respiration). DNA strand breakage, ROS generation, oxidative damage to proteins and lipids were used as markers of oxidative stress. Sodium azide conferred a statistically significant protection in terms of lipid oxidation and cell survival, suggesting that singlet oxygen might play an important role in UV-B induced cell inactivation. Mannitol exerted a significant protection against DNA strand breakage and protein carbonylation, assigning hydroxyl radicals to DNA and protein damage. The addition of exogenous CAT and SOD significantly protected the capacity for glucose uptake and respiration, suggesting that superoxide and H(2)O(2) are involved in the impairment of activity during UV-B exposure. The observation that amendment with ROS scavengers can sometimes also exert a pro-oxidant effect suggests that the intracellular oxidant status of the cell ultimately determines the efficiency of antioxidant defenses.

  17. Genetic and Functional Studies of Genes that Regulate DNA-Damage-Induced Cell Death

    DTIC Science & Technology

    2004-11-01

    AD Award Number: DAMD17-01-1-0145 TITLE: Genetic and Functional Studies of Genes that Regulate DNA-damage-induced Cell Death PRINCIPAL INVESTIGATOR...and Functional Studies of Genes that Regulate DAMD17-01-1-0145 DNA-damage-induced Cell Death 6. A UTHOR(S) Zhou Songyang, Ph.D. 7. PERFORMING ORGANIZA...mechanisms of genes that regulate DNA damage induced cell death are much less well studied. We have proposed to establish a genetic system to screen for

  18. 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

  19. Exercise-induced muscle damage and the potential protective role of estrogen.

    PubMed

    Kendall, Becky; Eston, Roger

    2002-01-01

    Exercise-induced muscle damage is a well documented phenomenon that often follows unaccustomed and sustained metabolically demanding activities. This is a well researched, but poorly understood area, including the actual mechanisms involved in the muscle damage and repair cycle. An integrated model of muscle damage has been proposed by Armstrong and is generally accepted. A more recent aspect of exercise-induced muscle damage to be investigated is the potential of estrogen to have a protective effect against skeletal muscle damage. Estrogen has been demonstrated to have a potent antioxidant capacity that plays a protective role in cardiac muscle, but whether this antioxidant capacity has the ability to protect skeletal muscle is not fully understood. In both human and rat studies, females have been shown to have lower creatine kinase (CK) activity following both eccentric and sustained exercise compared with males. As CK is often used as an indirect marker of muscle damage, it has been suggested that female muscle may sustain less damage. However, these findings may be more indicative of the membrane stabilising effect of estrogen as some studies have shown no histological differences in male and female muscle following a damaging protocol. More recently, investigations into the potential effect of estrogen on muscle damage have explored the possible role that estrogen may play in the inflammatory response following muscle damage. In light of these studies, it may be suggested that if estrogen inhibits the vital inflammatory response process associated with the muscle damage and repair cycle, it has a negative role in restoring normal muscle function after muscle damage has occurred. This review is presented in two sections: firstly, the processes involved in the muscle damage and repair cycle are reviewed; and secondly, the possible effects that estrogen has upon these processes and muscle damage in general is discussed. The muscle damage and repair cycle is

  20. Protective effects of curcumin on amyloid-β-induced neuronal oxidative damage.

    PubMed

    Huang, Han-Chang; Chang, Ping; Dai, Xue-Ling; Jiang, Zhao-Feng

    2012-07-01

    To investigate the protective effects of curcumin against amyloid-β (Aβ)-induced neuronal damage. Primary rat cortical neurons were cultured with different treatments of Aβ and curcumin. Neuronal morphologies, viability and damage were assessed. Neuronal oxidative stress was assessed, including extracellular hydrogen peroxide and intracellular reactive oxygen species. The abilities of curcumin to scavenge free radicals and to inhibit Aβ aggregation and β-sheeted formation are further assessed and discussed. Curcumin preserves cell viability, which is decreased by Aβ. The results of changed morphology, released Lactate dehydrogenases and cell viability assays indicate that curcumin protects Aβ-induced neuronal damage. Curcumin depresses Aβ-induced up-regulation of neuronal oxidative stress. The treatment sequence impacts the protective effect of curcumin on Aβ-induced neuronal damage. Curcumin shows a more protective effect on neuronal oxidative damage when curcumin was added into cultured neurons not later than Aβ, especially prior to Aβ. The abilities of curcumin to scavenge free radicals and to inhibit the formation of β-sheeted aggregation are both beneficial to depress Aβ-induced oxidative damage. Curcumin prevents neurons from Aβ-induced oxidative damage, implying the therapeutic usage for the treatment of Alzheimer's disease patients.

  1. 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

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

    PubMed

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

    2013-02-01

    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.

  3. RNA damage in biological conflicts and the diversity of responding RNA repair systems

    PubMed Central

    Burroughs, A. Maxwell; Aravind, L.

    2016-01-01

    RNA is targeted in biological conflicts by enzymatic toxins or effectors. A vast diversity of systems which repair or ‘heal’ this damage has only recently become apparent. Here, we summarize the known effectors, their modes of action, and RNA targets before surveying the diverse systems which counter this damage from a comparative genomics viewpoint. RNA-repair systems show a modular organization with extensive shuffling and displacement of the constituent domains; however, a general ‘syntax’ is strongly maintained whereby systems typically contain: a RNA ligase (either ATP-grasp or RtcB superfamilies), nucleotidyltransferases, enzymes modifying RNA-termini for ligation (phosphatases and kinases) or protection (methylases), and scaffold or cofactor proteins. We highlight poorly-understood or previously-uncharacterized repair systems and components, e.g. potential scaffolding cofactors (Rot/TROVE and SPFH/Band-7 modules) with their respective cognate non-coding RNAs (YRNAs and a novel tRNA-like molecule) and a novel nucleotidyltransferase associating with diverse ligases. These systems have been extensively disseminated by lateral transfer between distant prokaryotic and microbial eukaryotic lineages consistent with intense inter-organismal conflict. Components have also often been ‘institutionalized’ for non-conflict roles, e.g. in RNA-splicing and in RNAi systems (e.g. in kinetoplastids) which combine a distinct family of RNA-acting prim-pol domains with DICER-like proteins. PMID:27536007

  4. 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.

  5. Can exercise training counteract doxorubicin-induced oxidative damage of testis proteome?

    PubMed

    Magalhães, José; Ascensão, António; Padrão, Ana I; Aleixo, Inês M; Santos-Alves, Estela; Rocha-Rodrigues, Sílvia; Ferreira, André; Korrodi-Gregório, Luis; Vitorino, Rui; Ferreira, Rita; Fardilha, Margarida

    2017-10-05

    The use of the chemotherapeutic drug doxorubicin (DOX) is limited by its toxicity in several organs such as testes. So, we analyzed the effect of endurance treadmill exercise training (EX) performed before sub-chronic DOX treatment on sperm count and motility, testes markers of oxidative damage and apoptosis. Tissue profiling of proteins more susceptible to oxidation was made to identify the molecular pathways regulated by oxidative modifications, as nitration and carbonylation. Twenty-four adult male rats were divided into four groups (n=6/group): sedentary saline (SED+SAL), sedentary sub-chronically injected with DOX (2mg-kg-1 per week, during 7 weeks; SED+DOX), 12 weeks trained saline (EX+SAL) and trained treated with DOX (EX+DOX). DOX treatment started 5 weeks after the beginning of the exercise program. Testes caspase-3, -8 and -9, as well as aconitase activities, the content of malondialdehyde (MDA), sulfhydryl groups (-SH), carbonyl and nitrotyrosine derivatives were determined. Modified proteins were identified by 2D-Western blot followed by MALDI-TOF/TOF mass spectrometry, and bioinformatic analysis was performed to assess the biological processes regulated by these chemical modifications. The decreased sperm motility induced by DOX was not modified by exercise. Significant increases in MDA content in SED+DOX and in caspase-3 and -9 activities in EX+DOX were found. Despite no significant differences in the levels of carbonylated and nitrated proteins, exercise modulated testis proteome susceptibility to oxidation in DOX-treated group, with less modified proteins identified. Zinc finger Ran-binding domain-containing protein 2 (ZRAB2) and AN1-type zinc finger protein 3 (ZFAN3) were among the proteins found oxidativelly modified. Although no marked alterations in testes oxidative damage were noticed, proteomic analysis of oxidativelly modified proteins highlighted the protective role of exercise against oxidative damage of some proteins involved in metabolism

  6. Oxidative stress contributes to cobalt oxide nanoparticles-induced cytotoxicity and DNA damage in human hepatocarcinoma cells

    PubMed Central

    Alarifi, Saud; Ali, Daoud; Y, Al Omar Suliman; Ahamed, Maqusood; Siddiqui, Maqsood A; Al-Khedhairy, Abdulaziz A

    2013-01-01

    Background Cobalt oxide nanoparticles (Co3O4NPs) are increasingly recognized for their utility in biological applications, magnetic resonance imaging, and drug delivery. However, little is known about the toxicity of Co3O4NPs in human cells. Methods We investigated the possible mechanisms of genotoxicity induced by Co3O4NPs in human hepatocarcinoma (HepG2) cells. Cell viability, reactive oxygen species (ROS), glutathione, thiobarbituric acid reactive substance, apoptosis, and DNA damage were assessed in HepG2 cells after Co3O4NPs and Co2+ exposure. Results Co3O4NPs elicited a significant (P < 0.01) reduction in glutathione with a concomitant increase in lipid hydroperoxide, ROS generation, superoxide dismutase, and catalase activity after 24- and 48-hour exposure. Co3O4NPs had a mild cytotoxic effect in HepG2 cells; however, it induced ROS and oxidative stress, leading to DNA damage, a probable mechanism of genotoxicity. The comet assay showed a statistically significant (P < 0.01) dose- and time-related increase in DNA damage for Co3O4NPs, whereas Co2+ induced less change than Co3O4NPs but significantly more than control. Conclusion Our results demonstrated that Co3O4NPs induced cytotoxicity and genotoxicity in HepG2 cells through ROS and oxidative stress. PMID:23326189

  7. Novobiocin Inhibits the Antimicrobial Resistance Acquired through DNA Damage-Induced Mutagenesis in Acinetobacter baumannii

    PubMed Central

    Jara, Luis M.; Pérez-Varela, María; Corral, Jordi; Arch, Marta; Cortés, Pilar; Bou, Germán; Barbé, Jordi

    2015-01-01

    Acinetobacter baumannii, a worldwide emerging nosocomial pathogen, acquires antimicrobial resistances in response to DNA-damaging agents, which increase the expression of multiple error-prone DNA polymerase components. Here we show that the aminocoumarin novobiocin, which inhibits the DNA damage response in Gram-positive bacteria, also inhibits the expression of error-prone DNA polymerases in this Gram-negative multidrug-resistant pathogen and, consequently, its potential acquisition of antimicrobial resistance through DNA damage-induced mutagenesis. PMID:26503651

  8. Alcoholic beverages and gastric epithelial cell viability: effect on oxidative stress-induced damage.

    PubMed

    Loguercio, C; Tuccillo, C; Federico, A; Fogliano, V; Del Vecchio Blanco, C; Romano, M

    2009-12-01

    Alcohol is known to cause damage to the gastric epithelium independently of gastric acid secretion. Different alcoholic beverages exert different damaging effects in the stomach. However, this has not been systematically evaluated. Moreover, it is not known whether the non-alcoholic components of alcoholic beverages also play a role in the pathogenesis of gastric epithelial cell damage. Therefore, this study was designed to evaluate whether different alcoholic beverages, at a similar ethanol concentration, exerted different damaging effect in gastric epithelial cells in vitro. Moreover, we evaluated whether pre-treatment of gastric epithelial cells with alcoholic beverages prevented oxidative stress-induced damage to gastric cells. Cell damage was assessed, in MKN-28 gastric epithelial cells, by MTT assay. Oxidative stress was induced by incubating cells with xanthine and xanthine oxidase. Gastric cell viability was assessed following 30, 60, and 120 minutes incubation with ethanol 17.5-125 mg/ml(-1) or different alcoholic beverages (i.e., beer, white wine, red wine, spirits) at comparable ethanol concentration. Finally, we assessed whether pre-incubation with red wine (with or without ethanol) prevented oxidative stress-induced cell damage. Red wine caused less damage to gastric epithelial cells in vitro compared with other alcoholic beverages at comparable ethanol concentration. Pre-treatment with red wine, but not with dealcoholate red wine, significantly and time-dependently prevented oxidative stress-induced cell damage. 1) red wine is less harmful to gastric epithelial cells than other alcoholic beverages; 2) this seems related to the non-alcoholic components of red wine, because other alcoholic beverages with comparable ethanol concentration exerted more damage than red wine; 3) red wine prevents oxidative stress-induced cell damage and this seems to be related to its ethanol content.

  9. Cryptococcus neoformans-induced macrophage lysosome damage crucially contributes to fungal virulence.

    PubMed

    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

    2015-03-01

    Upon ingestion by macrophages, Cryptococcus neoformans can survive and replicate intracellularly unless the macrophages become classically activated. The mechanism enabling intracellular replication is not fully understood; neither are the mechanisms that allow classical activation to counteract replication. C. neoformans-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 C. neoformans-containing lung cells compared with C. neoformans-free cells. Among C. neoformans-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 C. neoformans replication. Experimental induction of lysosome damage increased C. neoformans replication. Activation of macrophages with IFN-γ abolished macrophage lysosome damage and enabled increased killing of C. neoformans. We conclude that induction of lysosome damage is an important C. neoformans survival strategy and that classical activation of host macrophages counters replication by preventing damage. Thus, therapeutic strategies that decrease lysosomal damage, or increase resistance to such damage, could be valuable in treating cryptococcal infections.

  10. Explosive-induced shock damage in copper and recompression of the damaged region

    SciTech Connect

    Turley, W. D. Stevens, G. D.; La Lone, B. M.; Hixson, R. S.; Cerreta, E. K.; Daykin, E. P.; Perez, C.; Graeve, O. A.; Novitskaya, E.; Rigg, P. A.; Veeser, L. R.

    2016-08-28

    We have studied the dynamic spall process for copper samples in contact with detonating low-performance explosives. When a triangular shaped shock wave from detonation moves through a sample and reflects from the free surface, tension develops immediately, one or more damaged layers can form, and a spall scab can separate from the sample and move ahead of the remaining target material. For dynamic experiments, we used time-resolved velocimetry and x-ray radiography. Soft-recovered samples were analyzed using optical imaging and microscopy. Computer simulations were used to guide experiment design. We observe that for some target thicknesses the spall scab continues to run ahead of the rest of the sample, but for thinner samples, the detonation product gases accelerate the sample enough for it to impact the spall scab several microseconds or more after the initial damage formation. Our data also show signatures in the form of a late-time reshock in the time-resolved data, which support this computational prediction. A primary goal of this research was to study the wave interactions and damage processes for explosives-loaded copper and to look for evidence of this postulated recompression event. We found both experimentally and computationally that we could tailor the magnitude of the initial and recompression shocks by varying the explosive drive and the copper sample thickness; thin samples had a large recompression after spall, whereas thick samples did not recompress at all. Samples that did not recompress had spall scabs that completely separated from the sample, whereas samples with recompression remained intact. This suggests that the hypothesized recompression process closes voids in the damage layer or otherwise halts the spall formation process. This is a somewhat surprising and, in some ways controversial, result, and the one that warrants further research in the shock compression community.

  11. Explosive-induced shock damage in copper and recompression of the damaged region

    NASA Astrophysics Data System (ADS)

    Turley, W. D.; Stevens, G. D.; Hixson, R. S.; Cerreta, E. K.; Daykin, E. P.; Graeve, O. A.; La Lone, B. M.; Novitskaya, E.; Perez, C.; Rigg, P. A.; Veeser, L. R.

    2016-08-01

    We have studied the dynamic spall process for copper samples in contact with detonating low-performance explosives. When a triangular shaped shock wave from detonation moves through a sample and reflects from the free surface, tension develops immediately, one or more damaged layers can form, and a spall scab can separate from the sample and move ahead of the remaining target material. For dynamic experiments, we used time-resolved velocimetry and x-ray radiography. Soft-recovered samples were analyzed using optical imaging and microscopy. Computer simulations were used to guide experiment design. We observe that for some target thicknesses the spall scab continues to run ahead of the rest of the sample, but for thinner samples, the detonation product gases accelerate the sample enough for it to impact the spall scab several microseconds or more after the initial damage formation. Our data also show signatures in the form of a late-time reshock in the time-resolved data, which support this computational prediction. A primary goal of this research was to study the wave interactions and damage processes for explosives-loaded copper and to look for evidence of this postulated recompression event. We found both experimentally and computationally that we could tailor the magnitude of the initial and recompression shocks by varying the explosive drive and the copper sample thickness; thin samples had a large recompression after spall, whereas thick samples did not recompress at all. Samples that did not recompress had spall scabs that completely separated from the sample, whereas samples with recompression remained intact. This suggests that the hypothesized recompression process closes voids in the damage layer or otherwise halts the spall formation process. This is a somewhat surprising and, in some ways controversial, result, and the one that warrants further research in the shock compression community.

  12. Explosive-induced shock damage in copper and recompression of the damaged region

    DOE PAGES

    Turley, William D.; Stevens, Gerald D.; Hixson, Robert Stewart; ...

    2016-08-31

    Here, we have studied the dynamic spall process for copper samples in contact with detonating low-performance explosives. When a triangular shaped shock wave from detonation moves through a sample and reflects from the free surface, tension develops immediately, one or more damaged layers can form, and a spall scab can separate from the sample and move ahead of the remaining target material. For dynamic experiments, we used time-resolved velocimetry and x-ray radiography. Soft-recovered samples were analyzed using optical imaging and microscopy. Computer simulations were used to guide experiment design. We observe that for some target thicknesses the spall scab continuesmore » to run ahead of the rest of the sample, but for thinner samples, the detonation product gases accelerate the sample enough for it to impact the spall scab several microseconds or more after the initial damage formation. Our data also show signatures in the form of a late-time reshock in the time-resolved data, which support this computational prediction. A primary goal of this research was to study the wave interactions and damage processes for explosives-loaded copper and to look for evidence of this postulated recompression event. We found both experimentally and computationally that we could tailor the magnitude of the initial and recompression shocks by varying the explosive drive and the copper sample thickness; thin samples had a large recompression after spall, whereas thick samples did not recompress at all. Samples that did not recompress had spall scabs that completely separated from the sample, whereas samples with recompression remained intact. This suggests that the hypothesized recompression process closes voids in the damage layer or otherwise halts the spall formation process. This is a somewhat surprising and, in some ways controversial, result, and the one that warrants further research in the shock compression community.« less

  13. Gastric mucosal damage induced by nonsalicylate nonsteroidal antiinflammatory drugs in rats is mediated systemically.

    PubMed

    Skeljo, M V; Giraud, A S; Yeomans, N D

    1993-11-01

    The gastric toxicities of an enteric-coated formulation and conventional indomethacin were compared in rats. Both formulations were equally damaging to the mucosa, suggesting that topical damage was not the major route of injury. The importance of systemically mediated damage was further determined by gastrotoxicity dose-response curves and pyloric ligation experiments in which indomethacin was administered either orally or parenterally, or into stomach or duodenum with the pylorus occluded. Gastric damage was significantly higher in those groups that had received the drug parenterally or intraduodenally. The extent of deeper mucosal damage, assessed histologically, was greater in parenterally dosed rats. In further experiments, oral and parenteral routes of administration of two other nonsalicylate NSAIDs, naproxen and sodium diclofenac, were found to be equally damaging to the mucosa. Our results show that indomethacin-induced gastric damage, unlike aspirin injury, is mediated mainly systemically. Enteric-coating may not be a useful strategy in reducing gastric injury by nonsalicylate, nonsteroidal antiinflammatory drugs.

  14. Hybrid molecular dynamics simulation for plasma induced damage analysis

    NASA Astrophysics Data System (ADS)

    Matsukuma, Masaaki

    2016-09-01

    In order to enable further device size reduction (also known as Moore's law) and improved power performance, the semiconductor industry is introducing new materials and device structures into the semiconductor fabrication process. Materials now include III-V compounds, germanium, cobalt, ruthenium, hafnium, and others. The device structure in both memory and logic has been evolving from planar to three dimensional (3D). One such device is the FinFET, where the transistor gate is a vertical fin made either of silicon, silicon-germanium or germanium. These changes have brought renewed interests in the structural damages caused by energetic ion bombardment of the fin sidewalls which are exposed to the ion flux from the plasma during the fin-strip off step. Better control of the physical damage of the 3D devices requires a better understanding of the damage formation mechanisms on such new materials and structures. In this study, the damage formation processes by ion bombardment have been simulated for Si and Ge substrate by Quantum Mechanics/Molecular Mechanics (QM/MM) hybrid simulations and compared to the results from the classical molecular dynamics (MD) simulations. In our QM/MM simulations, the highly reactive region in which the structural damage is created is simulated with the Density Functional based Tight Binding (DFTB) method and the region remote from the primary region is simulated using classical MD with the Stillinger-Weber and Moliere potentials. The learn on the fly method is also used to reduce the computational load. Hence our QM/MM simulation is much faster than the full QC-MD simulations and the original QM/MM simulations. The amorphous layers profile simulated with QM/MM have obvious differences in their thickness for silicon and germanium substrate. The profile of damaged structure in the germanium substrate is characterized by a deeper tail then in silicon. These traits are also observed in the results from the mass selected ion beam

  15. Cluster Ion Bombardment-Induced Surface Damage of Si

    NASA Astrophysics Data System (ADS)

    Ascheron, C. E.; Akizuki, M.; Matsuo, J.; Insepov, Z.; Takaoka, G. H.; Yamada, I.

    Surface damage of single-crystalline Si caused by irradiation with Ar-ion cluster beams of different energies has been studied in comparison with that caused by Ar-monomer ion beams. The defected layers have been characterized by RBS channeling, XTEM, and ellipsometry. The experimental results are interpreted on the basis of TRIM and molecular dynamics simulations of the interaction processes with the target. It is found that cluster irradiation damages only a very thin near-surface layer which has a smooth interface to the undamaged substrate. Cluster-ion bombardment forms an oxide layer on the surface by the activation of adsorbed O atoms and substrate atoms.

  16. 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.

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

    PubMed

    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.

  18. 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

  19. DNA-damage response during mitosis induces whole-chromosome missegregation.

    PubMed

    Bakhoum, Samuel F; Kabeche, Lilian; Murnane, John P; Zaki, Bassem I; Compton, Duane A

    2014-11-01

    Many cancers display both structural (s-CIN) and numerical (w-CIN) chromosomal instabilities. Defective chromosome segregation during mitosis has been shown to cause DNA damage that induces structural rearrangements of chromosomes (s-CIN). In contrast, whether DNA damage can disrupt mitotic processes to generate whole chromosomal instability (w-CIN) is unknown. Here, we show that activation of the DNA-damage response (DDR) during mitosis selectively stabilizes kinetochore-microtubule (k-MT) attachments to chromosomes through Aurora-A and PLK1 kinases, thereby increasing the frequency of lagging chromosomes during anaphase. Inhibition of DDR proteins, ATM or CHK2, abolishes the effect of DNA damage on k-MTs and chromosome segregation, whereas activation of the DDR in the absence of DNA damage is sufficient to induce chromosome segregation errors. Finally, inhibiting the DDR during mitosis in cancer cells with persistent DNA damage suppresses inherent chromosome segregation defects. Thus, the DDR during mitosis inappropriately stabilizes k-MTs, creating a link between s-CIN and w-CIN. The genome-protective role of the DDR depends on its ability to delay cell division until damaged DNA can be fully repaired. Here, we show that when DNA damage is induced during mitosis, the DDR unexpectedly induces errors in the segregation of entire chromosomes, thus linking structural and numerical chromosomal instabilities. ©2014 American Association for Cancer Research.

  20. 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.…

  1. Cannabidiol reduces lung injury induced by hypoxic-ischemic brain damage in newborn piglets.

    PubMed

    Arruza, Luis; Pazos, Maria Ruth; Mohammed, Nagat; Escribano, Natalia; Lafuente, Hector; Santos, Martín; Alvarez-Díaz, Francisco J; Hind, William; Martínez-Orgado, Jose

    2017-07-01

    BackgroundBrain hypoxic-ischemic (HI) damage induces distant inflammatory lung damage in newborn pigs. We aimed to investigate the effects of cannabidiol (CBD) on lung damage in this scenario.MethodsNewborn piglets received intravenous vehicle, CBD, or CBD+WAY100635 (5-HT1A receptor antagonist) after HI brain damage (carotid flow interruption and FiO2 0.10 for 30 min). Total lung compliance (TLC), oxygenation index (OI), and extravascular lung water content (EVLW) were monitored for 6 h. Histological damage, interleukin (IL)-1β concentration, and oxidative stress were assessed in brain and lung tissue. Total protein content was determined in bronchoalveolar lavage fluid (BALF).ResultsCBD prevented HI-induced deleterious effects on TLC and OI and reduced lung histological damage, modulating inflammation (decreased leukocyte infiltration and IL-1 concentration) and reducing protein content in BALF and EVLW. These effects were related to CBD-induced anti-inflammatory changes in the brain. HI did not increase oxidative stress in the lungs. In the lungs, WAY100635 blunted the beneficial effects of CBD on histological damage, IL-1 concentration, and EVLW.ConclusionsCBD reduced brain HI-induced distant lung damage, with 5-HT1A receptor involvement in these effects. Whether the effects of CBD on the lungs were due to the anti-inflammatory effects on the brain or due to the direct effects on the lungs remains to be elucidated.

  2. 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.…

  3. 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.

  4. 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.

  5. Effect of Creatine Supplementation on Muscle Damage and Repair Following Eccentrically-Induced Damage to the Elbow Flexor Muscles

    PubMed Central

    McKinnon, Neal B.; Graham, Mitchell T.; Tiidus, Peter M.

    2012-01-01

    We investigated effects of creatine (Cr) supplementation (CrS) on exercise-induced muscle damage. Untrained males and females (N = 27) ages 18-25, with no CrS history in the past 4 months, were randomly assigned to CrS (creatine and carbohydrate) (n = 9), placebo (P) (carbohydrate only) (n = 9), or control (C) (no supplements) groups (n = 9). Participants followed a 5-day Cr loading protocol of 40 g·day-1, divided for 5 days prior to exercise, reduced to 10 g g·day-1 for 5 days following exercise. Testing consisted of 5 maximal isometric contractions at 90 arm flexion with the preferred arm on a CYBEX NORM dynamometer, assessed prior to, immediately following, and 24, 48, 72, and 96 hours post muscle-damaging procedures. Damage was induced to the elbow flexor muscles using 6 sets of 10 eccentric contractions at 75 °/sec, 90 °/sec and 120 °/sec. Participants were asked to rate their muscle soreness on a scale of 1-10. Data was analyzed using repeated-measures ANOVA, with an alpha of 0.05. No significant differences were found between muscle force loss and rate of recovery or muscle soreness between groups over the 96 hr recovery period (p > 0.05). Across all 3 experimental groups an initial decrease in force was observed, followed by a gradual recovery. Significant differences were found between baseline and all others times (p = 0.031,0 .022, 0.012, 0.001 respectively), and between the 48 hour and 96 hour time periods (p = 0.034). A weak negative correlation between subjectively rated muscle soreness and mean peak isometric force loss (R2 = 0.0374 at 96 hours), suggested that muscle soreness and muscle force loss may not be directly related. In conclusion, 5 days of Cr loading, followed by a Cr maintenance protocol did not reduce indices of muscle damage or speed recovery of upper body muscles following eccentrically induced muscle damage. Key points Creatine supplementation has been suggested as a means to diminish exercise induced muscle damage and speed

  6. RNase H enables efficient repair of R-loop induced DNA damage

    PubMed Central

    Amon, Jeremy D; Koshland, Douglas

    2016-01-01

    R-loops, three-stranded structures that form when transcripts hybridize to chromosomal DNA, are potent agents of genome instability. This instability has been explained by the ability of R-loops to induce DNA damage. Here, we show that persistent R-loops also compromise DNA repair. Depleting endogenous RNase H activity impairs R-loop removal in Saccharomyces cerevisiae, causing DNA damage that occurs preferentially in the repetitive ribosomal DNA locus (rDNA). We analyzed the repair kinetics of this damage and identified mutants that modulate repair. We present a model that the persistence of R-loops at sites of DNA damage induces repair by break-induced replication (BIR). This R-loop induced BIR is particularly susceptible to the formation of lethal repair intermediates at the rDNA because of a barrier imposed by RNA polymerase I. DOI: http://dx.doi.org/10.7554/eLife.20533.001 PMID:27938663

  7. Relative biological effectiveness (RBE) and distal edge effects of proton radiation on early damage in vivo.

    PubMed

    Sørensen, Brita Singers; Bassler, Niels; Nielsen, Steffen; Horsman, Michael R; Grzanka, Leszek; Spejlborg, Harald; Swakoń, Jan; Olko, Paweł; Overgaard, Jens

    2017-08-23

    The aim of the present study was to examine the RBE for early damage in an in vivo mouse model, and the effect of the increased linear energy transfer (LET) towards the distal edge of the spread-out Bragg peak (SOBP). The lower part of the right hind limb of CDF1 mice was irradiated with single fractions of either 6 MV photons, 240 kV photons or scanning beam protons and graded doses were applied. For the proton irradiation, the leg was either placed in the middle of a 30-mm SOBP, or to assess the effect in different positions, irradiated in 4 mm intervals from the middle of the SOBP to behind the distal dose fall-off. Irradiations were performed with the same dose plan at all positions, corresponding to a dose of 31.25 Gy in the middle of the SOBP. Endpoint of the study was early skin damage of the foot, assessed by a mouse foot skin scoring system. The MDD50 values with 95% confidence intervals were 36.1 (34.2-38.1) Gy for protons in the middle of the SOBP for score 3.5. For 6 MV photons, it was 35.9 (34.5-37.5) Gy and 32.6 (30.7-34.7) Gy for 240 kV photons for score 3.5. The corresponding RBE was 1.00 (0.94-1.05), relative to 6 MV photons and 0.9 (0.85-0.97) relative to 240 kV photons. In the mice group positioned at the SOBP distal dose fall-off, 25% of the mice developed early skin damage compared with 0-8% in other groups. LETd,z = 1 was 8.4 keV/μm at the distal dose fall-off and the physical dose delivered was 7% lower than in the central SOBP position, where LETd,z =1 was 3.3 keV/μm. Although there is a need to expand the current study to be able to calculate an exact enhancement ratio, an enhanced biological effect in vivo for early skin damage in the distal edge was demonstrated.

  8. Organophosphate-induced brain damage: mechanisms, neuropsychiatric and neurological consequences, and potential therapeutic strategies.

    PubMed

    Chen, Yun

    2012-06-01

    Organophosphate (OP)-induced brain damage is defined as progressive damage to the brain, resulting from the cholinergic neuronal excitotoxicity and dysfunction induced by OP-induced irreversible AChE inhibition. This delayed secondary neuronal damage that occurs mainly in the cholinergic regions of the brain that contain dense accumulations of cholinergic neurons and the majority of cholinergic projection, might be largely responsible for persistent profound neuropsychiatric and neurological impairments (memory, cognitive, mental, emotional, motor and sensory deficits) in the victims of OP poisoning. Neuroprotective strategies for attenuating OP-induced brain damage should target different development stages of OP-induced brain damage, and may include but not limited to: (1) Antidote therapies with atropine and related efficient anticholinergic drugs; (2) Anti-excitotoxic therapies targeting attenuation of cerebral edema and inflammatory reaction, blockage of calcium influx, inhibition of apoptosis program, and the control of seizures; (3) Neuroprotective strategies using cytokines, antioxidants and NMDAR antagonists (a single drug or a combination of drugs) to slow down the process of secondary neuronal damage; and (4) Therapies targeting individual symptoms or clusters of chronic neuropsychiatric and neurological symptoms. These neuroprotective strategies may help limit or prevent secondary neuronal damage at the early stage of OP poisoning and attenuate the subsequent neuropsychiatric and neurological impairments, thus reducing the long-term disability caused by exposure to OPs. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Antecedent glycemic control reduces severe hypoglycemia-induced neuronal damage in diabetic rats.

    PubMed

    Reno, Candace M; Tanoli, Tariq; Bree, Adam; Daphna-Iken, Dorit; Cui, Chen; Maloney, Susan E; Wozniak, David F; Fisher, Simon J

    2013-06-15

    Brain damage due to severe hypoglycemia occurs in insulin-treated people with diabetes. This study tests the hypothesis that chronic insulin therapy that normalizes elevated blood glucose in diabetic rats would be neuroprotective against brain damage induced by an acute episode of severe hypoglycemia. Male Sprague-Dawley rats were split into three groups: 1) control, non-diabetic; 2) STZ-diabetic; and 3) insulin-treated STZ-diabetic. After 3 wk of chronic treatment, unrestrained awake rats underwent acute hyperinsulinemic severe hypoglycemic (10-15 mg/dl) clamps for 1 h. Rats were subsequently analyzed for brain damage and cognitive function. Severe hypoglycemia induced 15-fold more neuronal damage in STZ-diabetic rats compared with nondiabetic rats. Chronic insulin treatment of diabetic rats, which nearly normalized glucose levels, markedly reduced neuronal damage induced by severe hypoglycemia. Fortunately, no cognitive defects associated with the hypoglycemia-induced brain damage were observed in any group. In conclusion, antecedent blood glucose control represents a major modifiable therapeutic intervention that can afford diabetic subjects neuroprotection against severe hypoglycemia-induced brain damage.

  10. Residual force enhancement following eccentric induced muscle damage.

    PubMed

    Power, Geoffrey A; Rice, Charles L; Vandervoort, Anthony A

    2012-06-26

    During lengthening of an activated skeletal muscle, the force maintained following the stretch is greater than the isometric force at the same muscle length. This is termed residual force enhancement (RFE), but it is unknown how muscle damage following repeated eccentric contractions affects RFE. Using the dorsiflexors, we hypothesised muscle damage will impair the force generating sarcomeric structures leading to a reduction in RFE. Following reference maximal voluntary isometric contractions (MVC) in 8 young men (26.5±2.8y) a stretch was performed at 30°/s over a 30° ankle excursion ending at the same muscle length as the reference MVCs (30° plantar flexion). Surface electromyography (EMG) of the tibialis anterior and soleus muscles was recorded during all tasks. The damage protocol involved 4 sets of 25 isokinetic (30°/s) lengthening contractions. The same measures were collected at baseline and immediately post lengthening contractions, and for up to 10min recovery. Following the lengthening contraction task, there was a 30.3±6.4% decrease in eccentric torque (P<0.05) and 36.2±9.7% decrease in MVC (P<0.05) compared to baseline. Voluntary activation using twitch interpolation and RMS EMG amplitude of the tibialis anterior remained near maximal without increased coactivation for MVC. Contrary to our hypothesis, RFE increased (∼100-250%) following muscle damage (P<0.05). It appears stretch provided a mechanical strategy for enhanced muscle function compared to isometric actions succeeding damage. Thus, active force of cross-bridges is decreased because of impaired excitation-contraction coupling but force generated during stretch remains intact because force contribution from stretched sarcomeric structures is less impaired.

  11. Genoprotective and hepatoprotective effects of Guarana (Paullinia cupana Mart. var. sorbilis) on CCl4-induced liver damage in rats.

    PubMed

    Kober, Helena; Tatsch, Etiane; Torbitz, Vanessa Dorneles; Cargnin, Lara Peruzzolo; Sangoi, Manuela Borges; Bochi, Guilherme Vargas; da Silva, Andreia Regina Haas; Barbisan, Fernanda; Ribeiro, Euler Esteves; da Cruz, Ivana Beatrice Mânica; Moresco, Rafael Noal

    2016-01-01

    Several biological effects of Paullinia cupana (guarana) have been demonstrated, but little information is available on its effects on the liver. The current study was designed to evaluate the hepatoprotective and genoprotective effects of powder seeds from guarana on CCl4-induced liver injury in rats. Male Wistar rats were pretreated with guarana powder (100, 300 and 600 mg/kg) or silymarin 100 mg/kg daily for 14 days before treatment with a single dose of CCl4 (50% CCl4, 1 mL/kg, intraperitoneally). The treatment with CCl4 significantly increased the serum activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In addition, CCl4 increased the DNA damage index in hepatocytes. Guarana in all concentrations was effective in decreasing the ALT and AST activities when compared with the CCl4-treated group. The treatment with guarana decreased DNA damage index when compared with the CCl4-treated group. In addition, the DNA damage index showed a significant positive correlation with AST and ALT. These results indicate that the guarana has hepatoprotective activity and prevents the DNA strand breakage in the CCl4-induced liver damage in rats.

  12. SNF2H interacts with XRCC1 and is involved in repair of H2O2-induced DNA damage.

    PubMed

    Kubota, Yoshiko; Shimizu, Shinji; Yasuhira, Shinji; Horiuchi, Saburo

    2016-07-01

    The protein XRCC1 has no inherent enzymatic activity, and is believed to function in base excision repair as a dedicated scaffold component that coordinates other DNA repair factors. Repair foci clearly represent the recruitment and accumulation of DNA repair factors at sites of damage; however, uncertainties remain regarding their organization in the context of nuclear architecture and their biological significance. Here we identified the chromatin remodeling factor SNF2H/SMARCA5 as a novel binding partner of XRCC1, with their interaction dependent on the casein kinase 2-mediated constitutive phosphorylation of XRCC1. The proficiency of repairing H2O2-induced damage was strongly impaired by SNF2H knock-down, and similar impairment was observed with knock-down of both XRCC1 and SNF2H simultaneously, suggesting their role in a common repair pathway. Most SNF2H exists in the nuclear matrix fraction, forming salt extraction-resistant foci-like structures in unchallenged nuclei. Remarkably, damage-induced formation of both PAR and XRCC1 foci depended on SNF2H, and the PAR and XRCC1 foci co-localized with the SNF2H foci. We propose a model in which a base excision repair complex containing damaged chromatin is recruited to specific locations in the nuclear matrix for repair, with this recruitment mediated by XRCC1-SNF2H interaction. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. BHT blocks NF-kappaB activation and ethanol-induced brain damage.

    PubMed

    Crews, Fulton; Nixon, Kimberly; Kim, Daniel; Joseph, James; Shukitt-Hale, Barbara; Qin, Liya; Zou, Jian

    2006-11-01

    Binge ethanol administration causes corticolimbic brain damage that models alcoholic neurodegeneration. The mechanism of binge ethanol-induced degeneration is unknown, but is not simple glutamate-N-methyl-D-aspartate (NMDA) excitotoxicity. To test the hypothesis that oxidative stress and inflammation are mechanisms of binge ethanol-induced brain damage, we administered 4 antioxidants, e.g., butylated hydroxytoluene (BHT), ebselen (Eb), vitamin E (VE), and blueberry (BB) extract, during binge ethanol treatment and assessed various measures of neurodegeneration. Adult Sprague-Dawley rats were treated with intragastric ethanol 3 times per day (8-12 g/kg/d) alone or in combination with antioxidants or isocaloric diet for 4 days. Animals were killed, and brains were perfused and extracted for histochemical silver stain determination of brain damage, markers of neurogenesis, or other immunohistochemistry. Some animals were used for determination of nuclear factor kappa B (NF-kappaB)-DNA binding by electrophoretic mobility shift assay (EMSA) or for reverse transcription-polymerase chain reaction (RT-PCR) of cyclooxygenase 2 (COX2). Binge ethanol induced corticolimbic brain damage and reduced neurogenesis. Treatment with BHT reversed binge induced brain damage and blocked ethanol inhibition of neurogenesis in all regions studied. Interestingly, the other antioxidants studied, e.g., Eb, VE, and BB, did not protect against binge-induced brain damage. Binge ethanol treatment also caused microglia activation, increased NF-kappaB-DNA binding and COX2 expression. Butylated hydroxytoluene reduced binge-induced NF-kappaB-DNA binding and COX2 expression. Binge-induced brain damage and activation of NF-kappaB-DNA binding are blocked by BHT. These studies support a neuroinflammatory mechanism of binge ethanol-induced brain damage.

  14. Relationship between recurrent liquefaction-induced damage and subsurface conditions in Midorigaoka, Japan

    SciTech Connect

    Wakamatsu, Kazue; Yoshida, Nozomu

    2008-07-08

    Midorigaoka, Kushiro City, northeast Japan, suffered liquefaction-induced ground failures during four successive earthquakes in the past thirty years. This paper presents the ground failures and their effects to structures observed in Midorigaoka during the earthquakes, and examines the relationships between recurrent liquefaction-induced damage and subsurface conditions. As a result, thick liquefiable fill, slope of the ground surface, and subsurface water conditions, which resulted primarily from filling a marshy valley, are found to be responsible on the damage.

  15. Lack of the Growth Factor Midkine Enhances Survival against Cisplatin-Induced Renal Damage

    PubMed Central

    Kawai, Hanayo; Sato, Waichi; Yuzawa, Yukio; Kosugi, Tomoki; Matsuo, Seiichi; Takei, Yoshifumi; Kadomatsu, Kenji; Muramatsu, Takashi

    2004-01-01

    Although cisplatin acts directly on proximal tubule epithelial cells and causes cell death, little is known regarding the biological significance of its secondary effects, such as inflammation. The growth factor midkine is highly expressed in the proximal tubule and exerts ambivalent activities as to cisplatin nephrotoxicity, ie, anti-apoptotic and chemotactic ones. Here we report that midkine-deficient mice show a significantly higher survival rate than wild-type mice. The levels of blood urea nitrogen and tubular degeneration and apoptosis were higher in wild-type mice despite the anti-apoptotic activity of midkine. We found that recruitment of neutrophils was more enhanced in wild-type mice, this being consistent with the chemotactic activity of midkine. Midkine expression in wild-type mice persisted for 24 hours, and then dramatically decreased. Preadministration of midkine anti-sense oligodeoxyribonucleotide to wild-type mice suppressed midkine expression, and consequently neutrophil infiltration. It is of note that neutrophil infiltration, apoptosis, and elevation of blood urea nitrogen became conspicuous sequentially, namely 1, 2, and 3 days after cisplatin administration, respectively. These findings suggest that early molecular events involving midkine induce inflammatory response and their circuits eventually enhance the death of the proximal tubule epithelial cells. The results indicate the crucial role of inflammation in cisplatin-induced renal damage, and provide a candidate molecular target for its prevention. PMID:15509530

  16. The poly(ADP-ribose)-dependent chromatin remodeler Alc1 induces local chromatin relaxation upon DNA damage.

    PubMed

    Sellou, Hafida; Lebeaupin, Théo; Chapuis, Catherine; Smith, Rebecca; Hegele, Anna; Singh, Hari R; Kozlowski, Marek; Bultmann, Sebastian; Ladurner, Andreas G; Timinszky, Gyula; Huet, Sébastien

    2016-12-01

    Chromatin relaxation is one of the earliest cellular responses to DNA damage. However, what determines these structural changes, including their ATP requirement, is not well understood. Using live-cell imaging and laser microirradiation to induce DNA lesions, we show that the local chromatin relaxation at DNA damage sites is regulated by PARP1 enzymatic activity. We also report that H1 is mobilized at DNA damage sites, but, since this mobilization is largely independent of poly(ADP-ribosyl)ation, it cannot solely explain the chromatin relaxation. Finally, we demonstrate the involvement of Alc1, a poly(ADP-ribose)- and ATP-dependent remodeler, in the chromatin-relaxation process. Deletion of Alc1 impairs chromatin relaxation after DNA damage, while its overexpression strongly enhances relaxation. Altogether our results identify Alc1 as an important player in the fast kinetics of the NAD(+)- and ATP-dependent chromatin relaxation upon DNA damage in vivo. © 2016 Sellou, Lebeaupin, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  17. The Involvement of the Oxidative Stress in Murine Blue LED Light-Induced Retinal Damage Model.

    PubMed

    Nakamura, Maho; Kuse, Yoshiki; Tsuruma, Kazuhiro; Shimazawa, Masamitsu; Hara, Hideaki

    2017-01-01

    The aim of study was to establish a mouse model of blue light emitting diode (LED) light-induced retinal damage and to evaluate the effects of the antioxidant N-acetylcysteine (NAC). Mice were exposed to 400 or 800 lx blue LED light for 2 h, and were evaluated for retinal damage 5 d later by electroretinogram amplitude and outer nuclear layer (ONL) thickness. Additionally, we investigated the effect of blue LED light exposure on shorts-wave-sensitive opsin (S-opsin), and rhodopsin expression by immunohistochemistry. Blue LED light induced light intensity dependent retinal damage and led to collapse of S-opsin and altered rhodopsin localization from inner and outer segments to ONL. Conversely, NAC administered at 100 or 250 mg/kg intraperitoneally twice a day, before dark adaptation and before light exposure. NAC protected the blue LED light-induced retinal damage in a dose-dependent manner. Further, blue LED light-induced decreasing of S-opsin levels and altered rhodopsin localization, which were suppressed by NAC. We established a mouse model of blue LED light-induced retinal damage and these findings indicated that oxidative stress was partially involved in blue LED light-induced retinal damage.

  18. Acrylonitrile-Induced Oxidative Stress and Oxidative DNA Damage in Male Sprague-Dawley Rats

    PubMed Central

    Kamendulis, Lisa M.; Klaunig, James E.

    2009-01-01

    Studies have demonstrated that the induction of oxidative stress may be involved in brain tumor induction in rats by acrylonitrile. The present study examined whether acrylonitrile induces oxidative stress and DNA damage in rats and whether blood can serve as a valid surrogate for the biomonitoring of oxidative stress induced by acrylonitrile in the exposed population. Male Sprague-Dawley rats were treated with 0, 3, 30, 100, and 200 ppm acrylonitrile in drinking water for 28 days. One group of rats were also coadministered N-acetyl cysteine (NAC) (0.3% in diet) with acrylonitrile (200 ppm in drinking water) to examine whether antioxidant supplementation was protective against acrylonitrile-induced oxidative stress. Direct DNA strand breakage in white blood cells (WBC) and brain was measured using the alkaline comet assay. Oxidative DNA damage in WBC and brain was evaluated using formamidopyrimidine DNA glycosylase (fpg)-modified comet assay and with high-performance liquid chromatography-electrochemical detection. No significant increase in direct DNA strand breaks was observed in brain and WBC from acrylonitrile-treated rats. However, oxidative DNA damage (fpg comet and 8′hydroxyl-2-deoxyguanosine) in brain and WBC was increased in a dose-dependent manner. In addition, plasma levels of reactive oxygen species (ROS) increased in rats administered acrylonitrile. Dietary supplementation with NAC prevented acrylonitrile-induced oxidative DNA damage in brain and WBC. A slight, but significant, decrease in the GSH:GSSG ratio was seen in brain at acrylonitrile doses > 30 ppm. These results provide additional support that the mode of action for acrylonitrile-induced astrocytomas involves the induction of oxidative stress and damage. Significant associations were seen between oxidative DNA damage in WBC and brain, ROS formation in plasma, and the reported tumor incidences. Since oxidative DNA damage in brain correlated with oxidative damage in WBC, these results suggest

  19. Laser-matter coupling mechanisms governing particulate-induced damage on optical surfaces

    NASA Astrophysics Data System (ADS)

    Matthews, M. J.; Feigenbaum, E.; Demos, S. G.; Raman, R. N.; Qiu, S. R.; Shen, N.; Harris, C.; Negres, R. A.; Norton, M.; Cross, D.; Rubenchik, A. M.

    2016-12-01

    A comprehensive study of laser-induced damage associated with particulate damage on optical surfaces is presented. Contaminant-driven damage on silica windows and multilayer dielectrics is observed to range from shallow pitting to more classical fracture-type damage, depending on particle-substrate material combination, as well as laser pulse characteristics. Ejection dynamics is studied in terms of plasma emission spectroscopy and pump-probe shadowgraphy. Our data is used to assess the momentum coupling between incident energy and the ejected plasma, which dominates the laser-particle-substrate interaction. Beam propagation analysis is also presented to characterize the impact of contaminant-driven surface pitting on optical performance.

  20. 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.

  1. Long-term exposure to high air pollution induces cumulative DNA damages in traffic policemen.

    PubMed

    Tan, Chaochao; Lu, Shijie; Wang, Yupeng; Zhu, Yan; Shi, Ting; Lin, Mingyue; Deng, Zhonghua; Wang, Zhu; Song, Nana; Li, Shuna; Yang, Pingting; Yang, Liyan; Liu, Yuanyuan; Chen, Zhiheng; Xu, Keqian

    2017-09-01

    The specific effects of long-term exposure to high air pollution on human health and biological remain unclear. To explore the adverse health effects as well as biological mechanisms and biomarkers for durative exposure to air pollution, 183 traffic policemen and 88 office policemen were enrolled in this study. The concentration of PM2.5 in both the traffic and office policemen's working environments were obtained. Detailed personal questionnaires were completed and levels of inflammation, oxidative stress and DNA damage markers of all participants were analyzed in this study. The average PM2.5 concentration of the intersections of main roads and the offices of control group were 132.4±48.9μg/m(3) and 50.80±38.6μg/m(3), respectively. The traffic policemen, who stably exposed to at least 2 times higher PM2.5 in their work area as compared with the control group, have a median average duration of 7.00years, and average cumulative intersection duty time reached 8030h. No statistically significant differences in the levels of inflammation markers were observed between the traffic and office policemen. However, the DNA damage markers in traffic policemen shared significant positive correlation with cumulative intersection duty time and higher than those in the office policemen. Multiple linear regression analysis demonstrated that the increase of cumulative intersection duty time by 1h per day for one year was associated with the increase in 8-hydroxy-20-deoxyguanosine of 0.329% (95% CI: 0.249% to 0.409%), tail DNA of 0.051% (95% CI: 0.041% to 0.061%), micronucleus frequency of 0.036‰ (95% CI: 0.03‰ to 0.043‰), and a decrease in glutathione of 0.482% (95% CI: -0.652% to -0.313%). These findings suggest that long-term exposure to high air pollution could induce cumulative DNA damages, supporting the hypothesis that durative exposure to air pollution is associated with an increased risk of cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. 4-hydroxybenzaldehyde-chitooligomers suppresses H2O2-induced oxidative damage in microglia BV-2 cells.

    PubMed

    Oh, Sea-Hun; Ryu, BoMi; Ngo, Dai-Hung; Kim, Won-Suk; Kim, Dong Gyu; Kim, Se-Kwon

    2017-02-22

    Positive charges of chitooligomer (COS) enable COS to interact with negatively charged anionic groups on the cell surface resulting in an improvement in the biological activity of COS and its derivatives. In this study, 4-hydroxybenzaldehyde-COS (HB-COS) was synthesized and investigated for its abilities against H2O2-induced oxidative stress in microglia BV-2 cells. Under oxidative stress, HB-COS significantly attenuated reactive oxygen species (ROS) generation and DNA oxidation, and upregulated the protein levels of antioxidative enzymes. HB-COS is therefore proposed as a potential protective agent against neuronal damage.

  3. Damage mechanisms for ultrasound-induced cavitation in tissue

    NASA Astrophysics Data System (ADS)

    Warnez, M.; Vlaisavljevich, E.; Xu, Z.; Johnsen, E.

    2017-03-01

    In a variety of biomedical applications, cavitation occurs in soft tissue. Although significant amounts of research have been performed on cavitation in water, bubble dynamics, and related bioeffects remain poorly understood. We use numerical simulations of spherical bubble dynamics in soft tissue to assess the extent to which viscoelasticity affects "known" and introduces "new" damage mechanisms. We find that deviatoric stresses - although not an important damage mechanism in water - are significantly enhanced and could be an important bioeffect mechanism in tissue. Both the viscoelastic properties and the nonlinear, large-collapse radius contribute to stress amplification in the surroundings. In addition, temperatures in the surrounding medium increase more in the Zener tissue than in water, due to viscous heating.

  4. Ultraviolet induced DNA damage and hereditary skin cancer

    SciTech Connect

    Regan, J.D.; Carrier, W.L.; Francis, A.A.

    1984-01-01

    Clearly, cells from normal individuals possess the ability to repair a variety of damage to DNA. Numerous studies indicate that defects in DNA repair may increase an individual's susceptibility to cancer. It is hoped that continued studies of the exact structural changes produced in the DNA by environmental insults, and the correlation of specific DNA changes with particulr cellular events, such as DNA repair, will lead to a better understanding of cell-killing, mutagenesis and carbinogenesis. 1 figure, 2 tables.

  5. Evaluating thermal damage induced by pulsed light with multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Gong, Wei; Xie, Shusen; Huang, Yimei

    2009-02-01

    Nonablative skin remodeling is a new light treatment approach for photodamaged skin. Compared to ablative CO2 or Er:YAG laser resurfacing, dermabrasion, and chemical peels, the clinical objective of nonablative skin remodeling is to maximize thermal damage to upper dermis while minimizing injury to the epidermis and surrounding tissue, consequently decreasing potential complications and shortening long recuperation periods. Histological analysis of preoperative and postoperative biopsies using H&E or special stains has indicated the dermal thermal injury, which resulting in collagen denaturation, is the most important mechanism of nonablative skin remodeling for improving skin situation. And the extent of improvement of skin situation corresponded to the formation of a new band of dense, compact collagen bundles in the papillary dermis. The diversity of individual skin condition influences the choice of pulsed light treatment parameters, and further influences the degree of dermal thermal damage, thus the efficacy of nonablative skin remodeling remains unstable. Recently, multiphoton microscopy has show a promising application for monitoring skin thermal damage, because collagen could produce strong second harmonic generation (SHG). And SHG intensity is presumably proportional to the percentage of collagen in dermis. In this paper, the auto-fluorescence (AF) intensity and SHG intensity of mice skin irradiated by pulsed Nd:YAG laser were measured and imaged with multiphoton microscope, and the results show the ratio of SHG to AF decreases with the increase of irradiation exposure dose, and could be a quantitative technique to assess dermal thermal damage, and could further benefit the choice of light treatment parameters.

  6. Neuroprotection for Nerve Agent-Induced Brain Damage

    DTIC Science & Technology

    2002-01-01

    nonconvulsive status epilepticus, either because of the distribution of the seizure focus or, more likely, because ATP stores are depleted and thus no...damaged due to seizures secondary to exposure to nerve agents. Preliminary work in this laboratory has demonstrated proof of concept using a compound not...initial life-threatening effects of nerve agents are likely to develop electrical seizure activity. Anticonvulsants such as diazepam can arrest

  7. Tubular Overexpression of Gremlin Induces Renal Damage Susceptibility in Mice

    PubMed Central

    Droguett, Alejandra; Krall, Paola; Burgos, M. Eugenia; Valderrama, Graciela; Carpio, Daniel; Ardiles, Leopoldo; Rodriguez-Diez, Raquel; Kerr, Bredford; Walz, Katherina; Ruiz-Ortega, Marta; Egido, Jesus; Mezzano, Sergio

    2014-01-01

    A growing number of patients are recognized worldwide to have chronic kidney disease. Glomerular and interstitial fibrosis are hallmarks of renal progression. However, fibrosis of the kidney remains an unresolved challenge, and its molecular mechanisms are still not fully understood. Gremlin is an embryogenic gene that has been shown to play a key role in nephrogenesis, and its expression is generally low in the normal adult kidney. However, gremlin expression is elevated in many human renal diseases, including diabetic nephropathy, pauci-immune glomerulonephritis and chronic allograft nephropathy. Several studies have proposed that gremlin may be involved in renal damage by acting as a downstream mediator of TGF-β. To examine the in vivo role of gremlin in kidney pathophysiology, we generated seven viable transgenic mouse lines expressing human gremlin (GREM1) specifically in renal proximal tubular epithelial cells under the control of an androgen-regulated promoter. These lines demonstrated 1.2- to 200-fold increased GREM1 expression. GREM1 transgenic mice presented a normal phenotype and were without proteinuria and renal function involvement. In response to the acute renal damage cause by folic acid nephrotoxicity, tubule-specific GREM1 transgenic mice developed increased proteinuria after 7 and 14 days compared with wild-type treated mice. At 14 days tubular lesions, such as dilatation, epithelium flattening and hyaline casts, with interstitial cell infiltration and mild fibrosis were significantly more prominent in transgenic mice than wild-type mice. Tubular GREM1 overexpression was correlated with the renal upregulation of profibrotic factors, such as TGF-β and αSMA, and with increased numbers of monocytes/macrophages and lymphocytes compared to wild-type mice. Taken together, our results suggest that GREM1-overexpressing mice have an increased susceptibility to renal damage, supporting the involvement of gremlin in renal damage progression. This

  8. Tubular overexpression of gremlin induces renal damage susceptibility in mice.

    PubMed

    Droguett, Alejandra; Krall, Paola; Burgos, M Eugenia; Valderrama, Graciela; Carpio, Daniel; Ardiles, Leopoldo; Rodriguez-Diez, Raquel; Kerr, Bredford; Walz, Katherina; Ruiz-Ortega, Marta; Egido, Jesus; Mezzano, Sergio

    2014-01-01

    A growing number of patients are recognized worldwide to have chronic kidney disease. Glomerular and interstitial fibrosis are hallmarks of renal progression. However, fibrosis of the kidney remains an unresolved challenge, and its molecular mechanisms are still not fully understood. Gremlin is an embryogenic gene that has been shown to play a key role in nephrogenesis, and its expression is generally low in the normal adult kidney. However, gremlin expression is elevated in many human renal diseases, including diabetic nephropathy, pauci-immune glomerulonephritis and chronic allograft nephropathy. Several studies have proposed that gremlin may be involved in renal damage by acting as a downstream mediator of TGF-β. To examine the in vivo role of gremlin in kidney pathophysiology, we generated seven viable transgenic mouse lines expressing human gremlin (GREM1) specifically in renal proximal tubular epithelial cells under the control of an androgen-regulated promoter. These lines demonstrated 1.2- to 200-fold increased GREM1 expression. GREM1 transgenic mice presented a normal phenotype and were without proteinuria and renal function involvement. In response to the acute renal damage cause by folic acid nephrotoxicity, tubule-specific GREM1 transgenic mice developed increased proteinuria after 7 and 14 days compared with wild-type treated mice. At 14 days tubular lesions, such as dilatation, epithelium flattening and hyaline casts, with interstitial cell infiltration and mild fibrosis were significantly more prominent in transgenic mice than wild-type mice. Tubular GREM1 overexpression was correlated with the renal upregulation of profibrotic factors, such as TGF-β and αSMA, and with increased numbers of monocytes/macrophages and lymphocytes compared to wild-type mice. Taken together, our results suggest that GREM1-overexpressing mice have an increased susceptibility to renal damage, supporting the involvement of gremlin in renal damage progression. This

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

    SciTech Connect

    Seidensticker, Max; Burak, Miroslaw; Kalinski, Thomas; Garlipp, Benjamin; Koelble, Konrad; Wust, Peter; Antweiler, Kai; Seidensticker, Ricarda; Mohnike, Konrad; Pech, Maciej; Ricke, Jens

    2015-02-15

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

  10. High glucose induces DNA damage in cultured human endothelial cells.

    PubMed Central

    Lorenzi, M; Montisano, D F; Toledo, S; Barrieux, A

    1986-01-01

    Morphologic and functional abnormalities of vascular endothelium are well recognized in diabetes. In view of our previous finding that high glucose concentrations accelerate death and hamper replication of cultured human endothelial cells, we have investigated in the same model the possibility that exposure to high glucose may result in DNA damage. DNA from human endothelial cells--but not from fibroblasts--exposed to 30 mM glucose for 9-14 d manifested an accelerated rate of unwinding in alkali indicative of an increased number of single strand breaks (P less than 0.001 vs. control). Endothelial cells exposed to high glucose also manifested an increased amount of hydroxy-urea-resistant thymidine incorporation (333 +/- 153 cpm/10(5) cells vs. 88 +/- 42 in control cells, mean +/- SD, P = 0.04), which is indicative of increased DNA repair synthesis. Neither DNA damage nor repair synthesis were increased by medium hypertonicity achieved with 30 mM mannitol. These findings suggest the possibility that, under conditions of high ambient glucose, excess glucose entry in cells that are insulin independent for glucose transport may, directly or indirectly, perturb DNA function. Further, they suggest the possibility that different individual capabilities to repair DNA damage--a process that is under genetic control--may represent a mechanism for different individual susceptibilities to development of diabetic vascular complication. PMID:3944257

  11. Laser induced damage in optical materials: 8th ASTM symposium.

    PubMed

    Glass, A J; Guenther, A H

    1977-05-01

    The Eighth Annual Symposium on Optical Materials for High Power Lasers (Boulder Damage Symposium) was hosted by the National Bureau of Standards in Boulder, Colorado, from 13 to 15 July 1976. 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 Energy Research and Development Administration, and the Office of Naval Research. About 160 scientists attended the Symposium, including representatives of the United Kingdom, France, Canada, and Brazil. The Symposium was divided into five half-day sessions concerning Bulk Material Properties and Thermal Behavior, Mirrors and Surfaces, Thin Film Properties, Thin Film Damage, and Scaling Laws and Fundamental Mechanisms. As in previous years, the emphasis of the papers presented at the Symposium was directed toward new frontiers and new developments. Particular emphasis was given to new materials for use at 10.6 microm in mirror substrates, windo s, and coatings. New techniques in film deposition and advances in diamond-turning of optics were described. The scaling of damage thresholds with pulse duration, focal area, and wavelength were discussed. Alexander J. Glass of Lawrence Livermore Laboratory and Arthur H. Guenther of the Air Force Weapons Laboratory were co-chairpersons of the Symposium. The Ninth Annual Symposium is scheduled for 4-6 October 1977 at the National Bureau of Standards, Boulder, Colorado.

  12. Few-cycle pulse laser-induced damage of thin films in air and vacuum ambience

    NASA Astrophysics Data System (ADS)

    Kafka, Kyle R. P.; Talisa, Noah; Tempea, Gabriel; Austin, Drake R.; Neacsu, Catalin; Chowdhury, Enam A.

    2016-12-01

    Laser-induced damage mechanisms were investigated for an ultra-broadband chirped mirror, as part of a systematic study of few-cycle pulse laser-induced damage threshold (LIDT) of widely-used ultra-broadband optics, in vacuum and in air, for single and multi-pulse regimes (S-on-1). Microscopic analysis of damage morphology suggests that three different damage mechanisms occur across the fluence range 0.15-0.4J/cm2, while no ablation was yet observed. The three regimes resulted in shallow swelling (< 10 nm tall), tall blistering ( 150 nm tall), and annular blistering (damage suppressed at highest intensity, forming a ring shape). Descriptions of the potential mechanisms are discussed.

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

    NASA Technical Reports Server (NTRS)

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

    2002-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    2002-01-01

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

  15. A statistical mechanics model to predict electromigration induced damage and void growth in solder interconnects

    NASA Astrophysics Data System (ADS)

    Wang, Yuexing; Yao, Yao; Keer, Leon M.

    2017-02-01

    Electromigration is an irreversible mass diffusion process with damage accumulation in microelectronic materials and components under high current density. Based on experimental observations, cotton type voids dominate the electromigration damage accumulation prior to cracking in the solder interconnect. To clarify the damage evolution process corresponding to cotton type void growth, a statistical model is proposed to predict the stochastic characteristic of void growth under high current density. An analytical solution of the cotton type void volume growth over time is obtained. The synchronous electromigration induced damage accumulation is predicted by combining the statistical void growth and the entropy increment. The electromigration induced damage evolution in solder joints is developed and applied to verify the tensile strength deterioration of solder joints due to electromigration. The predictions agree well with the experimental results.

  16. Single-molecule visualization of ROS-induced DNA damage in large DNA molecules.

    PubMed

    Lee, Jinyong; Kim, Yongkyun; Lim, Sangyong; Jo, Kyubong

    2016-02-07

    We present a single molecule visualization approach for the quantitative analysis of reactive oxygen species (ROS) induced DNA damage, such as base oxidation and single stranded breaks in large DNA molecules. We utilized the Fenton reaction to generate DNA damage with subsequent enzymatic treatment using a mixture of three types of glycosylases to remove oxidized bases, and then fluorescent labeling on damaged lesions via nick translation. This single molecule analytical platform provided the capability to count one or two damaged sites per λ DNA molecule (48.5 kb), which were reliably dependent on the concentrations of hydrogen peroxide and ferrous ion at the micromolar level. More importantly, the labeled damaged sites that were visualized under a microscope provided positional information, which offered the capability of comparing DNA damaged sites with the in silico genomic map to reveal sequence specificity that GTGR is more sensitive to oxidative damage. Consequently, single DNA molecule analysis provides a sensitive analytical platform for ROS-induced DNA damage and suggests an interesting biochemical insight that the genome primarily active during the lysogenic cycle may have less probability for oxidative DNA damage.

  17. Ethanolic extract of Moringa oleifera Lam. leaves protect the pre-pubertal spermatogonial cells from cyclophosphamide-induced damage.

    PubMed

    Nayak, Guruprasad; Honguntikar, Sachin D; Kalthur, Sneha Guruprasad; D'Souza, Antony Sylvan; Mutalik, Srinivas; Setty, Manjunath M; Kalyankumar, Raksha; Krishnamurthy, Hanumanthappa; Kalthur, Guruprasad; Adiga, Satish Kumar

    2016-04-22

    Moringa oleifera Lam. is widely cultivated in Asian and African countries for its medicinal and dietary significance. The leaves are highly nutritious and are known to possess various biological activities. Pre-pubertal Swiss albino male mice were injected with single dose of cyclophosphamide (CP, 200mg/kg body weight) or ethanolic extract of Moringa oleifera leaves (MOE, 100mg/kg body weight) intraperitoneally. In combination group, MOE was administered 24h prior to CP injection. CP induced a significant decrease in testicular weight (p<0.01) and depletion of germ cells (p<0.001) and higher level of DNA damage (p<0.001) compared to control. The expression of P53, Bax, Cytochrome C (Cyt C) was increased while there was a decrease in the expression of Bcl2, c-Kit and Oct4. Administration of MOE 24h prior to CP treatment ameliorated the depletion (p<0.001), DNA damage (p<0.001) and apoptosis (p<0.01) of germ cells induced by CP. The mitigating effect of MOE appears to be mediated by up-regulating the expression of c-Kit and Oct4 transcripts in P53-independent manner. MOE protects the spermatogonial cells from CP-induced damage by modulating the apoptotic response elicited by CP and therefore can be considered as an efficient method of male fertility preservation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Relationship between the repair of radiation-induced DNA damage and recovery from potentially lethal damage in 9L rat brain tumor cells. [Gamma radiation

    SciTech Connect

    vanAnkeren, S.C.; Wheeler, K.T.

    1984-03-01

    The kinetics of repair of radiation-induced DNA damage and recovery from radiation-induced potentially lethal damage (PLD) for fed plateau-phase 9L/Ro rat brain tumor cells were compared after single doses of gamma-radiation and after combined treatment with 3 micrograms of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU)/ml given 16 hr prior to irradiation. DNA damage and repair were assayed using alkaline filter elution, while cell survival was assayed by colony formation. Repair of radiation-induced DNA damage and recovery from radiation-induced PLD followed statistically identical biphasic kinetics; the fast-phase half-times were 4.1 +/- 0.3 (S.D.) min and 4.0 +/- 0.8 min, while the slow-phase half-times were 59.7 +/- 11.2 min and 78.7 +/- 34.1 min, respectively. Treatment with BCNU prior to irradiation resulted in both additional DNA damage and increased cell kill. When DNA damage and cell survival after the combined treatment were corrected for the contribution from BCNU given alone, no inhibition of either repair of radiation-induced DNA damage or of recovery from radiation-induced PLD was observed. However, postirradiation hypertonic treatment inhibited both DNA repair and recovery from radiation-induced PLD. These correlations between the kinetics of the molecular and cellular repair processes support a role for repair of radiation-induced DNA damage in recovery from radiation-induced PLD. The lack of inhibition by BCNU of both repair of radiation-induced DNA damage and of recovery from radiation-induced PLD also demonstrates that these are not the mechanisms by which BCNU enhances radiation-induced cytotoxicity in 9L cells.

  19. Classification of climate-change-induced stresses on biological diversity.

    PubMed

    Geyer, Juliane; Kiefer, Iris; Kreft, Stefan; Chavez, Veronica; Salafsky, Nick; Jeltsch, Florian; Ibisch, Pierre L

    2011-08-01

    Conservation actions need to account for and be adapted to address changes that will occur under global climate change. The identification of stresses on biological diversity (as defined in the Convention on Biological Diversity) is key in the process of adaptive conservation management. We considered any impact of climate change on biological diversity a stress because such an effect represents a change (negative or positive) in key ecological attributes of an ecosystem or parts of it. We applied a systemic approach and a hierarchical framework in a comprehensive classification of stresses to biological diversity that are caused directly by global climate change. Through analyses of 20 conservation sites in 7 countries and a review of the literature, we identified climate-change-induced stresses. We grouped the identified stresses according to 3 levels of biological diversity: stresses that affect individuals and populations, stresses that affect biological communities, and stresses that affect ecosystem structure and function. For each stress category, we differentiated 3 hierarchical levels of stress: stress class (thematic grouping with the coarsest resolution, 8); general stresses (thematic groups of specific stresses, 21); and specific stresses (most detailed definition of stresses, 90). We also compiled an overview of effects of climate change on ecosystem services using the categories of the Millennium Ecosystem Assessment and 2 additional categories. Our classification may be used to identify key climate-change-related stresses to biological diversity and may assist in the development of appropriate conservation strategies. The classification is in list format, but it accounts for relations among climate-change-induced stresses. © 2011 Society for Conservation Biology.

  20. Induced superficial chondrocyte death reduces catabolic cartilage damage in murine posttraumatic osteoarthritis.

    PubMed

    Zhang, Minjie; Mani, Sriniwasan B; He, Yao; Hall, Amber M; Xu, Lin; Li, Yefu; Zurakowski, David; Jay, Gregory D; Warman, Matthew L

    2016-08-01

    Joints that have degenerated as a result of aging or injury contain dead chondrocytes and damaged cartilage. Some studies have suggested that chondrocyte death precedes cartilage damage, but how the loss of chondrocytes affects cartilage integrity is not clear. In this study, we examined whether chondrocyte death undermines cartilage integrity in aging and injury using a rapid 3D confocal cartilage imaging technique coupled with standard histology. We induced autonomous expression of diphtheria toxin to kill articular surface chondrocytes in mice and determined that chondrocyte death did not lead to cartilage damage. Moreover, cartilage damage after surgical destabilization of the medial meniscus of the knee was increased in mice with intact chondrocytes compared with animals whose chondrocytes had been killed, suggesting that chondrocyte death does not drive cartilage damage in response to injury. These data imply that chondrocyte catabolism, not death, contributes to articular cartilage damage following injury. Therefore, therapies targeted at reducing the catabolic phenotype may protect against degenerative joint disease.

  1. The ATM Kinase Induces MicroRNA Biogenesis in the DNA Damage Response

    PubMed Central

    Zhang, Xinna; Wan, Guohui; Berger, Franklin G.; He, Xiaoming; Lu, Xiongbin

    2011-01-01

    SUMMARY The DNA damage response involves a complex network of processes that detect and repair DNA damage. Here we show that miRNA biogenesis is globally induced upon DNA damage in an ATM-dependent manner. About one fourth of miRNAs are significantly up-regulated after DNA damage, while loss of ATM abolishes their induction. KSRP (KH-type splicing regulatory protein) is a key player that translates DNA damage signaling to miRNA biogenesis. The ATM kinase directly binds to and phosphorylates KSRP, leading to enhanced interaction between KSRP and pri-miRNAs and increased KSRP activity in miRNA processing. Mutations of the ATM phosphorylation sites of KSRP impaired its activity in regulating miRNAs. These findings reveal a mechanism by which DNA damage signaling is linked to miRNA biogenesis. PMID:21329876

  2. Fracture Induced Sub-Band Absorption as a Precursor to Optical Damage on Fused Silica Surfaces

    SciTech Connect

    Miller, P E; Bude, J D; Suratwala, T I; Shen, N; Laurence, T A; Steele, W A; Menapace, J; Feit, M D; Wong, L L

    2010-03-05

    The optical damage threshold of indentation induced flaws on fused silica surfaces was explored. Mechanical flaws were characterized by laser damaged testing, SEM, optical, and photoluminescence microscopy. Localized polishing, chemical etching, and the control of indentation morphology were used to isolate the structural features which limit optical damage. A thin defect layer on fracture surfaces, including those smaller than the wavelength of visible light, was found to be the dominant source of laser damage initiation during illumination with 355nm, 3ns laser pulses. Little evidence was found that either displaced or densified material or fluence intensification plays a significant role in optical damage at fluences >35J/cm{sup 2}. Elimination of the defect layer was shown to increase the overall damage performance of fused silica optics.

  3. A model for predicting damage induced fatigue life of laminated composite structural components

    NASA Technical Reports Server (NTRS)

    Allen, David H.; Lo, David C.; Georgiou, Ioannis T.; Harris, Charles E.

    1990-01-01

    This paper presents a model for predicting the life of laminated composite structural components subjected to fatigue induced microstructural damage. The model uses the concept of continuum damage mechanics, wherein the effects of microcracks are incorporated into a damage dependent lamination theory instead of treating each crack as an internal boundary. Internal variables are formulated to account for the effects of both matrix cracks and internal delaminations. Evolution laws for determining the damage variables as functions of ply stresses are proposed, and comparisons of predicted damage evolution are made to experiment. In addition, predicted stiffness losses, as well as ply stresses are shown as functions of damage state for a variety of stacking sequences.

  4. The effect of phytosterol protects rats against 4-nitrophenol-induced liver damage.

    PubMed

    Chen, Jiaqin; Song, Meiyan; Li, Yansen; Zhang, Yonghui; Taya, Kazuyoshi; Li, ChunMei

    2016-01-01

    We investigated the effect of phytosterol (PS) in regard to liver damage induced by 4-nitrophenol (PNP). Twenty rats were randomly divided into four groups (Control, PS, PNP, and PNP+PS). The PS and PNP+PS groups were pretreated with PS for one week. The PNP and PNP+PS groups were injected subcutaneously with PNP for 28 days. The control group received a basal diet and was injected with vehicle alone. Treatment with PS prevented the elevation of the total bilirubin levels, as well as an increase in serum alkaline transaminase and aspartate transaminase, which are typically caused by PNP-induced liver damage. Histopathologically showed that liver damage was significantly mitigated by PS treatment. However, there was no significant change in antioxidant enzyme activities, and the Nrf2-antioxidant system was not activated after treatment with PS. These results suggest that PS could mitigate liver damage induced by PNP, but does not enhance antioxidant capacity.

  5. Modelling biological and chemically induced precipitation of calcium phosphate in enhanced biological phosphorus removal systems.

    PubMed

    Barat, R; Montoya, T; Seco, A; Ferrer, J

    2011-06-01

    The biologically induced precipitation processes can be important in wastewater treatment, in particular treating raw wastewater with high calcium concentration combined with Enhanced Biological Phosphorus Removal. Currently, there is little information and experience in modelling jointly biological and chemical processes. This paper presents a calcium phosphate precipitation model and its inclusion in the Activated Sludge Model No 2d (ASM2d). The proposed precipitation model considers that aqueous phase reactions quickly achieve the chemical equilibrium and that aqueous-solid change is kinetically governed. The model was calibrated using data from four experiments in a Sequencing Batch Reactor (SBR) operated for EBPR and finally validated with two experiments. The precipitation model proposed was able to reproduce the dynamics of amorphous calcium phosphate (ACP) formation and later crystallization to hydroxyapatite (HAP) under different scenarios. The model successfully characterised the EBPR performance of the SBR, including the biological, physical and chemical processes.

  6. Sodium tanshinone IIA sulfonate attenuates radiation-induced fibrosis damage in cardiac fibroblasts.

    PubMed

    Gu, Jing; Li, Hai-Long; Wu, Hong-Yan; Gu, Mei; Li, Ying-Dong; Wang, Xiao-Gang; Ming, Hai-Xia; Dong, Xiao-Li; Liu, Kai

    2014-01-01

    The main pathological change in radiation-induced heart disease is fibrosis. Emerging evidence has indicated that sodium tanshinone IIA sulfonate (STS) was used for treating fibrosis diseases. The present study was undertaken to characterize the effect of STS on radiation-induced cardiac fibrosis (RICF) on cultured cardiac fibroblasts (CFs). CFs were irradiated with 1 or 2 Gy X-rays, and the expression of TGF-β1 and collagen I (Col-1) increased, indicating that low-dose X-rays promoted fibrosis damage effect. The fibrosis damage was accompanied by morphologic changes in the endoplasmic reticulum (ER), as well as an increase in the expression of the ER stress-related molecules, GRP78 and CHOP. Administration of STS reduced ROS production and decreased the expression of Col-1, TGF-β1, p-Smad2/3, GRP78, and CHOP in irradiated CFs, thus weakening the radiation-induced fibrosis damage and ER stress. Radiation-induced fibrosis damage was observed on a cellular level. The involvement of ER stress in radiation-induced fibrosis damage was demonstrated for the first time. STS attenuated the fibrosis damage effect in CFs and this effect may be related to its antioxidant action, and also related to its inhibition of ER stress and TGF-β1-Smad pathway. These results suggest that STS shows a good prospect in clinical prevention and treatment of RICF.

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

    PubMed

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

    2016-10-27

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

  8. Laser-induced fluorescence-cued, laser-induced breakdown spectroscopy biological-agent detection

    SciTech Connect

    Hybl, John D.; Tysk, Shane M.; Berry, Shaun R.; Jordan, Michael P

    2006-12-01

    Methods for accurately characterizing aerosols are required for detecting biological warfare agents. Currently, fluorescence-based biological agent sensors provide adequate detection sensitivity but suffer from high false-alarm rates. Combining single-particle fluorescence analysis with laser-induced breakdown spectroscopy (LIBS) provides additional discrimination and potentially reduces false-alarm rates. A transportable UV laser-induced fluorescence-cued LIBS test bed has been developed and used to evaluate the utility of LIBS for biological-agent detection. Analysis of these data indicates that LIBS adds discrimination capability to fluorescence-based biological-agent detectors.However, the data also show that LIBS signatures of biological agent simulants are affected by washing. This may limit the specificity of LIBS and narrow the scope of its applicability in biological-agent detection.

  9. The Influence of Shielding on the Biological Effectiveness of Accelerated Particles for the Induction of Chromosome Damages

    NASA Technical Reports Server (NTRS)

    George, K.; Cucinotta, F. A.

    2006-01-01

    Chromosome damage was assessed in human peripheral blood lymphocytes after in vitro exposure to the either Si-28 (490 or 600 MeV/n), Ti-48 (1000 MeV/n), or Fe-56 (600, 1000, or 5000 MeV/n). LET values for these ions ranged from approximately 50 to 174 keV/micrometers and doses ranged from 10 to 200 cGy. The effect of either aluminum or polyethylene shielding on the induction of chromosome aberrations was investigated for each ion. Chromosome exchanges were measured using fluorescence in situ hybridization (FISH) with whole chromosome probes in cells collected 48-56 hours after irradiation using a chemical-induced premature chromosome condensation (PCC) technique. The yield of chromosomal aberrations increased linearly with dose and the relative biological effectiveness (RBE) for the primary beams, estimated from the initial slope of the dose response curve for total chromosomal exchanges with respect to gamma-rays, ranged from 14 to 35. The RBE values increased with LET, reaching a maximum for the 1 GeV/n Fe ions with LET of 150 keV/micrometers, and decreased with further increases in LET. When LET of the primary beam was in the region of increasing RBE (i.e. below approximately 100 keV/micrometers), the addition of shielding material increased the effectiveness per unit dose. Whereas shielding decreased the effectiveness per unit dose when the LET of the primary particle beam was higher than 150 keV/micrometers.

  10. Biological Effectiveness of Accelerated Particles for the Induction of Chromosome Damage Measured in Metaphase and Interphase Human Lymphocytes

    NASA Technical Reports Server (NTRS)

    George, Kerry; Durante, Marco; Willingham, Veronica; Wu, Honglu; Yang, Tracy C.; Cucinotta, Francis A.

    2003-01-01

    Chromosome aberrations were investigated in human lymphocytes after in vitro exposure to 1H-, 3He-, 12C-, 40Ar-, 28Si-, 56Fe-, or 197Au-ion beams, with LET ranging from approximately 0.4-1393 keV/microm in the dose range of 0.075-3 Gy. Dose-response curves for chromosome exchanges, measured at the first mitosis postirradiation using fluorescence in situ hybridization (FISH) with whole-chromosome probes, were fitted with linear or linear-quadratic functions. The relative biological effectiveness (RBE) was estimated from the initial slope of the dose-response curve for chromosomal damage with respect to low- or high-dose-rate gamma rays. Estimates of RBEmax values for mitotic spreads, which ranged from near 0.7 to 11.1 for total exchanges, increased with LET, reaching a maximum at about 150 keV/microm, and decreased with further increase in LET. RBEs for complex aberrations are undefined due to the lack of an initial slope for gamma rays. Additionally, the effect of mitotic delay on RBE values was investigated by measuring chromosome aberrations in interphase after chemically induced premature chromosome condensation (PCC), and values were up to threefold higher than for metaphase analysis.

  11. Biological Effectiveness of Accelerated Particles for the Induction of Chromosome Damage Measured in Metaphase and Interphase Human Lymphocytes

    NASA Technical Reports Server (NTRS)

    George, Kerry; Durante, Marco; Willingham, Veronica; Wu, Honglu; Yang, Tracy C.; Cucinotta, Francis A.

    2003-01-01

    Chromosome aberrations were investigated in human lymphocytes after in vitro exposure to 1H-, 3He-, 12C-, 40Ar-, 28Si-, 56Fe-, or 197Au-ion beams, with LET ranging from approximately 0.4-1393 keV/microm in the dose range of 0.075-3 Gy. Dose-response curves for chromosome exchanges, measured at the first mitosis postirradiation using fluorescence in situ hybridization (FISH) with whole-chromosome probes, were fitted with linear or linear-quadratic functions. The relative biological effectiveness (RBE) was estimated from the initial slope of the dose-response curve for chromosomal damage with respect to low- or high-dose-rate gamma rays. Estimates of RBEmax values for mitotic spreads, which ranged from near 0.7 to 11.1 for total exchanges, increased with LET, reaching a maximum at about 150 keV/microm, and decreased with further increase in LET. RBEs for complex aberrations are undefined due to the lack of an initial slope for gamma rays. Additionally, the effect of mitotic delay on RBE values was investigated by measuring chromosome aberrations in interphase after chemically induced premature chromosome condensation (PCC), and values were up to threefold higher than for metaphase analysis.

  12. The Influence of Shielding on the Biological Effectiveness of Accelerated Particles for the Induction of Chromosome Damages

    NASA Technical Reports Server (NTRS)

    George, K.; Cucinotta, F. A.

    2006-01-01

    Chromosome damage was assessed in human peripheral blood lymphocytes after in vitro exposure to the either Si-28 (490 or 600 MeV/n), Ti-48 (1000 MeV/n), or Fe-56 (600, 1000, or 5000 MeV/n). LET values for these ions ranged from approximately 50 to 174 keV/micrometers and doses ranged from 10 to 200 cGy. The effect of either aluminum or polyethylene shielding on the induction of chromosome aberrations was investigated for each ion. Chromosome exchanges were measured using fluorescence in situ hybridization (FISH) with whole chromosome probes in cells collected 48-56 hours after irradiation using a chemical-induced premature chromosome condensation (PCC) technique. The yield of chromosomal aberrations increased linearly with dose and the relative biological effectiveness (RBE) for the primary beams, estimated from the initial slope of the dose response curve for total chromosomal exchanges with respect to gamma-rays, ranged from 14 to 35. The RBE values increased with LET, reaching a maximum for the 1 GeV/n Fe ions with LET of 150 keV/micrometers, and decreased with further increases in LET. When LET of the primary beam was in the region of increasing RBE (i.e. below approximately 100 keV/micrometers), the addition of shielding material increased the effectiveness per unit dose. Whereas shielding decreased the effectiveness per unit dose when the LET of the primary particle beam was higher than 150 keV/micrometers.

  13. Laser induced damage in optical materials: eleventh ASTM symposium.

    PubMed

    Bennett, H E; Glass, A J; Guenther, A H; Newnam, B

    1980-07-15

    The eleventh Symposium on Optical Materials for High-Power Lasers (Boulder Damage Symposium) was held at the National Bureau of Standards in Boulder, Colorado, 30-31 October 1979. 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 Projects Agency, the Department of Energy, and the Office of Naval Research. About 150 scientists attended the symposium, including representatives of the United Kingdom, France, Canada, Japan, West Germany, and Denmark. The symposium was divided into sessions concerning transparent optical materials and the measurement of their properties, mirrors and surfaces, thin film characteristics, thin film damage, considerations for high-power systems, and finally theory and breakdown. As in previous years, the emphasis of the papers presented at the symposium was directed toward new frontiers and new developments. Particular emphasis was given to materials for high-power apparatus. The wavelength range of prime interest was 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 discussed in detail. Harold E. Bennett of the Naval Weapons Center, Alexander J. Glass of the Lawrence Livermore Laboratory, Arthur H. Guenther of the Air Force Weapons Laboratory, and Brian E. Newnam of the Los Alamos Scientific Laboratory were cochairpersons. The twelfth annual symposium is scheduled for 30 September-1 October 1980 at the National Bureau of Standards, Boulder, Colorado.

  14. 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. © The Author(s) 2015.

  15. The influence of shielding on the biological effectiveness of accelerated particles for the induction of chromosome damage

    NASA Astrophysics Data System (ADS)

    George, K.; Cucinotta, F. A.

    Several experiments were conduced aimed at studying the influence of shielding on biological effectiveness of high-energy ions Chromosome damage was assessed in human peripheral blood lymphocytes after in vitro exposure to the either 28 Si 490 or 600 MeV n 48 Ti 1000 MeV n or 56 Fe 600 1000 or 5000 MeV n LET values for these ions ranged from approximately 50 to 174 keV mu m and doses ranged from 10 to 200 cGy The effect of aluminum or polyethylene shielding on the induction of chromosome aberrations was investigated for each ion Chromosome exchanges were measured using fluorescence in situ hybridization FISH with whole chromosome probes in cells collected 48-56 hours after irradiation using a chemical-induced premature chromosome condensation PCC technique The yield of chromosomal aberrations increased linearly with dose The relative biological effectiveness RBE for the primary beams estimated from the initial slope of the dose response curve for total chromosomal exchanges with respect to gamma -rays ranged from 14 to 35 The RBE values increased with LET to a maximum for the 1 GeV n Fe ions with LET of 150 keV mu m and decreased with further increase in LET When the LET of the primary beam was in the region of increasing RBE below approximately 100 keV mu m the addition of shielding material increased the effectiveness per unit dose However shielding decreased the effectiveness per unit dose when the LET of the primary particle beam was higher than150 keV mu m

  16. Alleviation of Aflatoxin B1-Induced Genomic Damage by Proanthocyanidins via Modulation of DNA Repair.

    PubMed

    Bakheet, Saleh A; Alhuraishi, Ahmed M; Al-Harbi, Naif O; Al-Hosaini, Khaled A; Al-Sharary, Shakir D; Attia, Mohammed M; Alhoshani, Ali R; Al-Shabanah, Othman A; Al-Harbi, Mohammed M; Imam, Faisal; Ahmad, Sheikh F; Attia, Sabry M

    2016-11-01

    In order to study the mechanisms underlying the alleviation of aflatoxin B1-induced genomic damage by proanthocyanidins (PAs), we examined the modulation of oxidative DNA damage induced by aflatoxin B1 in PAs-pretreated animals. The effects of PAs on changes in the expression of DNA damage and repair genes induced by aflatoxin B1 were also evaluated in rat marrow cells. Administration of PAs before aflatoxin B1 significantly mitigated aflatoxin B1-induced oxidative DNA damage in a dose-dependent manner. Aflatoxin B1 treatment induced significant alterations in the expression of specific DNA repair genes, and the pre-treatment of rats with PAs ameliorated the altered expression of these genes. Conclusively, PAs protect against aflatoxin B1-induced oxidative DNA damage in rats. These protective effects are attributed to the antioxidant effects of PA and enhanced DNA repair through modulation of DNA repair gene expression. Therefore, PAs are a promising chemoprotective agent for averting genotoxic risks associated with aflatoxin B1 exposure.

  17. Dissecting the Molecular Mechanism of Ionizing Radiation-Induced Tissue Damage in the Feather Follicle

    PubMed Central

    Chen, Xi; Liao, Chunyan; Chu, Qiqi; Zhou, Guixuan; Lin, Xiang; Li, Xiaobo; Lu, Haijie; Xu, Benhua; Yue, Zhicao

    2014-01-01

    Ionizing radiation (IR) is a common therapeutic agent in cancer therapy. It damages normal tissue and causes side effects including dermatitis and mucositis. Here we use the feather follicle as a model to investigate the mechanism of IR-induced tissue damage, because any perturbation of feather growth will be clearly recorded in its regular yet complex morphology. We find that IR induces defects in feather formation in a dose-dependent manner. No abnormality was observed at 5 Gy. A transient, reversible perturbation of feather growth was induced at 10 Gy, leading to defects in the feather structure. This perturbation became irreversible at 20 Gy. Molecular and cellular analysis revealed P53 activation, DNA damage and repair, cell cycle arrest and apoptosis in the pathobiology. IR also induces patterning defects in feather formation, with disrupted branching morphogenesis. This perturbation is mediated by cytokine production and Stat1 activation, as manipulation of cytokine levels or ectopic Stat1 over-expression also led to irregular feather branching. Furthermore, AG-490, a chemical inhibitor of Stat1 signaling, can partially rescue IR-induced tissue damage. Our results suggest that the feather follicle could serve as a useful model to address the in vivo impact of the many mechanisms of IR-induced tissue damage. PMID:24586618

  18. Dissecting the molecular mechanism of ionizing radiation-induced tissue damage in the feather follicle.

    PubMed

    Chen, Xi; Liao, Chunyan; Chu, Qiqi; Zhou, Guixuan; Lin, Xiang; Li, Xiaobo; Lu, Haijie; Xu, Benhua; Yue, Zhicao

    2014-01-01

    Ionizing radiation (IR) is a common therapeutic agent in cancer therapy. It damages normal tissue and causes side effects including dermatitis and mucositis. Here we use the feather follicle as a model to investigate the mechanism of IR-induced tissue damage, because any perturbation of feather growth will be clearly recorded in its regular yet complex morphology. We find that IR induces defects in feather formation in a dose-dependent manner. No abnormality was observed at 5 Gy. A transient, reversible perturbation of feather growth was induced at 10 Gy, leading to defects in the feather structure. This perturbation became irreversible at 20 Gy. Molecular and cellular analysis revealed P53 activation, DNA damage and repair, cell cycle arrest and apoptosis in the pathobiology. IR also induces patterning defects in feather formation, with disrupted branching morphogenesis. This perturbation is mediated by cytokine production and Stat1 activation, as manipulation of cytokine levels or ectopic Stat1 over-expression also led to irregular feather branching. Furthermore, AG-490, a chemical inhibitor of Stat1 signaling, can partially rescue IR-induced tissue damage. Our results suggest that the feather follicle could serve as a useful model to address the in vivo impact of the many mechanisms of IR-induced tissue damage.

  19. Guanine-specific DNA damage induced by γ-irradiated histone

    PubMed Central

    2005-01-01

    In γ-irradiation, •OH is directly generated from water and causes DNA damage leading to carcinogenesis. Exposure of proteins to γ-irradiation, in the presence of oxygen, gives high yields of hydroperoxides. To clarify whether these hydroperoxides, particularly those formed on DNA-binding histone proteins, participate in γ-irradiation-induced carcinogenesis, experiments using 32P-labelled DNA fragments obtained from human cancer-related genes were undertaken. Histone protein-hydroperoxides induced significant DNA damage in the presence of Cu(I). Histone H1- and H3-hydroperoxides showed stronger DNA damage compared with histone H2A- and H4-hydroperoxides at 0.7 μM. Histone H1-hydroperoxides caused Cu(I)-dependent DNA damage predominantly at guanine residues, especially at 5′-GGC-3′, 5′-GGA-3′, 5′-GGT-3′ and single G bases. In contrast, histone H3-hydroperoxides/Cu(I) induced DNA damage at 5′-G in GG sequences; this sequence specificity is identical with that generated by 2,2′-azobis (2-amidinopropane) dihydrochloride, which is known to produce peroxyl radicals (RO2•). The difference in site specificity of DNA damage induced by histone H1- and H3-hydroperoxides may arise from their amino acid composition or their mode of binding to DNA. The histone H1-hydroperoxides/Cu(I) system also induced 8-oxo-7,8-dihydro-2′-deoxyguanosine formation in calf thymus DNA. It is concluded that histone protein-hydroperoxides can induce guanine-specific DNA damage, which may contribute to γ-irradiation-induced carcinogenesis. PMID:15698381

  20. Laser induced damage in optical materials: ninth ASTM symposium.

    PubMed

    Glass, A J; Guenther, A H

    1978-08-01

    The Ninth Annual Symposium on Optical Materials for High Power Lasers (Boulder Damage Symposium) was held at the National Bureau of Standards in Boulder, Colorado, 4-6 October 1977. The symposium was 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 (formerly ERDA), and the Office of Naval Research. About 185 scientists attended, including representatives of the United Kingdom, France, Canada, Australia, Union of South Africa, and the Soviet Union. The Symposium was divided into sessions concerning Laser Windows and Materials, Mirrors and Surfaces, Thin Films, Laser Glass and Glass Lasers, and Fundamental Mechanisms. As in previous years, the emphasis of the papers 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 were also discussed. Alexander J. Glass of Lawrence Livermore Laboratory and Arthur H. Guenther of the Air Force Weapons Laboratory were co-chairpersons. The Tenth Annual Symposium is scheduled for 12-14 September 1978 at the National Bureau of Standards, Boulder, Colorado.

  1. Acid sphingomyelinase deficiency protects from cisplatin-induced gastrointestinal damage.

    PubMed

    Rebillard, A; Rioux-Leclercq, N; Muller, C; Bellaud, P; Jouan, F; Meurette, O; Jouan, E; Vernhet, L; Le Quément, C; Carpinteiro, A; Schenck, M; Lagadic-Gossmann, D; Gulbins, E; Dimanche-Boitrel, M T

    2008-11-20

    Cisplatin is one of the most effectively used chemotherapeutic agents for cancer treatment. However, in humans, important cytotoxic side effects are observed including dose-limiting renal damage and profound gastrointestinal symptomatology. The toxic responses to cisplatin in mice are similar to those in human patients. Here, we evaluated whether the acid sphingomyelinase (Asm) mediates at least some of the toxic in vivo effects of cisplatin. To this end, we determined the toxic effects of a single intraperitoneal dose of cisplatin (27 mg/kg) in wild type (Asm(+/+)) and Asm-deficient mice (Asm(-/-)). Tissue injury and apoptosis were determined histologically on hematoxylin-eosin and TUNEL (terminal deoxynucleotidyl transferase (TdT)-mediated nick end labeling) stainings 3, 12, 36 and 72 h after treatment. Our results revealed severe toxicity of cisplatin in Asm(+/+) mice with increased numbers of apoptotic cells in the thymus and small intestine. In marked contrast, Asm(-/-) mice were resistant to cisplatin and no apoptosis was observed in these organs after treatment. Moreover, cisplatin treatment primarily triggered apoptosis of endothelial cells in microvessels of intestine and thymus, an effect that was absent in mice lacking Asm. The data thus suggest that at least some toxic effects of cisplatin are mediated by the Asm in vivo resulting in early death of endothelial cells and consecutive organ damage.

  2. Mycosporine glycine protects biological systems against photodynamic damage by quenching singlet oxygen with a high efficiency.

    PubMed

    Suh, Hwa-Jin; Lee, Hyun-Woo; Jung, Jin

    2003-08-01

    This report concerns physiological function of mycosporine-like amino acids (MAA) as an active defense against the photooxidative effects of sunlight in marine organisms. Mycosporine glycine (MG) is a representative member of MAA family and was found to effectively suppress various detrimental effects of the Type-II photosensitization in biological systems, such as inactivation of mitochondrial electron transport, lipid peroxidation of microsomes, hemolysis of erythrocytes and growth inhibition of Escherichia coli. The presence of MG in solutions of eosin Y or methylene blue resulted in a marked decrease in the level of singlet oxygen (1O2) produced by the sensitizers under illumination. The rate constant of 1O2 quenching by MG was determined to be 5.6 x 10(7) M(-1) s(-1) by the time-resolved 1O2 luminescence decay method, which is higher than, or at least comparable to, the values for 1O2 reaction of well-known quenchers such as 1,4-diazabicyclo[2,2,2]octane and furfuryl alcohol. The results suggest that MG probably together with some other active MAA may play an important role in protecting marine organisms against sunlight damage by eliminating 1O2 generated from certain endogenous photosensitizers.

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

    EPA Science Inventory

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

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

    EPA Science Inventory

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

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

    EPA Science Inventory

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

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

    EPA Science Inventory

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

  7. Toxoplasma gondii infection can induce retinal DNA damage: an experimental study

    PubMed Central

    El-Sayed, Nagwa Mostafa; Aly, Eman Mohamed

    2014-01-01

    AIM To detect whether Toxoplasma gondii (T. gondii) infection of mice can induce retinal DNA damage. METHODS A total of 20 laboratory-bred male Swiss albino mice were used and divided into four groups: control group (non-infected animals); T. gondii infected group; immunosuppressed infected group; and infected group treated with sulfadiazine and pyrimethamine. Mice eyes were collected 6wk post infection and retinas were obtained. Each retina was immediately processed for comet assay and the frequency of tailed nuclei (DNA damage) was calculated. In addition, retinal DNA damage was revealed by various comet assay parameters that were provided by the image analysis software including tail length, percentage of DNA in the tail, percentage of tailed cells and tail moment. RESULTS The obtained results showed that T. gondii infection induced a statistically significant increase in the frequency of tailed nuclei, tail length, percentage of DNA in the tail, and tail moment in mice retinal cells compared to the control group (which showed some degree of DNA damage). In immunosuppressed infected group, retinal DNA damage was severing and there was significant increase in various comet assay parameters compared to both control and infected groups. After treatment with sulfadiazine and pyrimethamine, retinal DNA damage decreased and all comet assay parameters showed a statistical significant decrease compared to infected groups. CONCLUSION T. gondii infection can induce DNA damage in mice retinal cells. PMID:24967186

  8. UV-induced DNA damage in Cyclops abyssorum tatricus populations from clear and turbid alpine lakes

    PubMed Central

    Tartarotti, Barbara; Saul, Nadine; Chakrabarti, Shumon; Trattner, Florian; Steinberg, Christian E. W.; Sommaruga, Ruben

    2014-01-01

    Zooplankton from clear alpine lakes thrive under high levels of solar UV radiation (UVR), but in glacially turbid ones they are more protected from this damaging radiation. Here, we present results from experiments done with Cyclops abyssorum tatricus to assess UV-induced DNA damage and repair processes using the comet assay. Copepods were collected from three alpine lakes of differing UV transparency ranging from clear to glacially turbid, and exposed to artificial UVR. In addition, photoprotection levels [mycosporine-like amino acids (MAAs) and lipophilic antioxidant capacity] were estimated in the test populations. Similar UV-induced DNA damage levels were observed among the copepods from all lakes, but background DNA damage (time zero and dark controls) was lowest in the copepods from the glacially turbid lake, resulting in a higher relative DNA damage accumulation. Most DNA strand breaks were repaired after recovery in the dark. Low MAA concentrations were found in the copepods from the glacially turbid lake, while the highest levels were observed in the population from the most UV transparent lake. However, the highest lipophilic antioxidant capacities were measured in the copepods from the lake with intermediate UV transparency. Photoprotection and the ability to repair DNA damage, and consequently reducing UV-induced damage, are part of the response mechanisms in zooplankton to changes in water transparency caused by glacier retreat. PMID:24616551

  9. Effects of fatigue induced damage on the longitudinal fracture resistance of cortical bone.

    PubMed

    Fletcher, Lloyd; Codrington, John; Parkinson, Ian

    2014-07-01

    As a composite material, cortical bone accumulates fatigue microdamage through the repetitive loading of everyday activity (e.g. walking). The accumulation of fatigue microdamage is thought to contribute to the occurrence of fragility fractures in older people. Therefore it is beneficial to understand the relationship between microcrack accumulation and the fracture resistance of cortical bone. Twenty longitudinally orientated compact tension fracture specimens were machined from a single bovine femur, ten specimens were assigned to both the control and fatigue damaged groups. The damaged group underwent a fatigue loading protocol to induce microdamage which was assessed via fluorescent microscopy. Following fatigue loading, non-linear fracture resistance tests were undertaken on both the control and damaged groups using the J-integral method. The interaction of the crack path with the fatigue induced damage and inherent toughening mechanisms were then observed using fluorescent microscopy. The results of this study show that fatigue induced damage reduces the initiation toughness of cortical bone and the growth toughness within the damage zone by three distinct mechanisms of fatigue-fracture interaction. Further analysis of the J-integral fracture resistance showed both the elastic and plastic component were reduced in the damaged group. For the elastic component this was attributed to a decreased number of ligament bridges in the crack wake while for the plastic component this was attributed to the presence of pre-existing fatigue microcracks preventing energy absorption by the formation of new microcracks.

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

    NASA Technical Reports Server (NTRS)

    Griko, Y. V.; Yan, Xiaoli

    2016-01-01

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

  11. Terbium fluorescence as a sensitive, inexpensive probe for UV-induced damage in nucleic acids.

    PubMed

    El-Yazbi, Amira F; Loppnow, Glen R

    2013-07-05

    Much effort has been focused on developing methods for detecting damaged nucleic acids. However, almost all of the proposed methods consist of multi-step procedures, are limited, require expensive instruments, or suffer from a high level of interferences. In this paper, we present a novel simple, inexpensive, mix-and-read assay that is generally applicable to nucleic acid damage and uses the enhanced luminescence due to energy transfer from nucleic acids to terbium(III) (Tb(3+)). Single-stranded oligonucleotides greatly enhance the Tb(3+) emission, but duplex DNA does not. With the use of a DNA hairpin probe complementary to the oligonucleotide of interest, the Tb(3+)/hairpin probe is applied to detect ultraviolet (UV)-induced DNA damage. The hairpin probe hybridizes only with the undamaged DNA. However, the damaged DNA remains single-stranded and enhances the intrinsic fluorescence of Tb(3+), producing a detectable signal directly proportional to the amount of DNA damage. This allows the Tb(3+)/hairpin probe to be used for sensitive quantification of UV-induced DNA damage. The Tb(3+)/hairpin probe showed superior selectivity to DNA damage compared to conventional molecular beacons probes (MBs) and its sensitivity is more than 2.5 times higher than MBs with a limit of detection of 4.36±1.2 nM. In addition, this probe is easier to synthesize and more than eight times cheaper than MBs, which makes its use recommended for high-throughput, quantitative analysis of DNA damage.

  12. Hypoxic-ischemic brain damage induces distant inflammatory lung injury in newborn piglets.

    PubMed

    Arruza, Luis; Pazos, M Ruth; Mohammed, Nagat; Escribano, Natalia; Lafuente, Hector; Santos, Martín; Alvarez-Díaz, Francisco J; Martínez-Orgado, Jose

    2016-03-01

    We aimed to investigate whether neonatal hypoxic-ischemic (HI) brain injury induces inflammatory lung damage. Thus, hypoxic (HYP, FiO2 10% for 30 min), ischemic (ISC, bilateral carotid flow interruption for 30 min), or HI event was performed in 1-2-d-old piglets. Dynamic compliance (Cdyn), oxygenation index (OI), and extravascular lung water (EVLW) were monitored for 6 h. Then, histologic damage was assessed in brain and lung (lung injury severity score). Total protein content (TPC) was determined in broncoalveolar lavage fluid (BALF), and IL-1β concentration was measured in lung and brain tissues and blood. Piglets without hypoxia or ischemia served as controls (SHM). HI-induced brain damage was associated with decreased Cdyn, increased OI and EVLW, and histologic lung damage (interstitial leukocyte infiltration, congestive hyperemia, and interstitial edema). BALF TPC was increased, suggesting inflammatory damage. In agreement, tissue IL-1β concentration increased in the brain and lung, in correspondence with increased IL-1β serum concentration. Neither HYP nor ISC alone led to brain or lung damage. HI brain damage in newborn piglets led to inflammatory lung damage, suggesting an additional mechanism accounting for the development of lung dysfunction after neonatal HI encephalopathy.

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

    SciTech Connect

    Cooper, Karen L.; King, Brenee S.; Sandoval, Monica M.; Liu, Ke Jian; Hudson, Laurie G.

    2013-06-01

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

  14. RNA m(6)A methylation regulates the ultraviolet-induced DNA damage response.

    PubMed

    Xiang, Yang; Laurent, Benoit; Hsu, Chih-Hung; Nachtergaele, Sigrid; Lu, Zhike; Sheng, Wanqiang; Xu, Chuanyun; Chen, Hao; Ouyang, Jian; Wang, Siqing; Ling, Dominic; Hsu, Pang-Hung; Zou, Lee; Jambhekar, Ashwini; He, Chuan; Shi, Yang

    2017-03-23

    Cell proliferation and survival require the faithful maintenance and propagation of genetic information, which are threatened by the ubiquitous sources of DNA damage present intracellularly and in the external environment. A system of DNA repair, called the DNA damage response, detects and repairs damaged DNA and prevents cell division until the repair is complete. Here we report that methylation at the 6 position of adenosine (m(6)A) in RNA is rapidly (within 2 min) and transiently induced at DNA damage sites in response to ultraviolet irradiation. This modification occurs on numerous poly(A)(+) transcripts and is regulated by the methyltransferase METTL3 (methyltransferase-like 3) and the demethylase FTO (fat mass and obesity-associated protein). In the absence of METTL3 catalytic activity, cells showed delayed repair of ultraviolet-induced cyclobutane pyrimidine adducts and elevated sensitivity to ultraviolet, demonstrating the importance of m(6)A in the ultraviolet-responsive DNA damage response. Multiple DNA polymerases are involved in the ultraviolet response, some of which resynthesize DNA after the lesion has been excised by the nucleotide excision repair pathway, while others participate in trans-lesion synthesis to allow replication past damaged lesions in S phase. DNA polymerase κ (Pol κ), which has been implicated in both nucleotide excision repair and trans-lesion synthesis, required the catalytic activity of METTL3 for immediate localization to ultraviolet-induced DNA damage sites. Importantly, Pol κ overexpression qualitatively suppressed the cyclobutane pyrimidine removal defect associated with METTL3 loss. Thus, we have uncovered a novel function for RNA m(6)A modification in the ultraviolet-induced DNA damage response, and our findings collectively support a model in which m(6)A RNA serves as a beacon for the selective, rapid recruitment of Pol κ to damage sites to facilitate repair and cell survival.

  15. Regulation of DNA damage-induced apoptosis by the c-Abl tyrosine kinase

    PubMed Central

    Yuan, Zhi-Min; Huang, Yinyin; Ishiko, Takatoshi; Kharbanda, Surender; Weichselbaum, Ralph; Kufe, Donald

    1997-01-01

    Activation of the c-Abl protein tyrosine kinase by certain DNA-damaging agents contributes to down-regulation of Cdk2 and G1 arrest by a p53-dependent mechanism. The present work investigates the potential role of c-Abl in apoptosis induced by DNA damage. Transient transfection studies with wild-type, but not kinase-inactive, c-Abl demonstrate induction of apoptosis. Cells that stably express inactive c-Abl exhibit resistance to ionizing radiation-induced loss of clonogenic survival and apoptosis. Cells null for c-abl are also impaired in the apoptotic response to ionizing radiation. We further show that cells deficient in p53 undergo apoptosis in response to expression of c-Abl and exhibit decreases in radiation-induced apoptosis when expressing inactive c-Abl. These findings suggest that c-Abl kinase regulates DNA damage-induced apoptosis. PMID:9037071

  16. Coupling statistics and heat transfer to study laser-induced crystal damage by nanosecond pulses.

    PubMed

    Duchateau, Guillaume; Dyan, Anthony

    2007-04-16

    By coupling statistics and heat transfer, we investigate numerically laser-induced crystal damage by multi-gigawatt nanosecond pulses. Our model is based on the heating of nanometric absorbing defects that may cooperate when sufficiently aggregated. In that configuration, they induce locally a strong increase of temperature that may lead to a subsequent damage. This approach allows to predict cluster size distribution and damage probabilities as a function of the laser fluence. By studying the influence of the pulse duration onto the laser-induced damage threshold, we have established scaling laws that link the critical laser fluence to its pulse duration tau. In particular, this approach provides an explanation to the deviation from the standard tau(1/2) scaling law that has been recently observed in laser-induced damage experiments with KH(2)PO(4) (KDP) crystals [J.J. Adams et al., Proc. of SPIE 5991, 5991R-1 (2005)]. In the present paper, despite the 3D problem is tackled, we focus our attention on a 1D modeling of thermal diffusion that is shown to provide more reliable predictions than the 3D one. These results indicate that absorbers involved in KDP damage may be associated with a collection of planar defects. First general comparisons with some experimental facts have been performed.

  17. A Topical Mitochondria-Targeted Redox-Cycling Nitroxide Mitigates Oxidative Stress-Induced Skin Damage.

    PubMed

    Brand, Rhonda M; Epperly, Michael W; Stottlemyer, J Mark; Skoda, Erin M; Gao, Xiang; Li, Song; Huq, Saiful; Wipf, Peter; Kagan, Valerian E; Greenberger, Joel S; Falo, Louis D

    2017-03-01

    Skin is the largest human organ, and it provides a first line of defense that includes physical, chemical, and immune mechanisms to combat environmental stress. Radiation is a prevalent environmental stressor. Radiation-induced skin damage ranges from photoaging and cutaneous carcinogenesis caused by UV exposure, to treatment-limiting radiation dermatitis associated with radiotherapy, to cutaneous radiation syndrome, a frequently fatal consequence of exposures from nuclear accidents. The major mechanism of skin injury common to these exposures is radiation-induced oxidative stress. Efforts to prevent or mitigate radiation damage have included development of antioxidants capable of reducing reactive oxygen species. Mitochondria are particularly susceptible to oxidative stress, and mitochondrial-dependent apoptosis plays a major role in radiation-induced tissue damage. We reasoned that targeting a redox cycling nitroxide to mitochondria could prevent reactive oxygen species accumulation, limiting downstream oxidative damage and preserving mitochondrial function. Here we show that in both mouse and human skin, topical application of a mitochondrially targeted antioxidant prevents and mitigates radiation-induced skin damage characterized by clinical dermatitis, loss of barrier function, inflammation, and fibrosis. Further, damage mitigation is associated with reduced apoptosis, preservation of the skin's antioxidant capacity, and reduction of irreversible DNA and protein oxidation associated with oxidative stress. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Depletion of enteric bacteria diminishes leukocyte infiltration following doxorubicin-induced small intestinal damage in mice.

    PubMed

    Carr, Jacquelyn S; King, Stephanie; Dekaney, Christopher M

    2017-01-01

    While enteric bacteria have been shown to play a critical role in other forms of intestinal damage, their role in mediating the response to the chemotherapeutic drug Doxorubicin (Doxo) is unclear. In this study, we used a mouse model of intestinal bacterial depletion to evaluate the role enteric bacteria play in mediating Doxo-induced small intestinal damage and, more specifically, in mediating chemokine expression and leukocyte infiltration following Doxo treatment. An understanding of this pathway may allow for development of intervention strategies to reduce chemotherapy-induced small intestinal damage. Mice were treated with (Abx) or without (NoAbx) oral antibiotics in drinking water for four weeks and then with Doxo. Jejunal tissues were collected at various time points following Doxo treatment and stained and analyzed for apoptosis, crypt damage and restitution, and macrophage and neutrophil number. In addition, RNA expression of inflammatory markers (TNFα, IL1-β, IL-10) and cytokines (CCL2, CC7, KC) was assessed by qRT-PCR. In NoAbx mice Doxo-induced damage was associated with rapid induction of apoptosis in jejunal crypt epithelium and an increase weight loss and crypt loss. In addition, we observed an increase in immune-modulating chemokines CCL2, CCL7 and KC and infiltration of macrophages and neutrophils. In contrast, while still positive for induction of apoptosis following Doxo treatment, Abx mice showed neither the overall weight loss nor crypt loss seen in NoAbx mice nor the increased chemokine expression and leukocyte infiltration. Enteric bacteria play a critical role in Doxo-induced small intestinal damage and are associated with an increase in immune-modulating chemokines and cells. Manipulation of enteric bacteria or the damage pathway may allow for prevention or treatment of chemotherapy-induced small intestinal damage.

  19. Depletion of enteric bacteria diminishes leukocyte infiltration following doxorubicin-induced small intestinal damage in mice

    PubMed Central

    Carr, Jacquelyn S.; King, Stephanie

    2017-01-01

    Background & aims While enteric bacteria have been shown to play a critical role in other forms of intestinal damage, their role in mediating the response to the chemotherapeutic drug Doxorubicin (Doxo) is unclear. In this study, we used a mouse model of intestinal bacterial depletion to evaluate the role enteric bacteria play in mediating Doxo-induced small intestinal damage and, more specifically, in mediating chemokine expression and leukocyte infiltration following Doxo treatment. An understanding of this pathway may allow for development of intervention strategies to reduce chemotherapy-induced small intestinal damage. Methods Mice were treated with (Abx) or without (NoAbx) oral antibiotics in drinking water for four weeks and then with Doxo. Jejunal tissues were collected at various time points following Doxo treatment and stained and analyzed for apoptosis, crypt damage and restitution, and macrophage and neutrophil number. In addition, RNA expression of inflammatory markers (TNFα, IL1-β, IL-10) and cytokines (CCL2, CC7, KC) was assessed by qRT-PCR. Results In NoAbx mice Doxo-induced damage was associated with rapid induction of apoptosis in jejunal crypt epithelium and an increase weight loss and crypt loss. In addition, we observed an increase in immune-modulating chemokines CCL2, CCL7 and KC and infiltration of macrophages and neutrophils. In contrast, while still positive for induction of apoptosis following Doxo treatment, Abx mice showed neither the overall weight loss nor crypt loss seen in NoAbx mice nor the increased chemokine expression and leukocyte infiltration. Conclusion Enteric bacteria play a critical role in Doxo-induced small intestinal damage and are associated with an increase in immune-modulating chemokines and cells. Manipulation of enteric bacteria or the damage pathway may allow for prevention or treatment of chemotherapy-induced small intestinal damage. PMID:28257503

  20. Molecular Hydrogen Therapy Ameliorates Organ Damage Induced by Sepsis.

    PubMed

    Zheng, Yijun; Zhu, Duming

    2016-01-01

    Since it was proposed in 2007, molecular hydrogen therapy has been widely concerned and researched. Many animal experiments were carried out in a variety of disease fields, such as cerebral infarction, ischemia reperfusion injury, Parkinson syndrome, type 2 diabetes mellitus, metabolic syndrome, chronic kidney disease, radiation injury, chronic hepatitis, rheumatoid arthritis, stress ulcer, acute sports injuries, mitochondrial and inflammatory disease, and acute erythema skin disease and other pathological processes or diseases. Molecular hydrogen therapy is pointed out as there is protective effect for sepsis patients, too. The impact of molecular hydrogen therapy against sepsis is shown from the aspects of basic vital signs, organ functions (brain, lung, liver, kidney, small intestine, etc.), survival rate, and so forth. Molecular hydrogen therapy is able to significantly reduce the release of inflammatory factors and oxidative stress injury. Thereby it can reduce damage of various organ functions from sepsis and improve survival rate. Molecular hydrogen therapy is a prospective method against sepsis.

  1. Space irradiation-induced damage to graphene films.

    PubMed

    Wang, Liping; Fan, Xiaoqiang; Li, Wen; Li, Hao; Zhu, Minhao; Pu, Jibin; Xue, Qunji

    2017-09-14

    Graphene with impressive electrical, optical, chemical and mechanical properties has promising potential applications for photoelectric devices and mechanical components installed on the space facilities, which will probably face hostile environments including high-energy particulate irradiation. Here we explored the effect of simulated space irradiation on the structure and properties of large-area single-layer and multi-layer graphene films (about four layers) including atomic oxygen (AO), electron (EL) and proton (PR). AO with strong oxidizing capacity reacts with carbon atoms of graphene films and generates carbon dioxide, high-energy PR leads to polymorphic atomic defects in graphene through collision and excitation effects. Miraculously, EL irradiation causes little damage to the graphene films because of the excellent conductivity. Graphene ripples are broken by irradiation and adapt their shape or structure with respect to the substrate via thermodynamic stability, which causes the change of the physical and mechanical properties of graphene.

  2. Oxidative damage induced in Vicia faba by coke plant wastewater.

    PubMed

    Liu, Yuxiang; Lv, Yongkang

    2011-10-01

    The present study investigated toxic impacts of coke plant wastewater over a concentration gradient of COD( Cr) 40-640 mg/l on malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) in roots and leaves of Vicia faba. MDA levels and SOD activities were significantly increased at all concentrations both in roots and leaves of Vicia faba; CAT and POD activities were significantly enhanced in roots at low concentrations and were significantly decreased at high concentrations (COD(Cr) 320 and 640 mg/l for CAT; COD( Cr) 640 mg/l for POD). In leaves, CAT and POD activities remained enhanced at all concentration and did not show significant difference at COD( Cr) 640 mg/l for CAT and COD(Cr) 40, 640 mg/l for POD. These results suggest that coke plant wastewater can cause oxidative damage in roots and leaves of Vicia faba and root enzymes seemed more sensitive to the wastewater.

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

    PubMed

    Bennett, H E; Glass, A J; Guenther, A H; Newnam, B

    1981-09-01

    The twelfth annual Symposium on Optical Materials for High Power Lasers (Boulder Damage Symposium) was held at the National Bureau of Standards in Boulder, Colorado, 30 Sept.-l Oct., 1980. The symposium was held under the auspices of ASTM Committee F-l, Subcommittee on Laser Standards, with the joint sponsorship of NBS, the Defense Advanced Research Projects Agency, the Department of Energy, the Office of Naval Research, and the Air Force Office of Scientific research. Over 150 scientists attended the symposium, including representatives of the United Kingdom, France, Japan, and West Germany. The symposium was divided into sessions concerning materials and measurements, mirrors and surfaces, thin films, and finally fundamental mechanisms. As in previous years, the emphasis of the papers presented at the symposium was directed toward new frontiers and new developments. Particular emphasis was given to materials for high power systems. The wavelength range of prime interest was 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 discussed in detail. Harold E. Bennett of the Naval Weapons Center, Alexander J. Glass of the Lawrence Livermore National Laboratory, Arthur H. Guenther of the Air Force Weapons Laboratory, and Brian E. Newnam of the Los Alamos National Laboratory were cochairmen of the symposium. The thirteenth annual symposium is scheduled for 17-18 Nov. 1981 at the National Bureau of Standards, Boulder, Colorado.

  4. Sulodexide prevents peripheral nerve damage in streptozotocin induced diabetic rats.

    PubMed

    Jin, Heung Yong; Lee, Kyung Ae; Song, Sun Kyung; Liu, Wei Jing; Choi, Ji Hae; Song, Chang Ho; Baek, Hong Sun; Park, Tae Sun

    2012-01-15

    We investigated whether sulodexide has additional protective effects against peripheral nerve damage caused by microvascular dysfunction in a rat model of diabetes. Female Sprague-Dawley (SD) rats were divided into the following 4 groups (n=7-9/group): Normal, Normal+Sulodexide (sulodexide 10mg/kg), diabetic group, and diabetic+Sulodexide (sulodexide 10mg/kg). We assessed current perception threshold, skin blood flow, superoxide dismutase, and proteinuria in experimental rats after oral administration of sulodexide for 20 weeks. We also performed morphometric analysis of sciatic nerves and intraepidermal nerve fibers of the foot. Superoxide dismutase activity in the blood and sciatic nerve were increased significantly after sulodexide treatment in the diabetic group. Current perception threshold was reduced at 2000 Hz (633.3 ± 24.15 vs 741.2 ± 23.5 μA, P<0.05) and skin blood flow was improved (10.90 ± 0.67 vs 8.85 ± 0.49 TPU, P<0.05) in the diabetic+Sulodexide group compared with the diabetic group. The mean myelinated axon area was significantly larger (56.6 ± 2.2 vs 49.8 ± 2.7 μm(2), P<0.05) and the intraepidermal nerve fiber density was significantly less reduced (6.27 ± 0.24 vs 5.40 ± 0.25/mm, P<0.05) in the diabetic+Sulodexide group compared to the diabetic group. Our results demonstrate that sulodexide exhibits protective effects against peripheral nerve damage in a rat experimental model of diabetes. Therefore, these findings suggest that sulodexide is a potential new therapeutic agent for diabetic peripheral neuropathy.

  5. Protective effects of topical application of a poorly soluble antioxidant astaxanthin liposomal formulation on ultraviolet-induced skin damage.

    PubMed

    Hama, Susumu; Takahashi, Kanako; Inai, Yuko; Shiota, Kanako; Sakamoto, Ryota; Yamada, Asako; Tsuchiya, Hiroyuki; Kanamura, Kiyoshi; Yamashita, Eiji; Kogure, Kentaro

    2012-08-01

    Astaxanthin (Asx) would be expected to prevent ultraviolet (UV)-induced skin damage, as it is regarded as a potent antioxidative carotenoid in biological membranes. However, it is difficult to administer Asx topically to skin because of its poor water solubility. In this study, we attempted to solve this problem by preparing liposomes containing Asx (Asx-lipo), which were dispersible in the water phase, and therefore, suitable for topical application to the skin. Asx-lipo was shown to have potent scavenging ability against chemiluminescence-dependent singlet oxygen production in the water phase. When Asx-lipo was applied to skin before UV exposure, UV-induced skin thickening was prevented. Interestingly, collagen reduction induced by UV exposure was also prevented by preadministration of Asx-lipo. In addition, topical administration of Asx-lipo containing cationic lipid inhibited melanin production in skin exposed to UV. Consequently, we succeeded in preventing UV-induced skin damage using a topical application of a liposomal formulation containing Asx.

  6. Modal characteristics of turbine blade packets under lacing wire damage induced mistuning

    NASA Astrophysics Data System (ADS)

    Chatterjee, Animesh; Kotambkar, Mangesh S.

    2015-05-01

    Effect of mistuning on turbo machine blade vibration in a packeted blade-disk system has become an important area of research in the recent past, mainly due to the critical applications in aero engines and power plant turbines. It has been shown that even a small mistuning can lead to stress build up through mode localization under forced vibration. Such mistuning can come from initial geometric blade to blade variation due to manufacturing tolerances or from a crack growing in the bladed disk system during operational life stages. The literature review indicates that researchers have mainly considered blade damage as a cause of mistuning. However, lacing wire damage, although not as catastrophic as blade damage, are more frequent in occurrences and often act as a precursor to subsequent blade damage. Detection of lacing wire damage is therefore equally important. Present work has investigated nature of mistuning induced by lacing wire damage and its effect on the characteristic modal properties. A damage severity index has been introduced and effect of damage on the blade group natural frequencies is investigated. Scope of developing a damage identification methodology in packeted blade-disk system is also discussed.

  7. Varied laser induced damage phenomena of gold coated gratings for pulse compression

    NASA Astrophysics Data System (ADS)

    Xia, Zhilin; Huang, Haopeng; Kong, Fanyu; Wang, Leilei; Jin, Yunxia

    2017-08-01

    In this paper, gold-coated gratings for pulse compression have been prepared and their laser damage experiments have been performed. Varied laser damage morphologies have been observed: when a 60 fs-pulsed laser with energy density slightly higher than the damage threshold was used, damage morphology with a characteristic of discrete distribution of small pits was appeared. These damage pits are linearly distributed at the junction of ridges and grooves. If the laser energy density is much higher than the damage threshold, the gold films was overall ablated and the grating structure disappeared. Besides, if the gold film has poor adhesion, it was peeled off. When a 450 ps-pulsed laser with energy density slightly higher than the damage threshold was used, part of grating ridges will be ablated and an obvious line exists between the ablated area and the unchanged area. In theory, the laser induced temperature field and stress field in gold-coated gratings were calculated based on the electromagnetic field using the finite element method. It is demonstrated that the temperature and thermal stress distribution characteristics are affected by the laser heating rate and the heat diffusion time (the calculated diffusion time ranges from 6 fs to 450 ps), which determines the laser damage characteristics. The possible damage drivers have electron hydrodynamic pressure, thermal ablation and thermal stress.

  8. Feasibility of OCT to detect radiation-induced esophageal damage in small animal models (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Jelvehgaran, Pouya; Alderliesten, Tanja; Salguero, Javier; Borst, Gerben; Song, Ji-Ying; van Leeuwen, Ton G.; de Boer, Johannes F.; de Bruin, Daniel M.; van Herk, Marcel B.

    2016-03-01

    Lung cancer survival is poor and radiotherapy patients often suffer serious treatment side effects. The esophagus is particularly sensitive leading to reduced food intake or even fistula formation. Only few direct techniques exist to measure radiation-induced esophageal damage, for which knowledge is needed to improve the balance between risk of tumor recurrence and complications. Optical coherence tomography (OCT) is a minimally-invasive imaging technique that obtains cross-sectional, high-resolution (1-10µm) images and is capable of scanning the esophageal wall up to 2-3mm depth. In this study we investigated the feasibility of OCT to detect esophageal radiation damage in mice. In total 30 mice were included in 4 study groups (1 main and 3 control groups). Mice underwent cone-beam CT imaging for initial setup assessment and dose planning followed by single-fraction dose delivery of 4, 10, 16, and 20Gy on 5mm spots, spaced 10mm apart. Mice were repeatedly imaged using OCT: pre-irradiation and up to 3 months post-irradiation. The control groups received either OCT only, irradiation only, or were sham-operated. We used histopathology as gold standard for radiation-induced damage diagnosis. The study showed edema in both the main and OCT-only groups. Furthermore, radiation-induced damage was primarily found in the highest dose region (distal esophagus). Based on the histopathology reports we were able to identify the radiation-induced damage in the OCT images as a change in tissue scattering related to the type of induced damage. This finding indicates the feasibility and thereby the potentially promising role of OCT in radiation-induced esophageal damage assessment.

  9. Gastrointestinal damage induced by celecoxib and rofecoxib in rats.

    PubMed

    Laudanno, O M; Cesolari, J A; Esnarriaga, J; Rista, L; Piombo, G; Maglione, C; Aramberry, L; Sambrano, J; Godoy, A; Rocaspana, A

    2001-04-01

    Five experimental models were developed in different groups of Wistar rats (N = 15) to study selective COX-2-inhibitor NSAIDs such as celecoxib and rofecoxib, as follows: (1) dose-dependent oral Celecoxib and Rofecoxib for 5 days, and 24 hr after oral indomethacin; (2) Same as 1 but subcutaneously; (3) gastric ulcer induced by glacial acetic acid; (4) duodenal ulcer induced by cysteamine; and (5) stress by immobilization and immersion in water at 15 degrees C for 6 hr. Celecoxib and Rofecoxib, either orally or subcutaneously, did not produce necrotic lesions in healthy gastrointestinal mucosa (0%), showing normal histology. In contrast, previously indomethacin-induced lesions were aggravated (90%, P < 0.001). Total necrosis in the small intestine as well as increased ulcers and perforation of gastric and duodenal ulcers induced by acetic acid and cysteamine were observed. There was also aggravation of the necrotic gastric area in stress (60-90%, P < 0.05). Celecoxib and rofecoxib showed neutrophilia (5000/mm3) similar to that with indomethacin. In contrast, there was no leukocyte infiltration in the gastric múcosa; thus, we can consider it a selective COX-2 NSAID. In conclusion, celecoxib and rofecoxib at doses causing COX-2 but not COX-1 inhibition did not produce toxic lesions in healthy gastrointestinal mucosa, yielding a broad therapeutic margin. In contrast, when administered in altered gastrointestinal mucosa, they aggravated and complicated gastric ulcers as well as necrosis in the small intestine, consequently restricting their clinical use.

  10. Extract from Armoracia rusticana and its flavonoid components protect human lymphocytes against oxidative damage induced by hydrogen peroxide.

    PubMed

    Gafrikova, Michala; Galova, Eliska; Sevcovicova, Andrea; Imreova, Petronela; Mucaji, Pavel; Miadokova, Eva

    2014-03-14

    DNA damage prevention is an important mechanism involved in cancer prevention by dietary compounds. Armoracia rusticana is cultivated mainly for its roots that are used in the human diet as a pungent spice. The roots represent rich sources of biologically active phytocompounds, which are beneficial for humans. In this study we investigated the modulation of H₂O₂ genotoxicity using the A. rusticana root aqueous extract (AE) and two flavonoids (kaempferol or quercetin). Human lymphocytes pre-treated with AE, kaempferol and quercetin were challenged with H₂O₂ and the DNA damage was assessed by the comet assay. At first we assessed a non-genotoxic concentration of AE and flavonoids, respectively. In lymphocytes challenged with H₂O₂ we proved that the 0.0025 mg·mL⁻¹ concentration of AE protected human DNA. It significantly reduced H₂O₂-induced oxidative damage (from 78% to 35.75%). Similarly, a non-genotoxic concentration of kaempferol (5 μg·mL⁻¹) significantly diminished oxidative DNA damage (from 83.3% to 19.4%), and the same concentration of quercetin also reduced the genotoxic effect of H₂O₂ (from 83.3% to 16.2%). We conclude that AE, kaempferol and quercetin probably act as antimutagens. The molecular mechanisms underlying their antimutagenic activity might be explained by their antioxidant properties.

  11. Modulation of DNA-Induced Damage and Repair Capacity in Humans after Dietary Intervention with Lutein-Enriched Fermented Milk

    PubMed Central

    Herrero-Barbudo, Carmen; Soldevilla, Beatriz; Pérez-Sacristán, Belén; Blanco-Navarro, Inmaculada; Herrera, Mercedes; Granado-Lorencio, Fernando; Domínguez, Gemma

    2013-01-01

    Dietary factors provide protection against several forms of DNA damage. Additionally, consumer demand for natural products favours the development of bioactive food ingredients with health benefits. Lutein is a promising biologically active component in the food industry. The EFSA Panel on Dietetic Products, Nutrition and Allergies considers that protection from oxidative damage may be a beneficial physiological effect but that a cause and effect relationship has not been established. Thus, our aim was to evaluate the safety and potential functional effect of a lutein-enriched milk product using the Comet Assay in order to analyze the baseline, the induced DNA-damage and the repair capacity in the lymphocytes of 10 healthy donors before and after the intake of the mentioned product. Our data suggest that the regular consumption of lutein-enriched fermented milk results in a significant increase in serum lutein levels and this change is associated with an improvement in the resistance of DNA to damage and the capacity of DNA repair in lymphocytes. Our results also support the lack of a genotoxic effect at the doses supplied as well as the absence of interactions and side effects on other nutritional and biochemicals markers. PMID:24040187

  12. Modulation of DNA-induced damage and repair capacity in humans after dietary intervention with lutein-enriched fermented milk.

    PubMed

    Herrero-Barbudo, Carmen; Soldevilla, Beatriz; Pérez-Sacristán, Belén; Blanco-Navarro, Inmaculada; Herrera, Mercedes; Granado-Lorencio, Fernando; Domínguez, Gemma

    2013-01-01

    Dietary factors provide protection against several forms of DNA damage. Additionally, consumer demand for natural products favours the development of bioactive food ingredients with health benefits. Lutein is a promising biologically active component in the food industry. The EFSA Panel on Dietetic Products, Nutrition and Allergies considers that protection from oxidative damage may be a beneficial physiological effect but that a cause and effect relationship has not been established. Thus, our aim was to evaluate the safety and potential functional effect of a lutein-enriched milk product using the Comet Assay in order to analyze the baseline, the induced DNA-damage and the repair capacity in the lymphocytes of 10 healthy donors before and after the intake of the mentioned product. Our data suggest that the regular consumption of lutein-enriched fermented milk results in a significant increase in serum lutein levels and this change is associated with an improvement in the resistance of DNA to damage and the capacity of DNA repair in lymphocytes. Our results also support the lack of a genotoxic effect at the doses supplied as well as the absence of interactions and side effects on other nutritional and biochemicals markers.

  13. Cerium Oxide Nanoparticles Induced Toxicity in Human Lung Cells: Role of ROS Mediated DNA Damage and Apoptosis

    PubMed Central

    Pandey, Alok K.

    2014-01-01

    Cerium oxide nanoparticles (CeO2 NPs) have promising industrial and biomedical applications. In spite of their applications, the toxicity of these NPs in biological/physiological environment is a major concern. Present study aimed to understand the molecular mechanism underlying the toxicity of CeO2 NPs on lung adenocarcinoma (A549) cells. After internalization, CeO2 NPs caused significant cytotoxicity and morphological changes in A549 cells. Further, the cell death was found to be apoptotic as shown by loss in mitochondrial membrane potential and increase in annexin-V positive cells and confirmed by immunoblot analysis of BAX, BCl-2, Cyt C, AIF, caspase-3, and caspase-9. A significant increase in oxidative DNA damage was found which was confirmed by phosphorylation of p53 gene and presence of cleaved poly ADP ribose polymerase (PARP). This damage could be attributed to increased production of reactive oxygen species (ROS) with concomitant decrease in antioxidant “glutathione (GSH)” level. DNA damage and cell death were attenuated by the application of ROS and apoptosis inhibitors N-acetyl-L- cysteine (NAC) and Z-DEVD-fmk, respectively. Our study concludes that ROS mediated DNA damage and cell cycle arrest play a major role in CeO2 NPs induced apoptotic cell death in A549 cells. Apart from beneficial applications, these NPs also impart potential harmful effects which should be properly evaluated prior to their use. PMID:24987704

  14. Geranylgeranylacetone protects against morphine-induced hepatic and renal damage in mice.

    PubMed

    Luo, Fu-Cheng; Zhao, Lu; Deng, Juan; Liang, Min; Zeng, Xian-Si; Liu, Hua; Bai, Jie

    2013-02-01

    The acute or chronic administration of opioid drugs may induce oxidative damage and cellular apoptosis in the liver and kidney, and hence result in hepatic and renal damage. Thioredoxin-1 (Trx-1) and heat shock protein 70 (Hsp70) are emerging as important modulators of cellular functions. They have been shown to be involved in cellular protective mechanisms against a variety of toxic stressors. The present study was designed to investigate the effects of geranylgeranylacetone (GGA), a pharmacological inducer of Trx-1 and Hsp70, on morphine-induced hepatic and renal damage. Morphine induced apoptosis in the liver and kidney through the mitochondria-mediated apoptosis pathway, but not the endoplasmic reticulum-mediated pathway. The activation of caspases-9 and -3 was attenuated by pre‑treatment with GGA. In addition, the morphine-induced increase of malondialdehyde (MDA) levels was suppressed by GGA. Furthermore, GGA enhanced morphine-induced expression of Trx-1 and Hsp70 in the liver and kidney. The findings of this study suggest that GGA may be a safe and novel therapeutic agent for morphine‑induced hepatic and renal damage.

  15. A FLUORESCENCE BASED ASSAY FOR DNA DAMAGE INDUCED BY TOXIC INDUSTRIAL CHEMICALS

    EPA Science Inventory

    Numerous natural and man-made agents are continuously released into the environment due to human activity. Many of these agents cause irreversible damage to the normal biological functions leading to morbidity and mortality in the exposed organisms. The possibility of deliberat...

  16. (WASHINGTON, DC) A FLUORESCENCE BASED ASSAY FOR DNA DAMAGE INDUCED BY TOXIC INDUSTRIAL CHEMICALS

    EPA Science Inventory

    Numerous natural and man-made agents are continuously released into the environment due to human activity. Many of these agents cause irreversible damage to the normal biological functions leading to morbidity and mortality in the exposed organisms. The possibility of deliberat...

  17. A FLUORESCENCE BASED ASSAY FOR DNA DAMAGE INDUCED BY TOXIC INDUSTRIAL CHEMICALS

    EPA Science Inventory

    Numerous natural and man-made agents are continuously released into the environment due to human activity. Many of these agents cause irreversible damage to the normal biological functions leading to morbidity and mortality in the exposed organisms. The possibility of deliberat...

  18. (WASHINGTON, DC) A FLUORESCENCE BASED ASSAY FOR DNA DAMAGE INDUCED BY TOXIC INDUSTRIAL CHEMICALS

    EPA Science Inventory

    Numerous natural and man-made agents are continuously released into the environment due to human activity. Many of these agents cause irreversible damage to the normal biological functions leading to morbidity and mortality in the exposed organisms. The possibility of deliberat...

  19. [Gastrointestinal damage induced by celecoxib and rofecoxib in rats].

    PubMed

    Laudanno, O M; Cesolari, J A; Esnarriaga, J; Rista, L; Piombo, G; Maglione, C; Aramberry, L J; Sambrano, J S; Godoy, A; Rocaspana, A

    2000-01-01

    Five experimental models were carried out in different groups of Wistar rats (n = 15) in order to study selective (cyclo-oxygenase) COX-2 non-steroid antiinflammatory inhibitors, such as celecoxib and rofecoxib, as follows: 1) Dose-dependent oral celecoxib and rofecoxib for 5 days, and 24 hours after oral indomethacin. 2) Same as 1, but subcutaneously. 3) Gastric ulcer induced by means of glacial acetic acid. 4) Duodenal ulcer induced by means of cysteamine. 5) Stress due to being kept under restraint and immersion in water at 15 degrees C for 6 hours. Celecoxib and rofecoxib, either orally or subcutaneously, did not produce necrotic injuries in healthy gastrointestinal mucosa (0%), showing normal histology. On the other hand, the injuries previously induced by indomethacin worsened (90%, p < 0.001). Total necrosis of small intestine as well as increased ulcer and perforation of gastric and duodenal ulcers induced by acetic acid and cysteamine were observed. There was also worsening of gastric necrotic area with stress (60-90%, p < 0.05). Celecoxib and rofecoxib showed neutrophilia (5,000/mm3) similar to that presented by indomethacin, but there was no leukocyte infiltration in the gastric mucosa; thus we can consider it a COX-2 selective NSAID (non-steroidal anti-inflammatory drug). Dose-dependent administration of celecoxib and rofecoxib as COX-2 inhibitors and non-COX-1 inhibitors, respectively, did not produce toxic injuries on healthy gastrointestinal mucosa, thus providing a broad therapeutic spectre. On the other hand, when administered in presence of altered gastrointestinal mucosa, they worsened and complicated gastric ulcers, and also induced necrosis in the small intestine, thereby restricting their clinical use.

  20. Organic honey supplementation reverses pesticide-induced genotoxicity by modulating DNA damage response.

    PubMed

    Alleva, Renata; Manzella, Nicola; Gaetani, Simona; Ciarapica, Veronica; Bracci, Massimo; Caboni, Maria Fiorenza; Pasini, Federica; Monaco, Federica; Amati, Monica; Borghi, Battista; Tomasetti, Marco

    2016-10-01

    Glyphosate (GLY) and organophosphorus insecticides such as chlorpyrifos (CPF) may cause DNA damage and cancer in exposed individuals through mitochondrial dysfunction. Polyphenols ubiquitously present in fruits and vegetables, have been viewed as antioxidant molecules, but also influence mitochondrial homeostasis. Here, honey containing polyphenol compounds was evaluated for its potential protective effect on pesticide-induced genotoxicity. Honey extracts from four floral organic sources were evaluated for their polyphenol content, antioxidant activity, and potential protective effects on pesticide-related mitochondrial destabilization, reactive oxygen and nitrogen species formation, and DNA damage response in human bronchial epithelial and neuronal cells. The protective effect of honey was, then evaluated in a residential population chronically exposed to pesticides. The four honey types showed a different polyphenol profile associated with a different antioxidant power. The pesticide-induced mitochondrial dysfunction parallels ROS formation from mitochondria (mtROS) and consequent DNA damage. Honey extracts efficiently inhibited pesticide-induced mtROS formation, and reduced DNA damage by upregulation of DNA repair through NFR2. Honey supplementation enhanced DNA repair activity in a residential population chronically exposed to pesticides, which resulted in a marked reduction of pesticide-induced DNA lesions. These results provide new insight regarding the effect of honey containing polyphenols on pesticide-induced DNA damage response. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Caryocar brasiliense camb protects against genomic and oxidative damage in urethane-induced lung carcinogenesis

    PubMed Central

    Colombo, N.B.R.; Rangel, M.P.; Martins, V.; Hage, M.; Gelain, D.P.; Barbeiro, D.F.; Grisolia, C.K.; Parra, E.R.; Capelozzi, V.L.

    2015-01-01

    The antioxidant effects of Caryocar brasiliense Camb, commonly known as the pequi fruit, have not been evaluated to determine their protective effects against oxidative damage in lung carcinogenesis. In the present study, we evaluated the role of pequi fruit against urethane-induced DNA damage and oxidative stress in forty 8-12 week old male BALB/C mice. An in vivo comet assay was performed to assess DNA damage in lung tissues and changes in lipid peroxidation and redox cycle antioxidants were monitored for oxidative stress. Prior supplementation with pequi oil or its extract (15 µL, 60 days) significantly reduced urethane-induced oxidative stress. A protective effect against DNA damage was associated with the modulation of lipid peroxidation and low protein and gene expression of nitric oxide synthase. These findings suggest that the intake of pequi fruit might protect against in vivo genotoxicity and oxidative stress. PMID:26200231

  2. Photoprotection beyond ultraviolet radiation--effective sun protection has to include protection against infrared A radiation-induced skin damage.

    PubMed

    Schroeder, P; Calles, C; Benesova, T; Macaluso, F; Krutmann, J

    2010-01-01

    Solar radiation is well known to damage human skin, for example by causing premature skin ageing (i.e. photoageing). We have recently learned that this damage does not result from ultraviolet (UV) radiation alone, but also from longer wavelengths, in particular near-infrared radiation (IRA radiation, 760-1,440 nm). IRA radiation accounts for more than one third of the solar energy that reaches human skin. While infrared radiation of longer wavelengths (IRB and IRC) does not penetrate deeply into the skin, more than 65% of the shorter wavelength (IRA) reaches the dermis. IRA radiation has been demonstrated to alter the collagen equilibrium of the dermal extracellular matrix in at least two ways: (a) by leading to an increased expression