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Sample records for direct genotoxic mode

  1. Further evidence against a direct genotoxic mode of action for arsenic-induced cancer

    PubMed Central

    Klein, Catherine B.; Leszczynska, Joanna; Hickey, Christina; Rossman, Toby G.

    2007-01-01

    Arsenic in drinking water, a mixture of arsenite and arsenate, is associated with increased skin and other cancers in Asia and Latin America, but not the United States. Arsenite alone in drinking water does not cause skin cancers in experimental animals, therefore it is not a complete carcinogen in skin. We recently showed that low concentrations of arsenite enhanced the tumorigenicity of solar UV irradiation in hairless mice, suggesting arsenic co-carcinogenesis with sunlight in skin cancer and perhaps with different carcinogenic partners for lung and bladder tumors. Cocarcinogenic mechanisms could include: blocking DNA repair, stimulating angiogenesis, altering DNA methylation patterns, dysregulating cell cycle control, induction of aneuploidy, and blocking apoptosis. Arsenicals are documented clastogens but not strong mutagens, with weak mutagenic activity reported at highly toxic concentrations of inorganic arsenic. Previously, we showed that arsenite, but not monomethylarsonous acid (MMA[III]), induced delayed mutagenesis in HOS cells. Here, we report new data on the mutagenicity of the trivalent methylated arsenic metabolites MMA(III) and dimethylarsinous acid [DMA(III)] at the gpt locus in Chinese hamster G12 cells. Both methylated arsenicals seemed mutagenic with apparent sublinear dose responses. However, significant mutagenesis occurred only at highly toxic concentrations of MMA(III). Most mutants induced by MMA(III) and DMA(III) mutants exhibited transgene deletions. Some non-deletion mutants exhibited altered DNA methylation. A critical discussion of cell survival leads us to conclude that clastogenesis occurs primarily at highly cytotoxic arsenic concentrations, casting further doubt as to whether a genotoxic mode of action (MOA) for arsenicals is supportable. PMID:17316729

  2. Further evidence against a direct genotoxic mode of action for arsenic-induced cancer

    SciTech Connect

    Klein, Catherine B.; Leszczynska, Joanna; Hickey, Christina; Rossman, Toby G.

    2007-08-01

    Arsenic in drinking water, a mixture of arsenite and arsenate, is associated with increased skin and other cancers in Asia and Latin America, but not the United States. Arsenite alone in drinking water does not cause skin cancers in experimental animals; therefore, it is not a complete carcinogen in skin. We recently showed that low concentrations of arsenite enhanced the tumorigenicity of solar UV irradiation in hairless mice, suggesting arsenic cocarcinogenesis with sunlight in skin cancer and perhaps with different carcinogenic partners for lung and bladder tumors. Cocarcinogenic mechanisms could include blocking DNA repair, stimulating angiogenesis, altering DNA methylation patterns, dysregulating cell cycle control, induction of aneuploidy and blocking apoptosis. Arsenicals are documented clastogens but not strong mutagens, with weak mutagenic activity reported at highly toxic concentrations of inorganic arsenic. Previously, we showed that arsenite, but not monomethylarsonous acid (MMA[III]), induced delayed mutagenesis in HOS cells. Here, we report new data on the mutagenicity of the trivalent methylated arsenic metabolites MMA(III) and dimethylarsinous acid [DMA(III)] at the gpt locus in Chinese hamster G12 cells. Both methylated arsenicals seemed mutagenic with apparent sublinear dose responses. However, significant mutagenesis occurred only at highly toxic concentrations of MMA(III). Most mutants induced by MMA(III) and DMA(III) exhibited transgene deletions. Some non-deletion mutants exhibited altered DNA methylation. A critical discussion of cell survival leads us to conclude that clastogenesis occurs primarily at highly cytotoxic arsenic concentrations, casting further doubt as to whether a genotoxic mode of action (MOA) for arsenicals is supportable.

  3. Considering mutagenicity and genotoxicity in the cancer mode ...

    EPA Pesticide Factsheets

    It is well known that genotoxicity plays a significant role in the development of tumor formation. Mutations in somatic cells can play a key role early in cancer initiation and might affect other stages of the carcinogenic process. Determination of carcinogens that operate through a genotoxic mode of action entails evaluation of the available data. One way of determining if a chemical is acting through a genotoxic mechanism is to assemble the relevant data (human, animal, in vivo, in vitro) of individual genetic end points, evaluating the data against a current acceptance criteria (study quality, methodology used etc.), and determining the weight of evidence based on both the available data as well as evaluating against other existing information such as epidemiological data, ADME information etc. This presentation will lay-out key, currently available genotoxicity information on naphthalene, styrene and ethylbenzene. These three chemicals were chosen because all three chemicals cause mouse lung tumors, in particular bronchiolar-alveolar adenomas and carcinomas. This analysis of the data will enable further understanding of the mode of action of mouse lung tumor formation and species differences, which will impact the hazard identification and use of mode of action in the risk assessment of naphthalene, styrene, and ethylbenzene.

  4. Genotoxic potential of glyphosate formulations: mode-of-action investigations.

    PubMed

    Heydens, William F; Healy, Charles E; Hotz, Kathy J; Kier, Larry D; Martens, Mark A; Wilson, Alan G E; Farmer, Donna R

    2008-02-27

    A broad array of in vitro and in vivo assays has consistently demonstrated that glyphosate and glyphosate-containing herbicide formulations (GCHF) are not genotoxic. Occasionally, however, related and contradictory data are reported, including findings of mouse liver and kidney DNA adducts and damage following intraperitoneal (ip) injection. Mode-of-action investigations were therefore undertaken to determine the significance of these contradictory data while concurrently comparing results from ip and oral exposures. Exposure by ip injection indeed produced marked hepatic and renal toxicity, but oral administration did not. The results suggest that ip injection of GCHF may induce secondary effects mediated by local toxicity rather than genotoxicity. Furthermore, these results continue to support the conclusion that glyphosate and GCHF are not genotoxic under exposure conditions that are relevant to animals and humans.

  5. Analysis of genotoxicity and the carcinogenic mode of action for ortho-phenylphenol.

    PubMed

    Brusick, David

    2005-06-01

    Ortho-phenylphenol (OPP) and its sodium salt (SOPP) are commercial products that have wide human exposure and have been shown in several studies to be rodent carcinogens. Genetic toxicology data were assessed in an attempt to understand the carcinogenic mode of action of OPP and SOPP. More than 130 studies were evaluated to determine if OPP, SOPP, or any of their enzymatic or nonenzymatic breakdown products react directly with DNA to induce mutation, changes in chromosome structure or number, DNA repair, or nonspecific DNA damage including strand breakage or covalent binding. The genotoxicity databases for OPP and SOPP are not only large but heterogeneous, requiring weight-of-evidence methods to arrive at a conclusion regarding their genotoxic properties and potential. Evidence derived from the available studies leads to the conclusion that study results showing OPP/SOPP directly interacting with DNA are equivocal. Clastogenicity was the most consistent type of genetic toxicity produced by OPP/SOPP (and their break-down products) and was consistently associated with other intracellular preneoplastic toxicity produced at super-threshold concentrations. The weight of evidence from the combined database supports the hypothesis that OPP/SOPP-induced DNA damage is a threshold-dependent response associated with target tissue toxicity, most likely induced by their breakdown products phenylhydroquinone and phenylbenzoquinone. It is possible that this threshold-dependent clastogenicity could contribute to the carcinogenic mode of action for OPP or SOPP.

  6. Prediction and classification of the modes of genotoxic actions using bacterial biosensors specific for DNA damages.

    PubMed

    Ahn, Joo-Myung; Hwang, Ee Taek; Youn, Chul-Hee; Banu, Danusia L; Kim, Byoung Chan; Niazi, Javed H; Gu, Man Bock

    2009-12-15

    We report on a novel approach to predict the mode of genotoxic action of chemicals using a series of DNA damage specific bioluminescent bacteria. For this, a group of seven different DNA damage sensing recombinant bioluminescent strains were employed. Each of these strains was tested against model DNA damaging agents, such as mitomycin C (MMC), 1-methyl-1-nitroso-N-methylguanidine (MNNG), nalidixic acid (Nal) and 4-nitroquinoline N-oxide (4-NQO). These biosensors were grouped based on their responses to a specific mode of genotoxic action, such as (a) DNA damage cascade response (biosensor with nrdA-, dinI- and sbmC-lux), (b) SOS response or DNA repair (strains carrying recA-, recN- and sulA-lux), and (c) DNA damage potentially by alkylation (biosensor with alkA-lux). The differential response patterns and its strength of these strains to various model genotoxicants allowed classifying the chemical's potential genotoxic mode. Therefore, it is possible to elucidate and classify the mode of genotoxic impacts of an unknown sample and that together they may be utilized in the pre-screening steps of new drugs, newly synthesized chemicals, food and environmental contaminants.

  7. Estimating potential genotoxicity for direct coal-liquefaction materials

    SciTech Connect

    Wilson, B.W.; Pelroy, R.A.; Renne, R.A.

    1981-05-01

    Fuels derived from coal liquefaction processes are chemically complex, highly aromatic mixtures, the specific constituency of which is fairly process-dependent. Genotoxicity, when found in these materials, is generally confined to the heavy-end fractions or full boiling range materials which contain heavy ends. The moderately polar or nitrogen base fractions of these heavy-end materials are generally the most mutagenically active. In some SRC-II heavy-end bottoms and the SRC-I solid product, however, the highly polar fractions contribute substantially to the mutagenicity. Specific compounds presently recognized as contributors or potential contributors to genotoxicity of the coal liquids studied include polycyclic primary aromatic amines, and to a much lesser extent, polycyclic aromatic hydrocarbons having four or more rings, certain polycyclic nitrogen heterocycles as well as certain polycyclic sulfur heterocyclics. The degree to which a given material has been subjected to reducing conditions during production appears to be an important parameter in determining its potential genotoxicity, the more severely reduced materials tending to be less genotoxic.

  8. Comparison of in vivo genotoxic and carcinogenic potency to augment mode of action analysis: Case study with hexavalent chromium.

    PubMed

    Thompson, Chad M; Bichteler, Anne; Rager, Julia E; Suh, Mina; Proctor, Deborah M; Haws, Laurie C; Harris, Mark A

    2016-04-01

    Recent analyses-highlighted by the International Workshops on Genotoxicity Testing Working Group on Quantitative Approaches to Genetic Toxicology Risk Assessment-have identified a correlation between (log) estimates of a carcinogen's in vivo genotoxic potency and in vivo carcinogenic potency in typical laboratory animal models, even when the underlying data have not been matched for tissue, species, or strain. Such a correlation could have important implications for risk assessment, including informing the mode of action (MOA) of specific carcinogens. When in vivo genotoxic potency is weak relative to carcinogenic potency, MOAs other than genotoxicity (e.g., endocrine disruption or regenerative hyperplasia) may be operational. Herein, we review recent in vivo genotoxicity and carcinogenicity data for hexavalent chromium (Cr(VI)), following oral ingestion, in relevant tissues and species in the context of the aforementioned correlation. Potency estimates were generated using benchmark doses, or no-observable-adverse-effect-levels when data were not amenable to dose-response modeling. While the ratio between log values for carcinogenic and genotoxic potency was ≥1 for many compounds, the ratios for several Cr(VI) datasets (including in target tissue) were less than unity. In fact, the ratios for Cr(VI) clustered closely with ratios for chloroform and diethanolamine, two chemicals posited to have non-genotoxic MOAs. These findings suggest that genotoxicity may not play a major role in the cancers observed in rodents following exposure to high concentrations of Cr(VI) in drinking water-a finding consistent with recent MOA and adverse outcome pathway (AOP) analyses concerning Cr(VI). This semi-quantitative analysis, therefore, may be useful to augment traditional MOA and AOP analyses. More case examples will be needed to further explore the general applicability and validity of this approach for human health risk assessment.

  9. Mutagenic and genotoxic potential of direct electric current in Escherichia coli and Salmonella thyphimurium strains.

    PubMed

    Gomes, Marina das Neves; Cardoso, Janine Simas; Leitão, Alvaro Costa; Quaresma, Carla Holandino

    2016-05-01

    Direct electric current has several therapeutic uses such as antibacterial and antiprotozoal action, tissues scarring and regeneration, as well as tumor treatment. This method has shown promising results in vivo and in vitro, with significant efficacy and almost no side effects. Considering lack of studies regarding direct electric current mutagenic and/or genotoxic effects, the present work evaluated both aspects by using five different bacterial experimental assays: survival of repair-deficient mutants, Salmonella-histidine reversion mutagenesis (Ames test), forward mutations to rifampicin resistance, phage reactivation, and lysogenic induction. In these experimental conditions, cells were submitted to an approach that allows evaluation of anodic, cathodic, and electro-ionic effects generated by 2 mA of direct electric current, with doses ranging from 0.36 to 3.60 Coulombs. Our results showed these doses did not induce mutagenic or genotoxic effects.

  10. Mode selective directional coupler for NLC

    SciTech Connect

    Tantawi, S.G.

    1994-10-01

    The design method for a high power, X-band, 50 dB, circular to rectangular directional coupler is presented. The circular guide is over moded and is intended to operate in TE{sub 01} mode. The rectangular guide operates at the fundamental TE{sub 10} mode. A small percentage of higher order modes in the circular guide can cause considerable errors in the measurements because the magnitude of the axial magnetic field of these modes is higher than that of the operating mode, especially near their cutoff. We used a Hamming window patten for the coupling slots to achieve mode selectivity. Comparison of theory and experiment will be presented.

  11. Evaluation of genotoxic effects of surface waters using a battery of bioassays indicating different mode of action.

    PubMed

    Han, Yingnan; Li, Na; Oda, Yoshimitsu; Ma, Mei; Rao, Kaifeng; Wang, Zijian; Jin, Wei; Hong, Gang; Li, Zhiguo; Luo, Yi

    2016-11-01

    With the burgeoning contamination of surface waters threatening human health, the genotoxic effects of surface waters have received much attention. Because mutagenic and carcinogenic compounds in water cause tumors by different mechanisms, a battery of bioassays that each indicate a different mode of action (MOA) is required to evaluate the genotoxic effects of contaminants in water samples. In this study, 15 water samples from two source water reservoirs and surrounding rivers in Shijiazhuang city of China were evaluated for genotoxic effects. Target chemical analyses of 14 genotoxic pollutants were performed according to the Environmental quality standards for surface water of China. Then, the in vitro cytokinesis-block micronucleus (CBMN) assay, based on a high-content screening technique, was used to detect the effect of chromosome damage. The SOS/umu test using strain TA1535/pSK1002 was used to detect effects on SOS repair of gene expression. Additionally, two other strains, NM2009 and NM3009, which are highly sensitive to aromatic amines and nitroarenes, respectively, were used in the SOS/umu test to avoid false negative results. In the water samples, only two of the genotoxic chemicals listed in the water standards were detected in a few samples, with concentrations that were below water quality standards. However, positive results for the CBMN assay were observed in two river samples, and positive results for the induction of umuC gene expression in TA1535/pSK1002 were observed in seven river samples. Moreover, positive results were observed for NM2009 with S9 and NM3009 without S9 in some samples that had negative results using the strain TA1535/pSK1002. Based on the results with NM2009 and NM3009, some unknown or undetected aromatic amines and nitroarenes were likely in the source water reservoirs and the surrounding rivers. Furthermore, these compounds were most likely the causative pollutants for the genotoxic effect of these water samples. Therefore

  12. A Mode-of-Action Approach for the Identification of Genotoxic Carcinogens

    PubMed Central

    Hernández, Lya G.; van Benthem, Jan; Johnson, George E.

    2013-01-01

    Distinguishing between clastogens and aneugens is vital in cancer risk assessment because the default assumption is that clastogens and aneugens have linear and non-linear dose-response curves, respectively. Any observed non-linearity must be supported by mode of action (MOA) analyses where biological mechanisms are linked with dose-response evaluations. For aneugens, the MOA has been well characterised as disruptors of mitotic machinery where chromosome loss via micronuclei (MN) formation is an accepted endpoint used in risk assessment. In this study we performed the cytokinesis-block micronucleus assay and immunofluorescence mitotic machinery visualisation in human lymphoblastoid (AHH-1) and Chinese Hamster fibroblast (V79) cell lines after treatment with the aneugen 17-β-oestradiol (E2). Results were compared to previously published data on bisphenol-A (BPA) and Rotenone data. Two concentration-response approaches (the threshold-[Td] and benchmark-dose [BMD] approaches) were applied to derive a point of departure (POD) for in vitro MN induction. BMDs were also derived from the most sensitive carcinogenic endpoint. Ranking comparisons of the PODs from the in vitro MN and the carcinogenicity studies demonstrated a link between these two endpoints for BPA, E2 and Rotenone. This analysis was extended to include 5 additional aneugens, 5 clastogens and 3 mutagens and further concentration and dose-response correlations were observed between PODs from the in vitro MN and carcinogenicity. This approach is promising and may be further extended to other genotoxic carcinogens, where MOA and quantitative information from the in vitro MN studies could be used in a quantitative manner to further inform cancer risk assessment. PMID:23675539

  13. Femtosecond direct-written integrated mode couplers.

    PubMed

    Riesen, Nicolas; Gross, Simon; Love, John D; Withford, Michael J

    2014-12-01

    We report the design and fabrication of three-dimensional integrated mode couplers operating in the C-band. These mode-selective couplers were inscribed into a boro-aluminosilicate photonic chip using the femtosecond laser direct-write technique. Horizontally and vertically written two-core couplers are shown to allow for the multiplexing of the LP11a and LP11b spatial modes of an optical fiber, respectively, with excellent mode extinction ratios (25-37 + dB) and low loss (~1 dB) between 1500 and 1580 nm. Furthermore, optimized fabrication parameters enable coupling ratios close to 100%. When written in sequence, the couplers allow for the multiplexing of all LP01, LP11a and LP11b modes. This is also shown to be possible using a single 3-dimensional three-core coupler. These integrated mode couplers have considerable potential to be used in mode-division multiplexing for increasing optical fiber capacity. The three-dimensional capability of the femtosecond direct-write technique provides the versatility to write linear cascades of such two- and three-core couplers into a single compact glass chip, with arbitrary routing of waveguides to ensure a small footprint. This technology could be used for high-performance, compact and cost-effective multiplexing of large numbers of modes of an optical fiber.

  14. ARSENIC (III) METHYLATED SPECIES REACT WITH DNA DIRECTLY AND COULD BE PROXIMATED/ULTIMATE GENOTOXIC FORMS OF ARSENIC

    EPA Science Inventory


    ARSENIC(III) METHYLATED SPECIES REACT WITH DNA DIRECTL Y AND COULD BE PROXIMATE/ULTIMATE GENOTOXIC FORMS OF ARSENIC


    Arsenite and arsenate (iAs, inorganic arsenic) have been thought to act as genotoxicants without reacting directly with DNA; neither iAs nor As(V) m...

  15. ARSENIC (III) METHYLATED SPECIES REACT WITH DNA DIRECTLY AND COULD BE PROXIMATED/ULTIMATE GENOTOXIC FORMS OF ARSENIC

    EPA Science Inventory


    ARSENIC(III) METHYLATED SPECIES REACT WITH DNA DIRECTL Y AND COULD BE PROXIMATE/ULTIMATE GENOTOXIC FORMS OF ARSENIC


    Arsenite and arsenate (iAs, inorganic arsenic) have been thought to act as genotoxicants without reacting directly with DNA; neither iAs nor As(V) m...

  16. Determination of genotoxic epoxide at trace level in drug substance by direct injection GC/MS.

    PubMed

    Chen, Liqin; Zhang, Wei; Hu, Steven

    2017-08-24

    A novel direct injection gas chromatography method coupled with selective ion monitoring mass spectrometry (GC/SIM-MS) was developed for quantitation of trace levels of high boiling point (HBP) epoxide genotoxic impurity (GTI) in drug substance. The injector temperature was optimized with the aims to minimize matrix effects and enhance SIM signal response. The final injector temperature 160°C was selected after balancing between these two factors. The column screening was conducted as well and MN OPTIMA delta-3 silica capillary column was selected since it showed good peak symmetry without column bleeding. The good linearity was established for the concentration in the range from 0.0045μg/mL to 0.5μg/mL with a R(2)=0.9999. The limit of detection (LOD) and the limit of quantitation (LOQ) were 0.0014μg/mL and 0.0045μg/mL, respectively. The recovery which ranged from 95.0% to 112.5% could meet the ICH acceptance criteria. The validation results demonstrated the good linearity, precision and accuracy of the method which can be further adopted as an adequate quality control tool for quantitation of epoxide impurity at trace levels in drug substance and drug product. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Genotoxicity of Tri- and Hexavalent Chromium Compounds In Vivo and Their Modes of Action on DNA Damage In Vitro

    PubMed Central

    Fang, Zhijia; Zhao, Min; Zhen, Hong; Chen, Lifeng; Shi, Ping; Huang, Zhiwei

    2014-01-01

    Chromium occurs mostly in tri- and hexavalent states in the environment. Hexavalent chromium [Cr(VI)] compounds are extensively used in diverse industries, and trivalent chromium [Cr(III)] salts are used as micronutrients and dietary supplements. In the present work, we report that they both induce genetic mutations in yeast cells. They both also cause DNA damage in both yeast and Jurkat cells and the effect of Cr(III) is greater than that of Cr(VI). We further show that Cr(III) and Cr(VI) cause DNA damage through different mechanisms. Cr(VI) intercalates DNA and Cr(III) interferes base pair stacking. Based on our results, we conclude that Cr(III) can directly cause genotoxicity in vivo. PMID:25111056

  18. In vitro approaches to develop weight of evidence (WoE) and mode of action (MoA) discussions with positive in vitro genotoxicity results.

    PubMed

    Kirkland, D J; Aardema, M; Banduhn, N; Carmichael, P; Fautz, R; Meunier, J-R; Pfuhler, S

    2007-05-01

    A recent analysis by Kirkland et al. [Kirkland, D., Aardema, M., Henderson, L. and Müller, L. (2005) Evaluation of the ability of a battery of 3 in vitro genotoxicity tests to discriminate rodent carcinogens and non-carcinogens. I. Sensitivity, specificity and relative predictivity. Mutat. Res. 584, 1-256] demonstrated an extremely high false positive rate for in vitro genotoxicity tests when compared with carcinogenicity in rodents. In many industries, decisions have to be made on the safety of new substances, and health risk to humans, without rodent carcinogenicity data being available. In such cases, the usual way to determine whether a positive in vitro genotoxicity result is relevant (i.e. indicates a hazard) for humans is to develop weight of evidence (WoE) or mode of action (MoA) arguments. These are based partly on further in vitro investigations, but usually rely heavily on tests for genotoxicity in one or more in vivo assays. However, for certain product types in the European Union, the use of animals for genotoxicity testing (as well as for other endpoints) will be prohibited within the next few years. Many different examples have been described that indicate DNA damage and genotoxic responses in vitro can arise through non-relevant in vitro events that are a result of the test systems and conditions used. The majority of these non-relevant in vitro events can be grouped under a category of 'overload of normal physiology' that would not be expected to occur in exposed humans. However, obtaining evidence in support of such MoAs is not easy, particularly for those industries prohibited from carrying out in vivo testing. It will become necessary to focus on in vitro studies to provide evidence of non-DNA, threshold or in vitro-specific processes and to discuss the potential for such genotoxic effects to occur in exposed humans. Toward this end, we surveyed the published literature for in vitro approaches that may be followed to determine whether a

  19. SOME INSIGHTS INTO THE MODE OF ACTION OF BUTADIENE BY EXAMINING THE GENOTOXICITY OF ITS METABOLITES

    EPA Science Inventory

    1,3-Butadiene (BTD) is an important commodity chemical and air pollutant that has been shown to be a potent carcinogen in mice, and to a lesser extent, a carcinogen in rats. To better assess butadiene's carcinogenic risk to humans, it is important to understand its mode of action...

  20. SOME INSIGHTS INTO THE MODE OF ACTION OF BUTADIENE BY EXAMINING THE GENOTOXICITY OF ITS METABOLITES

    EPA Science Inventory

    1,3-Butadiene (BTD) is an important commodity chemical and air pollutant that has been shown to be a potent carcinogen in mice, and to a lesser extent, a carcinogen in rats. To better assess butadiene's carcinogenic risk to humans, it is important to understand its mode of action...

  1. Normal mode sound field of a directional radiator

    NASA Astrophysics Data System (ADS)

    Zhang, R.; Zhu, B.

    1987-12-01

    In this paper, the sound field of a general type of directional radiator in a stratified medium is treated, and the concept of directivity is applied to calculation of the normal modes. The result shows that the normal mode field of a directional radiator can be obtained by supplementing the normal mode expression of an omnidirectional point source with the directional excitation function, which is dependent on the position and directivity of the radiator. In addition, the normal mode fields of radiators with vertical-symmetrical, vertical-antisymmetrical, single-sided and sharp directivities are calculated, respectively. For a vertical line array in a homogeneous water layer, if the source distribution is proportional to the eigenfunction of some normal mode, the zeros of the directional excitation function correspond precisely to the directions of the eigenrays of other normal modes.

  2. Some insights into the mode of action of butadiene by examining the genotoxicity of its metabolites.

    PubMed

    Kligerman, A D; Hu, Y

    2007-03-20

    1,3-Butadiene (BTD) is an important commodity chemical and air pollutant that has been shown to be a potent carcinogen in mice, and to a lesser extent, a carcinogen in rats. To better assess butadiene's carcinogenic risk to humans, it is important to understand its mode of action and how this relates to differences in responses among species. In a series of in vitro experiments, lymphocytes from rats, mice, and humans were exposed to 3,4-epoxy-1-butene (EB) or 1,2:3,4-diepoxybutane (DEB) for 1h at the G(0) stage of the cell cycle, stimulated to divide, and cultured to assess the ability of these metabolites to induce sister chromatid exchange (SCE) and chromosome aberrations (CAs). EB induced no increases in SCEs or CAs in the cells from the three species. DEB was a potent SCE- and CA-inducer, with the results being similar in each rodent species. The response for SCEs seen in the human cells was more complex, with genetic polymorphism for glutathione-S-transferases (GST) possibly modulating the response. The single cell gel electrophoresis assay was used on genetically engineered V79 cell lines to investigate a possible influence of GST status. Experiments were also conducted to investigate the reason for EB's failure to induce SCEs or CAs in G(0) cells. The results indicate that EB-induced DNA damage was repaired before DNA synthesis in unstimulated lymphocytes, but EB caused a large increase in SCEs if actively cycling cells were treated. Thus, the results indicate that DEB damage is persistent in G(0) cells, and DEB is a much more potent genotoxicant than EB. The carcinogenic effect of butadiene will most likely depend on the degree to which DEB is produced and reaches target tissues, and to a lesser extent on the ability of EB to reach actively dividing or repair deficient cells.

  3. On-chip optical mode exchange using tapered directional coupler

    PubMed Central

    Zhang, Zhonglai; Hu, Xiao; Wang, Jian

    2015-01-01

    We present an on-chip optical mode exchange between two multiplexed modes by using tapered directional couplers on silicon-on-insulator platform. The device consisting of mode multiplexing and mode exchange is compact with relatively large fabrication error tolerance. The simulation results show efficient higher order mode excitation and mode exchange. A low excess loss less than 0.5 dB and high extinction ratio larger than 15 dB over 10 nm wavelength range from 1535 to 1545 nm are achieved. PMID:26530728

  4. Adaptive control of waveguide modes using a directional coupler.

    PubMed

    Lu, Peng; Shipton, Matthew; Wang, Anbo; Xu, Yong

    2014-08-25

    Using adaptive optics (AO) and a directional coupler, we demonstrate adaptive control of linearly polarized (LP) modes in a two mode fiber. The AO feedback is provided by the coupling ratio of the directional coupler, and does not depend on the spatial profiles of optical field distributions. As a proof of concept demonstration, this work confirms the feasibility of using AO and all fiber devices to control the waveguide modes in a multimode network in a quasi-distributed manner.

  5. Genotoxicity of ochratoxin A and structurally related compounds in Escherichia coli strains: studies on their mode of action.

    PubMed

    Malaveille, C; Brun, G; Bartsch, H

    1991-01-01

    Ochratoxin A, ochratoxin alpha (its major metabolite in rodents) and seven structurally related substances were assayed for SOS DNA repair inducing activity in Escherichia coli PQ37 strain. At a concentration range of 0.1-4 mM, ochratoxin A, chloroxine, 5-chloro-8-quinolinol, 4-chloro-meta-cresol and chloroxylenol were found to induce SOS-DNA repair in the absence of an exogenous metabolic activation system. Ochratoxin B, ochratoxin alpha, 5-chlorosalicylic acid and citrinin were inactive, but all except ochratoxin alpha were cytotoxic. Thus, the presence of a chlorine at C-5 in ochratoxin A and in other analogues appears to be one determinant of their genotoxicity. In order to ascertain whether this reactivity involves a bacterial glutathione conjugation reaction, we investigated the modifying effect on the genotoxicity of ochratoxin A of amino oxyacetic acid, an inhibitor of cysteine conjugate beta-lyase. Amino oxyacetic acid decreased the cytotoxicity of ochratoxin A but did not alter its genotoxic activity, suggesting the formation of a cytotoxic thiol-containing derivative. The way in which ochratoxin A and some of its active analogues induce SOS DNA repair activity was further investigated in E. coli PQ37 and in three derived strains (PQ300, OG100 and OG400, containing deletions within the oxy R regulon). The response in PQ37 strain was measured in the absence and presence of Trolox C, a hydrosoluble form of vitamin E. Trolox C completely quenched the genotoxicity of ochratoxin A, which was no greater in mutated than in wild type strains. These results implicate an ochratoxin A-derived free radical rather than reduced oxygen species as genotoxic intermediate(s) in bacteria.

  6. PROXIMATE OR ULTIMATE GENOTOXIC FORMS OF ARSENIC: METHYLATED ARSENIC(III) SPECIES THAT REACT DIRECTLY WITH DNA

    EPA Science Inventory


    PROXIMATE OR ULTIMATE GENOTOXIC FORMS OF ARSENIC: METHYLATED ARSENIC(III) SPECIES THAT REACT DIRECTL Y WITH DNA.

    Abstract:

    Although inorganic arsenic (iAs), arsenite or arsenate, is genotoxic, there has been no demonstration that iAs or a methylated metabolite...

  7. PROXIMATE OR ULTIMATE GENOTOXIC FORMS OF ARSENIC: METHYLATED ARSENIC(III) SPECIES THAT REACT DIRECTLY WITH DNA

    EPA Science Inventory


    PROXIMATE OR ULTIMATE GENOTOXIC FORMS OF ARSENIC: METHYLATED ARSENIC(III) SPECIES THAT REACT DIRECTL Y WITH DNA.

    Abstract:

    Although inorganic arsenic (iAs), arsenite or arsenate, is genotoxic, there has been no demonstration that iAs or a methylated metabolite...

  8. Protective effects of garlic sulfur compounds against DNA damage induced by direct- and indirect-acting genotoxic agents in HepG2 cells.

    PubMed

    Belloir, C; Singh, V; Daurat, C; Siess, M H; Le Bon, A M

    2006-06-01

    The aim of this study was to assess the antigenotoxic activity of several garlic organosulfur compounds (OSC) in the human hepatoma cell line HepG2, using comet assay. The OSC selected were allicin (DADSO), diallyl sulfide (DAS), diallyl disulfide (DADS), S-allyl cysteine (SAC) and allyl mercaptan (AM). To explore their potential mechanisms of action, two approaches were performed: (i) a pre-treatment protocol which allowed study of the possible modulation of drug metabolism enzymes by OSC before treatment of the cells with the genotoxic agent; (ii) a co-treatment protocol by which the ability of OSC to scavenge direct-acting compounds was assessed. Preliminary studies showed that, over the concentration range tested (5-100 microM), the studied OSC neither affected cell viability nor induced DNA damage by themselves. In the pre-treatment protocol, aflatoxin B1 genotoxicity was significantly reduced by all the OSC tested except AM. DADS was the most efficient OSC in reducing benzo(a)pyrene genotoxicity. SAC and AM significantly decreased DNA breaks in HepG2 cells treated with dimethylnitrosamine. Additionally, all the OSC studied were shown to decrease the genotoxicity of the direct-acting compounds, hydrogen peroxide and methyl methanesulfonate. This study demonstrated that garlic OSC displayed antigenotoxic activity in human metabolically competent cells.

  9. A Simple and Direct LC-MS Method for Determination of Genotoxic Impurity Hydroxylamine in Pharmaceutical compounds.

    PubMed

    Kumar, Thangarathinam; Ramya, Mohandass; Srinivasan, Viswanathan; Xavier, N

    2017-08-01

    Hydroxylamine is a known genotoxic impurity compound that needs to be controlled down to ppm level in pharmaceutical processes. It is difficult to detect using conventional analytical techniques due to its physio-chemical properties like lack of chromophore, low molecular weight, absence of carbon atom and high polarity. In addition to that, analysis of the pharmaceutical samples encounters considerable obstruction from matrix components that greatly overshadow the response of hydroxylamine. This study describes a simple, sensitive and direct Liquid Chromatographic-Mass Spectrometric method (LC-MS) for detection of hydroxylamine in pharmaceutical compounds. The LC-MS method was detected up to 0.008 ppm of hydroxylamine with S/N > 3.0 and quantified up to 0.025 ppm of hydroxylamine with S/N ratio >10.0. This validated method can be applied as a generic method to detect the hydroxylamine for pharmaceutical process control and drug substance release. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. Variable mode bi-directional and uni-directional computer communication system

    DOEpatents

    Cornett, Frank N.; Jenkins, Philip N.; Bowman, Terrance L.; Placek, Joseph M.; Thorson, Gregory M.

    2004-12-14

    A variable communication systems comprising a plurality of transceivers and a control circuit connected to the transceivers to configure the transceivers to operate in a bi-directional mode and a uni-directional mode at different times using different transfer methods to transfer data.

  11. Azimuthal Directivity of Fan Tones Containing Multiple Modes

    NASA Technical Reports Server (NTRS)

    Heidelberg, Laurence J.; Sutliff, Daniel L.; Nallasamy, M.

    1997-01-01

    The directivity of fan tone noise is generally measured and plotted in the sideline or flyover plane and it is assumed that this curve is the same for all azimuthal angles. When two or more circumferential (m-order) modes of the same tone are present in the fan duct, an interference pattern develops in the azimuthal direction both in the duct and in the farfield. In this investigation two m-order modes of similar power were generated in a large low speed fan. Farfield measurements and a finite element propagation code both show substantial variations in the azimuthal direction. Induct mode measurement were made and used as input to the code. Although these tests may represent a worst case scenario, the validity of the current practice of assuming axisymmetry should be questioned.

  12. Bioethanol Blending Reduces Nanoparticle, PAH, and Alkyl- and Nitro-PAH Emissions and the Genotoxic Potential of Exhaust from a Gasoline Direct Injection Flex-Fuel Vehicle.

    PubMed

    Muñoz, Maria; Heeb, Norbert V; Haag, Regula; Honegger, Peter; Zeyer, Kerstin; Mohn, Joachim; Comte, Pierre; Czerwinski, Jan

    2016-11-01

    Bioethanol as an alternative fuel is widely used as a substitute for gasoline and also in gasoline direct injection (GDI) vehicles, which are quickly replacing traditional port-fuel injection (PFI) vehicles. Better fuel efficiency and increased engine power are reported advantages of GDI vehicles. However, increased emissions of soot-like nanoparticles are also associated with GDI technology with yet unknown health impacts. In this study, we compare emissions of a flex-fuel Euro-5 GDI vehicle operated with gasoline (E0) and two ethanol/gasoline blends (E10 and E85) under transient and steady driving conditions and report effects on particle, polycyclic aromatic hydrocarbon (PAH), and alkyl- and nitro-PAH emissions and assess their genotoxic potential. Particle number emissions when operating the vehicle in the hWLTC (hot started worldwide harmonized light-duty vehicle test cycle) with E10 and E85 were lowered by 97 and 96% compared with that of E0. CO emissions dropped by 81 and 87%, while CO2 emissions were reduced by 13 and 17%. Emissions of selected PAHs were lowered by 67-96% with E10 and by 82-96% with E85, and the genotoxic potentials dropped by 72 and 83%, respectively. Ethanol blending appears to reduce genotoxic emissions on this specific flex-fuel GDI vehicle; however, other GDI vehicle types should be analyzed.

  13. Direct quantification of gamma H2AX by cell-based high throughput screening for evaluation of genotoxicity of pesticides in a human thyroid cell lines.

    PubMed

    Hershman, Jerome M; France, Bryan; Hon, Kevin; Damoiseaux, Robert

    2017-08-01

    Genotoxicity is thought to be the cause of many cancers. Genotoxicity due to environmental toxins may be partly responsible for the dramatic increase in the incidence of papillary thyroid cancer over the past two decades. Here, we present a fully automatable assay platform that directly quantifies the phosphorylation of nuclear histone gamma H2AX (γH2AX), a specific cellular marker for DNA double strand breaks (DSBs) via immunohistochemistry and laser scanning cytometry. It multiplexes γH2AX with total cell number measured as propidium iodide and calculates the percentage of cells with DSBs. Validation of this assay using NTHY-ori-3-1 human thyroid cells and etoposide showed that it was an excellent choice for high throughput applications. We used the assay to test the genotoxic effects of the EPA Toxcast Phase 1 pesticide library of 309 compounds. Compounds were evaluated in dose response and the DSB was quantified. We found that 19 pesticides induce DSB in vitro, highlighting a need to further assess these pesticides for their long-term oncogenic effects on the thyroid gland. Environ. Mol. Mutagen. 58:522-528, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  14. Rapid and simultaneous determination of sulfonate ester genotoxic impurities in drug substance by liquid chromatography coupled to tandem mass spectrometry: comparison of different ionization modes.

    PubMed

    Guo, Tian; Shi, Yuanyuan; Zheng, Li; Feng, Feng; Zheng, Feng; Liu, Wenyuan

    2014-08-15

    Two ionization techniques for liquid chromatography-mass spectrometry (LC-MS) determination of sulfonate ester potentially genotoxic impurities (PGIs) were evaluated. Twelve PGIs including methyl, ethyl, propyl and isopropyl esters of methanesulfonate, benzenesulfonate and p-toluenesulfonate were studied in this research. Electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) sources were compared in terms of performance and quality parameters for detection of the twelve PGIs. Their mass spectra obtained by APCI and ESI were very different in both fragment ions and relative abundances. In APCI negative ion mode the twelve sulfonate esters showed their stable precursor ions of [M-alkyl](-), which readily yielded product ions of [M-alkyl-CH3](-) (for aliphatic sulfonate esters) or [M-alkyl-SO2](-) (for aromatic sulfonate esters) with collision-induced dissociation (CID) applied; and working in selected reaction monitoring (SRM) mode has allowed limits of detection to be decreased. In the case of ESI ionization, these compounds showed their precursor ions [M+H](+), but their abundance was easily competed by formation of ions [M+NH4](+) and/or [M+Na](+), which led to poor analytical sensitivity and reproducibility. Although mobile phase additives could enhance the responses of adduct ions like [M+NH4](+) and [M+Na](+), no improvement was obtained when using SRM mode. Twelve sulfonate esters were systematically compared and APCI was shown to be a better ionization technique for rapid and sensitive determination of these PGIs. Performance of the developed approach for rapid determination of 12 PGIs was also evaluated. Quality parameters were established and good precision (relative standard deviations <8%) and very low limits (2-4ng/mL) of detection were obtained, mainly when using APCI in SRM mode.

  15. Chiral modes and directional lasing at exceptional points

    PubMed Central

    Peng, Bo; Özdemir, Şahin Kaya; Liertzer, Matthias; Chen, Weijian; Kramer, Johannes; Yılmaz, Huzeyfe; Wiersig, Jan; Yang, Lan

    2016-01-01

    Controlling the emission and the flow of light in micro- and nanostructures is crucial for on-chip information processing. Here we show how to impose a strong chirality and a switchable direction of light propagation in an optical system by steering it to an exceptional point (EP)—a degeneracy universally occurring in all open physical systems when two eigenvalues and the corresponding eigenstates coalesce. In our experiments with a fiber-coupled whispering-gallery-mode (WGM) resonator, we dynamically control the chirality of resonator modes and the emission direction of a WGM microlaser in the vicinity of an EP: Away from the EPs, the resonator modes are nonchiral and laser emission is bidirectional. As the system approaches an EP, the modes become chiral and allow unidirectional emission such that by transiting from one EP to another one the direction of emission can be completely reversed. Our results exemplify a very counterintuitive feature of non-Hermitian physics that paves the way to chiral photonics on a chip. PMID:27274059

  16. Direct Optical Probing of Transverse Electric Mode in Graphene

    PubMed Central

    Menabde, Sergey G.; Mason, Daniel R.; Kornev, Evgeny E.; Lee, Changhee; Park, Namkyoo

    2016-01-01

    Unique electrodynamic response of graphene implies a manifestation of an unusual propagating and localised transverse-electric (TE) mode near the spectral onset of interband transitions. However, excitation and further detection of the TE mode supported by graphene is considered to be a challenge for it is extremely sensitive to excitation environment and phase matching condition adherence. Here for the first time, we experimentally prove an existence of the TE mode by its direct optical probing, demonstrating significant coupling to an incident wave in electrically doped multilayer graphene sheet at room temperature. We believe that proposed technique of careful phase matching and obtained access to graphene’s TE excitation would stimulate further studies of this unique phenomenon, and enable its potential employing in various fields of photonics as well as for characterization of graphene. PMID:26898892

  17. Genotoxic effects of the carbamate insecticide Pirimor-50® in Vicia faba root tip meristems and human lymphocyte culture after direct application and treatment with its metabolic extracts.

    PubMed

    Valencia-Quintana, Rafael; Gómez-Arroyo, Sandra; Sánchez-Alarcón, Juana; Milić, Mirta; Olivares, José Luis Gómez; Waliszewski, Stefan M; Cortés-Eslava, Josefina; Villalobos-Pietrini, Rafael; Calderón-Segura, María Elena

    2016-12-01

    The aim of the study was to evaluate genotoxic effects of Pirimor-50®, a pirimicarb-based formulation (50 % active ingredient), in human lymphocyte cultures and Vicia faba root meristems. Furthermore, the objective was to examine a combined influence of insecticide treatment with mammalian microsomal S9 and vegetal S10 metabolic fractions or S10 mix metabolic transformation extracts (after Vicia faba primary roots treatment with Pirimor-50®). We used sister chromatid exchange assay-SCE and measured cell cycle progression and proliferation (proportion of M1-M3 metaphases and replication index ratio-RI). Two processes were used for plant promutagen activation: in vivo activation-Pirimor-50® was applied for 4 h to the plant and then S10 mix was added to lymphocytes; and, in vitro activation-lymphocytes were treated with Pirimor-50® and S10 or S9 for 2 h. Direct treatment induced significantly higher SCE frequencies in meristems at 0.01 mg mL-1. In lymphocytes, significantly higher SCE was at 1 mg mL-1 with decrease in RI and M1-M3 metaphase proportions at 0.5 mg mL-1 and cell division stop at 2.5 mg mL1. S10 mix lymphocyte treatment showed significantly elevated SCE values at 2-2.5 mg mL-1, with cell death at 3 mg mL-1. Lymphocyte treatment with Pirimor-50® together with S9 or S10 showed slightly elevated SCE frequency but had a significant influence on RI decrease, with lowest values in S9 treatment. Since no data are available on the genotoxicity of Pirimor-50®, this study is one of the first to evaluate and compare its direct effect in two bioassays, animal and vegetal, and also the effect of plant and animal metabolism on its genotoxic potential.

  18. Laser dissection sampling modes for direct mass spectral analysis.

    PubMed

    Cahill, John F; Kertesz, Vilmos; Van Berkel, Gary J

    2016-03-15

    Laser microdissection coupled directly with mass spectrometry provides the capability of on-line analysis of substrates with high spatial resolution, high collection efficiency, and freedom on shape and size of the sampling area. Establishing the merits and capabilities of the different sampling modes that the system provides is necessary in order to select the best sampling mode for characterizing analytically challenging samples. The capabilities of laser ablation spot sampling, laser ablation raster sampling, and laser 'cut and drop' sampling modes of a hybrid optical microscopy/laser ablation liquid vortex capture electrospray ionization mass spectrometry system were compared for the analysis of single cells and tissue. Single Chlamydomonas reinhardtii cells were monitored for their monogalactosyldiacylglycerol (MGDG) and diacylglyceryltrimethylhomo-Ser (DGTS) lipid content using the laser spot sampling mode, which was capable of ablating individual cells (~4-15 μm) even when agglomerated together. Turbid Allium Cepa cells (~150 μm) having unique shapes difficult to precisely measure using the other sampling modes could be ablated in their entirety using laser raster sampling. Intact microdissections of specific regions of a cocaine-dosed mouse brain tissue were compared using laser 'cut and drop' sampling. Since in laser 'cut and drop' sampling whole and otherwise unmodified sections are captured into the probe, 100% collection efficiencies were achieved. Laser ablation spot sampling has the highest spatial resolution of any sampling mode, while laser ablation raster sampling has the highest sampling area adaptability of the sampling modes. Laser ablation spot sampling has the highest spatial resolution of any sampling mode, useful in this case for the analysis of single cells. Laser ablation raster sampling was best for sampling regions with unique shapes that are difficult to measure using other sampling modes. Laser 'cut and drop' sampling can be used for

  19. Arsenic Is A Genotoxic Carcinogen

    EPA Science Inventory

    Arsenic is a recognized human carcinogen; however, there is controversy over whether or not it should be considered a genotoxic carcinogen. Many possible modes of action have been proposed on how arsenic induces cancer, including inhibiting DNA repair, altering methylation patter...

  20. Arsenic Is A Genotoxic Carcinogen

    EPA Science Inventory

    Arsenic is a recognized human carcinogen; however, there is controversy over whether or not it should be considered a genotoxic carcinogen. Many possible modes of action have been proposed on how arsenic induces cancer, including inhibiting DNA repair, altering methylation patter...

  1. Genotoxicity of organic extracts from atmospheric particles

    SciTech Connect

    Courtois, Y.A.; Min, S.; Lachenal, C.; Jacquot-Deschamps, J.M.; Callais, F.; Festy, B.

    1988-01-01

    Experiments to evaluate the genotoxic potentialities of urban air particles sampled in Paris (France) after organic solvent extraction have been carried out using four in vitro genotoxicity tests. The two bacterial tests (the Ames test and the SOS Chromotest) demonstrate the genotoxicity of the organic extracts of atmospheric particles; two additional tests (induction of 6-thioguanine mutants and sister chromatid exchanges), carried out on V79 Chinese hamster cells, also confirm these potentialities. These results show clearly that particulate organic extracts induce point mutations in both bacteria and mammalian cells, or the cellular response (SOS repair) to these mutations in bacteria; likewise, they are responsible for clastogenic effects in mammalian cells. Genotoxicity is due either to direct genotoxic chemicals or to active metabolic products of the action of microsomal enzymes. The optimalization of testing procedures is discussed in order to appreciate the contribution of genotoxicity tests to the study of atmospheric pollution.

  2. Lamb wave (A0 mode) scattering directionality at defects

    NASA Astrophysics Data System (ADS)

    Fromme, Paul

    2017-02-01

    Localized and distributed guided ultrasonic waves array systems offer an efficient way for the structural health monitoring of large structures. The detection sensitivity for fatigue cracks depends on the orientation of the crack relative to the location of the sensor elements. Crack-like defects have a directionality pattern of the scattered field depending on the angle of the incident wave relative to the defect orientation and on the ratio of the defect depth and length to the wavelength. From FE simulations it has been shown that for cracks and notches almost no energy is scattered in certain directions from the defect, i.e., the data processing algorithm must take into account that for some transducer combinations no change in the signal even for a significant defect will be detected. The scattered wave field directionality pattern for an incident low frequency A0 Lamb wave mode was predicted from 3D Finite Element simulations and verified from experimental measurements at machined part-through and through-thickness notches using a laser interferometer. Good agreement was found and the directionality pattern can be predicted accurately. The amplitude of the scattered wave was quantified for a systematic variation of the angle of the incident wave relative to the defect orientation, the defect depth, and the ratio of the characteristic defect size to the wavelength. Based on these results the detection sensitivity for crack-like defects in plate structures using guided wave sensor arrays can be quantified.

  3. Bacterial genotoxicity bioreporters

    PubMed Central

    Biran, Alva; Yagur‐Kroll, Sharon; Pedahzur, Rami; Buchinger, Sebastian; Reifferscheid, Georg; Ben‐Yoav, Hadar; Shacham‐Diamand, Yosi; Belkin, Shimshon

    2010-01-01

    Summary Ever since the introduction of the Salmonella typhimurium mammalian microsome mutagenicity assay (the ‘Ames test’) over three decades ago, there has been a constant development of additional genotoxicity assays based upon the use of genetically engineered microorganisms. Such assays rely either on reversion principles similar to those of the Ames test, or on promoter–reporter fusions that generate a quantifiable dose‐dependent signal in the presence of potential DNA damaging compounds and the induction of repair mechanisms; the latter group is the subject of the present review. Some of these assays were only briefly described in the scientific literature, whereas others have been developed all the way to commercial products. Out of these, only one, the umu‐test, has been fully validated and ISO‐ and OECD standardized. Here we review the main directions undertaken in the construction and testing of bacterial‐based genotoxicity bioassays, including the attempts to incorporate at least a partial metabolic activation capacity into the molecular design. We list the genetic modifications introduced into the tester strains, compare the performance of the different assays, and briefly describe the first attempts to incorporate such bacterial reporters into actual genotoxicity testing devices. PMID:21255340

  4. Near-Infrared Dioxetane Luminophores with Direct Chemiluminescence Emission Mode.

    PubMed

    Green, Ori; Gnaim, Samer; Blau, Rachel; Eldar-Boock, Anat; Satchi-Fainaro, Ronit; Shabat, Doron

    2017-09-20

    Chemiluminescent luminophores are considered as one of the most sensitive families of probes for detection and imaging applications. Due to their high signal-to-noise ratios, luminophores with near-infrared (NIR) emission are particularly important for in vivo use. In addition, light with such long wavelength has significantly greater capability for penetration through organic tissue. So far, only a few reports have described the use of chemiluminescence systems for in vivo imaging. Such systems are always based on an energy-transfer process from a chemiluminescent precursor to a nearby emissive fluorescent dye. Here, we describe the development of the first chemiluminescent luminophores with a direct mode of NIR light emission that are suitable for use under physiological conditions. Our strategy is based on incorporation of a substituent with an extended π-electron system on the excited species obtained during the chemiexcitation pathway of Schaap's adamantylidene-dioxetane probe. In this manner, we designed and synthesized two new luminophores with direct light emission wavelength in the NIR region. Masking of the luminophores with analyte-responsive groups has resulted in turn-ON probes for detection and imaging of β-galactosidase and hydrogen peroxide. The probes' ability to image their corresponding analyte/enzyme was effectively demonstrated in vitro for β-galactosidase activity and in vivo in a mouse model of inflammation. We anticipate that our strategy for obtaining NIR luminophores will open new doors for further exploration of complex biomolecular systems using non-invasive intravital chemiluminescence imaging techniques.

  5. Multihit mode direct-detection laser radar system using a Geiger-mode avalanche photodiode.

    PubMed

    Oh, Min Seok; Kong, Hong Jin; Kim, Tae Hoon; Hong, Keun Ho; Kim, Byung Wook; Park, Dong Jo

    2010-03-01

    In this paper, a direct-detection laser radar system that uses a Geiger-mode avalanche photodiode (GAPD) of relatively short dead time (45 ns) is described. A passively Q-switched microchip laser is used as a laser source and a compact peripheral component interconnect system, which includes a time-to-digital converter (TDC), is set up for fast signal processing. With both the GAPD and the TDC functioning multistop acquisition, the system operates in a multihit mode. The software for the three-dimensional visualization and an algorithm for the removal of noise are developed. It is shown that the single-shot precision of the system is approximately 10 cm (sigma) and the precision is improved by increasing the number of laser pulses to be averaged so that the precision of approximately 1 cm (sigma) was acquired with more than 150 laser pulses scattered from the target. The accuracy of the system is measured to be 12 cm when the energy of the emitted laser pulse varies with a factor of 7.

  6. Toxic, cytotoxic, and genotoxic effects of a glyphosate formulation (Roundup®SL-Cosmoflux®411F) in the direct-developing frog Eleutherodactylus johnstonei.

    PubMed

    Meza-Joya, Fabio Leonardo; Ramírez-Pinilla, Martha Patricia; Fuentes-Lorenzo, Jorge Luis

    2013-06-01

    The aerial spraying of glyphosate formulations in Colombia to eradicate illegal crops has generated great concern about its possible impact on nontarget organisms, particularly amphibians. This study evaluated the toxic, cytotoxic, and genotoxic effects of a glyphosate formulation (Roundup®SL-Cosmoflux®411F) in the direct-developing frog Eleutherodactylus johnstonei by estimating the median lethal application rate (LC50 ), median hemolytic application rate (HD50 ), and extent of DNA damage using the in vitro and in vivo Comet assays. Toxicity results indicated that the application rate [37.4 µg acid equivalent (a.e.)/cm(2) ] equivalent to that used in aerial spraying (3.74 kg a.e./ha) is not lethal in male and female adult frogs, whereas neonates are highly sensitive. Glyphosate formulation at application rates above 5.4 µg a.e./cm(2) (in vivo) and concentrations above 95 µg a.e./mL (in vitro) showed clear evidence of cytotoxicity. In vivo and in vitro exposure of E. johnstonei erythrocytes to the glyphosate formulation induced DNA breaks in a dose-dependent manner with statistically significant values (P < 0.05) at all doses tested. DNA damage initially increased with the duration of exposure and then decreased, suggesting that DNA repair events were occurring during in vivo and in vitro exposures. These results are discussed from the perspective of possible ecotoxicological risks to anuran species from exposure to glyphosate formulation. Copyright © 2013 Wiley Periodicals, Inc.

  7. Direct electrical-to-optical conversion and light modulation in micro whispering-gallery-mode resonators

    NASA Technical Reports Server (NTRS)

    Maleki, Lute (Inventor); Levi, Anthony F. J. (Inventor)

    2005-01-01

    Techniques for directly converting an electrical signal into an optical signal by using a whispering gallery mode optical resonator formed of a dielectric material that allows for direct modulation of optical absorption by the electrical signal.

  8. Mode control and direct modulation for waveguide-coupled square microcavity lasers

    NASA Astrophysics Data System (ADS)

    Yang, Yue-De; Xiao, Zhi-Xiong; Weng, Hai-Zhong; Xiao, Jin-Long; Huang, Yong-Zhen

    2016-11-01

    Lasing mode control and direct modulation characteristics have been investigated for waveguide-coupled unidirectional-emission square microcavity lasers. A quasi-analytical model is introduced to analyze the mode field distributions and quality (Q) factors for the confined modes inside the square optical microcavities with directly coupled waveguide, where high-Q whispering-gallery-like (WG-like) modes are induced by the mode coupling between doubly-degenerate modes. AlGaInAs/InP waveguide-coupled unidirectional-emission square microcavity lasers are fabricated by using standard planar technology, and electrically-injected lasing is realized at room temperature. The lasing modes are controlled by properly designing the lasing cavity, output waveguide and injection pattern. Dual-transverse-mode lasing with a tunable wavelength interval from 0.25 to 0.39 nm is realized by using a spatially selective current injection to modulate the refractive index, as the mode field distributions of different transverse are spatially separated. The wavelength interval can be further increased to a few nanometers by reducing the cavity size and replacing the flat sidewalls with circular arcs. The field distributions of WG-like modes distribute uniformly in square microcavity, which avoid the burning-induced carrier diffusion in high-speed direct modulation. A small-signal modulation 3dB bandwidth exceeding 16 GHz, and an open eye diagram at 25 Gb/s are demonstrated for the high-speed direct modulated square microcavity laser.

  9. Genotoxicity studies on the azo dye Direct Red 2 using the in vivo mouse bone marrow micronucleus test.

    PubMed

    Rajaguru, P; Fairbairn, L J; Ashby, J; Willington, M A; Turner, S; Woolford, L A; Chinnasamy, N; Rafferty, J A

    1999-07-21

    The clastogenicity of the azo dye Direct Red 2 (DR2) has been investigated using the murine bone marrow micronucleus assay. A potent dose-dependent response was observed following oral gavage of DR2 up to 4 mg/kg, after which significant toxicity to the erythroid compartment was observed. The route of administration had a significant effect on the frequency of micronucleus formation: intraperitoneal injection was approximately two-fold less clastogenic than the equivalent dose delivered orally (p<0.05). The requirement for activation of DR2 by intestinal microflora was indicated by the fact that mice given acid-treated water prior to administration of DR2 showed a significant reduction (40%; p<0.001) in micronucleated polychromatic erythrocyte formation. The implications of these findings for the health and safety of occupationally exposed workers are discussed.

  10. Direct dark mode excitation by symmetry matching of a single-particle-based metasurface

    NASA Astrophysics Data System (ADS)

    Burokur, Shah Nawaz; Lupu, Anatole; de Lustrac, André

    2015-01-01

    This paper provides evidence for a direct dark mode excitation mechanism in a metasurface structure. The dark mode excitation mechanism is entirely determined by structures' symmetry and does not depend on near-field coupling between elements. In our examples, we consider single-element based metasurface composed of two V antennas connected in an antisymmetric arrangement. Both experimental and modeling results show an efficient excitation of magnetic dipolar mode in such structures. The direct dark mode excitation mechanism provides a design that is more robust with respect to technology imperfections. The considered approach opens promising perspectives for new types of nanostructure designs and greatly relaxes fabrication constraints for the optical domain.

  11. Interactions between directly- and parametrically-driven vibration modes in a micromechanical resonator

    NASA Astrophysics Data System (ADS)

    Westra, H. J. R.; Karabacak, D. M.; Brongersma, S. H.; Crego-Calama, M.; van der Zant, H. S. J.; Venstra, W. J.

    2011-10-01

    The interactions between parametrically- and directly-driven vibration modes of a clamped-clamped beam resonator are studied. An integrated piezoelectric transducer is used for direct and parametric excitation. First, the parametric amplification and oscillation of a single mode are analyzed by the power and phase dependence below and above the threshold for parametric oscillation. Then, the motion of a parametrically-driven mode is detected by the induced change in resonance frequency in another mode of the same resonator. The resonance frequency shift is the result of the nonlinear coupling between the modes by the displacement-induced tension in the beam. These nonlinear modal interactions result in the quadratic relation between the resonance frequency of one mode and the amplitude of another mode. The amplitude of a parametrically-oscillating mode depends on the square root of the pump frequency. Combining these dependencies yields a linear relation between the resonance frequency of the directly-driven mode and the frequency of the parametrically-oscillating mode.

  12. Single-mode waveguide optical isolator based on direction-dependent cutoff frequency.

    PubMed

    Tang, Lingling; Drezdzon, Samuel M; Yoshie, Tomoyuki

    2008-09-29

    A single-mode-waveguide optical isolator based on propagation direction dependent cut-off frequency is proposed. The isolation bandwidth is the difference between the cut-off frequencies of the lowest forward and backward propagating modes. Perturbation theory is used for analyzing the correlation between the material distribution and the bandwidth. The mode profile determines an appropriate distribution of non-reciprocal materials.

  13. Tunable continuous wave single-mode dye laser directly pumped by a diode laser

    NASA Astrophysics Data System (ADS)

    Stefanska, D.; Suski, M.; Furmann, B.

    2017-04-01

    In this work, a tunable continuous wave single-mode ring dye laser (a modified version of Coherent model CR 699-21), directly optically pumped by an economy-class diode laser, has been set up. The laser was operated on Coumarin 498, and its generation profile covered part of the green spectral region not easily accessible in single-mode operation. The performance of the laser in both broad-band and single-mode operation regimes was studied. It was proved that optical pumping by diode lasers allows one to obtain single-mode operation of dye lasers that is sufficiently stable for high-resolution spectroscopy applications.

  14. Direct dark modes excitation in bi-layered enantiomeric atoms-based metasurface through symmetry matching.

    PubMed

    Bochkova, Elena; Burokur, Shah Nawaz; de Lustrac, André; Lupu, Anatole

    2016-01-15

    We provide evidence for the mechanism of direct dark mode excitation in a metasurface composed of bi-layered Z-shaped enantiomeric meta-atoms. The electromagnetic behavior of the structure is investigated through both numerical simulations and experimental measurements in the microwave domain. We demonstrate direct field coupling excitation of second higher order electric mode under normal incidence based only on symmetry matching conditions. The proposed approach provides a better flexibility in engineering dark mode resonances that do not rely on hybridization mechanism and presents important advantages for multi-spectral sensor applications.

  15. Magnetic Reconnection Processes Involving Modes Propagating in the Ion Diamagnetic Velocity Direction

    NASA Astrophysics Data System (ADS)

    Buratti, P.; Coppi, B.; Pucella, G.; Zhou, T.

    2013-10-01

    Experiments in weakly collisional plasma regimes, (e.g. neutral beam heated plasmas in the H-regime), measuring the Doppler shift associated with the plasma local rotation, have shown that the toroidal mode phase velocity vph in the frame with Er = 0 is in the direction of the ion diamagnetic velocity. For ohmically heated plasmas, with higher collisionalities, vph in the laboratory frame is in the direction of the electron diamagnetic velocity, but plasma rotation is reversed as well, and vph, in the Er = 0 frame, is in the ion diamagnetic velocity direction. Theoretically, two classes of reconnecting modes should emerge: drift-tearing modes and ``inductive modes'' that depend on the effects of a finite plasma inductivity. The former modes, with vph in the direction of the electron diamagnetic velocity, require the pre-excitation of a different kind of mode in order to become unstable in weakly collisional regimes. The second kind of modes has a growth rate associated with the relevant finite ion viscosity. A comprehensive theory is presented. Sponsored in part by the US DOE.

  16. Selection of lasing direction in single mode semiconductor square ring cavities

    SciTech Connect

    Lee, Jin-Woong; Kim, Kyoung-Youm; Moon, Hee-Jong; Hyun, Kyung-Sook

    2016-02-07

    We propose and demonstrate a selection scheme of lasing direction by imposing a loss imbalance structure into the single mode square ring cavity. The control of the traveling direction is realized by introducing a taper-step section in one of the straight waveguides of the square ring cavity. It was shown by semi-analytic calculation that the taper-step section in the cavity provides effective loss imbalance between two travelling directions as the round trip repeats. Various kinds of square cavities were fabricated using InGaAsP/InGaAs multiple quantum well semiconductor materials in order to test the direction selectivity while maintaining the single mode. We also measured the pump power dependent lasing spectra to investigate the maintenance property of the lasing direction. The experimental results demonstrated that the proposed scheme is an efficient means for a unidirectional lasing in a single mode laser.

  17. A multi-mode operation control strategy for flexible microgrid based on sliding-mode direct voltage and hierarchical controls.

    PubMed

    Zhang, Qinjin; Liu, Yancheng; Zhao, Youtao; Wang, Ning

    2016-03-01

    Multi-mode operation and transient stability are two problems that significantly affect flexible microgrid (MG). This paper proposes a multi-mode operation control strategy for flexible MG based on a three-layer hierarchical structure. The proposed structure is composed of autonomous, cooperative, and scheduling controllers. Autonomous controller is utilized to control the performance of the single micro-source inverter. An adaptive sliding-mode direct voltage loop and an improved droop power loop based on virtual negative impedance are presented respectively to enhance the system disturbance-rejection performance and the power sharing accuracy. Cooperative controller, which is composed of secondary voltage/frequency control and phase synchronization control, is designed to eliminate the voltage/frequency deviations produced by the autonomous controller and prepare for grid connection. Scheduling controller manages the power flow between the MG and the grid. The MG with the improved hierarchical control scheme can achieve seamless transitions from islanded to grid-connected mode and have a good transient performance. In addition the presented work can also optimize the power quality issues and improve the load power sharing accuracy between parallel VSIs. Finally, the transient performance and effectiveness of the proposed control scheme are evaluated by theoretical analysis and simulation results.

  18. Musical scales and evaluations of happiness and awkwardness: effects of pitch, direction, and scale mode.

    PubMed

    Collier, W G; Hubbard, T L

    2001-01-01

    Participants rated the perceived happiness, brightness, awkwardness, pitch velocity, and tempo change of ascending and descending musical scales in four modes (natural, melodic, and harmonic minor modes and the major mode). Only minor differences between ratings of natural, harmonic, or melodic minor scales or between ratings of parallel and relative major scales were found. Ascending scales were rated as happier, brighter, and more accelerating than were descending scales; ascending minor scales were rated as faster and more awkward than were descending minor scales. Musical keys in each mode were compared, and significant differences were found. Musical keys that started on a higher pitch were rated as happier, brighter, and faster and as speeding up more than were keys that started on a lower pitch. The data were consistent with previous findings and suggest that pitch and direction (contour), rather than mode or key, influence listeners' judgments of musical stimuli.

  19. Direct measurement of the Wigner characteristic function of an arbitrary multi-mode entangled traveling field

    NASA Astrophysics Data System (ADS)

    Xu, Yejun; Liang, Xiudong; Cheng, Jianming; Tai, Yunjiao; Song, Jun

    2014-03-01

    We present a simple proposal to measure arbitrary multi-mode entangled traveling field state based on a Mach-Zehnder interferometer in theory. Our method directly yields the characteristic function of the Wigner function without a demanding data analysis and can be easily carried out by recent technological advances. Especially, it is a very effective reconstruction proposal for an entangled traveling field with a small number of modes from the experimental point of view. We demonstrate the scheme for the example of a two-mode squeezed vacuum state to illustrate how similar the reconstructed state is to the ideal one via controlling the values of phase shifts.

  20. Sliding mode pulse-width modulation technique for direct torque controlled induction motor drive

    NASA Astrophysics Data System (ADS)

    Bounadja, M.; Belarbi, A. W.; Belmadani, B.

    2010-05-01

    This paper presents a novel pulse-width modulation technique based sliding mode approach for direct torque control of an induction machine drive. Methodology begins with a sliding mode control of machine's torque and stator flux to generate the reference voltage vector and to reduce parameters sensitivity. Then, the switching control of the three-phase inverter is developed using sliding mode concept to make the system tracking reference voltage inputs. The main features of the proposed methodologies are the high tracking accuracy and the much easier implementation compared to the space vector modulation. Simulations are carried out to confirm the effectiveness of proposed control algorithms.

  1. Genotoxicity in the rodent urinary bladder.

    PubMed

    King, C; Wang, C; Gorelick, N; Frederick, C

    1995-09-01

    Elucidation of the mechanisms by which a chemical may induce urinary bladder tumours in rodents can be expected to provide insight into the relative risk from that agent. The methodologies for exploring whether tumour induction may be a response to direct genotoxic effect of the compound have been successfully applied to the bladders of both mice and rats. Thus, with experimental approaches that utilize adduct detection through the use of immunochemical and postlabelling techniques, unscheduled DNA synthesis and mutagenicity as studied with transgenic animals it is possible to obtain fundamental information on the genotoxic potential of carcinogens in the target bladder. Application of these experimental approaches to carcinogens for which the mechanisms of action are not known should permit assessment of the likelihood that genotoxic or non-genotoxic mechanisms are involved in the tumour induction process. Moreover, such studies may provide knowledge of the molecular pathways that are involved in the action of genotoxic agents, thus enabling judgements to be made as to whether humans are subject to tumour induction by the chemical.

  2. Genotoxicity investigations on nanomaterials.

    PubMed

    Oesch, Franz; Landsiedel, Robert

    2012-07-01

    This review is based on the lecture presented at the April 2010 nanomaterials safety assessment Postsatellite to the 2009 EUROTOX Meeting and summarizes genotoxicity investigations on nanomaterials published in the open scientific literature (up to 2008). Special attention is paid to the relationship between particle size and positive versus negative outcome, as well as the dependence of the outcome on the test used. Salient conclusions and outstanding recommendations emerging from the information summarized in this review are as follows: recognize that nanomaterials are not all the same; therefore know and document what nanomaterial has been tested and in what form; take nanomaterials specific properties into account; in order to make your results comparable with those of others and on other nanomaterials: use or at least include in your studies standardized methods; use in vivo studies to put in vitro results into perspective; take uptake and distribution of the nanomaterial into account; and in order to become able to make extrapolations to risk for human: learn about the mechanism of nanomaterials genotoxic effects. Past experience with standard non-nanosubstances already had shown that mechanisms of genotoxic effects can be complex and their elucidation can be demanding, while there often is an immediate need to assess the genotoxic hazard. Thus, a practical and pragmatic approach to genotoxicity investigations of novel nanomaterials is the use of a battery of standard genotoxicity testing methods covering a wide range of mechanisms. Application of these standard methods to nanomaterials demands, however, adaptations, and the interpretation of results from the genotoxicity testing of nanomaterials needs additional considerations exceeding those used for standard size materials.

  3. METHYLATED TRIVALENT ARSENIC SPECIES ARE GENOTOXIC

    EPA Science Inventory

    ABSTRACT

    The genotoxic effects of arsenic compounds are generally believed to result from other than direct interacton with DNA. The reactivties of methyloxarsine (MAsIII) and iododimethylarsine (DMAsIII), two methylated trivalent arsenicals, toward supercoiled X174 RFI ...

  4. A fuzzy logic sliding mode controlled electronic differential for a direct wheel drive EV

    NASA Astrophysics Data System (ADS)

    Ozkop, Emre; Altas, Ismail H.; Okumus, H. Ibrahim; Sharaf, Adel M.

    2015-11-01

    In this study, a direct wheel drive electric vehicle based on an electronic differential system with a fuzzy logic sliding mode controller (FLSMC) is studied. The conventional sliding surface is modified using a fuzzy rule base to obtain fuzzy dynamic sliding surfaces by changing its slopes using the global error and its derivative in a fuzzy logic inference system. The controller is compared with proportional-integral-derivative (PID) and sliding mode controllers (SMCs), which are usually preferred to be used in industry. The proposed controller provides robustness and flexibility to direct wheel drive electric vehicles. The fuzzy logic sliding mode controller, electronic differential system and the overall electrical vehicle mechanism are modelled and digitally simulated by using the Matlab software. Simulation results show that the system with FLSMC has better efficiency and performance compared to those of PID and SMCs.

  5. Direct picosecond time resolution of unimolecular reactions initiated by local mode excitation

    NASA Technical Reports Server (NTRS)

    Scherer, N. F.; Doany, F. E.; Zewail, A. H.; Perry, J. W.

    1986-01-01

    Attention is given to the first results of direct, picosec measurements of the Delta-nu(OH) 5 local mode transition of H2O2. These time-resolved studies yield a direct measure of the unimolecular dissociation rate, and furnish a lower limit for the rate of energy redistribution from the OH stretch to the O-O reaction coordinate. The data thus determined may be used to ascertain the domain of validity for statistical unimolecular reaction rate theories.

  6. Analysis of the influence of the mode type on microstrip antenna directive properties

    NASA Astrophysics Data System (ADS)

    Bem, Daniel J.; Katulski, Ryszard J.

    The subject of this paper is the analysis of the mode type influence on the directive properties of a microstrip antenna with a rectangular radiating element. Investigations in this field were carried out using the aperture model of the antenna. The results of numerical investigations are presented.

  7. Directional asymmetry of nystagmus elicitation in humans during step and sinusoidal modes of lateral linear acceleration.

    PubMed

    Katayama, N; Mori, S

    2001-09-01

    We investigated nystagmus elicitation in 50 normal subjects who were exposed interaurally to linear acceleration with step (rectangular) and sinusoidal modes of oscillation using a linear accelerator. Relatively strong G-loads of 0.3-0.5 G at a 10 m stroke were applied to subjects who looked at a memorized target in darkness, with the head and trunk tightly restrained in the upright sitting position. Horizontal and vertical eye movements were recorded by electrooculography (EOG). Various levels of G-directional preponderance (DP), including completely one-sided, were observed similarly in either stimulus mode, strongly suggesting that directional asymmetry in nystagmus elicitation may be a functional characteristic in the otolith-ocular response, in contrast to the canal-ocular response. The effects of G-load increase were less congruent between the two stimulus modes. In the step-mode oscillation, the desaccaded slow eye position which corresponds to the vestibuloocular reflex (VOR) was saw-toothed in shape as was the stimulus velocity curve, but the baseline often drifted slowly and DP-dependently in the direction opposite to the fast phase of nystagmus. When the slow phase velocity (SPV), a slope of the saw-tooth, was adjusted mathematically for such slow drift, it revealed that the adjusted SPVs were almost symmetrical between rightward and leftward G-directions. These results suggest that DP generation is separate from VOR generation which is primarily symmetrical.

  8. Genotoxicity of swine effluents.

    PubMed

    Techio, V H; Stolberg, J; Kunz, A; Zanin, E; Perdomo, C C

    2011-01-01

    This study aimed at the investigation of genotoxic effects of swine effluents from different stages of a treatment system for swine wastes through bioassay of stamen hairs and micronuclei in Tradescantia (clone BNL 4430). No significant differences (p≥0.05) regarding the genic mutations were found in the bioassay of stamen hairs, independently of the effluent analysed. For the genotoxicity test with micronuclei, the plants exposed to raw wastes, to sludge, and to effluent of the biodigester have presented higher rates of chromosomal damages (micronuclei), with significant differences in relation to the control group and other effluent of the waste treatment system (p≤0.05). The association between the chemical parameters and the genotoxicity data have shown that the variables COD and TKN have presented significant correlation (p≤0.05) with the number of mutagenic events in the tetrads.

  9. H-mode power threshold, grad-B drift direction and ion collisionality

    NASA Astrophysics Data System (ADS)

    Power, H. M.; Shaing, K. C.

    2001-10-01

    An explanation on the dependence of the H-mode power threshold on the direction of the grad-B drift in diverted tokamaks is presented in the context of the H-mode theory based on the orbit loss and the subsequent turbulence suppression. Here, B is the magnetic field strength. It is shown using the results of a numerical calculation [ A. V. Chankin and G. M. McCracken, Nucl. Fusion 10, 1459(1993)] that ion collisionality that defines the onset of the orbit loss depends on the direction of the grad-B drift. The connection length is shorter when grad-B drift is toward the X-point than away from it. Judging from the sensitivity of the power threshold on the grad-B drift direction, we conclude that power threshold must be a simple function of ion collisionality among other dimensionless parameters.

  10. How large customer direct power transaction mode give consideration to power generation cleaning and power saving

    NASA Astrophysics Data System (ADS)

    Liu, Yu; Zeng, Ming; Liu, Wei; Li, Ran

    2017-05-01

    The so-called Large Customers' Direct Power Transaction, refers to the mode that the users on high voltage level, or being seized of hold the large power or independent power distribution, have the qualification of purchasing electricity directly from the generation companies and pay reasonable electricity transmission and distribution fee to the power network enterprises because the transaction is through its transmission channel. The Direct Purchase promotes the marketization level of electricity trading, but there are some problems in its developing process, especially whether promotes the green optimal allocation of power resources, this paper aims to explore the solution.

  11. Full time directional versus user selectable microphone modes in hearing aids.

    PubMed

    Ricketts, Todd; Henry, Paula; Gnewikow, David

    2003-10-01

    The purpose of this experiment was to systematically examine hearing aid benefit as measured by speech recognition and self-assessment methods across omnidirectional and directional hearing aid modes. These data were used to compare directional benefit as measured by speech recognition in the laboratory to hearing aid wearer's perceptions of benefit in everyday environments across full-time directional, full-time omnidirectional, and user selectable directional fittings. Identification of possible listening situations that resulted in different self reported hearing aid benefit as a function of microphone type was a secondary objective of this experiment. Fifteen adults with symmetrical, sloping sensorineural hearing loss were fitted bilaterally with in-the-ear (ITE) directional hearing aids. Measures of hearing aid benefit included the Profile of Hearing Aid Benefit (PHAB), the Connected Sentence Test (CST), the Hearing in Noise Test (HINT), and a daily use log. Additionally, two new subscales were developed for administration with the PHAB. These subscales were developed to specifically address situations in which directional hearing aids may provide different degrees of benefit than omnidirectional hearing aids. Participants completed these measures in three conditions: omnidirectional only (O), directional only with low-frequency gain compensation (D), and user-selectable directional/omnidirectional (DO). Results from the speech intelligibility in noise testing indicated significantly more hearing aid benefit in directional modes than omnidirectional. PHAB results indicated more benefit on the background noise subscale (BN) in the DO condition than in the O condition; however, this directional advantage was not present for the D condition. Although the reliability of the newly proposed subscales is as yet unknown, the data were interpreted as revealing a directional advantage in situations where the signal of interest was in front of the participant and a

  12. Critical review of the current and future challenges associated with advanced in vitro systems towards the study of nanoparticle (secondary) genotoxicity.

    PubMed

    Evans, Stephen J; Clift, Martin J D; Singh, Neenu; de Oliveira Mallia, Jefferson; Burgum, Michael; Wills, John W; Wilkinson, Thomas S; Jenkins, Gareth J S; Doak, Shareen H

    2017-01-01

    With the need to understand the potential biological impact of the plethora of nanoparticles (NPs) being manufactured for a wide range of potential human applications, due to their inevitable human exposure, research activities in the field of NP toxicology has grown exponentially over the last decade. Whilst such increased research efforts have elucidated an increasingly significant knowledge base pertaining to the potential human health hazard posed by NPs, understanding regarding the possibility for NPs to elicit genotoxicity is limited. In vivo models are unable to adequately discriminate between the specific modes of action associated with the onset of genotoxicity. Additionally, in line with the recent European directives, there is an inherent need to move away from invasive animal testing strategies. Thus, in vitro systems are an important tool for expanding our mechanistic insight into NP genotoxicity. Yet uncertainty remains concerning their validity and specificity for this purpose due to the unique challenges presented when correlating NP behaviour in vitro and in vivo This review therefore highlights the current state of the art in advanced in vitro systems and their specific advantages and disadvantages from a NP genotoxicity testing perspective. Key indicators will be given related to how these systems might be used or improved to enhance understanding of NP genotoxicity.

  13. Critical review of the current and future challenges associated with advanced in vitro systems towards the study of nanoparticle (secondary) genotoxicity

    PubMed Central

    Evans, Stephen J.; Clift, Martin J. D.; Singh, Neenu; de Oliveira Mallia, Jefferson; Burgum, Michael; Wills, John W.; Wilkinson, Thomas S.; Jenkins, Gareth J. S.; Doak, Shareen H.

    2017-01-01

    With the need to understand the potential biological impact of the plethora of nanoparticles (NPs) being manufactured for a wide range of potential human applications, due to their inevitable human exposure, research activities in the field of NP toxicology has grown exponentially over the last decade. Whilst such increased research efforts have elucidated an increasingly significant knowledge base pertaining to the potential human health hazard posed by NPs, understanding regarding the possibility for NPs to elicit genotoxicity is limited. In vivo models are unable to adequately discriminate between the specific modes of action associated with the onset of genotoxicity. Additionally, in line with the recent European directives, there is an inherent need to move away from invasive animal testing strategies. Thus, in vitro systems are an important tool for expanding our mechanistic insight into NP genotoxicity. Yet uncertainty remains concerning their validity and specificity for this purpose due to the unique challenges presented when correlating NP behaviour in vitro and in vivo. This review therefore highlights the current state of the art in advanced in vitro systems and their specific advantages and disadvantages from a NP genotoxicity testing perspective. Key indicators will be given related to how these systems might be used or improved to enhance understanding of NP genotoxicity. PMID:27815329

  14. Effect of direct dissipative coupling of two competing modes on intensity fluctuations in a quantum-dot-microcavity laser

    NASA Astrophysics Data System (ADS)

    Fanaei, M.; Foerster, A.; Leymann, H. A. M.; Wiersig, J.

    2016-10-01

    We investigate two-mode photon correlations in a quantum-dot-microcavity laser with special emphasis on the effects induced by a direct coupling of two competing modes due to the dissipative character of the laser resonator. Numerical results based on a microscopic semiconductor theory reveal an enhanced autocorrelation of both modes and an enhanced anticorrelation between the modes. A detailed analysis is given in terms of dark and bright modes. It is shown that above the lasing threshold the original modes build up a bright mode coupled to the quantum dots and a dark mode, which interacts only indirectly with the quantum dots. We demonstrate that a populated dark mode can enable an efficient transfer of photons between the two original cavity modes, mediating an effective coupling between them.

  15. Genotoxicity assessment of 4-methylimidazole: regulatory perspectives.

    PubMed

    Morita, Takeshi; Uneyama, Chikako

    2016-01-01

    4-Methylimidazole (4-MI) is formed as a result of the Maillard reaction process, and therefore is found in many foods and beverages. It is also found in soft drinks (i.e., cola) as a by-product in the production of some caramel colors. NTP bioassays revealed clear evidence of lung carcinogenicity of 4-MI in male and female mice, but not in rats and then IARC classified 4-MI as group 2B carcinogen. Genotoxicity studies with 4-MI were negative in the Ames tests and in the erythrocyte micronucleus tests with mice or rats. US California EPA (CEPA) evaluated the testing has not been adequately comprehensive to rule out a genotoxic mode of action; as target tissue of the carcinogenicity of 4-MI was lung, the lung should be used as a source tissue for in vitro metabolic activation system. Thus, CEPA defined the No Significant Risk Level (NSRL) for 10(-5) lifetime risk level of cancer by 4-MI as 29 μg/day based on the non-threshold approach. As higher levels of 4-MI than the NSRL were identified in some kinds of cola, health concerns of 4-MI were drawn the attention. On the other hand, other regulatory bodies (e.g., European Food Safety Authority, EFSA) showed no concerns of 4-MI from the use of caramel colors in food. EFSA evaluated 4-MI is not genotoxic, so, non-observed adverse effect level of 4-MI was considered to be 80 mg/kg/day. In this paper, genotoxic assessments of 4-MI in different regulatory bodies are presented and the risk evaluation of 4-MI is discussed based on new genotoxicity data.

  16. Nonlinear mode switching in lithium niobate nanowaveguides to control light directionality.

    PubMed

    Escalé, Marc Reig; Sergeyev, Anton; Geiss, Reinhard; Grange, Rachel

    2017-02-20

    The ability of nanowaveguides to confine and guide light has been applied for developing optical applications such as nanolasers, optical switching and localized imaging. These and others applications can be further complemented by the optical control of the guided modes within the nanowaveguide, which in turn dictates the light emission pattern. It has been shown that the light directionality can be shaped by varying the nanowire cross-sections. Here, we demonstrate that the directionality of the light can be modified using a single nanowaveguide with a nonlinear phenomenon such as second-harmonic generation. In individual lithium niobate nanowaveguides, we use second-harmonic modal phase-matching and we apply it to switch the guided modes within its sub-micron cross-section. In doing so, we can vary the light directionality of the generated light from straight (0° with respect to the propagation direction) to large spread angles (almost 54°). Further, we characterize the directionality of the guided light by means of optical Fourier transformation and show that the directionality of the guided light changes for different wavelengths.

  17. Branching fractions and direct CP asymmetries of charmless decay modes at the Tevatron

    SciTech Connect

    Morello, Michael; /Pisa, Scuola Normale Superiore /INFN, Pisa

    2006-12-01

    The authors present new CDF results on the branching fractions and time-integrated direct CP asymmetries for B{sup 0} and B{sub s}{sup 0} decay modes into pairs of charmless charged hadrons (pion or kaon). The data set for this update amounts to 1 fb{sup -1} of {bar p}p collisions at {radical}s = 1.96 TeV. They report the first observation of the B{sub s}{sup 0} {yields} K{sup -}{pi}{sup +} mode and a measurement of its branching fraction and direct CP asymmetry. They also observe for the first time two charmless decays of b-baryon: {Lambda}{sub b}{sup 0} {yields} p{pi}{sup -} and {Lambda}{sub b}{sup 0} {yields} pK{sup -}.

  18. Frequency splitter based on the directional emission from surface modes in dielectric photonic crystal structures

    SciTech Connect

    Tasolamprou, Anna C.; Zhang, Lei; Kafesaki, Maria; Koschny, Thomas; Soukoulis, Costas M.

    2015-05-19

    We demonstrate the numerical design and the experimental validation of frequency dependent directional emission from a dielectric photonic crystal structure. The wave propagates through a photonic crystal line-defect waveguide, while a surface layer at the termination of the photonic crystal enables the excitation of surface modes and a subsequent grating layer transforms the surface energy into outgoing propagating waves of the form of a directional beam. Furthermore, the angle of the beam is controlled by the frequency and the structure operates as a frequency splitter in the intermediate and far field region.

  19. Mixed gravity mode growth during directional dendritic solidification aboard the KC-135

    NASA Technical Reports Server (NTRS)

    Grugel, Richard N.

    1989-01-01

    NASA's KC-135, which flies a cyclic parabolic route designed to furnish periods of low gravity alternating with periods of high gravity, has been used to directionally solidify a superalloy and a FE-C-Si alloy. Probable transient effects, due to the rapid changes in the gravity levels, must be taken into account. An effort is presently made to show that experimental design is especially critical in the case of dendritic directional solidification experiments in which mixed gravity modes occur; inappropriate design easily leads to anomalous structures and data.

  20. Differential genotoxicity mechanisms of silver nanoparticles and silver ions.

    PubMed

    Li, Yan; Qin, Taichun; Ingle, Taylor; Yan, Jian; He, Weiwei; Yin, Jun-Jie; Chen, Tao

    2017-01-01

    In spite of many reports on the toxicity of silver nanoparticles (AgNPs), the mechanisms underlying the toxicity are far from clear. A key question is whether the observed toxicity comes from the silver ions (Ag(+)) released from the AgNPs or from the nanoparticles themselves. In this study, we explored the genotoxicity and the genotoxicity mechanisms of Ag(+) and AgNPs. Human TK6 cells were treated with 5 nM AgNPs or silver nitrate (AgNO3) to evaluate their genotoxicity and induction of oxidative stress. AgNPs and AgNO3 induced cytotoxicity and genotoxicity in a similar range of concentrations (1.00-1.75 µg/ml) when evaluated using the micronucleus assay, and both induced oxidative stress by measuring the gene expression and reactive oxygen species in the treated cells. Addition of N-acetylcysteine (NAC, an Ag(+) chelator) to the treatments significantly decreased genotoxicity of Ag(+), but not AgNPs, while addition of Trolox (a free radical scavenger) to the treatment efficiently decreased the genotoxicity of both agents. In addition, the Ag(+) released from the highest concentration of AgNPs used for the treatment was measured. Only 0.5 % of the AgNPs were ionized in the culture medium and the released silver ions were neither cytotoxic nor genotoxic at this concentration. Further analysis using electron spin resonance demonstrated that AgNPs produced hydroxyl radicals directly, while AgNO3 did not. These results indicated that although both AgNPs and Ag(+) can cause genotoxicity via oxidative stress, the mechanisms are different, and the nanoparticles, but not the released ions, mainly contribute to the genotoxicity of AgNPs.

  1. Effect of Temperature Gradient Direction in the Catalyst Nanoparticle on CNTs Growth Mode

    PubMed Central

    2010-01-01

    To improve the understanding on CNT growth modes, the various processes, including thermal CVD, MP-CVD and ECR-CVD, have been used to deposit CNTs on nanoporous SBA-15 and Si wafer substrates with C2H2 and H2 as reaction gases. The experiments to vary process parameter of ΔT, defined as the vector quantities of temperature at catalyst top minus it at catalyst bottom, were carried out to demonstrate its effect on the CNT growth mode. The TEM and TGA analyses were used to characterize their growth modes and carbon yields of the processes. The results show that ΔT can be used to monitor the temperature gradient direction across the catalyst nanoparticle during the growth stage of CNTs. The results also indicate that the tip-growth CNTs, base-growth CNTs and onion-like carbon are generally fabricated under conditions of ΔT > 0, <0 and ~0, respectively. Our proposed growth mechanisms can be successfully adopted to explain why the base- and tip-growth CNTs are common in thermal CVD and plasma-enhanced CVD processes, respectively. Furthermore, our experiments have also successfully demonstrated the possibility to vary ΔT to obtain the desired growth mode of CNTs by thermal or plasma-enhanced CVD systems for different applications. PMID:20730080

  2. 60-GHz Millimeter-wave Over Fiber with Directly Modulated Dual-mode Laser Diode

    NASA Astrophysics Data System (ADS)

    Tsai, Cheng-Ting; Lin, Chi-Hsiang; Lin, Chun-Ting; Chi, Yu-Chieh; Lin, Gong-Ru

    2016-06-01

    A directly modulated dual-mode laser diode (DMLD) with third-order intermodulation distortion (IMD3) suppression is proposed for a 60-GHz millimeter-wave over fiber (MMWoF) architecture, enabling new fiber-wireless communication access to cover 4-km single-mode-fiber (SMF) and 3-m wireless 16-QAM OFDM transmissions. By dual-mode injection-locking, the throughput degradation of the DMLD is mitigated with saturation effect to reduce its threshold, IMD3 power and relative intensity noise to 7.7 mA, -85 dBm and -110.4 dBc/Hz, respectively, providing huge spurious-free dynamic range of 85.8 dB/Hz2/3. This operation suppresses the noise floor of the DMLD carried QPSK-OFDM spectrum by 5 dB. The optical receiving power is optimized to restrict the power fading effect for improving the bit error rate to 1.9 × 10-3 and the receiving power penalty to 1.1 dB. Such DMLD based hybrid architecture for 60-GHz MMW fiber-wireless access can directly cover the current optical and wireless networks for next-generation indoor and short-reach mobile communications.

  3. 60-GHz Millimeter-wave Over Fiber with Directly Modulated Dual-mode Laser Diode

    PubMed Central

    Tsai, Cheng-Ting; Lin, Chi-Hsiang; Lin, Chun-Ting; Chi, Yu-Chieh; Lin, Gong-Ru

    2016-01-01

    A directly modulated dual-mode laser diode (DMLD) with third-order intermodulation distortion (IMD3) suppression is proposed for a 60-GHz millimeter-wave over fiber (MMWoF) architecture, enabling new fiber-wireless communication access to cover 4-km single-mode-fiber (SMF) and 3-m wireless 16-QAM OFDM transmissions. By dual-mode injection-locking, the throughput degradation of the DMLD is mitigated with saturation effect to reduce its threshold, IMD3 power and relative intensity noise to 7.7 mA, −85 dBm and −110.4 dBc/Hz, respectively, providing huge spurious-free dynamic range of 85.8 dB/Hz2/3. This operation suppresses the noise floor of the DMLD carried QPSK-OFDM spectrum by 5 dB. The optical receiving power is optimized to restrict the power fading effect for improving the bit error rate to 1.9 × 10−3 and the receiving power penalty to 1.1 dB. Such DMLD based hybrid architecture for 60-GHz MMW fiber-wireless access can directly cover the current optical and wireless networks for next-generation indoor and short-reach mobile communications. PMID:27297267

  4. 60-GHz Millimeter-wave Over Fiber with Directly Modulated Dual-mode Laser Diode.

    PubMed

    Tsai, Cheng-Ting; Lin, Chi-Hsiang; Lin, Chun-Ting; Chi, Yu-Chieh; Lin, Gong-Ru

    2016-06-14

    A directly modulated dual-mode laser diode (DMLD) with third-order intermodulation distortion (IMD3) suppression is proposed for a 60-GHz millimeter-wave over fiber (MMWoF) architecture, enabling new fiber-wireless communication access to cover 4-km single-mode-fiber (SMF) and 3-m wireless 16-QAM OFDM transmissions. By dual-mode injection-locking, the throughput degradation of the DMLD is mitigated with saturation effect to reduce its threshold, IMD3 power and relative intensity noise to 7.7 mA, -85 dBm and -110.4 dBc/Hz, respectively, providing huge spurious-free dynamic range of 85.8 dB/Hz(2/3). This operation suppresses the noise floor of the DMLD carried QPSK-OFDM spectrum by 5 dB. The optical receiving power is optimized to restrict the power fading effect for improving the bit error rate to 1.9 × 10(-3 )and the receiving power penalty to 1.1 dB. Such DMLD based hybrid architecture for 60-GHz MMW fiber-wireless access can directly cover the current optical and wireless networks for next-generation indoor and short-reach mobile communications.

  5. Nanoparticle Toxicity Mechanisms: Genotoxicity

    NASA Astrophysics Data System (ADS)

    Botta, Alain; Benameur, Laı̈la

    Despite the relatively small amount of convincing experimental data, the potentially genotoxic nature of certain nanoparticles seems plausible, owing in particular to the presence of reactive oxygen species (ROS) such as the superoxide anion O2 • - , the hydroxyl radical • OH, and singlet oxygen 1O2, and reactive nitrogen species (RNS) such as nitrogen monoxide NO, the peroxynitrite anion ONOO - , the peroxynitrite radical ONOO • , and dinitrogen trioxide N2O3, a powerful nitration agent.

  6. Genotoxicity of monosodium glutamate.

    PubMed

    Ataseven, Nazmiye; Yüzbaşıoğlu, Deniz; Keskin, Ayten Çelebi; Ünal, Fatma

    2016-05-01

    Monosodium glutamate (MSG) is one of the most widely used flavor enhancers throughout the world. The aim of this study is to investigate the genotoxic potential of MSG by using chromosome aberrations (CAs), sister-chromatid exchanges (SCEs), cytokinesis-blocked micronucleus (CBMN), and random amplified polymorphic DNA-polimerase chain reaction (RAPD-PCR) in cultured human lymphocytes and alkaline comet assays in isolated human lymphocytes, which were incubated with six concentrations (250, 500, 1000, 2000, 4000 and 8000 μg/mL) of MSG. The result of this study indicated that MSG significantly and dose dependently increased the frequencies of CAs, SCE and MN in all treatments and times, compared with control. However, the replication (RI) and nuclear division indices (NDI) were not affected. In this paper, in vitro genotoxic effects of the MSG was also investigated on human peripheral lymphocytes by analysing the RAPD-PCR with arbitrary 10-mer primers. The changes occurring in RAPD profiles after MSG treatment include increase or decrease in band intensity and gain or loss of bands. In the comet assay, this additive caused DNA damage at all concentrations in isolated human lymphocytes after 1-h in vitro exposure. Our results demonstrate that MSG is genotoxic to the human peripheral blood lymphocytes in vitro.

  7. Direct observation of transition to electron Bernstein waves from electromagnetic mode by three mode-conversion scenarios in the dipole confinement torus plasma

    NASA Astrophysics Data System (ADS)

    Uchijima, K.; Takemoto, T.; Morikawa, J.; Ogawa, Y.

    2015-06-01

    Direct measurement experiments on the mode conversion to the electron Bernstein wave (EBW) have been conducted in dipole confinement torus plasmas for three excitation scenarios; i.e. perpendicular injections of an eXtraordinary mode (X-mode) from the low- and high-magnetic-field sides, and the oblique injection of an Ordinary mode (O-mode) from the low-magnetic-field side. By inserting probe antennas into plasmas, wave propagation has been directly measured. At plasma conditions for the EBW excitation, several characteristics which indicate the mode conversion to the EBWs have been observed; i.e. a short wavelength wave, an electrostatic and longitudinal mode, backward propagation at the upper hybrid resonance (UHR) region. Meanwhile, the wavelengths experimentally observed might be slightly longer than those of theoretical prediction. In the case of the oblique injection of the O-mode, it has been identified that the window of the injection angle for the excitation of the EBW would be quite limited, and the optimum angle seems to be roughly in agreement with theory. These experimental results might support that the electromagnetic waves injected outside of torus plasmas reach to the UHR region and convert wave characteristics to the EBWs for three excitation scenarios.

  8. Automatically determining the origin direction and propagation mode of high-frequency radar backscatter

    NASA Astrophysics Data System (ADS)

    Burrell, Angeline G.; Milan, Stephen E.; Perry, Gareth W.; Yeoman, Timothy K.; Lester, Mark

    2015-12-01

    Elevation angles of returned backscatter are calculated at Super Dual Auroral Radar Network radars using interferometric techniques. These elevation angles allow the altitude of the reflection point to be estimated, an essential piece of information for many ionospheric studies. The elevation angle calculation requires knowledge of the azimuthal return angle. This directional angle is usually assumed to lie along a narrow beam from the front of the radar, even though the signals are known to return from both in front of and behind the radar. If the wrong direction of return is assumed, large uncertainties will be introduced through the azimuthal return angle. This paper introduces a means of automatically determining the correct direction of arrival and the propagation mode of backscatter. The application of this method will improve the accuracy of backscatter elevation angle data and aid in the interpretation of both ionospheric and ground backscatter observations.

  9. Direct numerical simulations of mack-mode damping on porous coated cones

    NASA Astrophysics Data System (ADS)

    Lüdeke, H.; Wartemann, V.

    2013-06-01

    The flow field over a 3 degree blunt cone is investigated with respect to a hypersonic stability analysis of the boundary-layer flow at Mach 6 with porous as well as smooth walls by comparing local direct numerical simulations (DNS) and linear stability theory (LST) data. The original boundary-layer profile is generated by a finite volume solver, using shock capturing techniques to generate an axisymmetric flow field. Local boundary-layer profiles are extracted from this flow field and hypersonic Mack-modes are superimposed for cone-walls with and without a porous surface used as a passive transition-reduction device. Special care is taken of curvature effects of the wall on the mode development over smooth and porous walls.

  10. Enhanced and directional emission of semiconductor nanowires tailored through leaky/guided modes.

    PubMed

    Paniagua-Domínguez, R; Grzela, G; Rivas, J Gómez; Sánchez-Gil, J A

    2013-11-07

    Photoluminescence from finite semiconductor nanowires is theoretically investigated, exploring and predicting their antenna-like properties for light emission in a variety of configurations of interest in Nanophotonics. The theoretical analysis is based on the leaky/guided mode dispersion relation for infinite nanowires, which govern the local density of available electromagnetic states. Light emission from finite nanowires is then numerically investigated in various scenarios with regard to its enhancement and directionality. A simple analytical model is derived that, upon tuning leaky/guided mode coupling through dipole position/orientation and nanowire length, allows us to predict their antenna-like behavior and thus to tailor photoluminescence (including magnetic dipole transitions) at will, with regard to both enhancement/inhibition and associated radiation patterns.

  11. Genotoxic activity of a technical toxaphene mixture and its photodegradation products in SOS genotoxicity tests.

    PubMed

    Bartos, Tomás; Skarek, Michal; Cupr, Pavel; Kosubová, Petra; Holoubek, Ivan

    2005-01-03

    Toxaphene (CAS No. 800-35-2) is a complex mixture of several hundred components that was used worldwide primarily as an agricultural pesticide with insecticide effects in the second half of the 20th century. In vitro investigations of the genotoxicity and mutagenicity of toxaphene were generally described in the literature, but they provided somewhat equivocal results. We re-evaluated the genotoxicity of technical toxaphene in two prokaryotic systems. The SOS Chromotest showed high sensitivity to toxaphene: three concentrations (40, 20 and 10 mg/l) were clearly positive and the dose-response effect was evident. In the umuC assay, a dose-dependent increase in genotoxic activity was observed at toxaphene concentrations from 2.5 to 40.0 mg/l, but these results were found to be not significant. The genotoxicity of toxaphene and its photodegradation products after UV-irradiation (3-6-9 h) at concentrations ranging from 7.5 to 60.0 mg/l was also examined in this study. An irradiated solution of technical toxaphene after 3 h showed no significant evidence of bacterial growth inhibition. However, exposure of Salmonella to 6 h UV-irradiated toxaphene showed a toxic effect compared with the negative control. After 9 h irradiation, a decrease of bacterial growth was observed. Activity of beta-galactosidase in the presence of a toxaphene solution was significantly increased after 6 and 9 h irradiation, reaching values that were 2.4- and 3.1-fold higher, respectively, than the control, which exceeded the criteria of significant genotoxicity. These results show that while technical toxaphene is a weak, direct-acting mutagen in some bacterial tests, a dose-dependent toxicity and genotoxicity of its photoproducts could be conclusively demonstrated by the umuC test.

  12. Direct Torque Control of a Small Wind Turbine with a Sliding-Mode Speed Controller

    NASA Astrophysics Data System (ADS)

    Sri Lal Senanayaka, Jagath; Karimi, Hamid Reza; Robbersmyr, Kjell G.

    2016-09-01

    In this paper. the method of direct torque control in the presence of a sliding-mode speed controller is proposed for a small wind turbine being used in water heating applications. This concept and control system design can be expanded to grid connected or off-grid applications. Direct torque control of electrical machines has shown several advantages including very fast dynamics torque control over field-oriented control. Moreover. the torque and flux controllers in the direct torque control algorithms are based on hvsteretic controllers which are nonlinear. In the presence of a sliding-mode speed control. a nonlinear control system can be constructed which is matched for AC/DC conversion of the converter that gives fast responses with low overshoots. The main control objectives of the proposed small wind turbine can be maximum power point tracking and soft-stall power control. This small wind turbine consists of permanent magnet synchronous generator and external wind speed. and rotor speed measurements are not required for the system. However. a sensor is needed to detect the rated wind speed overpass events to activate proper speed references for the wind turbine. Based on the low-cost design requirement of small wind turbines. an available wind speed sensor can be modified. or a new sensor can be designed to get the required measurement. The simulation results will be provided to illustrate the excellent performance of the closed-loop control system in entire wind speed range (4-25 m/s).

  13. Low doses and thresholds in genotoxicity: from theories to experiments.

    PubMed

    Zito, R

    2001-09-01

    The absence of threshold in the action of genotoxic carcinogens was theoretically postulated more than thirty years ago, but continuously challenged for scientific and practical reasons. The direct experimental demonstration of the presence of a threshold for genotoxic damage is precluded by the insufficient sensitivity of the biological methods presently available. In the last twenty years the sensitivity of the methods for quantitative determination of the DNA adducts of the carcinogens was enormously improved, demonstrating linearity of the dose/adducts pattern over dose intervals of more than million-fold. The arguments more often advanced for the presence of a threshold for genotoxic carcinogens were mainly based on the action of intracellular scavengers, detoxification enzymes and repair systems, being able to block completely the genotoxic carcinogens at very low doses. This hypothesis is disproved by the constant presence of DNA adducts at extremely low doses of different carcinogens, whatever their chemical structure can be. On the other hand if genotoxic damage results from damage to proteins involved in cell division, like tubulin, there is a threshold dose for such genotoxic effects. The detailed knowledge of the genotoxicity mechanism is therefore needed for a sound carcinogenic risk assessment. Most of the genotoxic carcinogens, or their metabolites, damage directly the DNA. In this case the absence of threshold must be assumed, not only for theoretical reasons, but for the results of the experiments quantitatively relating DNA damage and very low doses of carcinogens. For the sake of clarity the "adjectivated" thresholds, like practical pragmatic, apparent and operational, must disappear from documents analysing the carcinogenic risk.

  14. Acquisition algorithm for direct-detection ladars with Geiger-mode avalanche photodiodes.

    PubMed

    Milstein, Adam B; Jiang, Leaf A; Luu, Jane X; Hines, Eric L; Schultz, Kenneth I

    2008-01-10

    An optimal algorithm for detecting a target using a ladar system employing Geiger-mode avalanche photodiodes (GAPDs) is presented. The algorithm applies to any scenario where a ranging direct detection ladar is used to determine the presence of a target against a sky background within a specified range window. A complete statistical model of the detection process for GAPDs is presented, including GAPDs that are inactive for a fixed period of time each time they fire. The model is used to develop a constant false alarm rate detection algorithm that minimizes acquisition time. Numerical performance predictions, simulation results, and experimental results are presented.

  15. Photovoltaic pumping system - Comparative study analysis between direct and indirect coupling mode

    NASA Astrophysics Data System (ADS)

    Harrag, Abdelghani; Titraoui, Abdessalem; Bahri, Hamza; Messalti, Sabir

    2017-02-01

    In this paper, P&O algorithm is used in order to improve the performance of photovoltaic water pumping system in both dynamic and static response. The efficiency of the proposed algorithm has been studied successfully using a DC motor-pump powered using controller by thirty six PV modules via DC-DC boost converter derived by a P&O MPPT algorithm. Comparative study results between the direct and indirect modes coupling confirm that the proposed algorithm can effectively improve simultaneously: accuracy, rapidity, ripple and overshoot.

  16. Whispering-gallery-mode microdisk lasers produced by femtosecond laser direct writing.

    PubMed

    Ku, Jin-Feng; Chen, Qi-Dai; Zhang, Ran; Sun, Hong-Bo

    2011-08-01

    We report in this Letter fabrication of whispering-gallery-mode microdisk lasers by femtosecond laser direct writing of dye-doped resins. Not only is well-defined disk shape upheld on an inverted cone-shaped supporter, but the disk also exhibits significant lasing actions characteristic of an abrupt increase of light output and the significant narrowing of the spectral lines when the threshold is approached. This work shows that the laser micronanofabrication technology is not only applicable to passive micro-optical components, but also it may play an important role in fabrication of active optoelectronic devices and their integrated photonic circuits.

  17. Large motion tracking control for thrust magnetic bearings with fuzzy logic, sliding mode, and direct linearization

    NASA Astrophysics Data System (ADS)

    Minihan, T. P.; Lei, S.; Sun, G.; Palazzolo, A.; Kascak, A. F.; Calvert, T.

    2003-06-01

    Conventional use of magnetic bearings relies on a zero reference to keep the rotor centered in the radial and axial axes. This paper compares different control methods developed for the alternate control task of tracking an axial dynamic target. Controllers based on fuzzy logic, sliding mode, and direct linearization were designed to meet this task. Performance criteria, such as maximum axial displacement, minimum phase lag and I2R power losses were compared for each controller. The large motion, tracking problem for a rotor has utility in applications where dynamic seal clearances are required. This has a variety of potential applications in turbo-machinery, such as active stall control.

  18. Evidence for breathing modes in direct current, pulsed, and high power impulse magnetron sputtering plasmas

    SciTech Connect

    Yang, Yuchen; Zhou, Xue; Liu, Jason X.; Anders, André

    2016-01-18

    We present evidence for breathing modes in magnetron sputtering plasmas: periodic axial variations of plasma parameters with characteristic frequencies between 10 and 100 kHz. A set of azimuthally distributed probes shows synchronous oscillations of the floating potential. They appear most clearly when considering the intermediate current regime in which the direction of azimuthal spoke motion changes. Breathing oscillations were found to be superimposed on azimuthal spoke motion. Depending on pressure and current, one can also find a regime of chaotic fluctuations and one of stable discharges, the latter at high current. A pressure-current phase diagram for the different situations is proposed.

  19. Inorganic arsenic: A non-genotoxic carcinogen.

    PubMed

    Cohen, Samuel M; Chowdhury, Aparajita; Arnold, Lora L

    2016-11-01

    Inorganic arsenic induces a variety of toxicities including cancer. The mode of action for cancer and non-cancer effects involves the metabolic generation of trivalent arsenicals and their reaction with sulfhydryl groups within critical proteins in various cell types which leads to the biological response. In epithelial cells, the response is cell death with consequent regenerative proliferation. If this continues for a long period of time, it can result in an increased risk of cancer. Arsenicals do not react with DNA. There is evidence for indirect genotoxicity in various in vitro and in vivo systems, but these involve exposures at cytotoxic concentrations and are not the basis for cancer development. The resulting markers of genotoxicity could readily be due to the cytotoxicity rather than an effect on the DNA itself. Evidence for genotoxicity in humans has involved detection of chromosomal aberrations, sister chromatid exchanges in lymphocytes and micronucleus formation in lymphocytes, buccal mucosal cells, and exfoliated urothelial cells in the urine. Numerous difficulties have been identified in the interpretation of such results, including inadequate assessment of exposure to arsenic, measurement of micronuclei, and potential confounding factors such as tobacco exposure, folate deficiency, and others. Overall, the data strongly supports a non-linear dose response for the effects of inorganic arsenic. In various in vitro and in vivo models and in human epidemiology studies there appears to be a threshold for biological responses, including cancer.

  20. A buffer direct injection and direct injection readout circuit with mode selection design for infrared focal plane arrays

    NASA Astrophysics Data System (ADS)

    Sun, Tai-Ping; Lu, Yi-Chuan; Kang, Lai-Li; Shieh, Hsiu-Li

    2014-03-01

    This paper proposes a solution to the excessive area penalty associated with traditional buffer direct injection (BDI) for single pixel. The proposed solution reduces the area and power consumption of BDI to combine the direct injection (DI) within a shared architecture, while a dual-mode readout circuit expands the functionality and performance of the array readout circuit of infrared sensor. An experimental array of 10 × 8 readout circuits was fabricated using TSMC 2P4M 0.35 μm 5 V technology. Measurements were obtained using a main clock with a frequency of 3 MHz and power consumption of 9.94 mW. The minimum input current was 119 pA in BDI and 1.85 pA in DI. The signal swing was 2 V, the root mean square noise voltage was 1.84 mV, and the signal-to-noise ratio was 60 dB. This approach is applicable to mid- and long-band sensors to increase injection efficiency and resolution.

  1. Identification of specific mRNA signatures as fingerprints for carcinogenesis in mice induced by genotoxic and nongenotoxic hepatocarcinogens.

    PubMed

    Kossler, Nadine; Matheis, Katja A; Ostenfeldt, Nina; Bach Toft, Dorthe; Dhalluin, Stéphane; Deschl, Ulrich; Kalkuhl, Arno

    2015-02-01

    Long-term rodent carcinogenicity studies for evaluation of chemicals and pharmaceuticals concerning their carcinogenic potential to humans are currently receiving critical revision. Additional data from mechanistic studies can support cancer risk assessment by clarifying the underlying mode of action. In the course of the IMI MARCAR project, a European consortium of EFPIA partners and academics, which aims to identify biomarkers for nongenotoxic carcinogenesis, a toxicogenomic mouse liver database was generated. CD-1 mice were orally treated for 3 and 14 days with 3 known genotoxic hepatocarcinogens: C.I. Direct Black 38, Dimethylnitrosamine and 4,4'-Methylenedianiline; 3 nongenotoxic hepatocarcinogens: 1,4-Dichlorobenzene, Phenobarbital sodium and Piperonyl butoxide; 4 nonhepatocarcinogens: Cefuroxime sodium, Nifedipine, Prazosin hydrochloride and Propranolol hydrochloride; and 3 compounds that show ambiguous results in genotoxicity testing: Cyproterone acetate, Thioacetamide and Wy-14643. By liver mRNA expression analysis using individual animal data, we identified 64 specific biomarker candidates for genotoxic carcinogens and 69 for nongenotoxic carcinogens for male mice at day 15. The majority of genotoxic carcinogen biomarker candidates possess functions in DNA damage response (eg, apoptosis, cell cycle progression, DNA repair). Most of the identified nongenotoxic carcinogen biomarker candidates are involved in regulation of cell cycle progression and apoptosis. The derived biomarker lists were characterized with respect to their dependency on study duration and gender and were successfully used to characterize carcinogens with ambiguous genotoxicity test results, such as Wy-14643. The identified biomarker candidates improve the mechanistic understanding of drug-induced effects on the mouse liver that result in hepatocellular adenomas and/or carcinomas in 2-year mouse carcinogenicity studies.

  2. Accuracy details in realistic CFD modeling of an industrial centrifugal pump in direct and reverse modes

    NASA Astrophysics Data System (ADS)

    Páscoa, J. C.; Silva, F. J.; Pinheiro, J. S.; Martins, D. J.

    2010-12-01

    Numerical computation of the flowfield inside a pump is herein used as a numerical laboratory, subject to the limitations of modeling assumptions and to experimental verification. A numerical computation of the flow inside a real industrial centrifugal pump is performed that includes a very sophisticated geometry. Conversely to other computations, in this test case no simplification of the geometry was introduced. Numerical computations are obtained using Spalart-Allmaras turbulence model. A detailed analysis of the turbulent flowstructure is performed for the design point and two off design conditions. Additional computations were performed in order to compare the numerical and experimental pump characteristics; these were obtained under normalized testing conditions. Further computations are presented for the pump working in reverse turbine mode (PAT). Detailed analyses of the flow allow a comparison of the internal flow losses when the pump is operating in direct and reverse mode. This is also useful to help in the selection of an adequate pump geometry that can work in both modes with best efficiency.

  3. Directional fluorescence emission by individual V-antennas explained by mode expansion.

    PubMed

    Vercruysse, Dries; Zheng, Xuezhi; Sonnefraud, Yannick; Verellen, Niels; Di Martino, Giuliana; Lagae, Liesbet; Vandenbosch, Guy A E; Moshchalkov, Victor V; Maier, Stefan A; Van Dorpe, Pol

    2014-08-26

    Specially designed plasmonic antennas can, by far-field interference of different antenna elements or a combination of multipolar antenna modes, scatter light unidirectionally, allowing for directional light control at the nanoscale. One of the most basic and compact geometries for such antennas is a nanorod with broken rotational symmetry, in the shape of the letter V. In this article, we show that these V-antennas unidirectionally scatter the emission of a local dipole source in a direction opposite the undirectional side scattering of a plane wave. Moreover, we observe high directivity, up to 6 dB, only for certain well-defined positions of the emitter relative to the antenna. By employing a rigorous eigenmode expansion analysis of the V-antenna, we fully elucidate the fundamental origin of its directional behavior. All findings are experimentally verified by measuring the radiation patterns of a scattered plane wave and the emission pattern of fluorescently doped PMMA positioned in different regions around the antenna. The fundamental interference effects revealed in the eigenmode expansion can serve as guidelines in the understanding and further development of nanoscale directional scatterers.

  4. Laser-direct writing of single mode and multi-mode polymer step index waveguide structures for optical backplanes and interconnection assemblies

    NASA Astrophysics Data System (ADS)

    Kruse, Kevin; Middlebrook, Christopher

    2015-01-01

    A laser direct writing (LDW) method is implemented as a cost efficient polymer waveguide (WG) fabrication method for prototyping large substrates for optical backplanes and optical interconnection assemblies. The LDW setup utilizes a 3-axis air-bearing motion platform to reduce WG fabrication error to within ±0.15 μm. A UV laser diode coupled single mode fiber with a focusing lens module is capable of LDW WGs at both multimode (50 μm) and single mode (6 μm) dimensions. Correlation between LDW parameters and fabricated WG dimensions using Dow Corning® OE-4140 UV-Cured Optical Elastomer (ncore = 1.5142, nclad = 1.5064) is discussed theoretically and confirmed experimentally for both applications. A theoretical model is developed and utilized for producing LDW multi-mode (0.04 dB/cm, λ = 850 nm) and single mode (0.55 dB/cm, λ = 1310 nm) WGs. Measured propagation losses of LDW WGs are comparable to losses of photolithographic multi-mode (0.04 dB/cm @ 850 nm) and single mode (0.59 dB/cm @ 1310 nm) WG builds. LDW multi-mode and single mode WG radial bend and crossing losses are evaluated for advanced optical communication channel routing capabilities and do not exhibit significant deviations from photolithographic-manufactured WG device loss.

  5. Carotid artery B-mode ultrasound image segmentation based on morphology, geometry and gradient direction

    NASA Astrophysics Data System (ADS)

    Sunarya, I. Made Gede; Yuniarno, Eko Mulyanto; Purnomo, Mauridhi Hery; Sardjono, Tri Arief; Sunu, Ismoyo; Purnama, I. Ketut Eddy

    2017-06-01

    Carotid Artery (CA) is one of the vital organs in the human body. CA features that can be used are position, size and volume. Position feature can used to determine the preliminary initialization of the tracking. Examination of the CA features can use Ultrasound. Ultrasound imaging can be operated dependently by an skilled operator, hence there could be some differences in the images result obtained by two or more different operators. This can affect the process of determining of CA. To reduce the level of subjectivity among operators, it can determine the position of the CA automatically. In this study, the proposed method is to segment CA in B-Mode Ultrasound Image based on morphology, geometry and gradient direction. This study consists of three steps, the data collection, preprocessing and artery segmentation. The data used in this study were taken directly by the researchers and taken from the Brno university's signal processing lab database. Each data set contains 100 carotid artery B-Mode ultrasound image. Artery is modeled using ellipse with center c, major axis a and minor axis b. The proposed method has a high value on each data set, 97% (data set 1), 73 % (data set 2), 87% (data set 3). This segmentation results will then be used in the process of tracking the CA.

  6. Two-Sided Pyramid Wavefront Sensor in the Direct Phase Mode

    SciTech Connect

    Phillion, D; Baker, K

    2006-04-12

    The two-sided pyramid wavefront sensor has been extensively simulated in the direct phase mode using a wave optics code. The two-sided pyramid divides the focal plane so that each half of the core only interferes with the speckles in its half of the focal plane. A relayed image of the pupil plane is formed at the CCD camera for each half. Antipodal speckle pairs are separated so that a pure phase variation causes amplitude variations in the two images. The phase is reconstructed from the difference of the two amplitudes by transforming cosine waves into sine waves using the Hilbert transform. There are also other corrections which have to be applied in Fourier space. The two-sided pyramid wavefront sensor performs extremely well: After two or three iterations, the phase error varies purely in y. The two-sided pyramid pair enables the phase to be completely reconstructed. Its performance has been modeled closed loop with atmospheric turbulence and wind. Both photon noise and read noise were included. The three-sided and four-sided pyramid wavefront sensors have also been studied in direct phase mode. Neither performs nearly as well as does the two-sided pyramid wavefront sensor.

  7. A Mode Detection Method Using the Azimuthal Directivity of a Turbofan Model

    NASA Technical Reports Server (NTRS)

    Thomas, R. H.; Farassat, F.; Clark, L. R.; Gerhold, C. H.; Kelly, J. J.; Becker, L. E.

    1999-01-01

    The azimuthal, far field directivity of a scale fan model was measured in high resolution. The model is a 12 inch diameter rotor with 16 blades followed by 40 stator vanes. The tests were conducted at the nominal 100% speed corresponding to a tip speed of 905 ft/sec. Measurement of the radiated sound field, forward of the fan, was made in an anechoic chamber with an inflow control device and a baffle separating the aft and forward radiated interaction noise. The acoustic field was surveyed with a circular hoop array of 16 microphones which was moved to 14 axial stations. At each axial station the hoop was rotated in half-degree increments to take 736 points in the azimuthal angle. In addition to sound pressure level, the phase angle relative to a reference microphone was measured at each point. The sound pressure level is shown to vary in patterns by 10-15 dB especially for the fundamental tone but also for the first and second harmonic. A far field mode detection method has been developed and used with the data which determines the modes generated by the fan and which then interact to form the azimuthal directivity.

  8. Efficient pre-ionization by direct X-B mode conversion in VEST

    NASA Astrophysics Data System (ADS)

    Jo, JongGab; Lee, H. Y.; Kim, S. C.; Kim, S. H.; An, Y. H.; Hwang, Y. S.

    2017-01-01

    Pre-ionization experiments with pure toroidal field have been carried out in VEST (Versatile Experiment Spherical Torus) to investigate the feasibility of direct XB mode conversion from perpendicular LFS (Low Field Side) injection for efficient pre-ionization. Pre-ionization plasmas are studied by measuring the electron density and temperature profiles with respect to microwave power and toroidal field strength, and 2D full wave cold plasma simulation using the COMSOL Multiphysics is performed for the comparison. It is experimentally figured out that exceeding the threshold microwave power (>3 kW), the parametric decay and localized collisional heating is observed near the UHR (Upper Hybrid Resonance), and the efficient XB mode conversion can be achieved in both short density scale length (Ln) and magnetic scale length (LB) region positioned at outboard and inboard sides, respectively. From the 2D full wave simulations, the reflection and tunneling of X-wave near the R-cutoff layer according to the measured electron density profiles are analyzed with electric field polarization and power flow. Threshold electric field and wave power density for parametric decay are evaluated at least more than 4.8 × 104 V/m and 100 W/cm2, respectively. This study shows that efficient pre-ionization schemes using direct XB mode conversion can be realized by considering the key factors such as Ln, LB, and transmitted wave power at the UHR. Application to Ohmic start-up experiment is carried out to confirm the effect of the pre-ionization schemes on tokamak plasma start-up in VEST.

  9. Threshold conditions for transitions to I-mode and H-mode with unfavourable ion grad B drift direction

    NASA Astrophysics Data System (ADS)

    Hubbard, A. E.; Whyte, D. G.; Churchill, R. M.; Dominguez, A.; Hughes, J. W.; Ma, Y.; Marmar, E. S.; Lin, Y.; Reinke, M. L.; White, A. E.

    2012-11-01

    Transitions from the L-mode regime to the I-mode regime, with an energy transport barrier, and to the H-mode regime with both an energy and particle transport barrier are studied on the Alcator C-Mod tokamak. Steady I-mode plasmas have been produced over a wide range of plasma field (3-6 T), current (0.8-1.35 MA), density and shaping in the unfavourable ion B × ∇B configuration. The power threshold for the L-I transition is higher than scalings for the L-H transition with favourable drift, and increases with plasma current as well as density. Threshold conditions for the I-H transition are more variable. In some conditions I-mode is maintained up to the maximum available ICRF power of 5 MW, nearly a factor of two above the L-I threshold, giving a robust operating window. Edge Te at the L-I transition is in the range 250-450 eV, over a range of current and density, about a factor of two higher than with favourable drift, while at the I-H transition it can be much higher (up to 1.1 keV) but is again widely variable. Heat pulses due to sawteeth may play a role in transitions. Controlled I-L back transitions indicate little power hysteresis.

  10. Directional thermal emission control by coupling between guided mode resonances and tunable plasmons in multilayered graphene

    NASA Astrophysics Data System (ADS)

    Ito, Kota; Iizuka, Hideo

    2016-10-01

    Directional thermal radiation is attracting interest because of its applicability to thermal management systems and mid-infrared light sources. Plasmons in a single graphene layer are tunable by the chemical potential, while the lateral wavenumber of the plasmon dispersion is too large for the directional coupling to the far field. In this paper, we achieve directional thermal radiation by utilizing tunable plasmons in multilayered graphene. The lateral wavenumber of the plasmon is shown to be reduced as the number of graphene layers increases, and the reduction is analytically explained. The thermally excited graphene plasmon couples to the guided mode resonance in a silicon grating through evanescent waves so as to realize angular-selective far-field emission. We develop a modal analysis in order to investigate the coupling condition. In addition, the directional thermal emission including asymmetric one can be tuned by varying the chemical potential of graphene layers. The calculated emissivity obtained by changing both the chemical potential and the height of the grating suggests the control of the angular heat flux profile.

  11. An instrument for direct observations of seismic and normal-mode rotational oscillations of the Earth

    PubMed Central

    Cowsik, R.

    2007-01-01

    The rotations around the vertical axis associated with the normal mode oscillations of the Earth and those induced by the seismic and other disturbances have been very difficult to observe directly. Such observations will provide additional information for 3D modeling of the Earth and for understanding earthquakes and other underground explosions. In this paper, we describe the design of an instrument capable of measuring the rotational motions associated with the seismic oscillations of the Earth, including the lowest frequency normal mode at ν ≈ 3.7 × 10−4 Hz. The instrument consists of a torsion balance with a natural frequency of ν0 ≈ 1.6 × 10−4 Hz, which is observed by an autocollimating optical lever of high angular resolution and dynamic range. Thermal noise limits the sensitivity of the apparatus to amplitudes of ≈ 1.5 × 10−9 rad at the lowest frequency normal mode and the sensitivity improves as ν−3/2 with increasing frequency. Further improvements in sensitivity by about two orders of magnitude may be achieved by operating the balance at cryogenic temperatures. Alternatively, the instrument can be made more robust with a reduced sensitivity by increasing ν0 to ≈10−2 Hz. This instrument thus complements the ongoing effort by Igel and others to study rotational motions using ring laser gyroscopes and constitutes a positive response to the clarion call for developments in rotation seismology by Igel, Lee, and Todorovska [H. Igel, W.H.K. Lee and M.I. Todorovska, AGU Fall Meeting 2006, Rotational Seismology Sessions: S22A,S23B, Inauguration of the International Working Group on Rotational Seismology (IWGoRS)]. PMID:17438268

  12. An instrument for direct observations of seismic and normal-mode rotational oscillations of the Earth.

    PubMed

    Cowsik, R

    2007-04-24

    The rotations around the vertical axis associated with the normal mode oscillations of the Earth and those induced by the seismic and other disturbances have been very difficult to observe directly. Such observations will provide additional information for 3D modeling of the Earth and for understanding earthquakes and other underground explosions. In this paper, we describe the design of an instrument capable of measuring the rotational motions associated with the seismic oscillations of the Earth, including the lowest frequency normal mode at nu approximately 3.7 x 10(-4) Hz. The instrument consists of a torsion balance with a natural frequency of nu(0) approximately 1.6 x 10(-4) Hz, which is observed by an autocollimating optical lever of high angular resolution and dynamic range. Thermal noise limits the sensitivity of the apparatus to amplitudes of approximately 1.5 x 10(-9) rad at the lowest frequency normal mode and the sensitivity improves as nu(-3/2) with increasing frequency. Further improvements in sensitivity by about two orders of magnitude may be achieved by operating the balance at cryogenic temperatures. Alternatively, the instrument can be made more robust with a reduced sensitivity by increasing nu(0) to approximately 10(-2) Hz. This instrument thus complements the ongoing effort by Igel and others to study rotational motions using ring laser gyroscopes and constitutes a positive response to the clarion call for developments in rotation seismology by Igel, Lee, and Todorovska [H. Igel, W.H.K. Lee and M.I. Todorovska, AGU Fall Meeting 2006, Rotational Seismology Sessions: S22A,S23B, Inauguration of the International Working Group on Rotational Seismology (IWGoRS)].

  13. Chemical sensing of in situ extracted organics by direct detection of mode-filtered light

    NASA Astrophysics Data System (ADS)

    Synovec, Robert E.; Bruckner, Carsten A.; Burgess, Lloyd W.; Foster, M. D.

    1994-10-01

    A novel chemical analyzer is described in which an optical fiber is inserted into a transparent capillary tube, such that the inner diameter of the tube is only a few microns larger than the outer diameter of the fiber cladding. This configuration is referred to as a torus column. When a sample volume is introduced to the torus column at a low flow rate, propagated light is mode-filtered due to a change in the critical angle at the core/clad interface, as a result of in-situ extracted chemical species. Conventionally, chemical species extracted into the cladding are sensed as a change in the transmitted light at the end of the fiber. An alternative approach, measuring this mode-filtered light directly along the side of the fiber, is reported. The new approach has a signal-to-noise advantage over the conventional approach. The result is a low volume sensor that temporally separates, as well as detects, chemical species that partition into the fiber cladding. The temporal information enhances sensor performance, providing first order information for subsequent data analysis. We have examined the modulation of the critical angle by chemical species of interest at steady-state concentrations, and as transient concentration profiles that were shifted in time. In summary, the analyzer has chemical selectivity provided by differences in the refractive index, distribution coefficient, and transient time of the concentration profile of each chemical species in a sample. The chemical analyzer should be a promising tool for process and environmental monitoring.

  14. Strategy for genotoxicity testing--metabolic considerations.

    PubMed

    Ku, Warren W; Bigger, Anita; Brambilla, Giovanni; Glatt, Hansruedi; Gocke, Elmar; Guzzie, Peggy J; Hakura, Atsushi; Honma, Masamitsu; Martus, Hans-Joerg; Obach, R Scott; Roberts, Stanley

    2007-02-03

    metabolic activation system, or direct testing of an isolated or synthesized metabolite. The working group also identified specific areas where more data or experiences need to be gained to reach consensus. These included defining a discrete exposure action trigger for safety assessment and when direct testing of a metabolite of interest is warranted versus the use of an alternative in vitro activation system, a universal recommendation for the timing of human ADME studies for drug candidates and the positioning of metabolite structural knowledge (through in silico systems, literature, expert analysis) in supporting metabolite safety qualification. Lastly, the working group outlined future considerations for refining the initially proposed strategies. These included the need for further evaluation of the current in vitro genotoxicity testing protocols that can potentially perturb or reduce the level of metabolic activity (potential alterations in metabolism associated with both the use of some solvents to solubilize test chemicals and testing to the guidance limit dose), and proposing broader evaluations of alternative metabolic activation sources or engineered test systems to further challenge the suitability of (or replace) the current induced liver S9 activation source.

  15. Multiple Enone-Directed Reactivity Modes Lead to the Selective Photochemical Fluorination of Polycyclic Terpenoid Derivatives.

    PubMed

    Pitts, Cody Ross; Bume, Desta Doro; Harry, Stefan Andrew; Siegler, Maxime A; Lectka, Thomas

    2017-02-15

    In the realm of aliphatic fluorination, the problem of reactivity has been very successfully addressed in recent years. In contrast, the associated problem of selectivity, that is, directing fluorination to specific sites in complex molecules, remains a great, fundamental challenge. In this report, we show that the enone functional group, upon photoexcitation, provides a solution. Based solely on orientation of the oxygen atom, site-selective photochemical fluorination is achieved on steroids and bioactive polycycles with up to 65 different sp(3) C-H bonds. We have also found that γ-, β-, homoallylic, and allylic fluorination are all possible and predictable through the theoretical modes reported herein. Lastly, we present a preliminary mechanistic hypothesis characterized by intramolecular hydrogen atom transfer, radical fluorination, and ultimate restoration of the enone. In all, these results provide a leap forward in the design of selective fluorination of complex substrates that should be relevant to drug discovery, where fluorine plays a prominent role.

  16. Structural damage identification with multi-objective DIRECT algorithm using natural frequencies and single mode shape

    NASA Astrophysics Data System (ADS)

    Cao, Pei; Yoo, David; Shuai, Qi; Tang, J.

    2017-04-01

    Structural damage identification has been continuously pursued in engineering practices to facilitate diagnosis and prognosis in structural health monitoring (SHM) systems. In SHM, the changes of modal parameters are frequently used as inputs. In this research, we employ the multiple damage location assurance criterion (MDLAC) to characterize the correlation between predictions of both frequency changes and single mode shape change with the measured data. The damage locations and severities can be obtained by maximizing the MDLAC values. Thereafter, a multi-objective optimization problem based on their MDLAC values can be formulated and optimized by applying a newly devised multi-objective DIRECT approach. The proposed approach offers practical attractions of only requiring a short amount of computational time, and the results are conclusive and repeatable.

  17. Mechanisms of fiber-induced genotoxicity.

    PubMed Central

    Jaurand, M C

    1997-01-01

    The mechanisms of particle-induced genotoxicity have been investigated mainly with asbestos fibers. The results are summarized and discussed in this paper. DNA damage can be produced by oxidoreduction processes generated by fibers. The extent of damage yield depends on experimental conditions: if iron is present, either on fibers or in the medium, damage is increased. However, iron reactivity does not explain all the results obtained in cell-free systems, as breakage of plasmid DNA was not directly associated with the amount of iron released by the fibers. The proximity of DNA to the site of generation of reactive oxygen species (ROS) is important because these species have an extremely short half-life. Damage to cellular DNA can be produced by oxidoreduction processes that originate from cells during phagocytosis. Secondary molecules that are more stable than ROS are probably involved in DNA damage. Oxidoreduction reactions originating from cells can induce mutations. Genotoxicity is also demonstrated by chromosomal damage associated with impaired mitosis, as evidenced by chromosome missegregation, spindle changes, alteration of cell cycle progression, formation of aneuploid and polyploid cells, and nuclear disruption. In some of these processes, the particle state and fiber dimensions are considered important parameters in the generation of genotoxic effects. PMID:9400703

  18. Genotoxic effects of metronidazole.

    PubMed

    Elizondo, G; Gonsebatt, M E; Salazar, A M; Lares, I; Santiago, P; Herrera, J; Hong, E; Ostrosky-Wegman, P

    1996-09-13

    Metronidazole (MTZ) is an effective agent used in the treatment of parasitic infections. Its genotoxic effects have been shown in a variety of prokaryotic systems; however, negative results have been reported in human in vivo studies. Due to its wide spread use, a study was performed to evaluate the chromosomal aberration frequencies in peripheral blood lymphocyte cultures from 10 individuals, before and after metronidazole treatment. A significant increase in the percentage of cells with chromatid and isochromatid breaks was observed after metronidazole treatment (1500 mg per day for 10 days). The percentages of cells with aberrations did not correlate with the levels of MTZ found in plasma. Individual variability was observed with respect to both the induction of aberrations and the concentration of MTZ in plasma. They could represent differences at the metabolic level, since metronidazole is known to be biotransformed by a polymorphic P450 cytochrome, and its metabolites have shown mutagenic activity.

  19. Mode- and Direction-Dependent Mechanical Energy Dissipation in Single-Crystal Resonators due to Anharmonic Phonon-Phonon Scattering

    NASA Astrophysics Data System (ADS)

    Iyer, Srikanth S.; Candler, Robert N.

    2016-03-01

    In this work, we determine the intrinsic mechanical energy dissipation limit for single-crystal resonators due to anharmonic phonon-phonon scattering in the Akhiezer (Ω τ ≪1 ) regime. The energy loss is derived using perturbation theory and the linearized Boltzmann transport equation for phonons, and includes the direction- and polarization-dependent mode-Grüneisen parameters in order to capture the strain-induced anharmonicity among phonon branches. This expression reveals the fundamental differences among the internal friction limits for different types of bulk-mode elastic waves. For cubic crystals, 2D-extensional modes have increased dissipation compared to width-extensional modes because the biaxial deformation opposes the natural Poisson contraction of the solid. Additionally, we show that shear-mode vibrations, which preserve volume, have significantly reduced energy loss because dissipative phonon-phonon scattering is restricted to pure-shear phonon branches, indicating that Lamé- or wineglass-mode resonators will have the highest upper limit on mechanical efficiency. Finally, we employ key simplifications to evaluate the quality factor limits for common mode shapes in single-crystal silicon devices, explicitly including the correct effective elastic storage moduli for different vibration modes and crystal orientations. Our expression satisfies the pressing need for a reliable analytical model that can predict the phonon-phonon dissipation limits for modern resonant microelectromechanical systems, where precise manufacturing techniques and accurate finite-element methods can be used to select particular vibrational mode shapes and crystal orientations.

  20. Measurements of Nitrogen Dioxide Total Column Amounts using a Brewer Double Spectrophotometer in Direct Sun Mode

    NASA Technical Reports Server (NTRS)

    Cede, Alexander; Herman, Jay; Richter, Andreas; Krotkov, Nickolay; Burrows, John

    2006-01-01

    NO2 column amounts were measured for the past 2 years at Goddard Space Flight Center, Greenbelt, Maryland, using a Brewer spectrometer in direct Sun mode. A new bootstrap method to calibrate the instrument is introduced and described. This technique selects the cleanest days from the database to obtain the solar reference spectrum. The main advantage for direct Sun measurements is that the conversion uncertainty from slant column to vertical column is negligible compared to the standard scattered light observations where it is typically on the order of 100% (2sigma) at polluted sites. The total 2sigma errors of the direct Sun retrieved column amounts decrease with solar zenith angle and are estimated at 0.2 to 0.6 Dobson units (DU, 1 DU approx. equal to 2.7 10(exp 16) molecules cm(exp -2)), which is more accurate than scattered light measurements for high NO2 amounts. Measured NO2 column amounts, ranging from 0 to 3 DU with a mean of 0.7 DU, show a pronounced daily course and a strong variability from day to day. The NO2 concentration typically increases from sunrise to noon. In the afternoon it decreases in summer and stays constant in winter. As expected from the anthropogenic nature of its source, NO2 amounts on weekends are significantly reduced. The measurements were compared to satellite retrievals from Scanning Image Absorption Spectrometer for Atmospheric Chartography (SCIAMACHY). Satellite data give the same average NO2 column and show a seasonal cycle that is similar to the ground data in the afternoon. We show that NO2 must be considered when retrieving aerosol absorption properties, especially for situations with low aerosol optical depth.

  1. Measurements of Nitrogen Dioxide Total Column Amounts using a Brewer Double Spectrophotometer in Direct Sun Mode

    NASA Technical Reports Server (NTRS)

    Cede, Alexander; Herman, Jay; Richter, Andreas; Krotkov, Nickolay; Burrows, John

    2006-01-01

    NO2 column amounts were measured for the past 2 years at Goddard Space Flight Center, Greenbelt, Maryland, using a Brewer spectrometer in direct Sun mode. A new bootstrap method to calibrate the instrument is introduced and described. This technique selects the cleanest days from the database to obtain the solar reference spectrum. The main advantage for direct Sun measurements is that the conversion uncertainty from slant column to vertical column is negligible compared to the standard scattered light observations where it is typically on the order of 100% (2sigma) at polluted sites. The total 2sigma errors of the direct Sun retrieved column amounts decrease with solar zenith angle and are estimated at 0.2 to 0.6 Dobson units (DU, 1 DU approx. equal to 2.7 10(exp 16) molecules cm(exp -2)), which is more accurate than scattered light measurements for high NO2 amounts. Measured NO2 column amounts, ranging from 0 to 3 DU with a mean of 0.7 DU, show a pronounced daily course and a strong variability from day to day. The NO2 concentration typically increases from sunrise to noon. In the afternoon it decreases in summer and stays constant in winter. As expected from the anthropogenic nature of its source, NO2 amounts on weekends are significantly reduced. The measurements were compared to satellite retrievals from Scanning Image Absorption Spectrometer for Atmospheric Chartography (SCIAMACHY). Satellite data give the same average NO2 column and show a seasonal cycle that is similar to the ground data in the afternoon. We show that NO2 must be considered when retrieving aerosol absorption properties, especially for situations with low aerosol optical depth.

  2. Direct experimental investigations of acoustic modes guided by a solid{endash}solid interface using optical interferometry

    SciTech Connect

    Matteie, C.; Jia, X.; Quentin, G.

    1997-09-01

    This paper presents direct field measurements of acoustic modes guided by the interface between two transparent solids. The measurement technique is based on the acousto-optical interaction inside the solid between the acoustic field and the probe laser beam of an interferometer. The main advantage of the method is its ability to measure acoustic strain fields in areas of difficult access with the classic detection methods. Moreover, it gives complete information about the dilatation strain field inside the solid, e.g., amplitude and phase. The propagation of a real velocity mode (Stoneley wave) is first illustrated. Then the situation of complex velocity modes is investigated for a Plexiglas{endash}fused quartz slip interface. This material combination supports two possible interface modes theoretically. These modes are simultaneously observed and the differences between their behavior are measured. {copyright} {ital 1997 Acoustical Society of America.}

  3. Design and fabrication of tubular scaffolds via direct writing in a melt electrospinning mode.

    PubMed

    Brown, Toby D; Slotosch, Anna; Thibaudeau, Laure; Taubenberger, Anna; Loessner, Daniela; Vaquette, Cedryck; Dalton, Paul D; Hutmacher, Dietmar W

    2012-12-01

    Flexible tubular structures fabricated from solution electrospun fibers are finding increasing use in tissue engineering applications. However it is difficult to control the deposition of fibers due to the chaotic nature of the solution electrospinning jet. By using non-conductive polymer melts instead of polymer solutions the path and collection of the fiber becomes predictable. In this work we demonstrate the melt electrospinning of polycaprolactone in a direct writing mode onto a rotating cylinder. This allows the design and fabrication of tubes using 20 μm diameter fibers with controllable micropatterns and mechanical properties. A key design parameter is the fiber winding angle, where it allows control over scaffold pore morphology (e.g. size, shape, number and porosity). Furthermore, the establishment of a finite element model as a predictive design tool is validated against mechanical testing results of melt electrospun tubes to show that a lesser winding angle provides improved mechanical response to uniaxial tension and compression. In addition, we show that melt electrospun tubes support the growth of three different cell types in vitro and are therefore promising scaffolds for tissue engineering applications.

  4. Direct measurement of optical force induced by near-field plasmonic cavity using dynamic mode AFM

    DOE PAGES

    Guan, Dongshi; Hang, Zhi Hong; Marset, Zsolt; ...

    2015-11-20

    Plasmonic nanostructures have attracted much attention in recent years because of their potential applications in optical manipulation through near-field enhancement. Continuing experimental efforts have been made to develop accurate techniques to directly measure the near-field optical force induced by the plasmonic nanostructures in the visible frequency range. In this work, we report a new application of dynamic mode atomic force microscopy (DM-AFM) in the measurement of the enhanced optical force acting on a nano-structured plasmonic resonant cavity. The plasmonic cavity is made of an upper gold-coated glass sphere and a lower quartz substrate patterned with an array of subwavelength goldmore » disks. In the near-field when the sphere is positioned close to the disk array, plasmonic resonance is excited in the cavity and the induced force by a 1550 nm infrared laser is found to be increased by an order of magnitude compared with the photon pressure generated by the same laser light. Lastly, the experiment demonstrates that DM-AFM is a powerful tool for the study of light induced forces and their enhancement in plasmonic nanostructures.« less

  5. Direct measurement of optical force induced by near-field plasmonic cavity using dynamic mode AFM

    SciTech Connect

    Guan, Dongshi; Hang, Zhi Hong; Marset, Zsolt; Liu, Hui; Kravchenko, Ivan I.; Chan, Ho Bun; Chan, C. T.; Tong, Penger

    2015-11-20

    Plasmonic nanostructures have attracted much attention in recent years because of their potential applications in optical manipulation through near-field enhancement. Continuing experimental efforts have been made to develop accurate techniques to directly measure the near-field optical force induced by the plasmonic nanostructures in the visible frequency range. In this work, we report a new application of dynamic mode atomic force microscopy (DM-AFM) in the measurement of the enhanced optical force acting on a nano-structured plasmonic resonant cavity. The plasmonic cavity is made of an upper gold-coated glass sphere and a lower quartz substrate patterned with an array of subwavelength gold disks. In the near-field when the sphere is positioned close to the disk array, plasmonic resonance is excited in the cavity and the induced force by a 1550 nm infrared laser is found to be increased by an order of magnitude compared with the photon pressure generated by the same laser light. Lastly, the experiment demonstrates that DM-AFM is a powerful tool for the study of light induced forces and their enhancement in plasmonic nanostructures.

  6. Direct Measurement of Optical Force Induced by Near-Field Plasmonic Cavity Using Dynamic Mode AFM

    PubMed Central

    Guan, Dongshi; Hang, Zhi Hong; Marcet, Zsolt; Liu, Hui; Kravchenko, I. I.; Chan, C. T.; Chan, H. B.; Tong, Penger

    2015-01-01

    Plasmonic nanostructures have attracted much attention in recent years because of their potential applications in optical manipulation through near-field enhancement. Continuing experimental efforts have been made to develop accurate techniques to directly measure the near-field optical force induced by the plasmonic nanostructures in the visible frequency range. In this work, we report a new application of dynamic mode atomic force microscopy (DM-AFM) in the measurement of the enhanced optical force acting on a nano-structured plasmonic resonant cavity. The plasmonic cavity is made of an upper gold-coated glass sphere and a lower quartz substrate patterned with an array of subwavelength gold disks. In the near-field when the sphere is positioned close to the disk array, plasmonic resonance is excited in the cavity and the induced force by a 1550 nm infrared laser is found to be increased by an order of magnitude compared with the photon pressure generated by the same laser light. The experiment demonstrates that DM-AFM is a powerful tool for the study of light induced forces and their enhancement in plasmonic nanostructures. PMID:26586455

  7. Evaluation of genotoxicity testing of FDA approved large molecule therapeutics.

    PubMed

    Sawant, Satin G; Fielden, Mark R; Black, Kurt A

    2014-10-01

    Large molecule therapeutics (MW>1000daltons) are not expected to enter the cell and thus have reduced potential to interact directly with DNA or related physiological processes. Genotoxicity studies are therefore not relevant and typically not required for large molecule therapeutic candidates. Regulatory guidance supports this approach; however there are examples of marketed large molecule therapeutics where sponsors have conducted genotoxicity studies. A retrospective analysis was performed on genotoxicity studies of United States FDA approved large molecule therapeutics since 1998 identified through the Drugs@FDA website. This information was used to provide a data-driven rationale for genotoxicity evaluations of large molecule therapeutics. Fifty-three of the 99 therapeutics identified were tested for genotoxic potential. None of the therapeutics tested showed a positive outcome in any study except the peptide glucagon (GlucaGen®) showing equivocal in vitro results, as stated in the product labeling. Scientific rationale and data from this review indicate that testing of a majority of large molecule modalities do not add value to risk assessment and support current regulatory guidance. Similarly, the data do not support testing of peptides containing only natural amino acids. Peptides containing non-natural amino acids and small molecules in conjugated products may need to be tested.

  8. Direct Observation of Mode-Coupling Instability in Two-Dimensional Plasma Crystals

    SciTech Connect

    Coueedel, L.; Nosenko, V.; Ivlev, A. V.; Zhdanov, S. K.; Thomas, H. M.; Morfill, G. E.

    2010-05-14

    Dedicated experiments on melting of two-dimensional plasma crystals were carried out. The melting was always accompanied by spontaneous growth of the particle kinetic energy, suggesting a universal plasma-driven mechanism underlying the process. By measuring three principal dust-lattice wave modes simultaneously, it is unambiguously demonstrated that the melting occurs due to the resonance coupling between two of the dust-lattice modes. The variation of the wave modes with the experimental conditions, including the emergence of the resonant (hybrid) branch, reveals exceptionally good agreement with the theory of mode-coupling instability.

  9. Beryllium: genotoxicity and carcinogenicity.

    PubMed

    Gordon, Terry; Bowser, Darlene

    2003-12-10

    Beryllium (Be) has physical-chemical properties, including low density and high tensile strength, which make it useful in the manufacture of products ranging from space shuttles to golf clubs. Despite its utility, a number of standard setting agencies have determined that beryllium is a carcinogen. Only a limited number of studies, however, have addressed the underlying mechanisms of the carcinogenicity and mutagenicity of beryllium. Importantly, mutation and chromosomal aberration assays have yielded somewhat contradictory results for beryllium compounds and whereas bacterial tests were largely negative, mammalian test systems showed evidence of beryllium-induced mutations, chromosomal aberrations, and cell transformation. Although inter-laboratory differences may play a role in the variability observed in genotoxicity assays, it is more likely that the different chemical forms of beryllium have a significant effect on mutagenicity and carcinogenicity. Because workers are predominantly exposed to airborne particles which are generated during the machining of beryllium metal, ceramics, or alloys, testing of the mechanisms of the mutagenic and carcinogenic activity of beryllium should be performed with relevant chemical forms of beryllium.

  10. Updated recommended lists of genotoxic and non-genotoxic chemicals for assessment of the performance of new or improved genotoxicity tests.

    PubMed

    Kirkland, David; Kasper, Peter; Martus, Hans-Jörg; Müller, Lutz; van Benthem, Jan; Madia, Federica; Corvi, Raffaella

    2016-01-01

    In 2008 we published recommendations on chemicals that would be appropriate to evaluate the sensitivity and specificity of new/modified mammalian cell genotoxicity tests, in particular to avoid misleading positive results. In light of new data it is appropriate to update these lists of chemicals. An expert panel was convened and has revised the recommended chemicals to fit the following different sets of characteristics: • Group 1: chemicals that should be detected as positive in in vitro mammalian cell genotoxicity tests. Chemicals in this group are all in vivo genotoxins at one or more endpoints, either due to DNA-reactive or non DNA-reactive mechanisms. Many are known carcinogens with a mutagenic mode of action, but a sub-class of probable aneugens has been introduced. • Group 2: chemicals that should give negative results in in vitro mammalian cell genotoxicity tests. Chemicals in this group are usually negative in vivo and non-DNA-reactive. They are either non-carcinogenic or rodent carcinogens with a non-mutagenic mode of action. • Group 3: chemicals that should give negative results in in vitro mammalian cell genotoxicity tests, but have been reported to induce gene mutations in mouse lymphoma cells, chromosomal aberrations or micronuclei, often at high concentrations or at high levels of cytotoxicity. Chemicals in this group are generally negative in vivo and negative in the Ames test. They are either non-carcinogenic or rodent carcinogens with an accepted non-mutagenic mode of action. This group contains comments as to any conditions that can be identified under which misleading positive results are likely to occur. This paper, therefore, updates these three recommended lists of chemicals and describes how these should be used for any test evaluation program.

  11. Genotoxicity and anti-genotoxicity of some traditional medicinal herbs.

    PubMed

    Romero-Jiménez, Magdalena; Campos-Sánchez, Juan; Analla, Mohamed; Muñoz-Serrano, Andrés; Alonso-Moraga, Angeles

    2005-08-01

    Six herbal infusions used worldwide (Matricaria chamomilla, Tilia cordata, Mentha piperita, Mentha pulegium, Uncaria tomentosa and Valeriana officinalis) were assayed for anti-genotoxicity using the Somatic Mutation And Recombination Test (SMART) in Drosophila melanogaster. All these infusions are traditionally used for various medical purposes, including anti-inflammatory processes. Hydrogen peroxide was used as an oxidative genotoxicant to test the anti-genotoxic potency of the medicinal infusions. None of these infusions showed a significant genotoxicity, quite the reverse they were able to behave as desmutagens, detoxifying the mutagen hydrogen peroxide. The phenolic content of such herbal infusions is argued to be the possible scavenger of reactive oxygen radicals produced by the hydrogen peroxide.

  12. Quercetin tests negative for genotoxicity in transcriptome analyses of liver and small intestine of mice.

    PubMed

    Hoek-van den Hil, Elise F; van Schothorst, Evert M; van der Stelt, Inge; Hollman, Peter C H; Keijer, Jaap; Rietjens, Ivonne M C M

    2015-07-01

    Given the positive results of quercetin in in vitro genotoxicity studies, the in vivo genotoxic properties of this important dietary flavonoid warrant testing, especially considering possible high intake via widely available food supplements. Here, this was done by transcriptome analyses of the most relevant tissues, liver and small intestine, of quercetin supplemented mice. Quercetin (0.33%) supplemented to a high-fat diet was administered to mice during 12 weeks. Serum alanine aminotransferase and aspartate aminotransferase levels revealed no indications for hepatotoxicity. Microarray pathway analysis of liver and small intestine showed no regulation of genotoxicity related pathways. Analysis of DNA damage related genes also did not point at genotoxicity. Furthermore, a published classifier set of transcripts for identifying genotoxic compounds did not indicate genotoxicity. Only two transcripts of the classifier set were regulated, but in the opposite direction compared with the genotoxic compounds 2-acetylaminofluorene (2-AAF) and aflatoxin B1 (AFB1). Based on the weight of evidence of three different types of analysis, we conclude that supplementation with quercetin at ~350 mg/kg bw/day for 12 weeks in mice showed no up-regulation of genotoxicity related pathways in liver and small intestine.

  13. Direct generation of 128-fs Gaussian pulses from a compensation-free fiber laser using dual mode-locking mechanisms

    NASA Astrophysics Data System (ADS)

    Peng, Junsong; Zhan, Li; Gu, Zhaochang; Qian, Kai; Luo, Shouyu; Shen, Qishun

    2012-03-01

    We have experimentally demonstrated the direct generation of 128-fs pulses in an all-anomalous-dispersion all-fiber mode-locked laser. The laser is free of dispersion compensation in the cavity based on standard single mode fiber (SMF). The time-bandwidth product is 0.536. The laser is achieved by using two mode-lockers, one is nonlinear polarization rotation (NPR), and the other is nonlinear amplifying loop mirror. The coexistence of dual mode-locking mechanisms can decrease the cavity length to 12-m, and also results in producing high-quality pulses with a Gaussian shape both on the pulse profile and spectrum, but without Kelly sidebands.

  14. Directional whispering gallery mode emission from Limaçon-shaped electrically pumped quantum dot micropillar lasers

    NASA Astrophysics Data System (ADS)

    Albert, F.; Hopfmann, C.; Eberspächer, A.; Arnold, F.; Emmerling, M.; Schneider, C.; Höfling, S.; Forchel, A.; Kamp, M.; Wiersig, J.; Reitzenstein, S.

    2012-07-01

    We experimentally demonstrate directional far field emission from whispering gallery modes (WGMs) in electrically driven quantum dot micropillar lasers. In-plane directionality of whispering gallery mode emission is obtained by patterning micropillars with Limaçon-shaped cross-section and an upper air-bridge contact for current injection. The micropillar lasers with radii R0 down to 4.5 μm show Q-factors of 40 000 and threshold currents of 40 μA at low temperature. We achieved a far field divergence of about 30° and a directionality of 1.67 ± 0.15 for an optimal Limaçon deformation factor ɛ ≈ 0.5. Parameter dependent studies of the directional emission as a function of ɛ reveal good qualitative agreement with theoretical predictions.

  15. All-fiber fused directional coupler for highly efficient spatial mode conversion.

    PubMed

    Ismaeel, Rand; Lee, Timothy; Oduro, Bernard; Jung, Yongmin; Brambilla, Gilberto

    2014-05-19

    We model and demonstrate a simple mode selective all-fiber coupler capable of exciting specific higher order modes in two- and few-mode fibres with high efficiency and purity. The coupler is based on inter-modally phase-matching the propagation constants in each arm of the asymmetric fused coupler, formed by dissimilar fibres. At a specific coupler diameter, the launched fundamental LP(01) mode is coupled into the higher order mode (LP(11), LP(21), LP(02)) in the other arm, over a broadband wave-length range around 1550 nm. Unlike other techniques, the demonstrated coupler is composed of a multimode fiber that is weakly fused with a phase matched conventional single mode telecom fiber (SMF-28). The beating between the supermodes at the coupler waist produces a periodic power transfer between the two arms, and therefore, by monitoring the beating while tapering, it is possible to obtain optimum selection for the desired mode. High coupling efficiencies in excess of 90% for all the higher order modes were recorded over 100 nm spectral range, while insertion losses remain as low as 0.5 dB. Coupling efficiency can be further enhanced by performing slow tapering at high temperature, in order to precisely control the coupler cross-section geometry.

  16. Current investigations into the genotoxicity of zinc oxide and silica nanoparticles in mammalian models in vitro and in vivo: carcinogenic/genotoxic potential, relevant mechanisms and biomarkers, artifacts, and limitations.

    PubMed

    Kwon, Jee Young; Koedrith, Preeyaporn; Seo, Young Rok

    2014-01-01

    Engineered nanoparticles (NPs) are widely used in many sectors, such as food, medicine, military, and sport, but their unique characteristics may cause deleterious health effects. Close attention is being paid to metal NP genotoxicity; however, NP genotoxic/carcinogenic effects and the underlying mechanisms remain to be elucidated. In this review, we address some metal and metal oxide NPs of interest and current genotoxicity tests in vitro and in vivo. Metal NPs can cause DNA damage such as chromosomal aberrations, DNA strand breaks, oxidative DNA damage, and mutations. We also discuss several parameters that may affect genotoxic response, including physicochemical properties, widely used assays/end point tests, and experimental conditions. Although potential biomarkers of nanogenotoxicity or carcinogenicity are suggested, inconsistent findings in the literature render results inconclusive due to a variety of factors. Advantages and limitations related to different methods for investigating genotoxicity are described, and future directions and recommendations for better understanding genotoxic potential are addressed.

  17. Current investigations into the genotoxicity of zinc oxide and silica nanoparticles in mammalian models in vitro and in vivo: carcinogenic/genotoxic potential, relevant mechanisms and biomarkers, artifacts, and limitations

    PubMed Central

    Kwon, Jee Young; Koedrith, Preeyaporn; Seo, Young Rok

    2014-01-01

    Engineered nanoparticles (NPs) are widely used in many sectors, such as food, medicine, military, and sport, but their unique characteristics may cause deleterious health effects. Close attention is being paid to metal NP genotoxicity; however, NP genotoxic/carcinogenic effects and the underlying mechanisms remain to be elucidated. In this review, we address some metal and metal oxide NPs of interest and current genotoxicity tests in vitro and in vivo. Metal NPs can cause DNA damage such as chromosomal aberrations, DNA strand breaks, oxidative DNA damage, and mutations. We also discuss several parameters that may affect genotoxic response, including physicochemical properties, widely used assays/end point tests, and experimental conditions. Although potential biomarkers of nanogenotoxicity or carcinogenicity are suggested, inconsistent findings in the literature render results inconclusive due to a variety of factors. Advantages and limitations related to different methods for investigating genotoxicity are described, and future directions and recommendations for better understanding genotoxic potential are addressed. PMID:25565845

  18. In silico prediction of genotoxicity.

    PubMed

    Wichard, Jörg D

    2016-12-12

    The in silico prediction of genotoxicity has made considerable progress during the last years. The main driver for the pharmaceutical industry is the ICH M7 guideline about the assessment of DNA reactive impurities. An important component of this guideline is the use of in silico models as an alternative approach to experimental testing. The in silico prediction of genotoxicity provides an established and accepted method that defines the first step in the assessment of DNA reactive impurities. This was made possible by the growing amount of reliable Ames screening data, the attempts to understand the activity pathways and the subsequent development of computer-based prediction systems. This paper gives an overview of how the in silico prediction of genotoxicity is performed under the ICH M7 guideline.

  19. Direct observation of dynamic modes excited in a magnetic insulator by pure spin current

    PubMed Central

    Demidov, V. E.; Evelt, M.; Bessonov, V.; Demokritov, S. O.; Prieto, J. L.; Muñoz, M.; Ben Youssef, J.; Naletov, V. V.; de Loubens, G.; Klein, O.; Collet, M.; Bortolotti, P.; Cros, V.; Anane, A.

    2016-01-01

    Excitation of magnetization dynamics by pure spin currents has been recently recognized as an enabling mechanism for spintronics and magnonics, which allows implementation of spin-torque devices based on low-damping insulating magnetic materials. Here we report the first spatially-resolved study of the dynamic modes excited by pure spin current in nanometer-thick microscopic insulating Yttrium Iron Garnet disks. We show that these modes exhibit nonlinear self-broadening preventing the formation of the self-localized magnetic bullet, which plays a crucial role in the stabilization of the single-mode magnetization oscillations in all-metallic systems. This peculiarity associated with the efficient nonlinear mode coupling in low-damping materials can be among the main factors governing the interaction of pure spin currents with the dynamic magnetization in high-quality magnetic insulators. PMID:27608533

  20. Genotoxicity of diuron and glyphosate in oyster spermatozoa and embryos.

    PubMed

    Akcha, F; Spagnol, C; Rouxel, J

    2012-01-15

    We investigated the effects of genotoxicant exposure in gametes and embryos to find a possible link between genotoxicity and reproduction/developmental impairment, and explore the impact of chemical genotoxicity on population dynamics. Our study focused on the genotoxic effects of two herbicides on oyster gametes and embryos: glyphosate (both as an active substance and in the Roundup formulation) and diuron. France is Europe's leading consumer of agrochemical substances and as such, contamination of France's coastal waters by pesticides is a major concern. Glyphosate and diuron are among the most frequently detected herbicides in oyster production areas; as oyster is a specie with external reproduction, its gametes and embryos are in direct contact with the surrounding waters and are hence particularly exposed to these potentially dangerous substances. In the course of this study, differences in genotoxic and embryotoxic responses were observed in the various experiments, possibly due to differences in pollutant sensitivity between the tested genitor lots. Glyphosate and Roundup had no effect on oyster development at the concentrations tested, whereas diuron significantly affected embryo-larval development from the lowest tested concentration of 0.05 μg L⁻¹, i.e. an environmentally realistic concentration. Diuron may therefore have a significant impact on oyster recruitment rates in the natural environment. Our spermiotoxicity study revealed none of the tested herbicides to be cytotoxic for oyster spermatozoa. However, the alkaline comet assay showed diuron to have a significant genotoxic effect on oyster spermatozoa at concentrations of 0.05 μg L⁻¹ upwards. Conversely, no effects due to diuron exposure were observed on sperm mitochondrial function or acrosomal membrane integrity. Although our initial results showed no negative effect on sperm function, the possible impact on fertilization rate and the consequences of the transmission of damaged DNA for

  1. Enhancement of directional broadband luminescence from a scintillation film via guided-mode resonance in a photonic crystal structure

    NASA Astrophysics Data System (ADS)

    Zhu, Zhichao; Liu, Bo; Cheng, Chuanwei; Zhang, Haifeng; Chen, Hong; Gu, Mu; Liu, Jinliang; Chen, Liang; Ouyang, Xiaoping; Xue, Chaofan; Wu, Yanqing

    2017-01-01

    Scintillation films play an important role in radiation detection. Improved light output and control of emission directionality are critical for practical applications. To obtain enhancement of broadband directional luminescence from a Lu2SiO5:Ce3+ scintillation film, a special photonic crystal structure is deposited on the film surface to provide multiple guided-mode resonances. The structure can be designed according to the application requirements. Numerical simulations are performed to analyze the enhancement. Overall, this method could be used when directional emission is required for radiation detection.

  2. A new asymmetric directional microphone algorithm with automatic mode-switching ability for binaural hearing support devices.

    PubMed

    Kim, Jinryoul; Nam, Kyoung Won; Yook, Sunhyun; Jang, Dong Pyo; Kim, In Young; Hong, Sung Hwa

    2015-06-01

    For hearing support devices, it is important to minimize the negative effect of ambient noises for speech recognition but also, at the same time, supply natural ambient sounds to the hearing-impaired person. However, conventional fixed bilateral asymmetric directional microphone (DM) algorithms cannot perform in such a way when the DM-mode device and a dominant noise (DN) source are placed on the same lateral hemisphere. In this study, a new binaural asymmetric DM algorithm that can overcome the defects of conventional algorithms is proposed. The proposed algorithm can estimate the position of a specific DN in the 90°-270° range and switch directional- and omnidirectional-mode devices automatically if the DM-mode device and the DN are placed in opposite lateral hemispheres. Computer simulation and KEMAR mannequin recording tests demonstrated that the performance of the conventional algorithm deteriorated when the DM-mode device and the DN were placed in the opposite hemisphere; in contrast, the performance of the proposed algorithm was consistently maintained regardless of directional variations in the DN. Based on these experimental results, the proposed algorithm may be able to improve speech quality and intelligibility for hearing-impaired persons who have similar degrees of hearing impairment in both ears.

  3. Genotoxicity and carcinogenicity studies of benzodiazepines.

    PubMed

    Brambilla, Giovanni; Carrozzino, Roberto; Martelli, Antonietta

    2007-12-01

    This survey is a compendium of genotoxicity and carcinogenicity information of benzodiazepines and benzodiazepine analogues. Data from 51 drugs were collected; 41 of them are still in the market. Of the 51 drugs, 12 (23.5%) do not have retrievable genotoxicity or carcinogenicity data. The remaining 39 (76.5%) have at least one genotoxicity or carcinogenicity test result. Of these 39, 12 (30.8%) have at least one positive finding: 9 tested positive in at least one genotoxicity assay, 8 in at least one carcinogenicity assay, and 5 gave a positive result in both at least one genotoxicity assay and at least one carcinogenicity assay. In terms of correlation between results of the various genotoxicity assays and absence of carcinogenic activity in mice and/or rats or in other species, none of the 11 non-carcinogenic drugs tested positive in one of the various genotoxicity assay systems. Concerning the predictivity of genetic toxicology findings for the result(s) of long-term carcinogenesis assays, 18 drugs had both genotoxicity and carcinogenicity data; of these 11 (61.1%) were neither genotoxic nor carcinogenic, 2 (11.1%) were carcinogenic in at least one sex of mice or rats but tested negative in genotoxicity assays, and 5 (27.8%) gave a positive response in at least one genotoxicity assay and in at least one carcinogenicity assay. Only 8 (19.5%) of the 41 marketed benzodiazepines and benzodiazepine analogues had all data required by current guidelines for testing of pharmaceuticals.

  4. The modes of physician remuneration and their effect on direct patient contact.

    PubMed

    Basu, Kisalaya; Mandelzys, David

    2008-01-01

    Initiatives such as primary care reform have allocated millions of dollars towards the Canadian health care system. The way physicians are remunerated affects the supply of physician services and as such is essential to these initiatives to facilitate policy goals. However, there exists a gap in understanding how different modes of remuneration affect physician-patient contact. This paper examines if there is a significant difference between the average full-time-equivalent (FTE) of family physicians (FPs) remunerated through fee-for-service (FFS), salary, and blended arrangements. We used Nova Scotia physician billings dataset which tracks every services performed by both FFS and salaried physicians over the fiscal year 2003 to 2004. We estimated two semi-logarithmic models to examine the relationship between (1) modes of remuneration and FTE, and (2) modes of remuneration and total services, using ordinary least squares method. The National Physician Survey shows a significant difference between the current modes of remuneration and the preferred modes of remuneration; thus ruling out the possibility of selectivity bias. The results show that compared to the FFS FPs, the salaried FPs and blended FPs produce on average 40.46% and 23.13% less FTE respectively. It also indicates that compared to the FFS FPs, the salaried FPs and blended FPs deliver 53.54% and 31.49% fewer services on average.

  5. Environmental effects of dredging. Evaluation of sediment genotoxicity. Workshop summary and conclusions. Technical notes

    SciTech Connect

    1990-10-01

    This Technical Note summarizes the proceedings of a workshop that was held March 6-8,1990, at the Environmental Laboratory, US Army Engineer Waterways Experiment Station. The purpose of the workshop was to gain guidance from recognized authorities for the development of sediment bioassays of genotoxicity, that is, mutagenicity, carcinogenicity, immunotoxicity, teratogenicity, and histopathologic potential. The conclusions of the workshop are being used to identify existing genotoxicity bioassays that show promise for application in evaluating sediments, to recommend modifications for testing sediments, and to help direct subsequent research and development of bioassays of genotoxicity by the US Army Corps of Engineers.

  6. A New Mode of Lecturing for Self-Directed Learning—Virtual Classroom on a DVD

    NASA Astrophysics Data System (ADS)

    Ambikairajah, Eliathamby; Epps, Julien; Sheng, Ming; Celler, Branko

    2008-05-01

    Results of a large four-year longitudinal study of issues affecting student learning has motivated the development of a new mode of teaching, which takes the context of student learning into account and enhances student understanding of subject material. This new mode of lecture delivery is based on digital capture and student-controlled, user-configurable playback of synchronized lecturer dynamic annotation and video. This approach was tested in a large undergraduate course during which lectures were delivered entirely via pre-recorded lecture material on DVD, and in which the face-to-face teaching time was used instead for focused discussion classes. We present the results of a study of this novel delivery mode, using an electronic whiteboard and DVD capture. Our evaluations show convincingly that students are better able to review and understand lecture material.

  7. Oscillation modes of direct current microdischarges with parallel-plate geometry

    SciTech Connect

    Stefanovic, Ilija; Kuschel, Thomas; Winter, Joerg; Skoro, Nikola; Maric, Dragana; Petrovic, Zoran Lj

    2011-10-15

    Two different oscillation modes in microdischarge with parallel-plate geometry have been observed: relaxation oscillations with frequency range between 1.23 and 2.1 kHz and free-running oscillations with 7 kHz frequency. The oscillation modes are induced by increasing power supply voltage or discharge current. For a given power supply voltage, there is a spontaneous transition from one to other oscillation mode and vice versa. Before the transition from relaxation to free-running oscillations, the spontaneous increase of oscillation frequency of relaxation oscillations form 1.3 kHz to 2.1 kHz is measured. Fourier transform spectra of relaxation oscillations reveal chaotic behavior of microdischarges. Volt-ampere (V-A) characteristics associated with relaxation oscillations describes periodical transition between low current, diffuse discharge, and normal glow. However, free-running oscillations appear in subnormal glow only.

  8. Optimization of substrate dielectric and mode of microstrip ring antenna for high efficiency and directivity

    NASA Astrophysics Data System (ADS)

    Vaitheeswaran Iyer, S. M.; Joshi, A. W.; Karekar, R. N.

    1993-07-01

    Fields of microstrip ring antennas are calculated using a theoretical formulation based on the Green's function in conjunction with the reflection coefficient matrix approach. The effect of surface wave excitation on the efficiency of space wave launching of an annular ring antenna is analyzed, focusing on the case when the antenna is operated at higher-order modes. It is shown that the ring antenna outperforms disk and rectangular patch antennas and exhibits optimized performance for the TM sub 12 mode, with a substrate dielectric constant of 6 with high gain, broad lobe width, and no side lobes. It is considered to be a good candidate for array synthesis even in MMIC.

  9. Residual-QSAR. Implications for genotoxic carcinogenesis

    PubMed Central

    2011-01-01

    Introduction Both main types of carcinogenesis, genotoxic and epigenetic, were examined in the context of non-congenericity and similarity, respectively, for the structure of ligand molecules, emphasizing the role of quantitative structure-activity relationship ((Q)SAR) studies in accordance with OECD (Organization for Economic and Cooperation Development) regulations. The main purpose of this report involves electrophilic theory and the need for meaningful physicochemical parameters to describe genotoxicity by a general mechanism. Residual-QSAR Method The double or looping multiple linear correlation was examined by comparing the direct and residual structural information against the observed activity. A self-consistent equation of observed-computed activity was assumed to give maximum correlation efficiency for those situations in which the direct correlations gave non-significant statistical information. Alternatively, it was also suited to describe slow and apparently non-noticeable cancer phenomenology, with special application to non-congeneric molecules involved in genotoxic carcinogenesis. Application and Discussions The QSAR principles were systematically applied to a given pool of molecules with genotoxic activity in rats to elucidate their carcinogenic mechanisms. Once defined, the endpoint associated with ligand-DNA interaction was used to select variables that retained the main Hansch physicochemical parameters of hydrophobicity, polarizability and stericity, computed by the custom PM3 semiempirical quantum method. The trial and test sets of working molecules were established by implementing the normal Gaussian principle of activities that applies when the applicability domain is not restrained to the congeneric compounds, as in the present study. The application of the residual, self-consistent QSAR method and the factor (or average) method yielded results characterized by extremely high and low correlations, respectively, with the latter resembling

  10. Residual-QSAR. Implications for genotoxic carcinogenesis.

    PubMed

    Putz, Mihai V

    2011-06-13

    Both main types of carcinogenesis, genotoxic and epigenetic, were examined in the context of non-congenericity and similarity, respectively, for the structure of ligand molecules, emphasizing the role of quantitative structure-activity relationship ((Q)SAR) studies in accordance with OECD (Organization for Economic and Cooperation Development) regulations. The main purpose of this report involves electrophilic theory and the need for meaningful physicochemical parameters to describe genotoxicity by a general mechanism. RESIDUAL-QSAR METHOD: The double or looping multiple linear correlation was examined by comparing the direct and residual structural information against the observed activity. A self-consistent equation of observed-computed activity was assumed to give maximum correlation efficiency for those situations in which the direct correlations gave non-significant statistical information. Alternatively, it was also suited to describe slow and apparently non-noticeable cancer phenomenology, with special application to non-congeneric molecules involved in genotoxic carcinogenesis. The QSAR principles were systematically applied to a given pool of molecules with genotoxic activity in rats to elucidate their carcinogenic mechanisms. Once defined, the endpoint associated with ligand-DNA interaction was used to select variables that retained the main Hansch physicochemical parameters of hydrophobicity, polarizability and stericity, computed by the custom PM3 semiempirical quantum method. The trial and test sets of working molecules were established by implementing the normal Gaussian principle of activities that applies when the applicability domain is not restrained to the congeneric compounds, as in the present study. The application of the residual, self-consistent QSAR method and the factor (or average) method yielded results characterized by extremely high and low correlations, respectively, with the latter resembling the direct activity to parameter QSARs

  11. Genotoxicity of titanium dioxide nanoparticles.

    PubMed

    Chen, Tao; Yan, Jian; Li, Yan

    2014-03-01

    Titanium dioxide nanoparticles (TiO(2)-NPs, <100 nm) are increasingly being used in pharmaceuticals and cosmetics due to the unique properties derived from their small sizes. However, their large surface-area to mass ratio and high redox potential may negatively impact human health and the environment. TiO(2)-NPs can cause inflammation, pulmonary damage, fibrosis, and lung tumors and they are possibly carcinogenic to humans. Because cancer is a disease involving mutation, there are a large number of studies on the genotoxicity of TiO(2)-NPs. In this article, we review the results that have been reported in the literature, with a focus on data generated from the standard genotoxicity assays. The data include genotoxicity results from the Ames test, in vitro and in vivo Comet assay, in vitro and in vivo micronucleus assay, sister chromatid exchange assay, mammalian cell hypoxanthine-guanine phosphoribosyl transferase gene assay, the wing somatic mutation and recombination assay, and the mouse phosphatidylinositol glycan, class A gene assay. Inconsistent results have been found in these assays, with both positive and negative responses being reported. The in vitro systems for assessing the genotoxicity of TiO(2)-NPs have generated a greater number of positive results than the in vivo systems, and tests for DNA and chromosome damage have produced more positive results than the assays measuring gene mutation. Nearly all tests for measuring the mutagenicity of TiO(2)-NPs were negative. The current data indicate that the genotoxicity of TiO(2)-NPs is mediated mainly through the generation of oxidative stress in cells.

  12. Direct X-B mode conversion for high-β national spherical torus experiment in nonlinear regime

    SciTech Connect

    Ali Asgarian, M. E-mail: maa@msu.edu; Parvazian, A.; Abbasi, M.; Verboncoeur, J. P.

    2014-09-15

    Electron Bernstein wave (EBW) can be effective for heating and driving currents in spherical tokamak plasmas. Power can be coupled to EBW via mode conversion of the extraordinary (X) mode wave. The most common and successful approach to study the conditions for optimized mode conversion to EBW was evaluated analytically and numerically using a cold plasma model and an approximate kinetic model. The major drawback in using radio frequency waves was the lack of continuous wave sources at very high frequencies (above the electron plasma frequency), which has been addressed. A future milestone is to approach high power regime, where the nonlinear effects become significant, exceeding the limits of validity for present linear theory. Therefore, one appropriate tool would be particle in cell (PIC) simulation. The PIC method retains most of the nonlinear physics without approximations. In this work, we study the direct X-B mode conversion process stages using PIC method for incident wave frequency f{sub 0} = 15 GHz, and maximum amplitude E{sub 0} = 10{sup 5 }V/m in the national spherical torus experiment (NSTX). The modelling shows a considerable reduction in X-B mode conversion efficiency, C{sub modelling} = 0.43, due to the presence of nonlinearities. Comparison of system properties to the linear state reveals predominant nonlinear effects; EBW wavelength and group velocity in comparison with linear regime exhibit an increment around ∼36% and 17%, respectively.

  13. In quantum direct communication an undetectable eavesdropper can always tell Ψ from Φ Bell states in the message mode

    NASA Astrophysics Data System (ADS)

    Pavičić, Mladen

    2013-04-01

    We show that in any quantum direct communication protocol that is based on Ψ and Φ Bell states, an eavesdropper can always tell Ψ from Φ states without altering the transmission in any way in the message mode. This renders all protocols that make use of only one Ψ state and one Φ state completely insecure in the message mode. All four-Bell-state protocols require a revision and this might be of importance for new implementations of entanglement-based cryptographic protocols. The detection rate of an eavesdropper is 25% per control transmission, i.e., a half of the rate in the two-state (ping-pong) protocol. An eavesdropper can detect control probes with certainty in the standard control transmission without a photon in the Alice-to-Bob's travel mode and with near certainty in a transmission with a fake photon in the travel mode. Resending of measured control photons via the travel mode would make an eavesdropper completely invisible.

  14. Direct assignment of molecular vibrations via normal mode analysis of the neutron dynamic pair distribution function technique

    SciTech Connect

    Fry-Petit, A. M. E-mail: afry@fullerton.edu; Sheckelton, J. P.; McQueen, T. M. E-mail: afry@fullerton.edu; Rebola, A. F.; Fennie, C. J.; Mourigal, M.; Valentine, M.; Drichko, N.

    2015-09-28

    For over a century, vibrational spectroscopy has enhanced the study of materials. Yet, assignment of particular molecular motions to vibrational excitations has relied on indirect methods. Here, we demonstrate that applying group theoretical methods to the dynamic pair distribution function analysis of neutron scattering data provides direct access to the individual atomic displacements responsible for these excitations. Applied to the molecule-based frustrated magnet with a potential magnetic valence-bond state, LiZn{sub 2}Mo{sub 3}O{sub 8}, this approach allows direct assignment of the constrained rotational mode of Mo{sub 3}O{sub 13} clusters and internal modes of MoO{sub 6} polyhedra. We anticipate that coupling this well known data analysis technique with dynamic pair distribution function analysis will have broad application in connecting structural dynamics to physical properties in a wide range of molecular and solid state systems.

  15. Direct and Inverse Techniques of Guided-Mode Resonance Filters Designs

    NASA Technical Reports Server (NTRS)

    Tibuleac, Sorin; Magnusson, Robert; Maldonado, Theresa A.; Zuffada, Cinzia

    1997-01-01

    Guided-mode resonances arise in single or multilayer waveguides where one or more homogeneous layers are replaced by diffraction gratings (Fig. 1.) The diffractive element enables an electromagnetic wave incident on a waveguide grating to be coupled to the waveguide modes supportable by the structure in the absence of the modulation (i.e. the difference between the high and low dielectric constants of the grating) at specific values of the wavelength and incident angle. The periodic modulation of the guide makes the structure leaky, preventing sustained propagation of modes in the waveguide and coupling the waves out into the substrate and cover. As the wavelength is varied around resonance a rapid variation in the intensities of the external propagating waves occurs. By selecting a grating period small enough to eliminate the higher-order propagating waves, an increase in the zero-order intensities up to 100% can result. The pronounced frequency selectivity of guided-mode resonances in dielectric waveguide gratings can be applied to design high-efficiency reflection and transmission filters [1-3].

  16. Mode selection in a directly diode-pumped Raman fibre laser using FBGs in a graded-index multimode fibre

    NASA Astrophysics Data System (ADS)

    Kablukov, S. I.; Zlobina, E. A.; Skvortsov, M. I.; Nemov, I. N.; Wolf, A. A.; Dostovalov, A. V.; Babin, S. A.

    2016-12-01

    We examine the selection of the fundamental transverse mode in a directly multimode-diode-pumped Raman laser with a cavity formed by fibre Bragg gratings (FBGs) in a graded-index fibre. The application of FBGs recorded by femtosecond radiation in the central region of the fibre core provides an unprecedentedly high (for lasers of this type) beam quality (M2 < 1.2) at a lasing power above 5 {\\text{W}}.

  17. Texture perception through direct and indirect touch: An analysis of perceptual space for tactile textures in two modes of exploration

    PubMed Central

    Yoshioka, T.; Bensamaïa, S. J.; Craig, J. C.; Hsiao, S. S.

    2007-01-01

    Considerable information about the texture of objects can be perceived remotely through a probe. It is not clear, however, how texture perception with a probe compares with texture perception with the bare finger. Here we investigate the perception of a variety of textured surfaces encountered daily (e.g., corduroy, paper, and rubber) using the two scanning modes—direct touch through the finger and indirect touch through a probe held in the hand—in two tasks. In the first task, subjects rated the overall pair-wise dissimilarity of the textures. In the second task, subjects rated each texture along three continua, namely, perceived roughness, hardness, and stickiness of the surfaces, shown previously as the primary dimensions of texture perception in direct touch. From the dissimilarity judgment experiment, we found that the texture percept is similar though not identical in the two scanning modes. From the adjective rating experiments, we found that while roughness ratings are similar, hardness and stickiness ratings tend to differ between scanning conditions. These differences between the two modes of scanning are apparent in perceptual space for tactile textures based on multidimensional scaling (MDS) analysis. Finally, we demonstrate that three physical quantities, vibratory power, compliance, and friction carry roughness, hardness, and stickiness information, predicting perceived dissimilarity of texture pairs with indirect touch. Given that different types of texture information are processed by separate groups of neurons across direct and indirect touch, we propose that the neural mechanisms underlying texture perception differ between scanning modes. PMID:17558923

  18. Genotoxicity of complex mixtures: CHO cell mutagenicity assay

    SciTech Connect

    Frazier, M.E.; Samuel, J.E.

    1985-02-01

    A Chinese hamster ovary (CHO) mammalian cell assay was used to evaluate the genotoxicity of complex mixtures (synthetic fuels). The genotoxicity (mutagenic potency) of the mixtures increased as the temperature of their boiling range increased. Most of the genotoxicity in the 750/sup 0/F+ boiling-range materials was associated with the neutral polycyclic aromatic hydrocarbon (PAH) fractions. Chemical analysis data indicate that the PAH fractions of high-boiling coal liquids contain a number of known chemical carcinogens, including five- and six-ring polyaromatics (e.g., benzo(a)pyrene) as well as four- and five-ring alkyl-substituted PAH (e.g., methylchrysene and dimethylbenzanthracenes); concentrations are a function of boiling point (bp). In vitro genotoxicity was also detected in fractions of nitrogen-containing polyaromatic compounds, as well as in those with aliphatics of hydroxy-containing PAH. Mutagenic activity of some fractions was detectable in the CHO assay in the absence of an exogenous metabolic activation system; in some instances, addition of exogenous enzymes and cofactors inhibited expression of the direct-acting mutagenic potential of the fraction. These data indicate that the organic matrix of the chemical fraction determines whether, and to what degree, various mutagens are expressed in the CHO assay. Therefore, the results of biological assays of these mixtures must be correlated with chemical analyses for proper interpretation of these data. 29 references, 16 figures, 4 tables.

  19. Mutagenicity and genotoxicity of coal fly ash water leachate

    SciTech Connect

    Chakraborty, R.; Mukherjee, A.

    2009-03-15

    Fly ash is a by-product of coal-fired electricity generation plants. The prevalent practice of disposal is as slurry of ash and water to storage or ash ponds located near power stations. This has lain to waste thousands of hectares of land all over the world. Since leaching is often the cause of off-site contamination and pathway of introduction into the human environment, a study on the genotoxic effects of fly ash leachate is essential. Leachate prepared from the fly ash sample was analyzed for metal content, and tested for mutagenicity and genotoxicity. Analyses of metals show predominance of the metals - sodium, silicon, potassium, calcium, magnesium, iron, manganese, zinc, and sulphate. The Ames Salmonella mutagenicity assay, a short-term bacterial reverse mutation assay, was conducted on two-tester strains of Salmonella typhimurium strains TA97a and TA102. For genotoxicity, the alkaline version of comet assay on fly ash leachate was carried in vitro on human blood cells and in vivo on Nicotiana plants. The leachate was directly mutagenic and induced significantconcentration-dependent increases in DNA damage in whole blood cells, lymphocytes, and in Nicotiana plants. The comet parameters show increases in tail DNA percentage (%), tail length (mu m), and olive tail moment (arbitrary units). Our results indicate that leachate from fly ash dumpsites has the genotoxic potential and may lead to adverse effects on vegetation and on the health of exposed human populations.

  20. Influence of equilibrium shear flow in the parallel magnetic direction on edge localized mode crash

    SciTech Connect

    Luo, Y.; Xiong, Y. Y.; Chen, S. Y.; Huang, J.; Tang, C. J.

    2016-04-15

    The influence of the parallel shear flow on the evolution of peeling-ballooning (P-B) modes is studied with the BOUT++ four-field code in this paper. The parallel shear flow has different effects in linear simulation and nonlinear simulation. In the linear simulations, the growth rate of edge localized mode (ELM) can be increased by Kelvin-Helmholtz term, which can be caused by the parallel shear flow. In the nonlinear simulations, the results accord with the linear simulations in the linear phase. However, the ELM size is reduced by the parallel shear flow in the beginning of the turbulence phase, which is recognized as the P-B filaments' structure. Then during the turbulence phase, the ELM size is decreased by the shear flow.

  1. Ultrafast Direct Modulation of a Single-Mode Photonic Crystal Nanocavity Light-Emitting Diode

    DTIC Science & Technology

    2011-11-15

    modulation speed results from the fast relaxation of the quantum dots used as the active material. By virtue of possessing a small mode volume, our LED...at room temperature, while the high modulation speed results from the fast relaxation of the quantum dots used as the active material. By virtue of...on optical pumping, and is difficult for on-chip integration. Recently, we demonstrated an electrically driven photonic crystal quantum dot (QD

  2. Direct link between boson-peak modes and dielectric α -relaxation in glasses

    NASA Astrophysics Data System (ADS)

    Cui, Bingyu; Milkus, Rico; Zaccone, Alessio

    2017-02-01

    We compute the dielectric response of glasses starting from a microscopic system-bath Hamiltonian of the Zwanzig-Caldeira-Leggett type and using an ansatz from kinetic theory for the memory function in the resulting generalized Langevin equation. The resulting framework requires the knowledge of the vibrational density of states (DOS) as input, which we take from numerical evaluation of a marginally stable harmonic disordered lattice, featuring a strong boson peak (excess of soft modes over Debye ˜ωp2 law). The dielectric function calculated based on this ansatz is compared with experimental data for the paradigmatic case of glycerol at T ≲Tg . Good agreement is found for both the reactive (real) part of the response and for the α -relaxation peak in the imaginary part, with a significant improvement over earlier theoretical approaches. On the low-frequency side of the α peak, the fitting supports the presence of ˜ωp4 modes at vanishing eigenfrequency as recently shown [E. Lerner, G. During, and E. Bouchbinder, Phys. Rev. Lett. 117, 035501 (2016), 10.1103/PhysRevLett.117.035501]. α -wing asymmetry and stretched-exponential behavior are recovered by our framework, which shows that these features are, to a large extent, caused by the soft boson-peak modes in the DOS.

  3. Influence of modes of metal transfer on grain structure and direction of grain growth in low nickel austenitic stainless steel weld metals

    SciTech Connect

    Mukherjee, Manidipto; Saha, Saptarshi; Pal, Tapan Kumar; Kanjilal, Prasanta

    2015-04-15

    The present study elaborately discussed the effect of different modes of metal transfer (i.e., short circuit mode, spray mode and pulse mode) on grain structure and direction of grain growth in low nickel austenitic stainless steel weld metals. Electron backscattered diffraction (EBSD) analysis was used to study the grain growth direction and grain structure in weld metals. The changes in grain structure and grain growth direction were found to be essentially varied with the weld pool shape and acting forces induced by modes of metal transfer at a constant welding speed. Short circuit mode of metal transfer owing to higher Marangoni force (M{sub a}) and low electromagnetic force (R{sub m}) promotes the lower weld pool volume (Γ) and higher weld pool maximum radius (r{sub m}). Short circuit mode also shows curved and tapered columnar grain structures and the grain growth preferentially occurred in <001> direction. In contrast, spray mode of metal transfer increases the Γ and reduces the r{sub m} values due to very high R{sub m} and typically reveals straight and broad columnar grain structures with preferential growth direction in <111>. In the pulse mode of metal transfer relatively high M{sub a} and R{sub m} simultaneously increase the weld pool width and the primary penetration which might encourage relatively complex grain growth directions in the weld pool and cause a shift of major intensity from <001> to <111> direction. It can also be concluded that the fusion zone grain structure and direction of grain growth are solely dependent on modes of metal transfer and remain constant for a particular mode of metal transfer irrespective of filler wire used. - Highlights: • Welded joints of LNiASS were prepared by varying modes of metal transfer. • Weld pool shape, grain structure and grain growth direction were studied. • Short circuit mode shows curved and tapered grain growth in <001> direction. • Spray mode shows straight and broad columnar grain growth

  4. Overview of genotoxic impurities in pharmaceutical development.

    PubMed

    Bercu, Joel P; Dobo, Krista L; Gocke, Elmar; McGovern, Timothy J

    2009-01-01

    This symposium focuses on the management of genotoxic impurities in the synthesis of pharmaceuticals. Recent developments in both Europe and United States require sponsors of new drug applications to develop processes to control the risks of potential genotoxic impurities. Genotoxic impurities represent a special case relative to the International Conference on Harmonisation Q3A/Q3B guidances, because genotoxicity tests used to qualify the drug substance may not be sufficient to demonstrate safety of a potentially genotoxic impurity. The default risk management approach for a genotoxic impurity is the threshold of toxicological concern unless a more specific risk characterization is appropriate. The symposium includes descriptions of industry examples where impurities are introduced and managed in the synthesis of a pharmaceutical. It includes recent regulatory developments such as the "staged threshold of toxicological concern" when administration is of short duration (eg, during clinical trials).

  5. The genotoxic contribution of wood smoke to indoor respirable suspended particles

    SciTech Connect

    Boone, P.M. ); Rossman, T.G. ); Daisey, J.M. )

    1989-01-01

    The effect of wood burning stoves on the genotoxicity of indoor respirable organic matter was investigated for four homes during the winter and spring of 1986. Paired samples, one collected when the stove was not used and one when wood was burned, were extracted with dichloromethane and acetone. Aliquots of the dichloromethane extracts were analyzed with and without metabolic activation using the Microscreen bioassay. The Microscreen is a rapid, sensitive bioassay which measures a broad genotoxic endpoint, {lambda}-prophage induction. Per nanogram of organic material, wood smoke proved to be a major source of indirect (observed with metabolic activation) but not direct genotoxins in homes. The increase in indirect genotoxicity for extracts from aerosol containing wood smoke is probably due to higher concentrations of polycyclic aromatic hydrocarbons in the wood smoke aerosol as well as other unidentified classes. The direct genotoxicity observed for extracts of aerosol not containing wood smoke decreased with metabolic activation. This direct genotoxicity may be related to cooking activities in the homes. The trends in genotoxicity observed per nanogram of organic material are more pronounced when expressed per m{sup 3} of air due to the higher percentage of extractable material in aerosol containing wood smoke.

  6. Direct modeling parameter signature analysis and failure mode prediction of physical systems using hybrid computer optimization

    NASA Technical Reports Server (NTRS)

    Drake, R. L.; Duvoisin, P. F.; Asthana, A.; Mather, T. W.

    1971-01-01

    High speed automated identification and design of dynamic systems, both linear and nonlinear, are discussed. Special emphasis is placed on developing hardware and techniques which are applicable to practical problems. The basic modeling experiment and new results are described. Using the improvements developed successful identification of several systems, including a physical example as well as simulated systems, was obtained. The advantages of parameter signature analysis over signal signature analysis in go-no go testing of operational systems were demonstrated. The feasibility of using these ideas in failure mode prediction in operating systems was also investigated. An improved digital controlled nonlinear function generator was developed, de-bugged, and completely documented.

  7. Cell-Based Genotoxicity Testing

    NASA Astrophysics Data System (ADS)

    Reifferscheid, Georg; Buchinger, Sebastian

    Genotoxicity test systems that are based on bacteria display an important role in the detection and assessment of DNA damaging chemicals. They belong to the basic line of test systems due to their easy realization, rapidness, broad applicability, high sensitivity and good reproducibility. Since the development of the Salmonella microsomal mutagenicity assay by Ames and coworkers in the early 1970s, significant development in bacterial genotoxicity assays was achieved and is still a subject matter of research. The basic principle of the mutagenicity assay is a reversion of a growth inhibited bacterial strain, e.g., due to auxotrophy, back to a fast growing phenotype (regain of prototrophy). Deeper knowledge of the ­mutation events allows a mechanistic understanding of the induced DNA-damage by the utilization of base specific tester strains. Collections of such specific tester strains were extended by genetic engineering. Beside the reversion assays, test systems utilizing the bacterial SOS-response were invented. These methods are based on the fusion of various SOS-responsive promoters with a broad variety of reporter genes facilitating numerous methods of signal detection. A very important aspect of genotoxicity testing is the bioactivation of ­xenobiotics to DNA-damaging compounds. Most widely used is the extracellular metabolic activation by making use of rodent liver homogenates. Again, genetic engineering allows the construction of highly sophisticated bacterial tester strains with significantly enhanced sensitivity due to overexpression of enzymes that are involved in the metabolism of xenobiotics. This provides mechanistic insights into the toxification and detoxification pathways of xenobiotics and helps explaining the chemical nature of hazardous substances in unknown mixtures. In summary, beginning with "natural" tester strains the rational design of bacteria led to highly specific and sensitive tools for a rapid, reliable and cost effective ­genotoxicity

  8. Evolution of genotoxicity test methods in Japan.

    PubMed

    Sofuni, Toshio

    2017-01-01

    The evolution of methods to assess genotoxicity of test compounds is thought to be one of the important subjects in The Japanese Environmental and Mutagen Society (JEMS). In 1970, the Ministry of Education of Japan (at that time) organized a research group (Organizer: Y. Tazima, National Institute of Genetics), and started a systematic research on the genotoxic effects induced by chemical substances. Considering the importance of this issue through the outcomes of the research group, JEMS was established in 1972, and President Tazima organized the 1st annual meeting in the August in Tokyo with the participation of experts in this field working in national institutes, universities and others in Japan. The discovery that food additives possessed genotoxic potential triggered various scientific activities in the field of genotoxicity. Another important point was the correlation between genotoxicity and carcinogenicity, in which the establishment of the reverse mutation assay played an important role. Other critical factors, such as side effects of drugs, occupational cancer, and environmental pollution due to genotoxic chemicals, emphasized the importance of genotoxicity tests for human safety. The tests performed to assess genotoxicity from 1960s to 1980s will be described to understand that many different genotoxic methodologies were discussed in these periods.

  9. Genotoxicity and carcinogenicity studies of antihistamines.

    PubMed

    Brambilla, Giovanni; Mattioli, Francesca; Robbiano, Luigi; Martelli, Antonietta

    2011-10-01

    This review provides a compendium of the results of genotoxicity and carcinogenicity assays performed on marketed antihistamines. Of the 70 drugs examined, 29 (41.4%) have at least one genotoxicity and/or carcinogenicity test result: 12 tested positive in at least one genotoxicity assay, six in at least one carcinogenicity assay, and four gave a positive response in both at least one genotoxicity assay and at least one carcinogenicity assay. Of 19 drugs with both genotoxicity and carcinogenicity data, eight were neither genotoxic nor carcinogenic, two were carcinogenic in at least one sex of mice or rats but tested negative in genotoxicity assays, five tested positive in at least one genotoxicity assay but were non-carcinogenic, and four gave a positive response in at least one genotoxicity assay and in at least one carcinogenicity assay. Only 12 (17.1%) of the 70 drugs examined have all data required by present guidelines for testing of pharmaceuticals, but it should be considered that a large fraction of them were developed and marketed prior the present regulatory climate.

  10. Appropriate In Vitro Methods for Genotoxicity Testing of Silver Nanoparticles

    PubMed Central

    Kim, Ha Ryong; Park, Yong Joo; Shin, Da Young; Oh, Seung Min

    2013-01-01

    Objectives We investigated the genotoxic effects of 40-59 nm silver nanoparticles (Ag-NPs) by bacterial reverse mutation assay (Ames test), in vitro comet assay and micronucleus (MN) assay. In particular, we directly compared the effect of cytochalasin B (cytoB) and rat liver homogenate (S9 mix) in the formation of MN by Ag-NPs. Methods Before testing, we confirmed that Ag-NPs were completely dispersed in the experimental medium by sonication (three times in 1 minute) and filtration (0.2 µm pore size filter), and then we measured their size in a zeta potential analyzer. After that the genotoxicity were measured and especially, S9 mix and with and without cytoB were compared one another in MN assay. Results Ames test using Salmonella typhimurium TA98, TA100, TA1535 and TA1537 strains revealed that Ag-NPs with or without S9 mix did not display a mutagenic effect. The genotoxicity of Ag-NPs was also evaluated in a mammalian cell system using Chinese hamster ovary cells. The results revealed that Ag-NPs stimulated DNA breakage and MN formation with or without S9 mix in a dose-dependent manner (from 0.01 µg/mL to 10 µg/mL). In particular, MN induction was affected by cytoB. Conclusions All of our findings, with the exception of the Ames test results, indicate that Ag-NPs show genotoxic effects in mammalian cell system. In addition, present study suggests the potential error due to use of cytoB in genotoxic test of nanoparticles. PMID:23440978

  11. Direct molecular-level characterization of different heterogeneous freezing modes on mica - Part 1

    NASA Astrophysics Data System (ADS)

    Abdelmonem, Ahmed

    2017-09-01

    The mechanisms behind heterogeneous ice nucleation are of fundamental importance to the prediction of the occurrence and properties of many cloud types, which influence climate and precipitation. Aerosol particles act as cloud condensation and freezing nuclei. The surface-water interaction of an ice nucleation particle plays a major, not well explored, role in its ice nucleation ability. This paper presents a real-time molecular-level comparison of different freezing modes on the surface of an atmospherically relevant mineral surface (mica) under varying supersaturation conditions using second-harmonic generation spectroscopy. Two sub-deposition nucleation modes were identified (one- and two-stage freezing). The nonlinear signal at the water-mica interface was found to drop following the formation of a thin film on the surface regardless of (1) the formed phase (liquid or ice) and (2) the freezing path (one or two step), indicating similar molecular structuring. The results also revealed a transient phase of ice at water-mica interfaces during freezing, which has a lifetime of around 1 min. Such information will have a significant impact on climate change, weather modification, and the tracing of water in hydrosphere studies.

  12. Direct imaging of delayed magneto-dynamic modes induced by surface acoustic waves.

    PubMed

    Foerster, Michael; Macià, Ferran; Statuto, Nahuel; Finizio, Simone; Hernández-Mínguez, Alberto; Lendínez, Sergi; Santos, Paulo V; Fontcuberta, Josep; Hernàndez, Joan Manel; Kläui, Mathias; Aballe, Lucia

    2017-09-01

    The magnetoelastic effect-the change of magnetic properties caused by the elastic deformation of a magnetic material-has been proposed as an alternative approach to magnetic fields for the low-power control of magnetization states of nanoelements since it avoids charge currents, which entail ohmic losses. Here, we have studied the effect of dynamic strain accompanying a surface acoustic wave on magnetic nanostructures in thermal equilibrium. We have developed an experimental technique based on stroboscopic X-ray microscopy that provides a pathway to the quantitative study of strain waves and magnetization at the nanoscale. We have simultaneously imaged the evolution of both strain and magnetization dynamics of nanostructures at the picosecond time scale and found that magnetization modes have a delayed response to the strain modes, adjustable by the magnetic domain configuration. Our results provide fundamental insight into magnetoelastic coupling in nanostructures and have implications for the design of strain-controlled magnetostrictive nano-devices.Understanding the effects of local dynamic strain on magnetization may help the development of magnetic devices. Foerster et al. demonstrate stroboscopic imaging that allows the observation of both strain and magnetization dynamics in nickel when surface acoustic waves are driven in the substrate.

  13. Direct power control of DFIG wind turbine systems based on an intelligent proportional-integral sliding mode control.

    PubMed

    Li, Shanzhi; Wang, Haoping; Tian, Yang; Aitouch, Abdel; Klein, John

    2016-09-01

    This paper presents an intelligent proportional-integral sliding mode control (iPISMC) for direct power control of variable speed-constant frequency wind turbine system. This approach deals with optimal power production (in the maximum power point tracking sense) under several disturbance factors such as turbulent wind. This controller is made of two sub-components: (i) an intelligent proportional-integral module for online disturbance compensation and (ii) a sliding mode module for circumventing disturbance estimation errors. This iPISMC method has been tested on FAST/Simulink platform of a 5MW wind turbine system. The obtained results demonstrate that the proposed iPISMC method outperforms the classical PI and intelligent proportional-integral control (iPI) in terms of both active power and response time. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

  14. Direct Geolocation of TerraSAR-X Spotlight Mode Image and Error Correction

    NASA Astrophysics Data System (ADS)

    Zhou, Xiao; Zeng, Qiming; Jiao, Jian; Zhang, Jingfa; Gong, Lixia

    2013-01-01

    The GERMAN TerraSAR-X mission was launched in June 2007, operating a versatile new-generation SAR sensor in X-band. Its Spotlight mode providing SAR images at very high resolution of about 1m. The product’s specified 3-D geolocation accuracy is tightened to 1m according to the official technical report. However, this accuracy is able to be achieved relies on not only robust mathematical basis of SAR geolocation, but also well knowledge of error sources and their correction. The research focuses on geolocation of TerraSAR-X spotlight image. Mathematical model and resolving algorithms have been analyzed. Several error sources have been researched and corrected especially. The effectiveness and accuracy of the research was verified by the experiment results.

  15. Distinct ETA Receptor Binding Mode of Macitentan As Determined by Site Directed Mutagenesis

    PubMed Central

    Gatfield, John; Mueller Grandjean, Celia; Bur, Daniel; Bolli, Martin H.; Nayler, Oliver

    2014-01-01

    The competitive endothelin receptor antagonists (ERA) bosentan and ambrisentan, which have long been approved for the treatment of pulmonary arterial hypertension, are characterized by very short (1 min) occupancy half-lives at the ETA receptor. The novel ERA macitentan, displays a 20-fold increased receptor occupancy half-life, causing insurmountable antagonism of ET-1-induced signaling in pulmonary arterial smooth muscle cells. We show here that the slow ETA receptor dissociation rate of macitentan was shared with a set of structural analogs, whereas compounds structurally related to bosentan displayed fast dissociation kinetics. NMR analysis showed that macitentan adopts a compact structure in aqueous solution and molecular modeling suggests that this conformation tightly fits into a well-defined ETA receptor binding pocket. In contrast the structurally different and negatively charged bosentan-type molecules only partially filled this pocket and expanded into an extended endothelin binding site. To further investigate these different ETA receptor-antagonist interaction modes, we performed functional studies using ETA receptor variants harboring amino acid point mutations in the presumed ERA interaction site. Three ETA receptor residues significantly and differentially affected ERA activity: Mutation R326Q did not affect the antagonist activity of macitentan, however the potencies of bosentan and ambrisentan were significantly reduced; mutation L322A rendered macitentan less potent, whereas bosentan and ambrisentan were unaffected; mutation I355A significantly reduced bosentan potency, but not ambrisentan and macitentan potencies. This suggests that – in contrast to bosentan and ambrisentan - macitentan-ETA receptor binding is not dependent on strong charge-charge interactions, but depends predominantly on hydrophobic interactions. This different binding mode could be the reason for macitentan's sustained target occupancy and insurmountable antagonism. PMID

  16. H-mode and Edge Physics on the Pegasus ST: Progress and Future Directions

    NASA Astrophysics Data System (ADS)

    Bongard, M. W.; Bodner, G. M.; Barr, J. L.; Burke, M. G.; Fonck, R. J.; Hinson, E. T.; Kriete, D. M.; Lewicki, B. T.; Perry, J. M.; Reusch, J. A.; Schlossberg, D. J.; Thome, K. E.; Winz, G. R.

    2015-11-01

    Ohmic H-modes are routinely attained on the Pegasus ST, in part due to the low L-H power threshold PLH arising from low-BT operation at A ~ 1 . Characteristics of H-mode include: improved τe, consistent with H98 ~ 1 edge current and pressure pedestal formation; and the occurrence of ELMs. Experiments in the past year have examined magnetic topology and density dependencies of PLH in detail. PLH exceeds ITER L-H scaling values by 10-20 ×, with PLH /PITPA 08 increasing sharply as A --> 1 . No PLH-minimizing density has been found. Unlike at high- A, PLH is insensitive to limited or diverted magnetic topologies to date. The low BT and modest pedestal values at A ~ 1 afford unique edge diagnostic accessibility to investigate ELMs and their nonlinear dynamics. Jedge (R , t) measured through a Type I ELM shows a complex pedestal collapse and filament ejection. These studies are being extended to higher Ip and longer pulse length with LHI startup to conserve Ohmic V-s and improve MHD stability. A modest-cost upgrade to the facility will enable detailed validation studies of nonlinear ELM dynamics and ELM control. This initiative will upgrade the centerstack, increasing BT by × 3 , Ohmic V-s by × 4 , and pulse lengths to 100 ms at A < 1 . 3 , as well as deploy a comprehensive 3D magnetic perturbation coil system with full poloidal coverage from frame coils and helical centerstack windings. Work supported by US DOE grant DE-FG02-96ER54375.

  17. The use of ex vivo human skin tissue for genotoxicity testing

    SciTech Connect

    Reus, Astrid A.; Usta, Mustafa; Krul, Cyrille A.M.

    2012-06-01

    As a result of the chemical legislation concerning the registration, evaluation, authorization and restriction of chemicals (REACH), and the Seventh Amendment to the Cosmetics Directive, which prohibits animal testing in Europe for cosmetics, alternative methods for safety evaluation of chemicals are urgently needed. Current in vitro genotoxicity assays are not sufficiently predictive for the in vivo situation, resulting in an unacceptably high number of misleading positives. For many chemicals and ingredients of personal care products the skin is the first site of contact, but there are no in vitro genotoxicity assays available in the skin for additional evaluation of positive or equivocal responses observed in regulatory in vitro genotoxicity assays. In the present study ex vivo human skin tissue obtained from surgery was used for genotoxicity evaluation of chemicals by using the comet assay. Fresh ex vivo human skin tissue was cultured in an air–liquid interface and topically exposed to 20 chemicals, including true positive, misleading positive and true negative genotoxins. Based on the results obtained in the present study, the sensitivity, specificity and accuracy of the ex vivo skin comet assay to predict in vivo genotoxicity were 89%, 90% and 89%, respectively. Donor and experimental variability were mainly reflected in the magnitude of the response and not the difference between the presence and absence of a genotoxic response. The present study indicates that human skin obtained from surgery is a promising and robust model for safety evaluation of chemicals that are in direct contact with the skin. -- Highlights: ► We use human skin obtained from surgery for genotoxicity evaluation of chemicals. ► We use the comet assay as parameter for genotoxicity in ex vivo human skin. ► Sensitivity, specificity and accuracy to predict in vivo genotoxins are determined. ► Sensitivity, specificity and accuracy are 89%, 90% and 90%, respectively. ► The method

  18. Heating mode transition in a hybrid direct current/dual-frequency capacitively coupled CF{sub 4} discharge

    SciTech Connect

    Zhang, Quan-Zhi; Wang, You-Nian; Bogaerts, Annemie

    2014-06-14

    Computer simulations based on the particle-in-cell/Monte Carlo collision method are performed to study the plasma characteristics and especially the transition in electron heating mechanisms in a hybrid direct current (dc)/dual-frequency (DF) capacitively coupled CF{sub 4} discharge. When applying a superposed dc voltage, the plasma density first increases, then decreases, and finally increases again, which is in good agreement with experiments. This trend can be explained by the transition between the four main heating modes, i.e., DF coupling, dc and DF coupling, dc source dominant heating, and secondary electron dominant heating.

  19. Broadband optoacoustic characterization of cMUT and PZT transducer directivity in receive mode

    NASA Astrophysics Data System (ADS)

    Rebling, Johannes; Warshavski, Omri; Meynier, Cyril; Razansky, Daniel

    2017-03-01

    Optoacoustic imaging is a rapidly developing area of biomedical imaging due its combination of rich optical contrast and ultrasound depth penetration. Just like conventional pulse-echo ultrasound imaging, optoacoustic tomography relies on the use of ultrasound detector arrays with a large number of elements. The precise knowledge of the transducer's sensitivity is crucial for the prediction of its performance for a given imaging task. Sensitivity characteristics such as the central frequency and bandwidth are routinely characterized. However, this characterization is typically performed solely under normal incidence since the measurement of the angle and frequency depended sensitivity (directivity) is difficult and time consuming with existing ultrasound characterization methods. We present a simple and fast characterization method for broadband directivity measurements of the angular transducer sensitivity based on the optoacoustic effect. The method utilizes a thin absorbing suture in order to generate omnidirectional and broadband optoacoustic signals, which are calibrated using a needle hydrophone. We applied this method to characterize and compare the directivity of a conventional piezoelectric (PZT) transducer to the directivity of a capacitive micromachined ultrasonic (cMUT) transducer. Both technologies showed a similar broadband response at normal incidence and the PZT transducer displayed a more than two times larger signal to noise ratio at normal incidence. However, the cMUT transducer's sensitivity was significantly less angle-depended and outperformed the PZT's sensitivity for angles larger than 20°.

  20. The cadmium–mercaptoacetic acid complex contributes to the genotoxicity of mercaptoacetic acid-coated CdSe-core quantum dots

    PubMed Central

    Tang, Weikun; Fan, Junpeng; He, Yide; Huang, Bihai; Liu, Huihui; Pang, Daiwen; Xie, Zhixiong

    2012-01-01

    Quantum dots (QDs) have many potential clinical and biological applications because of their advantages over traditional fluorescent dyes. However, the genotoxicity potential of QDs still remains unclear. In this paper, a plasmid-based system was designed to explore the genotoxic mechanism of QDs by detecting changes in DNA configuration and biological activities. The direct chemicobiological interactions between DNA and mercaptoacetic acid-coated CdSecore QDs (MAA–QDs) were investigated. After incubation with different concentrations of MAA–QDs (0.043, 0.13, 0.4, 1.2, and 3.6 μmol/L) in the dark, the DNA conversion of the covalently closed circular (CCC) DNA to the open circular (OC) DNA was significantly enhanced (from 13.9% ± 2.2% to 59.9% ± 12.8%) while the residual transformation activity of plasmid DNA was greatly decreased (from 80.7% ± 12.8% to 13.6% ± 0.8%), which indicated that the damages to the DNA structure and biological activities induced by MAA–QDs were concentration-dependent. The electrospray ionization mass spectrometry data suggested that the observed genotoxicity might be correlated with the cadmium–mercaptoacetic acid complex (Cd–MAA) that is formed in the solution of MAA–QDs. Circular dichroism spectroscopy and transformation assay results indicated that the Cd–MAA complex might interact with DNA through the groove-binding mode and prefer binding to DNA fragments with high adenine and thymine content. Furthermore, the plasmid transformation assay could be used as an effective method to evaluate the genotoxicities of nanoparticles. PMID:22679373

  1. Development of a mixed mode adsorption process for the direct product sequestration of an extracellular protease from microbial batch cultures.

    PubMed

    Hamilton, G E; Luechau, F; Burton, S C; Lyddiatt, A

    2000-04-28

    Direct product sequestration of extracellular proteins from microbial batch cultures can be achieved by continuous or intermittent broth recycle through an external extractive loop. Here, we describe the development of a fluidisable, mixed mode adsorbent, designed to tolerate increasing ionic strength (synonymous with extended productive batch cultures). This facilitated operations for the integrated recovery of an extracellular acid protease from cultures of Yarrowia lipolytica. Mixed mode adsorbents were prepared using chemistries containing hydrophobic and ionic groups. Matrix hydrophobicity and titration ranges were matched to the requirements of integrated protease adsorption. A single expanded bed was able to service the productive phase of growth without recourse to the pH adjustment of the broth previously required for ion exchange adsorption. This resulted in increased yields of product, accompanied by further increases in enzyme specific activity. A step change from pH 4.5 to 2.6, across the isoelectric point of the protease, enabled high resolution fixed bed elution induced by electrostatic repulsion. The generic application of mixed mode chemistries, which combine the physical robustness of ion-exchange ligands in sanitisation and sterilisation procedures with a selectivity, which approaches that of affinity interactions, is discussed.

  2. Superresolution direction finding algorithms for the characterisation of multi-moded HF signals

    NASA Astrophysics Data System (ADS)

    Zatman, M. A.; Strangeways, H. J.

    1994-07-01

    In this work three superresolution direction finding algorithms for use with arbitrary array geometries are described, all of which are capable of dealing with coherent signals, as typically found in the multi-path environment. DOSE is a quick single snapshot algorithm developed by the authors which operates on the received data vector. The IMP and Maximum Likelihood (ML) algorithms are used to process time averaged data covariance matrices. All three algorithms attempt in different ways to find a multi-dimensional solution to the inverse problem of direction finding. It is shown that calibration of arrays of identical elements is simplified by the use of these multi-dimensional algorithms when compared to 1 dimensional methods such as MUSIC. A common methodology for the implementation of these multi-dimensional algorithms is presented, and a quick method of implementing the ML algorithm and determining the number of signals present is described.

  3. Measurement of direct photon emission in the K(L) ---> pi+ pi- gamma decay mode

    SciTech Connect

    Abouzaid, E.; Arenton, M.; Barker, A.R.; Bellantoni, L.; Bellavance, A.; Blucher, E.; Bock, G.J.; Cheu, E.; Coleman, R.; Corcoran, M.D.; Corti, G.; /Virginia U. /Wisconsin U., Madison

    2006-04-01

    In this paper the KTeV collaboration reports the analysis of 112.1 x 10{sup 3} candidate K{sub L} {yields} {pi}{sup +}{pi}{sup -}{gamma} decays including a background of 671 {+-} 41 events with the objective of determining the photon production mechanisms intrinsic to the decay process. These decays have been analyzed to extract the relative contributions of the Cp violating bremsstrahlung process and the CP conserving M1 and CP violating E1 direct photon emission processes. The M1 direct photon emission amplitude and its associated vector form factor parameterized as |{bar g}{sub M1}|(1 + a{sub 1}/a{sub 2}/(M{sub {rho}}{sup 2}-M{sub K}{sup 2}) + 2M{sub K}E{sub {gamma}}) have been measured to be |{bar g}{sub M1}| = 1.198 {+-} 0.035(stat) {+-} 0.086(syst) and a{sub 1}/a{sub 2} = =0.738 {+-} 0.007(stat) {+-} 0.018(syst) GeV{sup 2}/c{sup 2} respectively. An upper limit for the CP violating E1 direct emission amplitude |g{sub E1}| {le} 0.1 (90%CL) has been found. The overall ratio of direct photon emission (DE) to total photon emission including the bremsstrahlung process (IB) has been determined to be DE/(DE + IB) = 0.689 {+-} 0.021 for E{sub {gamma}} {ge} 20 MeV.

  4. Numerical simulation of drop deformations and breakup modes caused by direct current electric fields

    NASA Astrophysics Data System (ADS)

    Paknemat, H.; Pishevar, A. R.; Pournaderi, P.

    2012-10-01

    A drop suspended in another fluid shows different dynamic behaviors in an electric field that depends on its physical properties. The phenomenon of drop deformation under the application of an electric field, in the absence of a net volume charge, is simply caused by the surface stresses. Therefore, an accurate method is required for numerical modeling of the electric driving force at the interface to handle all of the discontinuities involved in the model. For this purpose, in this study the level set method is used along with the ghost fluid method to investigate the responses of three types of drop in the presence of an electric field. Moreover, to demonstrate the accuracy of the method, the breakup modes of each electric model are carefully simulated. Finally, the results of the simulations are compared with similar numerical and experimental results from the literature. The simulation results indicate the accuracy of the method for modeling of the phenomenon over a wide range of electric capillary numbers, and particularly for the capture of the drop profile at the instant of disintegration.

  5. Quantifying direct DQPSK receiver with integrated photodiode array by assessing an adapted common-mode rejection ratio

    NASA Astrophysics Data System (ADS)

    Wang, J.; Lauermann, M.; Zawadzki, C.; Brinker, W.; Zhang, Z.; de Felipe, D.; Keil, N.; Grote, N.; Schell, M.

    2011-12-01

    In this work, a direct DQPSK receiver was fabricated, which comprises a polymer waveguide based delay-line interferometer (DLI); a polymer based optical hybrid, and two monolithic pairs of > 25 GHz bandwidth photodiodes that are vertically coupled to the polymer planar lightwave circuit (PLC) via integrated 45° mirrors. The common mode rejection ratio (CMRR) is used to characterize the performance of coherent receivers, by indicating the electrical power balance between the balanced detectors. However, the standard CMRR can only be measured when the PDs can be illuminated separately. Also, the standard CMRR does not take into account the errors in the relative phases of the receiver outputs. We introduce an adapted CMRR to characterize the direct receiver, which takes into account the unequal responsivities of the PDs, the uneven split of the input power by the DLI and hybrid, the phase error and the extinction ratio of the DLI and hybrid.

  6. Viral Vectors: The Road to Reducing Genotoxicity.

    PubMed

    David, Rhiannon M; Doherty, Ann T

    2017-02-01

    Viral vector use in gene therapy has highlighted several safety concerns, including genotoxic events. Generally, vector-mediated genotoxicity results from upregulation of cellular proto-oncogenes via promoter insertion, promoter activation, or gene transcript truncation, with enhancer-mediated activation of nearby genes the primary mechanism reported in gene therapy trials. Vector-mediated genotoxicity can be influenced by virus type, integration target site, and target cell type; different vectors have distinct integration profiles which are cell-specific. Non-viral factors, including patient age, disease, and dose can also influence genotoxic potential, thus the choice of test models and clinical trial populations is important to ensure they are indicative of efficacy and safety. Efforts have been made to develop viral vectors with less risk of insertional mutagenesis, including self-inactivating (SIN) vectors, enhancer-blocking insulators, and microRNA targeting of vectors, although insertional mutagenesis is not completely abrogated. Here we provide an overview of the current understanding of viral vector-mediated genotoxicity risk from factors contributing to viral vector-mediated genotoxicity to efforts made to reduce genotoxicity, and testing strategies required to adequately assess the risk of insertional mutagenesis. It is clear that there is not a 'one size fits all' approach to vector modification for reducing genotoxicity, and addressing these challenges will be a key step in the development of therapies such as CRISPR-Cas9 and delivery of future gene-editing technologies.

  7. Dermal fibroblast infiltration of poly(ε-caprolactone) scaffolds fabricated by melt electrospinning in a direct writing mode.

    PubMed

    Farrugia, Brooke L; Brown, Toby D; Upton, Zee; Hutmacher, Dietmar W; Dalton, Paul D; Dargaville, Tim R

    2013-06-01

    Melt electrospinning in a direct writing mode is a recent additive manufacturing approach to fabricate porous scaffolds for tissue engineering applications. In this study, we describe porous and cell-invasive poly (ε-caprolactone) scaffolds fabricated by combining melt electrospinning and a programmable x-y stage. Fibers were 7.5 ± 1.6 µm in diameter and separated by interfiber distances ranging from 8 to 133 µm, with an average of 46 ± 22 µm. Micro-computed tomography revealed that the resulting scaffolds had a highly porous (87%), three-dimensional structure. Due to the high porosity and interconnectivity of the scaffolds, a top-seeding method was adequate to achieve fibroblast penetration, with cells present throughout and underneath the scaffold. This was confirmed histologically, whereby a 3D fibroblast-scaffold construct with full cellular penetration was produced after 14 days in vitro. Immunohistochemistry was used to confirm the presence and even distribution of the key dermal extracellular matrix proteins, collagen type I and fibronectin. These results show that melt electrospinning in a direct writing mode can produce cell invasive scaffolds, using simple top-seeding approaches.

  8. Direct demonstration of unique mode of natural peptide binding to the type 2 cholecystokinin receptor using photoaffinity labeling.

    PubMed

    Dong, Maoqing; Miller, Laurence J

    2013-08-01

    Direct analysis of mode of peptide docking using intrinsic photoaffinity labeling has provided detailed insights for the molecular basis of cholecystokinin (CCK) interaction with the type 1 CCK receptor. In the current work, this technique has been applied to the closely related type 2 CCK receptor that also binds the natural full agonist peptide, CCK, with high affinity. A series of photolabile CCK analog probes with sites of covalent attachment extending from position 26 through 32 were characterized, with the highest affinity analogs that possessed full biological activity utilized in photoaffinity labeling. The position 29 probe, incorporating a photolabile benzoyl-phenylalanine in that position, was shown to bind with high affinity and to be a full agonist, with potency not different from that of natural CCK, and to covalently label the type 2 CCK receptor in a saturable, specific and efficient manner. Using proteolytic peptide mapping, mutagenesis, and radiochemical Edman degradation sequencing, this probe was shown to establish a covalent bond with type 2 CCK receptor residue Phe¹²⁰ in the first extracellular loop. This was in contrast to its covalent attachment to Glu³⁴⁵ in the third extracellular loop of the type 1 CCK receptor, directly documenting differences in mode of docking this peptide to these receptors.

  9. Advanced methodology for measuring the extensive elastic compliance and mechanical loss directly in k31 mode piezoelectric ceramic plates

    NASA Astrophysics Data System (ADS)

    Majzoubi, Maryam; Shekhani, Husain N.; Bansal, Anushka; Hennig, Eberhard; Scholehwar, Timo; Uchino, Kenji

    2016-12-01

    Dielectric, elastic, and piezoelectric constants, and their corresponding losses are defined under constant conditions of two categories; namely, intensive (i.e., E, electric field or T, stress), and extensive (i.e., D, dielectric displacement or x, strain) ones. So far, only the intensive parameters and losses could be measured directly in a k31 mode sample. Their corresponding extensive parameters could be calculated indirectly using the coupling factor and "K" matrix. However, the extensive loss parameters, calculated through this indirect method, could have large uncertainty, due to the error propagation in calculation. In order to overcome this issue, extensive losses should be measured separately from the measurable intensive ones in lead-zirconate-titanate (PZT) k31 mode rectangular plate ceramics. We propose a new mechanical-excitation methodology, using a non-destructive testing approach by means of a partial electrode configuration, instead of the conventional full electrode configuration. For this purpose, a non-electrode sample was prepared, where the electrode covered only 10% of the top and bottom surfaces at the center to actuate the whole sample, and also monitor the responding vibration. The admittance spectrum of this sample, corresponds to PZT properties under dielectric displacement D constant condition. Furthermore, ceramics with partial-electrodes were also prepared to create short and open circuit boundary conditions, attributing to resonance and anti-resonance modes. In the proposed way, we were able to measure both intensive and extensive elastic compliances and mechanical losses directly for the first time. The accuracy of this new method is compared with the conventional measurements by use of indirect calculations. The preliminary results (by neglecting the 10% actuator part difference at this point) were obtained, which were in good agreements (less than 3% difference) with the previous indirect method.

  10. Validation of a human cell based high-throughput genotoxicity assay 'Anthem's Genotoxicity screen' using ECVAM recommended lists of genotoxic and non-genotoxic chemicals.

    PubMed

    Rajakrishna, Lakshmi; Krishnan Unni, Salini; Subbiah, Madhuri; Sadagopan, Sathish; Nair, Ayyappan R; Chandrappa, Ravindra; Sambasivam, Ganesh; Sukumaran, Sunil Kumar

    2014-02-01

    A novel high throughput-enabled human cell based screen, Anthem's Genotoxicity screen, was developed to achieve higher specificity for predicting in vivo genotoxins by an in vitro method. The assay employs engineered human colon carcinoma cell line; HCT116 cells that are stably engineered with three promoter-reporter cassettes such that an increased reporter activity reflects the activation of associated signaling events in a human cell. The current study focuses on the evaluation of sensitivity and specificity of Anthem's Genotoxicity screen using 62 compounds recommended by the European Centre for the Validation of Alternative Methods (ECVAM). The concordance of Anthem's Genotoxicity screen with in vivo tests was 95.5% with sensitivity of 95.2% and specificity of 95.7%. Thus Anthem's Genotoxicity screen, a high-throughput mechanism based genotox indicator test can be employed by a variety of industries for rapid screening and early detection of potential genotoxins.

  11. Genotoxic and mutagenic effects of sewage sludge on higher plants.

    PubMed

    Corrêa Martins, Maria Nilza; de Souza, Victor Ventura; Souza, Tatiana da Silva

    2016-02-01

    Sewage treatment yields sludge, which is often used as a soil amendment in agriculture and crop production. Although the sludge contains elevated concentrations of macro and micronutrients, high levels of inorganic and organic compounds with genotoxic and mutagenic properties are present in sludge. Application of sludge in agriculture is a pathway for direct contact of crops to toxic chemicals. The objective of this study was to compile information related to the genotoxic and mutagenic effects of sewage sludge in different plant species. In addition, data are presented on toxicological effects in animals fed with plants grown in soils supplemented with sewage sludge. Despite the benefits of using sewage sludge as organic fertilizer, the data showcased in this review suggest that this residue can induce genetic damage in plants. This review alerts potential risks to health outcomes after the intake of food cultivated in sewage sludge-amended soils.

  12. Genotoxicity assessment of amaranth and allura red using Saccharomyces cerevisiae.

    PubMed

    Jabeen, Hafiza Sumara; ur Rahman, Sajjad; Mahmood, Shahid; Anwer, Sadaf

    2013-01-01

    Amaranth (E123) and Allura red (E129), very important food azo dyes used in food, drug, paper, cosmetic and textile industries, were assessed for their genotoxic potential through comet assay in yeast cells. Comet assay was standardized by with different concentration of H(2)O(2). Concentrations of Amaranth and Allura red were maintained in sorbitol buffer starting from 9.76 to 5,000 μg/mL and 1 × 10(4) cells were incubated at two different incubation temperatures 28 and 37°C. Amaranth (E123) and Allura red (E129) were found to exhibit their genotoxic effect directly in Saccharomyces cerevisiae. No significant genotoxic activity was observed for Amaranth and Allura red at 28°C but at 37°C direct relation of Amaranth concentration with comet tail was significant and no positive relation was seen with time exposure factor. At 37°C the minimum concentration of Amaranth and Allura red at which significant DNA damage observed through comet assay was 1,250 μg/mL in 2nd h post exposure time. The results indicated that food colors should be carefully used in baking products as heavy concentration of food colors could affect the fermentation process of baking.

  13. The influence of organic solvents on estimates of genotoxicity and antigenotoxicity in the SOS chromotest

    PubMed Central

    Quintero, Nathalia; Stashenko, Elena E.; Fuentes, Jorge Luis

    2012-01-01

    In this work, the toxicity and genotoxicity of organic solvents (acetone, carbon tetrachloride, dichloromethane, dimethylsulfoxide, ethanol, ether and methanol) were studied using the SOS chromotest. The influence of these solvents on the direct genotoxicity induced by the mutagens mitomycin C (MMC) and 4-nitroquinoline-1-oxide (4-NQO) were also investigated. None of the solvents were genotoxic in Escherichia coli PQ37. However, based on the inhibition of protein synthesis assessed by constitutive alkaline phosphatase activity, some solvents (carbon tetrachloride, dimethylsulfoxide, ethanol and ether) were toxic and incompatible with the SOS chromotest. Solvents that were neither toxic nor genotoxic to E. coli (acetone, dichloromethane and methanol) significantly reduced the genotoxicity of MMC and 4-NQO. When these solvents were used to dissolve vitamin E they increased the antigenotoxic activity of this compound, possibly through additive or synergistic effects. The relevance of these results is discussed in relation to antigenotoxic studies. These data indicate the need for careful selection of an appropriate diluent for the SOS chromotest since some solvents can modulate genotoxicity and antigenotoxicity. PMID:22888301

  14. FtsZ Directs a Second Mode of Peptidoglycan Synthesis in Escherichia coli▿

    PubMed Central

    Varma, Archana; de Pedro, Miguel A.; Young, Kevin D.

    2007-01-01

    Certain penicillin binding protein mutants of Escherichia coli grow with spirillum-like morphologies when the FtsZ protein is inhibited, suggesting that FtsZ might govern aspects of cell wall growth other than those strictly associated with septation. While investigating the mechanism of spiral cell formation, we discovered conditions for visualizing this second function of FtsZ. Normally, inhibiting the cytoskeleton protein MreB forces E. coli cells to grow as smoothly enlarging spheres from which the poles disappear, yielding coccoid or lemon-shaped forms. However, when FtsZ and MreB were inhibited simultaneously in a strain lacking PBP 5 and PBP 7, the resulting cells ballooned outward but retained conspicuous rod-shaped extensions at sites representing the original poles. This visual phenotype was paralleled by the biochemistry of sacculus growth. Muropeptides are usually inserted homogeneously into the lateral cell walls, but when FtsZ polymerization was inhibited, the incorporation of new material occurred mainly in the central regions of cells and was significantly lower in those portions of side walls abutting a pole. Thus, reduced precursor incorporation into side walls near the poles explained why these regions retained their rod-like morphology while the rest of the cell grew spherically. Also, inhibiting FtsZ increased the amount of pentapeptides in sacculi by about one-third. Finally, the MreB protein directed the helical or diagonal incorporation of new peptidoglycan into the wall, but the location of that incorporation depended on whether FtsZ was active. In sum, the results indicate that in addition to nucleating cell septation in E. coli, FtsZ can direct the insertion of new peptidoglycan into portions of the lateral wall. PMID:17513471

  15. Genotoxic activity of organic chemicals in drinking water.

    PubMed

    Meier, J R

    1988-11-01

    The information summarized in this review provides substantial evidence for the widespread presence of genotoxins in drinking water. In many, if not most cases, the genotoxic activity can be directly attributed to the chlorination stage of drinking water treatment. The genotoxic activity appears to originate primarily from reactions of chlorine with humic substances in the source waters. Genotoxic activity in drinking water concentrates has been most frequently demonstrated using bacterial mutagenicity tests but results with mammalian cell assay systems are generally consistent with the findings from the bacterial assays. There is currently no evidence for genotoxic damage following in vivo exposures to animals. In some locations genotoxic contaminants of probable industrial and/or agricultural origin occur in the source waters and contribute substantially to the genotoxic activity of finished drinking waters. The method used for sample concentration can have an important bearing on study results. In particular, organic acids account for most of the mutagenicity of chlorinated drinking water, and their recovery from water requires a sample acidification step prior to extraction or XAD resin adsorption. Considerable work has been done to determine the identity of the compounds responsible for the mutagenicity of organic concentrates of drinking water. Recently, one class of acidic compounds, the chlorinated hydroxyfuranones, has been shown to be responsible for a major part of the mutagenic activity. Strategies for drinking water treatment that have been evaluated with respect to reduction of genotoxins in drinking water include granular activated carbon (GAC) filtration, chemical destruction, and the use of alternative means of treatment (i.e., ozone, chlorine dioxide, and monochloramine). GAC treatment has been found to be effective for removal of mutagens from drinking water even after the GAC is beyond its normal use for organic carbon removal. All disinfectant

  16. Cranial muscle development in frogs with different developmental modes: direct development versus biphasic development.

    PubMed

    Ziermann, Janine M; Diogo, Rui

    2014-04-01

    Normal development in anurans includes a free swimming larva that goes through metamorphosis to develop into the adult frog. We have investigated cranial muscle development and adult cranial muscle morphology in three different anuran species. Xenopus laevis is obligate aquatic throughout lifetime, Rana(Lithobates) pipiens has an aquatic larvae and a terrestrial adult form, and Eleutherodactylus coqui has direct developing juveniles that hatch from eggs deposited on leaves (terrestrial). The adult morphology shows hardly any differences between the investigated species. Cranial muscle development of E. coqui shows many similarities and only few differences to the development of Rana (Lithobates) and Xenopus. The differences are missing muscles of the branchial arches (which disappear during metamorphosis of biphasic anurans) and a few heterochronic changes. The development of the mandibular arch (adductor mandibulae) and hyoid arch (depressor mandibulae) muscles is similar to that observed in Xenopus and Rana (Lithobates), although the first appearance of these muscles displays a midmetamorphic pattern in E. coqui. We show that the mix of characters observed in E. coqui indicates that the larval stage is not completely lost even without a free swimming larval stage. Cryptic metamorphosis is the process in which morphological changes in the larva/embryo take place that are not as obvious as in normal metamorphosing anurans with a clear biphasic lifestyle. During cryptic metamorphosis, a normal adult frog develops, indicating that the majority of developmental mechanisms towards the functional adult cranial muscles are preserved.

  17. [Genotoxicity research thought and method on traditional Chinese medicine].

    PubMed

    Han, Jia-yin; Yi, Yan; Liang, Ai-hua; Zhang, Yu-shi; Li, Chun-ying; Zhao, Yong; Wang, Lian-mei; Li, Gui-qin

    2015-07-01

    Genotoxicity research takes an important place in traditional Chinese medicine safety evaluation. Genotoxicity test on traditional Chinese medicine has been paid great attention since 1970s. Currently, the most developed genotoxicity test methods included: bacterial reverse mutation test and mouse lymphoma assay which are used to detect relevant genetic changes, micronucleus test and chromosomal analysis which are used to measure chromosomal aberration, and single cell electrophoresis assay which is used to test DNA damage. This article reviews research progress on genotoxicity of traditional Chinese medicine, evaluation methods of genotoxicity, the problems and solutions on genotoxicity evaluation of traditional Chinese medicine, and new technique used in genotoxicity test.

  18. Separation of glycosylated caseinomacropeptide at pilot scale using membrane adsorption in direct-capture mode.

    PubMed

    Kreuss, Markus; Kulozik, Ulrich

    2009-12-11

    A direct-capture anion-exchange membrane adsorption process for the separation of a pure glycosylated (gCMP) fraction of caseinomacropeptide (CMP) was successfully developed at pilot plant scale. The method was evolved using a commercial CMP isolate as feedstock as well as fresh sweet whey from skim milk. The former resulted in a binding capacity (BC) of 0.28 mg gCMP/cm(2) membrane surface with a purity of 97% while the latter afforded a gCMP fraction with a purity of 91% and a BC of 0.21 mg gCMP/cm(2) membrane surface. The main difference was a significant fouling of the membrane adsorber module when the whey was applied, which resulted in a loss of 46% BC after at least five loading/elution cycles. This effect was not observed using the pure CMP isolates and indicates a blocking of the ion-exchange ligands. Triglycerides, as detected by lipid analysis, as well as protein aggregates and casein-flocculates, are mainly responsible for the fouling process. The fouling was decreased using microfiltered whey or by increasing the temperature of the adsorption process. Additionally, a method of repeated elution was shown to decrease the volume of the eluate as well as the NaCl consumption of the elution buffer. The process development further included a desalting and concentration step, which was performed by a 10 kDa ultrafiltration/diafiltration (UF/DF). The efficiency of the UF was strongly influenced by the pH of the solutions and showed best performance at pH 4.1 for the eluate. The residual solution had to be adjusted at pH 6.5 as there was a strong decrease of flux at lower pH levels.

  19. Numerical investigation of polarization insensitive two-mode division (De)multiplexer based on an asymmetric directional coupler

    NASA Astrophysics Data System (ADS)

    Truong, Cao Dung; Trinh, M. Tuan; Dang, Hoai Bac; Nguyen, Van Tho

    2017-02-01

    We propose a polarization insensitive two-mode division (de)multiplexer based on a silicon-on-insulator platform operating with a broadband, low insertion and scattering loss, and small crosstalk. By using an asymmetric directional coupler, two-mode (de)multiplexing functions for both polarization TE and TM states can be realized by the numerical simulation. Simulated results using a three dimensional beam propagation method (3D-BPM) incorporated with an effective index method (EIM) show high performance of the device with an operation efficiency above 81.2% (i.e., insertion loss is less than 0.9 dB) in the range of ±5 nm around the central wavelength of 1550 nm. Fabrication tolerances also have proved suitability to current manufacture technologies for the planar waveguides. Besides a low scattering loss of the sidewall roughness and a little influence of dispersion, a small footprint can bring the device to applications of high bitrate and compact on-chip silicon photonic integrated circuits.

  20. Operational condition for direct single-mode-fiber coupled free-space optical terminal under strong atmospheric turbulence

    NASA Astrophysics Data System (ADS)

    Arimoto, Yoshinori

    2012-03-01

    The author describes the key design feature of a newly developed compact free-space optical terminal, which can achieve robust direct single-mode-fiber-coupling with advanced bidirectional beacon tracking system and excellent operational performance under various adverse weather conditions, such as strong atmospheric turbulences and rain/snow falls. The author found that there is a good correlation between the scintillation index of beacon/signal receiving intensities and the signal fading depth. Therefore, the signal link quality can be predicted from the beacon scintillation index using the classical Rytov theory. According to the outdoor experimental results, it can be concluded that the scintillation index of the beacon beam should be less than 0.1 for stable and reliable communication links.

  1. Genotoxic, antigenotoxic and phytochemical assessment of Terminalia actinophylla ethanolic extract.

    PubMed

    Pádua, P F M R; Dihl, R R; Lehmann, M; de Abreu, B R R; Richter, M F; de Andrade, H H R

    2013-12-01

    Terminalia actinophylla has been used for anti-diarrheic and haemostatic purposes in Brazil. The fly spot data obtained after exposure of marker-heterozygous Drosophila melanogaster larvae to T. actinophylla ethanolic extract (TAE) in the standard (ST) and high bioactivation (HB) crosses revealed that TAE did not induce any statistically significant increment in any spot categories. Differences between the two crosses are related to cytochrome P450 (CYPs) levels. In this sense, our data pointed out the absence of TAE-direct and indirect mutagenic and recombinagenic action in the Somatic Mutation and Recombination Test (SMART). When the anti-genotoxicity of TAE was analyzed, neither mitomycin C (MMC) nor ethylmethanesulfonate (EMS) genotoxicity was modified by the post-exposure to TAE, which suggests that TAE has no effect on the mechanisms involved in the processing of the lesions induced by both genotoxins. In the mwh/flr(3) genotype, co-treatment with TAE may lead to a significant protection against the genotoxicity of MMC and a weak but significant effect in the toxic genetic action of EMS. The overall findings suggested that the favorable modulations by TAE could be, at least in part, due to its antioxidative potential. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. High speed flux feedback for tuning a universal field oriented controller capable of operating in direct and indirect field orientation modes

    DOEpatents

    De Doncker, R.W.A.A.

    1992-09-01

    The direct (d) and quadrature (q) components of flux, as sensed by flux sensors or determined from voltage and current measurements in a direct field orientation scheme, are processed rapidly and accurately to provide flux amplitude and angular position values for use by the vector rotator of a universal field-oriented (UFO) controller. Flux amplitude (linear or squared) is provided as feedback to tune the UFO controller for operation in direct and indirect field orientation modes and enables smooth transitions from one mode to the other. 3 figs.

  3. High speed flux feedback for tuning a universal field oriented controller capable of operating in direct and indirect field orientation modes

    DOEpatents

    De Doncker, Rik W. A. A.

    1992-01-01

    The direct (d) and quadrature (q) components of flux, as sensed by flux sensors or determined from voltage and current measurements in a direct field orientation scheme, are processed rapidly and accurately to provide flux amplitude and angular position values for use by the vector rotator of a universal field-oriented (UFO) controller. Flux amplitude (linear or squared) is provided as feedback to tune the UFO controller for operation in direct and indirect field orientation modes and enables smooth transitions from one mode to the other.

  4. Method for direct detection of pitch angle scattering of energetic electrons caused by whistler mode chorus emissions

    NASA Astrophysics Data System (ADS)

    Kitahara, M.; Katoh, Y.

    2016-06-01

    The Wave-Particle Interaction Analyzer (WPIA), a new instrument proposed by Fukuhara et al. (2009), measures the relative phase angle between the wave magnetic field vector and the velocity vector of each particle and calculates the energy exchange from waves to particles. In this study, we expand its applicability by proposing a method of using the WPIA to directly detect pitch angle scattering of resonant particles by plasma waves by calculating the g values. The g value is defined as the accumulation value of the Lorentz force acting on each particle and indicates the lost momentum of waves. We apply the proposed method to the results of a one-dimensional electron hybrid simulation reproducing the generation of whistler mode chorus emissions around the magnetic equator. Using the wave and particle data obtained at fixed observation points assumed in the simulation system, we conduct a pseudo-observation of the simulation result using the WPIA and analyze the g values. Our analysis yielded significant values indicating the strong pitch angle scattering for electrons in the kinetic energy and pitch angle ranges satisfying the cyclotron resonance condition with the reproduced chorus emissions. The results of this study demonstrate that the proposed method enables us to directly and quantitatively identify the location at which pitch angle scattering occurs in the simulation system and that the method can be applied to the results of space-based observations by the forthcoming Exploration of energization and Radiation in Geospace (ERG) satellite.

  5. Genomic approaches for investigating mechanisms of genotoxicity.

    PubMed

    Caba, Ebru; Aubrecht, Jiri

    2006-01-01

    The current genetic toxicity testing battery enables an accurate and effective detection of genotoxicity associated with exposure to chemicals. However, the interpretation of the data in light of the relevant risk to humans is often difficult due to limited insight into underlying genotoxic mechanisms. Thus, the development of experimental approaches capable of differentiating genotoxic mechanisms is expected to facilitate risk assessment. Recent progress in science and technology has enabled the investigation of the stress response associated with chemical exposure at the genomic level. For instance, gene expression profile analysis, transcriptomics, was proposed as a tool for evaluating toxic mechanisms. In addition, the advancement in genetic tools has allowed the study of stress response on a functional level, functional genomics. This review will outline a number of recent developments in genomic analyses of genotoxic stress response and provide a perspective on their application in genetic toxicology.

  6. Assessing of genotoxicity of 16 centralized source-waters in China by means of the SOS/umu assay and the micronucleus test: initial identification of the potential genotoxicants by use of a GC/MS method and the QSAR Toolbox 3.0.

    PubMed

    Ye, Yan; Weiwei, Jiang; Na, Li; Mei, Ma; Donghong, Wang; Zijian, Wang; Kaifeng, Rao

    2014-03-15

    Only few studies were conducted to assess genotoxicity of centralized source waters in China and almost none of them dealt with the causal relationship between the genotoxic effect and genotoxicants. In this work, 16 centralized source waters in China were sampled from five river systems and genotoxicity of their organic extracts was assessed by use of the SOS/umu test for DNA-damaging effect and the miniaturized flow cytometry-based micronucleus (MN) test for chromosome-damaging effect. In addition, initial identification of potential genotoxicants for the six samples from the Yangtze River was done with a GC/MS method and the QSAR toolbox 3.0. The results demonstrate that eight samples showed both indirect and direct DNA-damaging effects, another four samples showed only indirect DNA-damaging effects, while chromosome-damaging effects were found for 14 out of the 16 samples, in which aneugenic and clastogenic modes of action were found for 4 and 10 samples, respectively. Both direct/indirect DNA-damaging effects and chromosome-damaging effects were induced by the six Yangtze River samples, and the existing different types of genotoxicant confirmed the results. Furthermore, o-phenylphenol was initially identified as the major cause for the DNA-damaging effects while PAHs, pesticides, phenol and anthraquinone were identified as ubiquitous chromosome-damaging agents among these samples. In conclusion, a combination of the SOS/umu test and the miniaturized flow cytometry-based MN test to detect both DNA-damaging and chromosome-damaging effects could be used as a comprehensive genotoxicity assessment tool for the evaluation and classification of genotoxicity of complex mixtures, and potential genotoxicants can be initially identified with additional information from chemical analysis and the QSAR toolbox.

  7. Evaluation of genotoxic and apoptotic potential of Hypericum adenotrichum Spach. in vitro.

    PubMed

    Sarimahmut, Mehmet; Balikci, Necmiye; Celikler, Serap; Ari, Ferda; Ulukaya, Engin; Guleryuz, Gurcan; Ozel, Mustafa Zafer

    2016-02-01

    Hypericum adenotrichum Spach. is an endemic plant from Turkey that is also used in folk medicine. In this study, following analyses of its chemical composition, the genotoxic/antigenotoxic effects of the methanol extract of H. adenotrichum in human lymphocyte culture were investigated using in vitro sister chromatid exchange, micronucleus and comet assays. In addition, the anti-growth effect of the extract was investigated in human breast cancer cell lines (MCF-7 and MDA-MB-231) using MTT and ATP viability assays. The mode of cell death was determined using fluorescence microscopy and biochemical methods. We found that the H. adenotrichum extract demonstrated cytotoxic and genotoxic effects in a cell type-dependent manner. At selected doses (125-500 μg/ml), the H. adenotrichum extract exhibited significant genotoxic activity in human lymphocytes, whereas it showed anti-growth effects on cancer cell lines between 0.2 and 100 μg/ml concentrations. The mode of cell death in cancer cells was shown to be apoptosis due to the presence of pyknotic nuclei, the cleavage of poly-(ADP-ribose) polymerase (PARP) and/or the activation of caspase-3. These results suggest that H. adenotrichum might show both cytotoxic and genotoxic effects depending on the cell type. This should be taken into account in its use for therapeutic purposes. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Employment of adult mammalian primary cells in toxicology: In vivo and in vitro genotoxic effects of environmentally significant N-nitrosodialkylamines in cells of the liver, lung, and kidney

    SciTech Connect

    Pool, B.L.; Brendler, S.Y.; Liegibel, U.M.; Schmezer, P. ); Tompa, A. )

    1990-01-01

    This report focuses on the use of freshly isolated primary mammalian cells from different tissues and organs of the rat for the rapid and efficient analysis of toxic and genotoxic chemicals. The cells are either treated in vitro or they are isolated from treated animals. Viability by trypan blue exclusion and DNA damage as single-strand breaks are monitored in either case. Therefore, it is possible to compare in vitro and in vivo results directly. N-nitrosamines with unique organ-specific modes in carcinogenesis were studied in vitro using hepatocytes derived from three species (rat, hamster, and pig) and in rat lung and kidney cells. The sensitive detection of all carcinogenic nitrosamines was achieved, although a pattern of cell-specific activation was not observable. The new modification of the in vivo approach allowed the sensitive detection of NDMA genotoxicity in hepatic and in extrahepatic tissues. It is important to point out that the method is an efficient tool for toxicokinetic studies with genotoxic carcinogens in vivo.

  9. Industry viewpoint on thresholds for genotoxic carcinogens.

    PubMed

    Morelli, M A

    2000-01-01

    Modern chemical control of pests has contributed to a dramatic improvement in public welfare since its introduction 50 years ago. Millions of lives have been saved through the control of disease vectors, and millions more have been improved by the use of chemicals to produce an inexpensive and abundant food supply. Hundreds of pesticidally active ingredients are in commercial use today, and among these are found genotoxic and nongenotoxic carcinogens. In the United States, the Environmental Protection Agency regulates carcinogens using threshold and nonthreshold approaches depending upon the outcome of a weight-of-evidence determination. More than one-half of all pesticides with some evidence of carcinogenic potential are regulated by the nonthreshold approach. The limitations on product use imposed by this approach have restricted the number of products available to growers and to the public. This restriction has had a direct impact on industry with respect to commercial success and financial returns on investment as well as an indirect impact on the industry's ability to fund the discovery and development of new compounds. This paper explores the question of how well regulation by the nonthreshold approach has achieved the goal of protecting public health, whether it does this better than the alternative use of the threshold approach, and whether the incremental protection it affords is a meaningful public benefit that justifies the aforementioned impacts on industry.

  10. Rat Pig-a mutation assay responds to the genotoxic carcinogen ethyl carbamate but not the non-genotoxic carcinogen methyl carbamate.

    PubMed

    Bemis, Jeffrey C; Labash, Carson; Avlasevich, Svetlana L; Carlson, Kristine; Berg, Ariel; Torous, Dorothea K; Barragato, Matthew; MacGregor, James T; Dertinger, Stephen D

    2015-05-01

    Determination of the mode of action of carcinogenic agents is an important factor in risk assessment and regulatory practice. To assess the ability of the erythrocyte-based Pig-a mutation assay to discriminate between genotoxic and non-genotoxic modes of action, the mutagenic response of Sprague Dawley rats exposed to methyl carbamate (MC) or ethyl carbamate (EC) was investigated. EC, a potent carcinogen, is believed to induce DNA damage through the formation of a DNA-reactive epoxide group, whereas the closely structurally related compound, MC, cannot form this epoxide and its weaker carcinogenic activity is thought to be secondary to inflammation and promotion of cell proliferation. The frequency of Pig-a mutant phenotype cells was monitored before, during, and after 28 consecutive days of oral gavage exposure to either MC (doses ranging from 125 to 500 mg/kg/day) or EC (250 mg/kg/day). Significant increases in the frequency of mutant reticulocytes were observed from Days 15 through 43, with a peak mean frequency of 19.9×10(-6) on Day 29 (i.e. 24.9-fold increase relative to mean vehicle control across all four sampling times). As expected, mutant erythrocyte responses lagged behind mutant reticulocyte responses, with a maximal mean frequency of 8.2×10(-6) on Day 43 (i.e. 16.4-fold increase). No mutagenic effects were observed with MC. A second indicator of in vivo genotoxicity, peripheral blood micronucleated reticulocytes, was also studied. This endpoint was responsive to EC (3.3-fold mean increase), but not to MC. These results support the hypothesis that genotoxicity contributes to the carcinogenicity of EC but not of MC, and illustrates the value of the Pig-a assay for discriminating between genotoxic and non-genotoxic modes of action. © The Author 2015. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. From Principal Component to Direct Coupling Analysis of Coevolution in Proteins: Low-Eigenvalue Modes are Needed for Structure Prediction

    PubMed Central

    Cocco, Simona; Monasson, Remi; Weigt, Martin

    2013-01-01

    Various approaches have explored the covariation of residues in multiple-sequence alignments of homologous proteins to extract functional and structural information. Among those are principal component analysis (PCA), which identifies the most correlated groups of residues, and direct coupling analysis (DCA), a global inference method based on the maximum entropy principle, which aims at predicting residue-residue contacts. In this paper, inspired by the statistical physics of disordered systems, we introduce the Hopfield-Potts model to naturally interpolate between these two approaches. The Hopfield-Potts model allows us to identify relevant ‘patterns’ of residues from the knowledge of the eigenmodes and eigenvalues of the residue-residue correlation matrix. We show how the computation of such statistical patterns makes it possible to accurately predict residue-residue contacts with a much smaller number of parameters than DCA. This dimensional reduction allows us to avoid overfitting and to extract contact information from multiple-sequence alignments of reduced size. In addition, we show that low-eigenvalue correlation modes, discarded by PCA, are important to recover structural information: the corresponding patterns are highly localized, that is, they are concentrated in few sites, which we find to be in close contact in the three-dimensional protein fold. PMID:23990764

  12. From principal component to direct coupling analysis of coevolution in proteins: low-eigenvalue modes are needed for structure prediction.

    PubMed

    Cocco, Simona; Monasson, Remi; Weigt, Martin

    2013-01-01

    Various approaches have explored the covariation of residues in multiple-sequence alignments of homologous proteins to extract functional and structural information. Among those are principal component analysis (PCA), which identifies the most correlated groups of residues, and direct coupling analysis (DCA), a global inference method based on the maximum entropy principle, which aims at predicting residue-residue contacts. In this paper, inspired by the statistical physics of disordered systems, we introduce the Hopfield-Potts model to naturally interpolate between these two approaches. The Hopfield-Potts model allows us to identify relevant 'patterns' of residues from the knowledge of the eigenmodes and eigenvalues of the residue-residue correlation matrix. We show how the computation of such statistical patterns makes it possible to accurately predict residue-residue contacts with a much smaller number of parameters than DCA. This dimensional reduction allows us to avoid overfitting and to extract contact information from multiple-sequence alignments of reduced size. In addition, we show that low-eigenvalue correlation modes, discarded by PCA, are important to recover structural information: the corresponding patterns are highly localized, that is, they are concentrated in few sites, which we find to be in close contact in the three-dimensional protein fold.

  13. Intensity modulation and direct detection Alamouti polarization-time coding for optical fiber transmission systems with polarization mode dispersion

    NASA Astrophysics Data System (ADS)

    Reza, Ahmed Galib; Rhee, June-Koo Kevin

    2016-07-01

    Alamouti space-time coding is modified in the form of polarization-time coding to combat against polarization mode dispersion (PMD) impairments in exploiting a polarization diversity multiplex (PDM) gain with simple intensity modulation and direct detection (IM/DD) in optical transmission systems. A theoretical model for the proposed IM/DD Alamouti polarization-time coding (APTC-IM/DD) using nonreturn-to-zero on-off keying signal can surprisingly eliminate the requirement of channel estimation for decoding in the low PMD regime, when a two-transmitter and two-receiver channel is adopted. Even in the high PMD regime, the proposed APTC-IM/DD still reveals coding gain demonstrating the robustness of APTC-IM/DD. In addition, this scheme can eliminate the requirements for a polarization state controller, a coherent receiver, and a high-speed analog-to-digital converter at a receiver. Simulation results reveal that the proposed APTC scheme is able to reduce the optical signal-to-noise ratio requirement by ˜3 dB and significantly enhance the PMD tolerance of a PDM-based IM/DD system.

  14. Genotoxicity evaluation of carvacrol in rats using a combined micronucleus and comet assay.

    PubMed

    Llana-Ruiz-Cabello, María; Maisanaba, Sara; Puerto, María; Prieto, Ana I; Pichardo, Silvia; Moyano, Rosario; González-Pérez, José A; Cameán, Ana M

    2016-12-01

    Genotoxic data of substances which could be incorporated into food packaging are required by the European Food Safety Authority. Due to its antioxidant and antibacterial properties carvacrol is one of these compounds. This work aims to study for the first time the in vivo genotoxic effects produced in rats orally exposed to 81, 256 or 810 mg cavacrol/kg body weight (bw) at 0, 24 and 45 h. A combination of the micronucleus assay (OECD 474) in bone marrow and the standard (OECD 489) and enzyme-modified comet assay was used to determine the genotoxicity on cells isolated from stomach and liver of exposed animals. In addition, a histopathological study was performed on the assayed tissues, and also in the lungs due to the volatility of carvacrol. Direct analytical pyrolysis was used to search for carvacrol in viscera and to ensure that the compound reaches stomach and liver cells. Results from MN-comet assay revealed that carvacrol (81-810 mg/kg bw) did not induce in vivo genotoxicity or oxidative DNA damage in any of the tissues investigated. Moreover, no histopathological changes were observed. Altogether, these results suggest lack of genotoxicity of carvacrol and therefore its good profile for its potential application as food preservative.

  15. Genotoxicity testing of cooked cured meat pigment (CCMP) and meat emulsion coagulates prepared with CCMP.

    PubMed

    Stevanović, M; Cadez, P; Zlender, B; Filipic, M

    2000-07-01

    The preformed cooked cured meat pigment (CCMP) synthesized directly from bovine red blood cells or through a hemin intermediate was found to be a viable colorant for application to comminuted pork as a nitrite substitute. However the genotoxicity of CCMP and meat emulsion coagulates prepared with CCMP has not been evaluated. Therefore the objectives of this work were to investigate genotoxicity of CCMP and the influence of CCMP addition on genotoxicity and the content of residual nitrite in model meat emulsion coagulates. Meat emulsions were prepared from white (musculus longissimus dorsi) and red (musculus quadriceps femoris) pork muscles with two different amounts of synthesized pigment CCMP. Comparatively, emulsions with fixed addition of nitrite salt and emulsions without any addition for color development were made. Genotoxicity of CCMP and meat emulsion coagulates was tested with the SOS/umu test and the Ames test. Neither CCMP nor meat emulsion coagulates prepared with CCMP or nitrite salt were genotoxic in the SOS/umu test. In the Ames test using Salmonella Typhimurium strains TA98 and TA100 samples of coagulates prepared with CCMP and with nitrite showed weak mutagenic activity in Salmonella Typhimurium strain TA100 but only in the absence of the metabolic activation, while CCMP was not mutagenic. Coagulates prepared with CCMP contained significantly less residual nitrite than coagulates prepared with nitrite salt. These results indicate that from the human health standpoint the substitution of nitrite salt with CCMP would be highly recommendable.

  16. Protective Effects of Quercetin against Dimethoate-Induced Cytotoxicity and Genotoxicity in Allium sativum Test

    PubMed Central

    Ahmad, Waseem; Shaikh, Sibhghatulla; Nazam, Nazia; Lone, Mohammad Iqbal

    2014-01-01

    The present investigation was directed to study the possible protective activity of quercetin—a natural antioxidant against dimethoate-induced cyto- and genotoxicity in meristematic cells of Allium sativum. So far there is no report on the biological properties of quercetin in plant test systems. Chromosome breaks, multipolar anaphase, stick chromosome, and mitotic activity were undertaken in the current study as markers of cyto- and genotoxicity. Untreated control, quercetin controls (@ 5, 10 and 20 μg/mL for 3 h), and dimethoate exposed groups (@ 100 and 200 μg/mL for 3 h) were maintained. For protection against cytogenotoxicity, the root tip cells treated with dimethoate at 100 and 200 μg/mL for 3 h and quercetin treatment at 5, 10, and 20 μg/mL for 16 h, prior to dimethoate treatment, were undertaken. Quercetin was found to be neither cytotoxic nor genotoxic in Allium sativum control at these doses. A significant increase (P < 0.05) in chromosomal aberrations was noted in dimethoate treated Allium. Pretreatment of Allium sativum with quercetin significantly (P < 0.05) reduced dimethoate-induced genotoxicity and cytotoxicity in meristematic cells, and these effects were dose dependent. In conclusion, quercetin has a protective role in the abatement of dimethoate-induced cyto- and genotoxicity in the meristematic cells of Allium sativum that resides, at least in part, on its antioxidant effects. PMID:27379342

  17. Protective Effects of Quercetin against Dimethoate-Induced Cytotoxicity and Genotoxicity in Allium sativum Test.

    PubMed

    Ahmad, Waseem; Shaikh, Sibhghatulla; Nazam, Nazia; Lone, Mohammad Iqbal

    2014-01-01

    The present investigation was directed to study the possible protective activity of quercetin-a natural antioxidant against dimethoate-induced cyto- and genotoxicity in meristematic cells of Allium sativum. So far there is no report on the biological properties of quercetin in plant test systems. Chromosome breaks, multipolar anaphase, stick chromosome, and mitotic activity were undertaken in the current study as markers of cyto- and genotoxicity. Untreated control, quercetin controls (@ 5, 10 and 20 μg/mL for 3 h), and dimethoate exposed groups (@ 100 and 200 μg/mL for 3 h) were maintained. For protection against cytogenotoxicity, the root tip cells treated with dimethoate at 100 and 200 μg/mL for 3 h and quercetin treatment at 5, 10, and 20 μg/mL for 16 h, prior to dimethoate treatment, were undertaken. Quercetin was found to be neither cytotoxic nor genotoxic in Allium sativum control at these doses. A significant increase (P < 0.05) in chromosomal aberrations was noted in dimethoate treated Allium. Pretreatment of Allium sativum with quercetin significantly (P < 0.05) reduced dimethoate-induced genotoxicity and cytotoxicity in meristematic cells, and these effects were dose dependent. In conclusion, quercetin has a protective role in the abatement of dimethoate-induced cyto- and genotoxicity in the meristematic cells of Allium sativum that resides, at least in part, on its antioxidant effects.

  18. Photoactivated hypericin is not genotoxic.

    PubMed

    Feruszová, Jana; Imreová, Petronela; Bodnárová, Kristína; Ševčovičová, Andrea; Kyzek, Stanislav; Chalupa, Ivan; Gálová, Eliška; Miadoková, Eva

    2016-04-01

    The study was designed to test the potential photogenotoxicity of hypericin (HYP) at three different levels: primary DNA damages, gene mutations and chromosome aberrations. Primary genetic changes were detected using the comet assay. The potential mutagenic activity of HYP was assessed using the Ames/Salmonella typhimurium assay. Finally, the ability of photoactivated HYP to induce chromosome aberrations was evaluated by the in vitro mammalian chromosome aberration test and compared to that of non-photoactivated HYP. The results have shown that photoactivated HYP can only induce primary DNA damages (single-strand DNA breaks), acting in a dose-response manner. This activity depended both on HYP concentrations and an intensity of the light energy needed for its photoactivation. However, mutagenic effect of photoactivated HYP evaluated in the Ames assay using three bacterial strains S. typhimurium (TA97, TA98 and TA100) was not confirmed. Moreover, photoactivated HYP in the range of concentrations (0.005-0.01 µg/ml) was not found to be clastogenic against HepG2 cells. Our findings from both the Ames assay and the chromosome aberrations test provide evidence that photoactivated HYP is not genotoxic, which might be of great importance mainly in terms of its use in the photodynamic therapy.

  19. METHYLATED ARSENICIII SPECIES ARE POTENTIAL PROXIMATE OR ULTIMATE GENOTOXIC FORMS OF ARSENIC

    EPA Science Inventory

    METHYLATED ARSENIC(III) SPECIES ARE POTENTIAL PROXIMATE OR UL TIMA TE GENOTOXIC FORMS OF ARSENIC

    Inorganic arsenic (iAs, arsenite and arsenate) has been thought to act as a genotoxicant without reacting directly with DNA; neither iAs nor As(V) methylated metabolites are e...

  20. METHYLATED ARSENICIII SPECIES ARE POTENTIAL PROXIMATE OR ULTIMATE GENOTOXIC FORMS OF ARSENIC

    EPA Science Inventory

    METHYLATED ARSENIC(III) SPECIES ARE POTENTIAL PROXIMATE OR UL TIMA TE GENOTOXIC FORMS OF ARSENIC

    Inorganic arsenic (iAs, arsenite and arsenate) has been thought to act as a genotoxicant without reacting directly with DNA; neither iAs nor As(V) methylated metabolites are e...

  1. IWGT report on quantitative approaches to genotoxicity risk ...

    EPA Pesticide Factsheets

    This is the second of two reports from the International Workshops on Genotoxicity Testing (IWGT) Working Group on Quantitative Approaches to Genetic Toxicology Risk Assessment (the QWG). The first report summarized the discussions and recommendations of the QWG related to the need for quantitative dose–response analysis of genetic toxicology data, the existence and appropriate evaluation of threshold responses, and methods to analyze exposure-response relationships and derive points of departure (PoDs) from which acceptable exposure levels could be determined. This report summarizes the QWG discussions and recommendations regarding appropriate approaches to evaluate exposure-related risks of genotoxic damage, including extrapolation below identified PoDs and across test systems and species. Recommendations include the selection of appropriate genetic endpoints and target tissues, uncertainty factors and extrapolation methods to be considered, the importance and use of information on mode of action, toxicokinetics, metabolism, and exposure biomarkers when using quantitative exposure-response data to determine acceptable exposure levels in human populations or to assess the risk associated with known or anticipated exposures. The empirical relationship between genetic damage (mutation and chromosomal aberration) and cancer in animal models was also examined. It was concluded that there is a general correlation between cancer induction and mutagenic and/or clast

  2. IWGT report on quantitative approaches to genotoxicity risk ...

    EPA Pesticide Factsheets

    This is the second of two reports from the International Workshops on Genotoxicity Testing (IWGT) Working Group on Quantitative Approaches to Genetic Toxicology Risk Assessment (the QWG). The first report summarized the discussions and recommendations of the QWG related to the need for quantitative dose–response analysis of genetic toxicology data, the existence and appropriate evaluation of threshold responses, and methods to analyze exposure-response relationships and derive points of departure (PoDs) from which acceptable exposure levels could be determined. This report summarizes the QWG discussions and recommendations regarding appropriate approaches to evaluate exposure-related risks of genotoxic damage, including extrapolation below identified PoDs and across test systems and species. Recommendations include the selection of appropriate genetic endpoints and target tissues, uncertainty factors and extrapolation methods to be considered, the importance and use of information on mode of action, toxicokinetics, metabolism, and exposure biomarkers when using quantitative exposure-response data to determine acceptable exposure levels in human populations or to assess the risk associated with known or anticipated exposures. The empirical relationship between genetic damage (mutation and chromosomal aberration) and cancer in animal models was also examined. It was concluded that there is a general correlation between cancer induction and mutagenic and/or clast

  3. Development of a Fish Cell Biosensor System for Genotoxicity Detection Based on DNA Damage-Induced Trans-Activation of p21 Gene Expression

    PubMed Central

    Geng, Deyu; Zhang, Zhixia; Guo, Huarong

    2012-01-01

    p21CIP1/WAF1 is a p53-target gene in response to cellular DNA damage. Here we report the development of a fish cell biosensor system for high throughput genotoxicity detection of new drugs, by stably integrating two reporter plasmids of pGL3-p21-luc (human p21 promoter linked to firefly luciferase) and pRL-CMV-luc (CMV promoter linked to Renilla luciferase) into marine flatfish flounder gill (FG) cells, referred to as p21FGLuc. Initial validation of this genotoxicity biosensor system showed that p21FGLuc cells had a wild-type p53 signaling pathway and responded positively to the challenge of both directly acting genotoxic agents (bleomycin and mitomycin C) and indirectly acting genotoxic agents (cyclophosphamide with metabolic activation), but negatively to cyclophosphamide without metabolic activation and the non-genotoxic agents ethanol and D-mannitol, thus confirming a high specificity and sensitivity, fast and stable response to genotoxic agents for this easily maintained fish cell biosensor system. This system was especially useful in the genotoxicity detection of Di(2-ethylhexyl) phthalate (DEHP), a rodent carcinogen, but negatively reported in most non-mammalian in vitro mutation assays, by providing a strong indication of genotoxicity for DEHP. A limitation for this biosensor system was that it might give false positive results in response to sodium butyrate and any other agents, which can trans-activate the p21 gene in a p53-independent manner. PMID:25585933

  4. Genotoxicity removal of reclaimed water during ozonation.

    PubMed

    Tang, Xin; Wu, Qianyuan; Yang, Yang; Hu, Hongying

    2014-06-01

    Genotoxicity in wastewater and reclaimed water now is gaining increased attention because of genotoxins' potential damage to the ecosystem and human health. The effect of ozonation on genotoxicity in reclaimed water was investigated. It was found that ozonation decreased the genotoxicy dramatically in three tertiary treatment plants. In the further batch ozonation experiment in laboratory, secondary effluent sample used exhibited the genotoxicity of (41.1 ± 4.1) μg 4NQO/L. Ozonation with a dose of 10 mg O3/L completely removed the genotoxicity in secondary effluent. However, after ozonation, the dissolved organic carbon value of the sample didn't change much but the specific ultraviolet absorbance (SUVA) value dropped sharply. With the help of Fourier transform infrared spectroscopy, ozonation was found to change chemical aliphatic carbon and C-O of the dissolved organic matter, which might be the reason of the significant decreases of SUVA and genotoxicity. Copyright © 2014 The Research Centre for Eco-Environmental Sciences, Chinese Academy of Sciences. Published by Elsevier B.V. All rights reserved.

  5. Genotoxicity studies on green tea catechin.

    PubMed

    Ogura, R; Ikeda, N; Yuki, K; Morita, O; Saigo, K; Blackstock, C; Nishiyama, N; Kasamatsu, T

    2008-06-01

    The beneficial effects of tea catechins are well documented. We evaluated the genotoxic potential of a green tea catechin preparation using established genotoxicity assays, including a bacterial reverse mutation assay (Ames test), a chromosomal aberration assay in cultured Chinese hamster lung cells (CHL/IU), a mouse lymphoma L5178Y/tk assay, and a bone marrow micronucleus (MN) assay in ICR CD mice and SD rats. No significant increases in the number of revertant colonies were observed in the Ames test, but positive responses were observed in two in vitro assays: the chromosomal aberration assay and mouse lymphoma L5178/tk assay. However, the in vivo study demonstrated no significant increase in micronucleated polychromatic erythrocytes (MNPCE) in the bone marrow of both ICR CD mice and SD rats administered a high dose of the green tea catechin preparation up to 2000mg/kg. Combined with favorable epidemiological information suggesting a chemopreventive effect of tea catechins on carcinogenesis, we conclude that green tea catechin presents no significant genotoxic concern under the anticipated conditions of use. These results are consistent with other genotoxicity studies of tea catechins, which show minimal, if any, genotoxic potential.

  6. Directionality control through selective excitation of low-order guided modes in thin-film InGaN photonic crystal light-emitting diodes

    SciTech Connect

    Rangel, Elizabeth; Matioli, Elison; Choi, Yong-Seok; Weisbuch, Claude; Speck, J. S.; Hu, Evelyn L.

    2011-01-01

    This letter explores the impact of quantum well placement and photonic crystal (PhC) etch depth on the emission directionality of thin-film InGaN PhC light-emitting diodes (LEDs). The far-field pattern of 800-nm-thick PhC LEDs is tuned by varying only the etch depth of a surface-patterned hexagonal PhC from 90 to 440 nm. This dependence on etch depth is shown to arise from the preferential excitation of a subset of the allowed guided modes. Selective excitation of the TE{sub 0} and TE{sub 1} modes is utilized to achieve a vertically directional emission pattern comprised of only these two modes.

  7. Exploring hydrocarbon-bearing shale formations with multi-component seismic technology and evaluating direct shear modes produced by vertical-force sources

    NASA Astrophysics Data System (ADS)

    Alkan, Engin

    It is essential to understand natural fracture systems embedded in shale-gas reservoirs and the stress fields that influence how induced fractures form in targeted shale units. Multicomponent seismic technology and elastic seismic stratigraphy allow geologic formations to be better images through analysis of different S-wave modes as well as the P-wave mode. Significant amounts of energy produced by P-wave sources radiate through the Earth as downgoing SV-wave energy. A vertical-force source is an effective source for direct SV radiation and provides a pure shear-wave mode (SV-SV) that should reveal crucial information about geologic surfaces located in anisotropic media. SV-SV shear wave modes should carry important information about petrophysical characteristics of hydrocarbon systems that cannot be obtained using other elastic-wave modes. Regardless of the difficulties of extracting good-quality SV-SV signal, direct shear waves as well as direct P and converted S energy should be accounted for in 3C seismic studies. Acquisition of full-azimuth seismic data and sampling data at small intervals over long offsets are required for detailed anisotropy analysis. If 3C3D data can be acquired with improved signal-to-noise ratio, more uniform illumination of targets, increased lateral resolution, more accurate amplitude attributes, and better multiple attenuation, such data will have strong interest by the industry. The objectives of this research are: (1) determine the feasibility of extracting direct SV-SV common-mid-point sections from 3-C seismic surveys, (2) improve the exploration for stratigraphic traps by developing systematic relationship between petrophysical properties and combinations of P and S wave modes, (3) create compelling examples illustrating how hydrocarbon-bearing reservoirs in low-permeable rocks (particularly anisotropic shale formations) can be better characterized using different Swave modes (P-SV, SV-SV) in addition to the conventional P

  8. The Preferability of Constrained Optimization in Determining the Number of Prompts, Modes of Discourse, and Raters in a Direct Writing Assessment.

    ERIC Educational Resources Information Center

    Parkes, Jay; Suen, Hoi K.

    This study demonstrates the advantages of using a constrained optimization algorithm to explore the optimal number of prompts, modes of discourse, and raters for achieving an acceptable level of reliability during a direct writing assessment. Writing samples elicited from 50 college students were rated by 3 graduate students and the scores…

  9. Information Leakage Problem in Efficient Bidirectional Quantum Secure Direct Communication with Single Photons in Both Polarization and Spatial-Mode Degrees of Freedom

    NASA Astrophysics Data System (ADS)

    Liu, Zhi-Hao; Chen, Han-Wu; Liu, Wen-Jie

    2016-11-01

    The information leakage problem in the efficient bidirectional quantum secure direct communication protocol with single photons in both polarization and spatial-mode degrees of freedom is pointed out. Next, a way to revise this protocol to a truly secure one is given. We hope people pay more attention to the information leakage problem in order to design truly secure quantum communication protocols.

  10. GENOTOXICITY OF TOBACCO SMOKE AND TOBACCO SMOKE CONDENSATE: A REVIEW

    EPA Science Inventory

    Genotoxicity of Tobacco Smoke and Tobacco Smoke Condensate: A Review
    Abstract
    This report reviews the literature on the genotoxicity of main-stream tobacco smoke and cigarette smoke condensate (CSC) published since 1985. CSC is genotoxic in nearly all systems in which it h...

  11. GENOTOXICITY OF TOBACCO SMOKE AND TOBACCO SMOKE CONDENSATE: A REVIEW

    EPA Science Inventory

    Genotoxicity of Tobacco Smoke and Tobacco Smoke Condensate: A Review
    Abstract
    This report reviews the literature on the genotoxicity of main-stream tobacco smoke and cigarette smoke condensate (CSC) published since 1985. CSC is genotoxic in nearly all systems in which it h...

  12. From the Cover: An Investigation of the Genotoxicity and Interference of Gold Nanoparticles in Commonly Used In Vitro Mutagenicity and Genotoxicity Assays.

    PubMed

    George, Jiya M; Magogotya, Millicent; Vetten, Melissa A; Buys, Antoinette V; Gulumian, Mary

    2017-03-01

    The suitability of 4 in vitro assays, commonly used for mutagenicity and genotoxicity assessment, was investigated in relation to treatment with 14 nm citrate-stabilized gold nanoparticles (AuNPs). Specifically, the Ames test was conducted without metabolic activation, where no mutagenic effects were observed. High resolution transmission electron microscopy and Cytoviva dark-field image analysis showed that AuNPs did not enter the bacterial cells, thus confirming the unreliability of the Ames test for nanoparticle mutagenicity studies. In addition, the Chinese hamster ovary (CHO) cell line was used for Comet, Chromosome aberration and Micronucleus assays. CHO cells were treated with AuNPs for 20 h at 37 °C. Cytotoxicity was not detected by cell impedance studies even though AuNP uptake was confirmed using Cytoviva image analysis. The DNA damage was statistically significant in treated cells when assessed by the Comet assay. However, minimal and nonstatistically significant chromosomal DNA damage was observed using the chromosome aberration and micronucleus assays. In this study, we showed that false positive results obtained with Comet assay may have been due to the possibility of direct contact between the residual, intracellular AuNPs and DNA during the assay procedure. Therefore, the chromosome aberration and micronucleus assays are better suited to assess the genotoxic effects of nanoparticles due to low probability of such direct contact occurring. Genotoxic effect of 14 and 20 nm citrate-stabilized, as well as, 14 nm PCOOH AuNPs were also investigated using chromosome aberration and micronucleus assays. Based on our acceptance criteria for a positive genotoxic response, none of the AuNPs were found to be genotoxic in either of these assays. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. Laser dissection sampling modes for direct mass spectral analysis [using a hybrid optical microscopy/laser ablation liquid vortex capture/electrospray ionization system

    SciTech Connect

    Cahill, John F.; Kertesz, Vilmos; Van Berkel, Gary J.

    2016-02-01

    Here, laser microdissection coupled directly with mass spectrometry provides the capability of on-line analysis of substrates with high spatial resolution, high collection efficiency, and freedom on shape and size of the sampling area. Establishing the merits and capabilities of the different sampling modes that the system provides is necessary in order to select the best sampling mode for characterizing analytically challenging samples. The capabilities of laser ablation spot sampling, laser ablation raster sampling, and laser 'cut and drop' sampling modes of a hybrid optical microscopy/laser ablation liquid vortex capture electrospray ionization mass spectrometry system were compared for the analysis of single cells and tissue. Single Chlamydomonas reinhardtii cells were monitored for their monogalactosyldiacylglycerol (MGDG) and diacylglyceryltrimethylhomo-Ser (DGTS) lipid content using the laser spot sampling mode, which was capable of ablating individual cells (4-15 m) even when agglomerated together. Turbid Allium Cepa cells (150 m) having unique shapes difficult to precisely measure using the other sampling modes could be ablated in their entirety using laser raster sampling. Intact microdissections of specific regions of a cocaine-dosed mouse brain tissue were compared using laser 'cut and drop' sampling. Since in laser 'cut and drop' sampling whole and otherwise unmodified sections are captured into the probe, 100% collection efficiencies were achieved. Laser ablation spot sampling has the highest spatial resolution of any sampling mode, while laser ablation raster sampling has the highest sampling area adaptability of the sampling modes. In conclusion, laser ablation spot sampling has the highest spatial resolution of any sampling mode, useful in this case for the analysis of single cells. Laser ablation raster sampling was best for sampling regions with unique shapes that are difficult to measure using other sampling modes. Laser 'cut and drop' sampling

  14. Laser dissection sampling modes for direct mass spectral analysis [using a hybrid optical microscopy/laser ablation liquid vortex capture/electrospray ionization system

    DOE PAGES

    Cahill, John F.; Kertesz, Vilmos; Van Berkel, Gary J.

    2016-02-01

    Here, laser microdissection coupled directly with mass spectrometry provides the capability of on-line analysis of substrates with high spatial resolution, high collection efficiency, and freedom on shape and size of the sampling area. Establishing the merits and capabilities of the different sampling modes that the system provides is necessary in order to select the best sampling mode for characterizing analytically challenging samples. The capabilities of laser ablation spot sampling, laser ablation raster sampling, and laser 'cut and drop' sampling modes of a hybrid optical microscopy/laser ablation liquid vortex capture electrospray ionization mass spectrometry system were compared for the analysis ofmore » single cells and tissue. Single Chlamydomonas reinhardtii cells were monitored for their monogalactosyldiacylglycerol (MGDG) and diacylglyceryltrimethylhomo-Ser (DGTS) lipid content using the laser spot sampling mode, which was capable of ablating individual cells (4-15 m) even when agglomerated together. Turbid Allium Cepa cells (150 m) having unique shapes difficult to precisely measure using the other sampling modes could be ablated in their entirety using laser raster sampling. Intact microdissections of specific regions of a cocaine-dosed mouse brain tissue were compared using laser 'cut and drop' sampling. Since in laser 'cut and drop' sampling whole and otherwise unmodified sections are captured into the probe, 100% collection efficiencies were achieved. Laser ablation spot sampling has the highest spatial resolution of any sampling mode, while laser ablation raster sampling has the highest sampling area adaptability of the sampling modes. In conclusion, laser ablation spot sampling has the highest spatial resolution of any sampling mode, useful in this case for the analysis of single cells. Laser ablation raster sampling was best for sampling regions with unique shapes that are difficult to measure using other sampling modes. Laser 'cut and drop

  15. Environmental genotoxicity: Probing the underlying mechanisms

    SciTech Connect

    Shugart, L.; Theodorakis, C.

    1993-12-31

    Environmental pollution is a complex issue because of the diversity of anthropogenic agents, both chemical and physical, that have been detected and catalogued. The consequences to biota from exposure to genotoxic agents present an additional problem because of the potential for these agents to produce adverse change at the cellular and organismal levels. Past studies in genetic toxicology at the Oak Ridge National Laboratory have focused on structural damage to the DNA of environmental species that may occur after exposure to genotoxic agents and the use of this information to document exposure and to monitor remediation. In an effort to predict effects at the population, community and ecosystem levels, current studies in genetic ecotoxicology are attempting to characterize the biological mechanisms at the gene level that regulate and limit the response of an individual organism to genotoxic factors in their environment.

  16. Screening Genotoxicity Chemistry with Microfluidic Electrochemiluminescent Arrays

    PubMed Central

    Bist, Itti; Bano, Kiran; Rusling, James F.

    2017-01-01

    This review describes progress in the development of electrochemiluminescent (ECL) arrays aimed at sensing DNA damage to identify genotoxic chemistry related to reactive metabolites. Genotoxicity refers to chemical or photochemical processes that damage DNA with toxic consequences. Our arrays feature DNA/enzyme films that form reactive metabolites of test chemicals that can subsequently react with DNA, thus enabling prediction of genotoxic chemical reactions. These high-throughput ECL arrays incorporating representative cohorts of human metabolic enzymes provide a platform for determining chemical toxicity profiles of new drug and environmental chemical candidates. The arrays can be designed to identify enzymes and enzyme cascades that produce the reactive metabolites. We also describe ECL arrays that detect oxidative DNA damage caused by metabolite-mediated reactive oxygen species. These approaches provide valuable high-throughput tools to complement modern toxicity bioassays and provide a more complete toxicity prediction for drug and chemical product development. PMID:28467352

  17. Natural Antioxidants Against Arsenic-Induced Genotoxicity.

    PubMed

    Kumar, Munesh; Lalit, Minakshi; Thakur, Rajesh

    2016-03-01

    Arsenic is present in water, soil, and air in organic as well as in inorganic forms. However, inorganic arsenic is more toxic than organic and can cause many diseases including cancers in humans. Its genotoxic effect is considered as one of its carcinogenic actions. Arsenic can cause DNA strand breaks, deletion mutations, micronuclei formation, DNA-protein cross-linking, sister chromatid exchange, and DNA repair inhibition. Evidences indicate that arsenic causes DNA damage by generation of reactive free radicals. Nutritional supplementation of antioxidants has been proven highly beneficial against arsenic genotoxicity in experimental animals. Recent studies suggest that antioxidants protect mainly by reducing excess free radicals via restoring the activities of cellular enzymatic as well as non-enzymatic antioxidants and decreasing the oxidation processes such as lipid peroxidation and protein oxidation. The purpose of this review is to summarize the recent literature on arsenic-induced genotoxicity and its mitigation by naturally derived antioxidants in various biological systems.

  18. Environmental genotoxicity: probing the underlying mechanisms.

    PubMed Central

    Shugart, L; Theodorakis, C

    1994-01-01

    Environmental pollution is a complex issue because of the diversity of anthropogenic agents, both chemical and physical, that have been detected and catalogued. The consequences to biota from exposure to genotoxic agents present an additional problem because of the potential for these agents to produce adverse change at the cellular and organismal levels. Past studies in genetic toxicology at the Oak Ridge National Laboratory have focused on structural damage to the DNA of environmental species that may occur after exposure to genotoxic agents and the use of this information to document exposure and to monitor remediation. In an effort to predict effects at the population, community, and ecosystem levels, current studies in genetic ecotoxicology are attempting to characterize the biologic mechanisms at the gene level that regulate and limit the response of an individual organism to genotoxic factors in their environment. PMID:7713026

  19. Immunocytotoxicity, cytogenotoxicity and genotoxicity of cadmium-based quantum dots in the marine mussel Mytilus galloprovincialis.

    PubMed

    Rocha, Thiago Lopes; Gomes, Tânia; Cardoso, Cátia; Letendre, Julie; Pinheiro, José Paulo; Sousa, Vânia Serrão; Teixeira, Margarida Ribau; Bebianno, Maria João

    2014-10-01

    There is an increased use of Quantum Dot (QDs) in biological and biomedical applications, but little is known about their marine ecotoxicology. So, the aim of this study was to investigate the possible immunocytotoxic, cytogenotoxic and genotoxic effects of cadmium telluride QDs (CdTe QDs) on the marine mussel Mytilus galloprovincialis. Mussels were exposed to 10 μg L(-1) of CdTe QDs or to soluble Cd [Cd(NO3)2] for 14 days and Cd accumulation, immunocytotoxicity [hemocyte density, cell viability, lysosomal membrane stability (LMS), differential cell counts (DCC)], cytogenotoxicity (micronucleus test and nuclear abnormalities assay) and genotoxicity (comet assay) were analyzed. Results show that in vivo exposure to QDs, Cd is accumulated in mussel soft tissues and hemolymph and induce immunotoxic effects mediated by a decrease in LMS, changes in DCC, as well as genotoxicity (DNA damage). However, QDs do not induce significant changes in hemocytes density, cell viability and cytogenetic parameters in opposition to Cd(2+). Soluble Cd is the most cytotoxic and cytogenotoxic form on Mytilus hemocytes due to a higher accumulation of Cd in tissues. Results indicate that immunotoxicity and genotoxicity of CdTe QDs and Cd(2+) are mediated by different modes of action and show that Mytilus hemocytes are important targets for in vivo QDs toxicity.

  20. Cobalt and antimony: genotoxicity and carcinogenicity.

    PubMed

    De Boeck, Marlies; Kirsch-Volders, Micheline; Lison, Dominique

    2003-12-10

    The purpose of this review is to summarise the data concerning genotoxicity and carcinogenicity of Co and Sb. Both metals have multiple industrial and/or therapeutical applications, depending on the considered species. Cobalt is used for the production of alloys and hard metal (cemented carbide), diamond polishing, drying agents, pigments and catalysts. Occupational exposure to cobalt may result in adverse health effects in different organs or tissues. Antimony trioxide is primarily used as a flame retardant in rubber, plastics, pigments, adhesives, textiles, and paper. Antimony potassium tartrate has been used worldwide as an anti-shistosomal drug. Pentavalent antimony compounds have been used for the treatment of leishmaniasis. Co(II) ions are genotoxic in vitro and in vivo, and carcinogenic in rodents. Co metal is genotoxic in vitro. Hard metal dust, of which occupational exposure is linked to an increased lung cancer risk, is proven to be genotoxic in vitro and in vivo. Possibly, production of active oxygen species and/or DNA repair inhibition are mechanisms involved. Given the recently provided proof for in vitro and in vivo genotoxic potential of hard metal dust, the mechanistic evidence of elevated production of active oxygen species and the epidemiological data on increased cancer risk, it may be advisable to consider the possibility of a new evaluation by IARC. Both trivalent and pentavalent antimony compounds are generally negative in non-mammalian genotoxicity tests, while mammalian test systems usually give positive results for Sb(III) and negative results for Sb(V) compounds. Assessment of the in vivo potential of Sb2O3 to induce chromosome aberrations (CA) gave conflicting results. Animal carcinogenicity data were concluded sufficient for Sb2O3 by IARC. Human carcinogenicity data is difficult to evaluate given the frequent co-exposure to arsenic. Possible mechanisms of action, including potential to produce active oxygen species and to interfere with

  1. Genotoxicity of drinking water disinfectants in plant bioassays.

    PubMed

    Monarca, Silvano; Feretti, Donatella; Zani, Claudia; Rizzoni, Marco; Casarella, Silvia; Gustavino, Bianca

    2005-08-01

    The genotoxicity of two widely used drinking water disinfectants, sodium hypochlorite (NaClO) and chlorine dioxide (ClO(2)), and a new disinfectant, peracetic acid (PAA, CH(3)-CO-COOH), was evaluated in three short-term plant tests: (1) induction of anaphase chromosome aberrations in the root cells of Allium cepa, (2) micronucleus induction in the root cells of Vicia faba, and (3) micronucleus induction in Tradescantia pollen cells. The study was carried out in the laboratory by directly exposing the plants to several concentrations of the disinfectants in redistilled water at unadjusted (acid) and adjusted (neutral) pHs. Both 0.1 and 0.2 mg/l NaClO induced chromosome aberrations in the Allium cepa test at acid pH, but concentrations up to 0.5 mg/l of all the disinfectants were negative at neutral pH. Concentrations ranging from 0.1 to 0.5 mg/l NaClO, ClO(2,) and PAA induced micronuclei in Vicia faba at acid pH, while 1-2 mg/l NaClO and ClO(2) and 0.5-2 mg/l PAA gave positive responses at neutral pH. Most of concentrations of ClO(2) produced positive responses in the Tradescantia micronucleus test. In general, the highest levels of genotoxicity were observed under acid conditions; at acid pH, significant effects were induced by low concentrations of ClO(2) and PAA. Since the test concentrations of disinfectants are typical of those encountered in the biocidal treatment of tap water and similar concentrations are consumed daily by a large number of people, the genotoxicity of these compounds may constitute a significant public health concern.

  2. Single-particle and collective mode couplings associated with 1- and 2-directional electronic ordering in metallic RTe3 (R = Ho, Dy, Tb)

    SciTech Connect

    Yusupov, R.V.; Mertelj, T.; Chu, J.-H.; Fisher, I.R.; Mihailovic, D.; /Stefan Inst., Ljubljana

    2010-02-15

    The coupling of phonons with collective modes and single-particle gap excitations associated with one (1d) and two-directional (2d) electronically-driven charge-density wave (CDW) ordering in metallic RTe{sub 3} is investigated as a function of rare-earth ion chemical pressure (R = Tb, Dy, Ho) using femtosecond pump-probe spectroscopy. From the T-dependence of the CDW gap {Delta}{sub CDW} and the amplitude mode (AM) we find that while the transition to a 1d-CDW ordered state at Tc1 initially proceeds in an exemplary mean-field (MF)-like fashion, below T{sub c1}, {Delta}{sub CDW} is depressed and departs from the MF behavior. The effect is apparently triggered by resonant mode-mixing of the amplitude mode (AM) with a totally symmetric phonon at 1.75 THz. At low temperatures, when the state evolves into a 2d-CDW ordered state at T{sub c2} in the DyTe{sub 3} and HoTe{sub 3}, additional much weaker mode mixing is evident but no soft mode is observed.

  3. Modulation of the genotoxicity of pesticides reacted with redox-modified smectite clay.

    PubMed

    Sorensen, Kara C; Stucki, Joseph W; Warner, Richard E; Wagner, Elizabeth D; Plewa, Michael J

    2005-10-01

    Pesticides are toxic agents intentionally released into the environment; their use raises public health and environmental concerns. In recent years there has been much attention to the biotic degradation of pesticides. Abiotic mechanisms in the soil can contribute to pesticide degradation yet the toxicological impact of such degradation is unclear. This study combines for the first time an investigation into abiotic mechanisms of degradation coupled with toxicological endpoints in mammalian cells. The genotoxicity of three commonly used agricultural pesticides was assessed before and after exposure to redox-modified clay minerals. The objectives of the study were to determine the genotoxicity of 2,4-dichlorophenoxy acetic acid (2,4-D), dicamba, and oxamyl, using single cell gel electrophoresis with Chinese hamster ovary (CHO) cells, and to determine the effect of the iron oxidation state in clay minerals (ferruginous smectite SWa-1) on the genotoxic potency of the pesticides. 2,4-D alone or following reaction with redox-modified clays did not induce DNA damage in CHO cells. Oxamyl alone induced a concentration-dependent increase in genomic DNA damage; however, its genotoxicity declined after reaction with reduced clay minerals. Dicamba was not genotoxic when directly analyzed. When dicamba was reacted with reduced clay, a concentration-dependent increase in genomic DNA damage was observed. This is the first reported case of a pesticide being converted into a genotoxin after exposure to redox-modified smectites. These data introduce a new paradigm on the interaction between redox-modified clays and pesticide-related environmental genotoxicity.

  4. Attenuation of G1 checkpoint function by the non-genotoxic carcinogen phenobarbital.

    PubMed

    Gonzales, A J; Christensen, J G; Preston, R J; Goldsworthy, T L; Tlsty, T D; Fox, T R

    1998-07-01

    Non-genotoxic chemical carcinogens are capable of inducing tumors in rodents without interacting with or directly altering the genetic material. Since a preponderance of evidence suggests that cancer results from the accumulation of genetic alterations, the mechanisms by which many non-genotoxic carcinogens induce genotoxic events remain unclear. The present study investigated whether the mitogenic, non-genotoxic carcinogen phenobarbital (PB) could alter cell-cycle checkpoint controls, thereby indirectly leading to the accumulation of genetic damage. Initial studies involved characterizing cell-cycle checkpoint responses to DNA damage in freshly isolated B6C3F1 mouse hepatocytes. These cells responded to bleomycin-induced DNA damage by arresting in G1 and G2. Cell-cycle arrest was coupled with p53 protein induction; however, p21WAF1 protein levels remained unchanged. Studies that utilized hepatocytes isolated from C57BL p53-/- mice showed that the DNA damage-induced G1 cell-cycle arrest was dependent on p53 function, but cell-cycle arrest in G2 was not affected by loss of p53. PB was able to delay and attenuate the G1 checkpoint response without altering G2 checkpoint function. A reduction in p53 protein, but not transcript levels, was observed in hepatocytes exposed to PB. Additionally, PB delayed and attenuated p53 protein induction during DNA damage, which suggests that changes in the p53 protein may be contributing to the attenuated G1 checkpoint response caused by PB. Altered G1 checkpoint function represents an epigenetic mechanism by which phenobarbital may prevent the detection and repair of DNA damage and indirectly increase the frequency of genotoxic events above that occurring spontaneously. Abrogation of checkpoint controls may, thus, play an important mechanistic role in mitogenic, non-genotoxic chemical carcinogenesis.

  5. High-power 880-nm diode-directly-pumped passively mode-locked Nd:YVO₄ laser at 1342 nm with a semiconductor saturable absorber mirror.

    PubMed

    Li, Fang-Qin; Liu, Ke; Han, Lin; Zong, Nan; Bo, Yong; Zhang, Jing-Yuan; Peng, Qin-Jun; Cui, Da-Fu; Xu, Zu-Yan

    2011-04-15

    A high-power 880-nm diode-directly-pumped passively mode-locked 1342 nm Nd:YVO₄ laser was demonstrated with a semiconductor saturable absorber mirror (SESAM). The laser mode radii in the laser crystal and on the SESAM were optimized carefully using the ABCD matrix formalism. An average output power of 2.3 W was obtained with a repetition rate of 76 MHz and a pulse width of 29.2 ps under an absorbed pump power of 12.1 W, corresponding to an optical-optical efficiency of 19.0% and a slope efficiency of 23.9%, respectively.

  6. A `shoelace' antenna system for direct excitation of C-Mod's quasi-coherent mode and boundary layer turbulence

    NASA Astrophysics Data System (ADS)

    Labombard, B.; Golfinopoulos, T.; Parker, R.; Burke, W.; Leccacorvi, R.; Vieira, R.; Zaks, J.; Granetz, R.; Greenwald, M.; Marmar, E.; Porkolab, M.; Wolfe, S.; Woskov, P.; Wuktich, S.

    2011-10-01

    Experiments indicate that short wavelength, drift-Alfvenic turbulence largely sets the transport levels in the plasma edge: pressure gradients in L and H-mode are `clamped' at canonical values of the MHD parameter (αMHD) ; broadband and coherent fluctuations have strong magnetic signatures, with k⊥ρs ~ 0.1 being prominent. A quasi-coherent mode (50 kHz < f < 150 kHz, 1 < k⊥ < 2 cm-1) drives particle transport in C-Mod's EDA H-modes, making them steady-state without ELMs. With the idea of exciting, controlling or otherwise exploiting this transport behavior, we are developing a novel, high k⊥ antenna system to drive drift-Alfvenic modes at the outer midplane with k⊥ ~ 1.5 cm-1. A `shoelace' style winding is placed in close proximity to the last-closed flux surface. In principle, this scheme inductively drives parallel current fluctuations that mimic intrinsic plasma fluctuations but at larger amplitude. Details of the antenna system design, its planned modes of operation and initial results will be presented. Supported by USDoE award DE-FC02-99ER54512.

  7. Method for protection against genotoxic mutagenesis

    DOEpatents

    Grdina, D.J.

    1996-01-30

    A method and pharmaceutical for protecting against genotoxic damage in irradiated cells are disclosed. Reduction of mutations at the hypoxanthine-guanine phosphoribosyl transferase locus is accomplished by administering an effective dose of a compound having protected sulfhydryl groups which metabolize in vivo to produce both free sulfhydryl groups and disulfides. 10 figs.

  8. Genotoxic activity of halogenated phenylglycine derivatives.

    PubMed

    Boto, Alicia; Gallardo, Juan A; Hernández, Rosendo; Ledo, Francisco; Muñoz, Ana; Murguía, José R; Menacho-Márquez, Mauricio; Orjales, Aurelio; Saavedra, Carlos J

    2006-12-01

    The discovery of genotoxic amino acids derived from phenylglycine, and possessing halogen substituents, is described. The utility of hypervalent iodine reagents in the synthesis of this class of compounds is highlighted. The mechanism of action of the (haloaryl)glycines was studied in Saccharomyces cerevisiae.

  9. Method for protection against genotoxic mutagenesis

    DOEpatents

    Grdina, David J.

    1996-01-01

    A method and pharmaceutical for protecting against genotoxic damage in irradiated cells. Reduction of mutations at the hypoxanthine-guanine phosphoribosyl transferase locus is accomplished by administering an effective dose of a compound having protected sulfhydryl groups which metabolize in vivo to produce both free sulfhydryl groups and disulfides.

  10. "Aspartame: A review of genotoxicity data".

    PubMed

    Kirkland, David; Gatehouse, David

    2015-10-01

    Aspartame is a methyl ester of a dipeptide of aspartic acid and phenylalanine. It is 200× sweeter than sucrose and is approved for use in food products in more than 90 countries around the world. Aspartame has been evaluated for genotoxic effects in microbial, cell culture and animal models, and has been subjected to a number of carcinogenicity studies. The in vitro and in vivo genotoxicity data available on aspartame are considered sufficient for a thorough evaluation. There is no evidence of induction of gene mutations in a series of bacterial mutation tests. There is some evidence of induction of chromosomal damage in vitro, but this may be an indirect consequence of cytotoxicity. The weight of evidence from in vivo bone marrow micronucleus, chromosomal aberration and Comet assays is that aspartame is not genotoxic in somatic cells in vivo. The results of germ cell assays are difficult to evaluate considering limited data available and deviations from standard protocols. The available data therefore support the conclusions of the European Food Safety Authority (EFSA) that aspartame is non-genotoxic. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Different Mode of Afferents Determines the Frequency Range of High Frequency Activities in the Human Brain: Direct Electrocorticographic Comparison between Peripheral Nerve and Direct Cortical Stimulation.

    PubMed

    Kobayashi, Katsuya; Matsumoto, Riki; Matsuhashi, Masao; Usami, Kiyohide; Shimotake, Akihiro; Kunieda, Takeharu; Kikuchi, Takayuki; Mikuni, Nobuhiro; Miyamoto, Susumu; Fukuyama, Hidenao; Takahashi, Ryosuke; Ikeda, Akio

    2015-01-01

    Physiological high frequency activities (HFA) are related to various brain functions. Factors, however, regulating its frequency have not been well elucidated in humans. To validate the hypothesis that different propagation modes (thalamo-cortical vs. cortico-coritcal projections), or different terminal layers (layer IV vs. layer II/III) affect its frequency, we, in the primary somatosensory cortex (SI), compared HFAs induced by median nerve stimulation with those induced by electrical stimulation of the cortex connecting to SI. We employed 6 patients who underwent chronic subdural electrode implantation for presurgical evaluation. We evaluated the HFA power values in reference to the baseline overriding N20 (earliest cortical response) and N80 (late response) of somatosensory evoked potentials (HFA(SEP(N20)) and HFA(SEP(N80))) and compared those overriding N1 and N2 (first and second responses) of cortico-cortical evoked potentials (HFA(CCEP(N1)) and HFA(CCEP(N2))). HFA(SEP(N20)) showed the power peak in the frequency above 200 Hz, while HFA(CCEP(N1)) had its power peak in the frequency below 200 Hz. Different propagation modes and/or different terminal layers seemed to determine HFA frequency. Since HFA(CCEP(N1)) and HFA induced during various brain functions share a similar broadband profile of the power spectrum, cortico-coritcal horizontal propagation seems to represent common mode of neural transmission for processing these functions.

  12. Different Mode of Afferents Determines the Frequency Range of High Frequency Activities in the Human Brain: Direct Electrocorticographic Comparison between Peripheral Nerve and Direct Cortical Stimulation

    PubMed Central

    Kobayashi, Katsuya; Matsumoto, Riki; Matsuhashi, Masao; Usami, Kiyohide; Shimotake, Akihiro; Kunieda, Takeharu; Kikuchi, Takayuki; Mikuni, Nobuhiro; Miyamoto, Susumu; Fukuyama, Hidenao; Takahashi, Ryosuke; Ikeda, Akio

    2015-01-01

    Physiological high frequency activities (HFA) are related to various brain functions. Factors, however, regulating its frequency have not been well elucidated in humans. To validate the hypothesis that different propagation modes (thalamo-cortical vs. cortico-coritcal projections), or different terminal layers (layer IV vs. layer II/III) affect its frequency, we, in the primary somatosensory cortex (SI), compared HFAs induced by median nerve stimulation with those induced by electrical stimulation of the cortex connecting to SI. We employed 6 patients who underwent chronic subdural electrode implantation for presurgical evaluation. We evaluated the HFA power values in reference to the baseline overriding N20 (earliest cortical response) and N80 (late response) of somatosensory evoked potentials (HFASEP(N20) and HFASEP(N80)) and compared those overriding N1 and N2 (first and second responses) of cortico-cortical evoked potentials (HFACCEP(N1) and HFACCEP(N2)). HFASEP(N20) showed the power peak in the frequency above 200 Hz, while HFACCEP(N1) had its power peak in the frequency below 200 Hz. Different propagation modes and/or different terminal layers seemed to determine HFA frequency. Since HFACCEP(N1) and HFA induced during various brain functions share a similar broadband profile of the power spectrum, cortico-coritcal horizontal propagation seems to represent common mode of neural transmission for processing these functions. PMID:26087042

  13. Ground and surface water for drinking: a laboratory study on genotoxicity using plant tests.

    PubMed

    Feretti, Donatella; Ceretti, Elisabetta; Gustavino, Bianca; Zerbini, Llaria; Zani, Claudia; Monarca, Silvano; Rizzoni, Marco

    2012-02-17

    Surface waters are increasingly utilized for drinking water because groundwater sources are often polluted. Several monitoring studies have detected the presence of mutagenicity in drinking water, especially from surface sources due to the reaction of natural organic matter with disinfectant. The study aimed to investigate the genotoxic potential of the products of reaction between humic substances, which are naturally present in surface water, and three disinfectants: chlorine dioxide, sodium hypochlorite and peracetic acid. Commercial humic acids dissolved in distilled water at different total organic carbon (TOC) concentrations were studied in order to simulate natural conditions of both ground water (TOC=2.5 mg/L) and surface water (TOC=7.5 mg/L). These solutions were treated with the biocides at a 1:1 molar ratio of C:disinfectant and tested for genotoxicity using the anaphase chromosomal aberration and micronucleus tests in Allium cepa, and the Vicia faba and Tradescantia micronucleus tests. The tests were carried out after different times and with different modes of exposure, and at 1:1 and 1:10 dilutions of disinfected and undisinfected humic acid solutions. A genotoxic effect was found for sodium hypochlorite in all plant tests, at both TOCs considered, while chlorine dioxide gave positive results only with the A.cepa tests. Some positive effects were also detected for PAA (A.cepa and Tradescantia). No relevant differences were found in samples with different TOC values. The significant increase in all genotoxicity end-points induced by all tested disinfectants indicates that a genotoxic potential is exerted even in the presence of organic substances at similar concentrations to those frequently present in drinking water.

  14. Ground and Surface Water for Drinking: A Laboratory Study on Genotoxicity Using Plant Tests

    PubMed Central

    Feretti, Donatella; Ceretti, Elisabetta; Gustavino, Bianca; Zerbini, llaria; Zani, Claudia; Monarca, Silvano; Rizzoni, Marco

    2012-01-01

    Surface waters are increasingly utilized for drinking water because groundwater sources are often polluted. Several monitoring studies have detected the presence of mutagenicity in drinking water, especially from surface sources due to the reaction of natural organic matter with disinfectant. The study aimed to investigate the genotoxic potential of the products of reaction between humic substances, which are naturally present in surface water, and three disinfectants: chlorine dioxide, sodium hypochlorite and peracetic acid. Commercial humic acids dissolved in distilled water at different total organic carbon (TOC) concentrations were studied in order to simulate natural conditions of both ground water (TOC=2.5 mg/L) and surface water (TOC=7.5 mg/L). These solutions were treated with the biocides at a 1:1 molar ratio of C:disinfectant and tested for genotoxicity using the anaphase chromosomal aberration and micronucleus tests in Allium cepa, and the Vicia faba and Tradescantia micronucleus tests. The tests were carried out after different times and with different modes of exposure, and at 1:1 and 1:10 dilutions of disinfected and undisinfected humic acid solutions. A genotoxic effect was found for sodium hypochlorite in all plant tests, at both TOCs considered, while chlorine dioxide gave positive results only with the A.cepa tests. Some positive effects were also detected for PAA (A.cepa and Tradescantia). No relevant differences were found in samples with different TOC values. The significant increase in all genotoxicity end-points induced by all tested disinfectants indicates that a genotoxic potential is exerted even in the presence of organic substances at similar concentrations to those frequently present in drinking water. PMID:25170443

  15. Direct Observation of Current in Type-I Edge-Localized-Mode Filaments on the ASDEX Upgrade Tokamak

    SciTech Connect

    Vianello, N.; Zuin, M.; Cavazzana, R.; Naulin, V.; Rasmussen, J. J.; Schrittwieser, R.; Ionita, C.; Mehlmann, F.

    2011-03-25

    Magnetically confined plasmas in the high confinement regime are regularly subjected to relaxation oscillations, termed edge localized modes (ELMs), leading to large transport events. Present ELM theories rely on a combined effect of edge current and the edge pressure gradients which result in intermediate mode number (n congruent with 10-15) structures (filaments) localized in the perpendicular plane and extended along the field lines. By detailed localized measurements of the magnetic field perturbation associated to type-I ELM filaments, it is shown that these filaments carry a substantial current.

  16. Measurements of the genotoxic potential of (xeno-)oestrogens in the bivalve mollusc Scrobicularia plana, using the Comet assay.

    PubMed

    Petridis, Panos; Jha, Awadhesh N; Langston, William J

    2009-08-13

    There is increasing concern about the fate and effects of (geno)toxic and endocrine disrupting chemicals in sediments, highlighting the need to develop suitable monitoring tools. The deposit-feeding bivalve mollusc Scrobicularia plana has been put forward as a promising bioindicator of sediment contamination in estuaries. The recent demonstration of intersex in S. plana populations has been attributed to the feminisation of male clams following exposure to (xeno-)oestrogens, yet the mode of action of these endocrine disrupting chemicals (EDCs) remains largely unclear. One hypothesis that warrants further investigation is the possible involvement of genotoxicity. The first objective of this study was to assess whether the blood cells of S. plana are suitable for genotoxicity screening, using the alkaline single cell gel electrophoresis (Comet) assay. This was demonstrated successfully by exposing blood cells under in vitro conditions to a range of concentrations of the reference genotoxin hydrogen peroxide (H(2)O(2)): strong correlations between H(2)O(2) concentration and various comet parameters were found. Subsequently, the Comet assay was used to test whether the natural oestrogen 17beta-oestradiol (E2) and the synthetic (xeno)oestrogens ethinyloestradiol (EE2) and nonylphenol (NP) can produce genotoxic effects in S. plana, which might indicate possible involvement of mutagenicity in the mode of action of intersex development. In these short-term tests, clear genotoxic effects (significantly more DNA in the comet tail) were demonstrated by all EDCs, albeit only at high doses: 100 ng/L E2, 1 microg/L EE2 and 100 microg/L NP in vitro; and 1 microg/L E2 and 1mg/L NP after a 6-day in vivo exposure. Nevertheless, this study provides valuable preliminary data on the application and sensitivity of S. plana blood cells and suggests that the Comet assay is a useful tool, to screen for genotoxicity in in faunal clams and to examine further the links with higher order

  17. Nanoceria have no genotoxic effect on human lens epithelial cells

    NASA Astrophysics Data System (ADS)

    Pierscionek, Barbara K.; Li, Yuebin; Yasseen, Akeel A.; Colhoun, Liza M.; Schachar, Ronald A.; Chen, Wei

    2010-01-01

    There are no treatments for reversing or halting cataract, a disease of the structural proteins in the eye lens, that has associations with other age-related degenerative conditions such as Alzheimer's disease. The incidence of cataract and associated conditions is increasing as the average age of the population rises. Protein folding diseases are difficult to assess in vivo as proteins and their age-related changes are assessed after extraction. Nanotechnology can be used to investigate protein changes in the intact lens as well as for a potential means of drug delivery. Nanoparticles, such as cerium oxide (CeO2) which have antioxidant properties, may even be used as a means of treating cataract directly. Prior to use in treatments, nanoparticle genotoxicity must be tested to assess the extent of any DNA or chromosomal damage. Sister chromatid exchanges were measured and DNA damage investigated using the alkaline COMET assay on cultured human lens epithelial cells, exposed to 5 and 10 µg ml-1 of CeO2 nanoparticles (nanoceria). Nanoceria at these dosages did not cause any DNA damage or significant increases in the number of sister chromatid exchanges. The absence of genotoxic effects on lens cells suggests that nanoceria, in the doses and exposures tested in this study, are not deleterious to the eye lens and have the potential for use in studying structural alterations, in developing non-surgical cataract treatments and in investigating other protein folding diseases.

  18. Role of nitric oxide in genotoxicity: implication for carcinogenesis.

    PubMed

    Felley-Bosco, E

    1998-03-01

    Reactive oxygen species can initiate carcinogenesis by virtue of their capacity to react with DNA and cause mutations. Recently, it has been suggested that nitric oxide (NO) and its derivatives produced in inflamed tissues could contribute to the carcinogenesis process. Genotoxicity of NO follows its reaction with oxygen and superoxide. It can be due either to direct DNA damage or indirect DNA damage. Direct damage includes DNA base deamination, peroxynitrite-induced adducts formation and single strand breaks in the DNA. Indirect damage is due to the interaction of NO reactive species with other molecules such as amines, thiols and lipids. The efficiency of one pathway or another might depend on the cellular antioxidant status or the presence of free metals.

  19. Gigahertz repetition rate, sub-femtosecond timing jitter optical pulse train directly generated from a mode-locked Yb:KYW laser.

    PubMed

    Yang, Heewon; Kim, Hyoji; Shin, Junho; Kim, Chur; Choi, Sun Young; Kim, Guang-Hoon; Rotermund, Fabian; Kim, Jungwon

    2014-01-01

    We show that a 1.13 GHz repetition rate optical pulse train with 0.70 fs high-frequency timing jitter (integration bandwidth of 17.5 kHz-10 MHz, where the measurement instrument-limited noise floor contributes 0.41 fs in 10 MHz bandwidth) can be directly generated from a free-running, single-mode diode-pumped Yb:KYW laser mode-locked by single-wall carbon nanotube-coated mirrors. To our knowledge, this is the lowest-timing-jitter optical pulse train with gigahertz repetition rate ever measured. If this pulse train is used for direct sampling of 565 MHz signals (Nyquist frequency of the pulse train), the jitter level demonstrated would correspond to the projected effective-number-of-bit of 17.8, which is much higher than the thermal noise limit of 50 Ω load resistance (~14 bits).

  20. Modeling and Direct Electric-Field Measurements of Passively Mode-Locked Quantum-Dot Lasers (Postprint)

    DTIC Science & Technology

    2010-07-01

    increased, a coexisting attractor appears around g0 = 2.15, and this state may be de- scribed as a steady-state mode-locked solution where the laser has...reveals pulse asymmetry that is obscured in any autocorrelation measurement and hidden in the spectrogram of Fig. 7. In contrast to the intensity, the

  1. In vivo genotoxicity of furan in F344 rats at cancer bioassay doses

    SciTech Connect

    Ding, Wei

    2012-06-01

    Furan, a potent rodent liver carcinogen, is found in many cooked food items and thus represents a human cancer risk. Mechanisms for furan carcinogenicity were investigated in male F344 rats using the in vivo Comet and micronucleus assays, combined with analysis of histopathological and gene expression changes. In addition, formamidopyrimidine DNA glycosylase (Fpg) and endonuclease III (EndoIII)-sensitive DNA damage was monitored as a measure of oxidative DNA damage. Rats were treated by gavage on four consecutive days with 2, 4, and 8 mg/kg bw furan, doses that were tumorigenic in 2-year cancer bioassays, and with two higher doses, 12 and 16 mg/kg. Rats were killed 3 h after the last dose, a time established as producing maximum levels of DNA damage in livers of furan-treated rats. Liver Comet assays indicated that both DNA strand breaks and oxidized purines and pyrimidines increased in a near-linear dose-responsive fashion, with statistically significant increases detected at cancer bioassay doses. No DNA damage was detected in bone marrow, a non-target tissue for cancer, and peripheral blood micronucleus assays were negative. Histopathological evaluation of liver from furan-exposed animals produced evidence of inflammation, single-cell necrosis, apoptosis, and cell proliferation. In addition, genes related to apoptosis, cell-cycle checkpoints, and DNA-repair were expressed at a slightly lower level in the furan-treated livers. Although a mixed mode of action involving direct DNA binding cannot be ruled out, the data suggest that furan induces cancer in rat livers mainly through a secondary genotoxic mechanism involving oxidative stress, accompanied by inflammation, cell proliferation, and toxicity. -- Highlights: ► Furan is a potent rodent liver carcinogen and represents a human cancer risk. ► Furan induces DNA damage in rat liver at cancer bioassay doses. ► Furan induces oxidative stress, inflammation and cell proliferation in rat liver. ► Expression of

  2. Genotoxicity and carcinogenicity studies of bronchodilators and antiasthma drugs.

    PubMed

    Brambilla, Giovanni; Mattioli, Francesca; Robbiano, Luigi; Martelli, Antonietta

    2013-05-01

    This survey is a compendium of genotoxicity and carcinogenicity information of bronchodilators and antiasthma drugs. Data from 46 marketed drugs were collected. Of these 46 drugs, 25 (54.3%) did not have retrievable genotoxicity or carcinogenicity data. The remaining 21 (45.7%) had at least one genotoxicity or carcinogenicity test result. Of these 21 drugs, 10 had at least one positive finding: three tested positive in at least one genotoxicity assay, eight in at least one carcinogenicity assay, and one of them gave positive results in both genotoxicity assay and carcinogenicity assay. Concerning the predictivity of genetic toxicology findings for the result(s) of long-term carcinogenesis assays, 15 drugs had both genotoxicity and carcinogenicity data: seven of them (46.6%) were neither genotoxic nor carcinogenic, 6 (40.0%) were carcinogenic in at least one sex of mice or rats but tested negative in genotoxicity assays, 1 (6.7%) tested positive in genotoxicity assay but was non-carcinogenic, and 1 (6.7%) gave positive responses in both genotoxicity and carcinogenicity assay. Only 11 (23.9%) of the 46 drugs considered had all data required by current guidelines for testing of pharmaceuticals, but a large fraction of them were developed and marketed prior to the present regulatory climate.

  3. Comparative efficacy of two microdoses of a potentized homoeopathic drug, Cadmium Sulphoricum, in reducing genotoxic effects produced by cadmium chloride in mice: a time course study

    PubMed Central

    Datta, Swapna S; Mallick, Palash P; Rahman Khuda-Bukhsh, Anisur AR

    2001-01-01

    Background Cadmium poisoning in the environment has assumed an alarming problem in recent years. Effective antimutagenic agents which can reverse or combat cadmium induced genotoxicity in mice have not yet been reported. Therefore, in the present study, following the homeopathic principle of "like cures like", we tested the efficacy of two potencies of a homeopathic drug, Cadmium Sulphoricum (Cad Sulph), in reducing the genotoxic effects of Cadmium chloride in mice. Another objective was to determine the relative efficacy of three administrative modes, i.e. pre-, post- and combined pre and post-feeding of the homeopathic drugs. For this, healthy mice, Mus musculus, were intraperitoneally injected with 0.008% solution of CdCl2 @ 1 ml/100 gm of body wt (i.e. 0.8 mcg/gm of bw), and assessed for the genotoxic effects through such studies as chromosome aberrations (CA), micronucleated erythrocytes (MNE), mitotic index (MI) and sperm head anomaly (SHA), keeping suitable succussed alcohol fed (positive) and CdCl2 untreated normal (negative) controls. The CdCl2 treated mice were divided into 3 subgroups, which were orally administered with the drug prior to, after and both prior to and after injection of CdCl2 at specific fixation intervals and their genotoxic effects were analyzed. Results While the CA, MNE and SHA were reduced in the drug fed series as compared to their respective controls, the MI showed an apparent increase. The combined pre- and post-feeding of Cad Sulph showed maximum reduction of the genotoxic effects. Conclusions Both Cad Sulph-30 and 200 were able to combat cadmium induced genotoxic effects in mice and that combined pre- and post-feeding mode of administration was found to be most effective in reducing the genotoxic effect of CdCl2 followed by the post-feeding mode. PMID:11737881

  4. Genotoxic substances in the St. Lawrence system. 1: Industrial genotoxins sorbed to particulate matter in the St. Lawrence, St. Maurice, and Saguenay rivers, Canada

    SciTech Connect

    White, P.A.; Rasmussen, J.B.; Blaise, C.

    1998-02-01

    Previous investigations of organic genotoxins in industrial effluents discharged into the St. Lawrence River system (Quebec, Canada) indicated that a substantial fraction of the genotoxicity is adsorbed to suspended particulate matter. This study used the SOS Chromotest to investigate the presence, potency, and behavior of particle-bound genotoxins in the downstream ecosystem. The results indicate that although extracts of both suspended and sedimented particulate matter are genotoxic, suspended particulate matter samples are more potent in the absence of S9 activation, with the reverse being true for bottom sediments. The results confirmed a positive relationship between the genotoxicity of bottom sediment extracts and sediment organic matter content. A similar relationship between organic matter content and total polycyclic aromatic hydrocarbon (PAH) concentration indicates that putative genotoxins have physicochemical properties similar to the PAH class of contaminants. Conversion of PAH values to benzo[a]pyrene equivalents indicates that measured PAHs only account for a small fraction ({approximately}10%) of the observed SOS Chromotest response. Sites that receive discharges from foundries, aluminum refineries, and petroleum refineries yielded several of the most genotoxic samples. Further analyses revealed that the genotoxicity of suspended and sedimented particulate matter extracts is empirically related to the genotoxicity of industrial discharges. Comparisons of total genotoxicity levels in suspended particulates and bottom sediments suggest that direct-acting substances adsorbed to suspended matter are rapidly degraded and/or converted to more stable progenotoxins upon deposition. Further research is required to test this hypothesis and investigate effects on indigenous biota.

  5. Comet assay evaluation of six chemicals of known genotoxic potential in rats.

    PubMed

    Hobbs, Cheryl A; Recio, Leslie; Streicker, Michael; Boyle, Molly H; Tanaka, Jin; Shiga, Atsushi; Witt, Kristine L

    2015-07-01

    As a part of an international validation of the in vivo rat alkaline comet assay (comet assay) initiated by the Japanese Center for the Validation of Alternative Methods (JaCVAM) we examined six chemicals for potential to induce DNA damage: 2-acetylaminofluorene (2-AAF), N-nitrosodimethylamine (DMN), o-anisidine, 1,2-dimethylhydrazine dihydrochloride (1,2-DMH), sodium chloride, and sodium arsenite. DNA damage was evaluated in the liver and stomach of 7- to 9-week-old male Sprague Dawley rats. Of the five genotoxic carcinogens tested in our laboratory, DMN and 1,2-DMH were positive in the liver and negative in the stomach, 2-AAF and o-anisidine produced an equivocal result in liver and negative results in stomach, and sodium arsenite was negative in both liver and stomach. 1,2-DMH and DMN induced dose-related increases in hedgehogs in the same tissue (liver) that exhibited increased DNA migration. However, no cytotoxicity was indicated by the neutral diffusion assay (assessment of highly fragmented DNA) or histopathology in response to treatment with any of the tested chemicals. Therefore, the increased DNA damage resulting from exposure to DMN and 1,2-DMH was considered to represent a genotoxic response. Sodium chloride, a non-genotoxic non-carcinogen, was negative in both tissues as would be predicted. Although only two (1,2-DMH and DMN) out of five genotoxic carcinogens produced clearly positive results in the comet assay, the results obtained for o-anisidine and sodium arsenite in liver and stomach cells are consistent with the known mode of genotoxicity and tissue specificity exhibited by these carcinogens. In contrast, given the known genotoxic mode-of-action and target organ carcinogenicity of 2-AAF, it is unclear why this chemical failed to convincingly increase DNA migration in the liver. Thus, the results of the comet assay validation studies conducted in our laboratory were considered appropriate for five out of the six test chemicals.

  6. Comet assay evaluation of six chemicals of known genotoxic potential in rats

    PubMed Central

    Hobbs, Cheryl A.; Recio, Leslie; Streicker, Michael; Boyle, Molly H.; Tanaka, Jin; Shiga, Atsushi; Witt, Kristine L.

    2015-01-01

    As a part of an International validation of the in vivo rat alkaline comet assay (comet assay) initiated by the Japanese Center for the Validation of Alternative Methods (JaCVAM) we examined six chemicals for potential to induce DNA damage: 2-acetylaminofluorene (2-AAF), N-nitrosodimethylamine (DMN), o-anisidine, 1,2-dimethylhydrazine dihydrochloride (1,2-DMH), sodium chloride, and sodium arsenite. DNA damage was evaluated in the liver and stomach of 7- to 9-week-old male Sprague Dawley rats. Of the five genotoxic carcinogens tested in our laboratory, DMN and 1,2-DMH were positive in the liver and negative in the stomach, 2-AAF and o-anisidine produced an equivocal result in liver and negative results in stomach, and sodium arsenite was negative in both liver and stomach. 1,2-DMH and DMN induced dose-related increases in hedgehogs in the same tissue (liver) that exhibited increased DNA migration. However, no cytotoxicity was indicated by the neutral diffusion assay (assessment of highly fragmented DNA) or histopathology in response to treatment with any of the tested chemicals. Therefore, the increased DNA damage resulting from exposure to DMN and 1,2-DMH was considered to represent a genotoxic response. Sodium chloride, a non-genotoxic non-carcinogen, was negative in both tissues as would be predicted. Although only two (1,2-DMH and DMN) out of five genotoxic carcinogens produced clearly positive results in the comet assay, the results obtained for o-anisidine and sodium arsenite in liver and stomach cells are consistent with the known mode of genotoxicity and tissue specificity exhibited by these carcinogens. In contrast, given the known genotoxic mode-of-action and target organ carcinogenicity of 2-AAF, it is unclear why this chemical failed to convincingly increase DNA migration in the liver. Thus, the results of the comet assay validation studies conducted in our laboratory were considered appropriate for five out of the six test chemicals. PMID:26212309

  7. Genotoxic effect of chronic exposure to DDT on lymphocytes, oral mucosa and breast cells of female rats.

    PubMed

    Canales-Aguirre, Alejandro; Padilla-Camberos, Eduardo; Gómez-Pinedo, Ulises; Salado-Ponce, Hugo; Feria-Velasco, Alfredo; De Celis, Ruth

    2011-02-01

    The genotoxicity of some environmental contaminants may affect human health directly by damaging genetic material and thus plays an important role in cancer development. Xenoestrogens are one kind of environmental pollutants that may alter hormonal routes or directly affect DNA. The number of available biomarkers used to assess genetic risk and cancer is very extensive. The present study evaluated genotoxicity produced by the pesticide DDT on systemic and mammary gland cells obtained from adult female Wistar rats. Oral mucosa cells micronuclei were assessed; the comet assay in peripheral blood-isolated lymphocytes and mammary epithelial cells was also carried out. Additionally, oxidative stress was studied in mammary tissue through a lipid peroxidation assay. Our data showed an increase in lipid peroxidation, product of an increase in free oxygen radical levels, which leads to an oxidative stress status. Our results suggest that DDT is genotoxic, not only for lymphocytes but also to mammary epithelial cells.

  8. Genotoxic Effect of Chronic Exposure to DDT on Lymphocytes, Oral Mucosa and Breast Cells of Female Rats

    PubMed Central

    Canales-Aguirre, Alejandro; Padilla-Camberos, Eduardo; Gómez-Pinedo, Ulises; Salado-Ponce, Hugo; Feria-Velasco, Alfredo; De Celis, Ruth

    2011-01-01

    The genotoxicity of some environmental contaminants may affect human health directly by damaging genetic material and thus plays an important role in cancer development. Xenoestrogens are one kind of environmental pollutants that may alter hormonal routes or directly affect DNA. The number of available biomarkers used to assess genetic risk and cancer is very extensive. The present study evaluated genotoxicity produced by the pesticide DDT on systemic and mammary gland cells obtained from adult female Wistar rats. Oral mucosa cells micronuclei were assessed; the comet assay in peripheral blood-isolated lymphocytes and mammary epithelial cells was also carried out. Additionally, oxidative stress was studied in mammary tissue through a lipid peroxidation assay. Our data showed an increase in lipid peroxidation, product of an increase in free oxygen radical levels, which leads to an oxidative stress status. Our results suggest that DDT is genotoxic, not only for lymphocytes but also to mammary epithelial cells. PMID:21556202

  9. Metabolically Competent Human Skin Models: Activation and Genotoxicity of Benzo[a]pyrene

    PubMed Central

    Henkler, Frank

    2013-01-01

    The polycyclic aromatic hydrocarbon (PAH) benzo[a]pyrene (BP) is metabolized into a complex pattern of BP derivatives, among which the ultimate carcinogen (+)-anti-BP-7,8-diol-9,10-epoxide (BPDE) is formed to certain extents. Skin is frequently in contact with PAHs and data on the metabolic capacity of skin tissue toward these compounds are inconclusive. We compared BP metabolism in excised human skin, commercially available in vitro 3D skin models and primary 2D skin cell cultures, and analyzed the metabolically catalyzed occurrence of seven different BP follow-up products by means of liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). All models investigated were competent to metabolize BP, and the metabolic profiles generated by ex vivo human skin and skin models were remarkably similar. Furthermore, the genotoxicity of BP and its derivatives was monitored in these models via comet assays. In a full-thickness skin, equivalent BP-mediated genotoxic stress was generated via keratinocytes. Cultured primary keratinocytes revealed a level of genotoxicity comparable with that of direct exposure to 50–100nM of BPDE. Our data demonstrate that the metabolic capacity of human skin ex vivo, as well as organotypic human 3D skin models toward BP, is sufficient to cause significant genotoxic stress and thus cutaneous bioactivation may potentially contribute to mutations that ultimately lead to skin cancer. PMID:23148024

  10. Assessment of the genotoxicity of quinolone and fluoroquinolones contaminated soil with the Vicia faba micronucleus test.

    PubMed

    Khadra, A; Pinelli, E; Lacroix, M Z; Bousquet-Melou, A; Hamdi, H; Merlina, G; Guiresse, M; Hafidi, M

    2012-02-01

    The genotoxicity of quinolone and fluroquinolones was assessed using the micronucleus (MN) test on Vicia faba roots by direct contact exposure to a solid matrix. Plants were exposed to quinolones (nalidixic acid) and fluoroquinolones (ciprofloxacin and enrofloxacin) alone or mixed with artificially contaminated soils. Four different concentrations of each of these antibiotics were tested (0.01, 0.1, 1 and 10 mg/Kg) for nalidixic acid and (0.005, 0.05, 0.5 and 5 mg/Kg) for ciprofloxacin and enrofloxacin. These antibiotics were also used in mixture. Exposure of Vicia faba plants to each antibiotic at the highest two concentrations showed significant MN induction. The lowest two concentrations had no significant genotoxic effect. The mixture of the three compounds induced a significant MN induction whatever the mixture tested, from 0.02 to 20 mg/Kg. The results indicated that a similar genotoxic effect was obtained with the mixture at 0.2 mg/Kg in comparison with each molecule alone at 5-10 mg/Kg. Data revealed a clear synergism of these molecules on Vicia faba genotoxicity.

  11. In Vitro and In Vivo Genotoxicity Assessment of Aristolochia manshuriensis Kom.

    PubMed Central

    Hwang, Youn-Hwan; Kim, Taesoo; Cho, Won-Kyung; Yang, Hye Jin; Kwak, Dong Hoon; Ha, Hyunil; Song, Kwang Hoon; Ma, Jin Yeul

    2012-01-01

    Arisolochiae species plants containing aristolochic acids I and II (AA I and AA II) are well known to cause aristolochic acid nephropathy (AAN). Recently, there are various approaches to use AAs-containing herbs after the removal of their toxic factors. However, there is little information about genotoxicity of Arisolochiae manshuriensis Kom. (AMK) per se. To obtain safety information for AMK, its genotoxicity was evaluated in accordance with OECD guideline. To evaluate genotoxicity of AMK, we tested bacterial reverse mutation assay, chromosomal aberration test, and micronucleus test. Here, we also determined the amounts of AA I and II in AMK (2.85 ± 0.08 and 0.50 ± 0.02 mg/g extract, resp.). In bacterial reverse mutation assay, AMK dose-dependently increased revertant colony numbers in TA98, TA100 and TA1537 regardless of metabolic activation. AMK increased the incidence of chromosomal aberration in Chinese hamster ovary-K1 cells, but there was no statistically significant difference. The incidences of micronucleus in bone marrow erythrocyte were significantly increased in mice after oral administration of AMK (5000 mg/kg), comparing with those of vehicle group (P < 0.05). The results of three standard tests suggest that the genotoxicity of AMK is directly related to the AAs contents in AMK. PMID:22844332

  12. Direct observation of self-energy signatures of the resonant collective mode in Bi2Sr2CaCu2O8 +δ

    NASA Astrophysics Data System (ADS)

    Mou, Daixiang; Kaminski, Adam; Gu, Genda

    2017-05-01

    We use high-resolution angle-resolved photoemission spectroscopy to study the resonant, collective excitation mode in the superconducting state of Bi2212. By collecting very high-quality data we found noteworthy features in the self-energy in the antinodal region, where the interaction of electrons with the mode is the strongest. This interaction leads to a pronounced peak in the scattering rate and we demonstrate that this feature is directly responsible for the well-known peak-dip-hump structure in cuprates. By studying how the weight of this peak changes with temperature we unequivocally demonstrate that interaction of electrons with the resonant mode in cuprates vanishes at Tc and is very much localized in the momentum space close to the antinode. These findings present a consistent picture of line shape and self-energy signatures of the electron-boson coupling in cuprates and resolve long-standing controversy surrounding this issue. The momentum dependence of the strength of electron-mode interaction enables development of quantitative theory of this phenomenon in cuprates.

  13. Direct observation of self-energy signatures of the resonant collective mode in Bi2Sr2CaCu2O8+δ

    DOE PAGES

    Mou, Daixiang; Kaminski, Adam; Gu, Genda

    2017-05-01

    Here, we use high-resolution angle-resolved photoemission spectroscopy to study the resonant, collective excitation mode in the superconducting state of Bi2212. By collecting very high-quality data we found noteworthy features in the self-energy in the antinodal region, where the interaction of electrons with the mode is the strongest. This interaction leads to a pronounced peak in the scattering rate and we demonstrate that this feature is directly responsible for the well-known peak-dip-hump structure in cuprates. By studying how the weight of this peak changes with temperature we unequivocally demonstrate that interaction of electrons with the resonant mode in cuprates vanishes atmore » Tc and is very much localized in the momentum space close to the antinode. These findings present a consistent picture of line shape and self-energy signatures of the electron-boson coupling in cuprates and resolve long-standing controversy surrounding this issue. The momentum dependence of the strength of electron-mode interaction enables development of quantitative theory of this phenomenon in cuprates.« less

  14. Direct measurement of loop gain and bandwidth of phase-locked loop for mode-locked laser.

    PubMed

    Hou, Dong; Tian, Jie; Sun, Fuyu; Huang, Xianhe

    2016-07-25

    A simple and robust technique for measuring the loop gain and bandwidth of a phase-locking loop (PLL) for mode-locked laser is proposed. This technique can be used for the real-time measurement of the PLL's real loop gain and bandwidth in a closed loop without breaking its locking state. The agreement of the experimental result and theoretical calculation proves the validity of the proposed technique for measuring the loop gain and bandwidth. This technique with a simple configuration can be easily expanded to other laser's locking system whose loop gain and bandwidth should be measured in advance.

  15. Direct Experimental Evidence for Current-Transfer Mode Operation of Nested Tungsten Wire Arrays at 16 19 MA

    NASA Astrophysics Data System (ADS)

    Cuneo, M. E.; Sinars, D. B.; Bliss, D. E.; Waisman, E. M.; Porter, J. L.; Stygar, W. A.; Lebedev, S. V.; Chittenden, J. P.; Sarkisov, G. S.; Afeyan, B. B.

    2005-06-01

    Nested tungsten wire arrays (20-mm on 12-mm diam.) are shown for the first time to operate in a current-transfer mode at 16 19 MA, even for azimuthal interwire gaps of 0.2 mm that are the smallest typically used for any array experiment. After current transfer, the inner wire array shows discrete wire ablation and implosion characteristics identical to that of a single array, such as axially nonuniform ablation, delayed acceleration, and trailing mass and current. The presence of trailing mass from the outer and the inner arrays may play a role in determining nested array performance.

  16. [Bacterial pigment prodigiosin and its genotoxic effects].

    PubMed

    Gur'ianov, I D; Karamova, N S; Iusupova, D V; Gnezdilov, O I; Koshkarova, L A

    2013-01-01

    The prodigiosin preparation was isolated and purified from Serratia marcescens ATCC 9986, using chromatographic methods. The analysis of the preparation by TLC, NMR-spectrometry and mass-spectrometry allowed to confirm the red pigment fraction as the prodigiosin and detect its purity. Originally, the specific features of the toxic and genotoxic effects of prodigiosin and the possibility of induction of mutations by pigment in the cells of Salmonella typhimurium TA 100 (Ames test) and chromosome damage of mammalian erythroblasts have been determined.

  17. [Evaluation of genotoxic and/or co-genotoxic effects in cells exposed in vitro to extremely-low frequency electromagnetic fields].

    PubMed

    Scassellati Sforzolini, G; Moretti, M; Villarini, M; Fatigoni, C; Pasquini, R

    2004-01-01

    During the last two decades, concerns have arisen regarding a possible association between extremely-low frequency (ELF) electromagnetic fields (EMF) exposure and cancer incidence (e.g. childhood acute leukaemia, cancer of the nervous system, and lymphomas). In 1979, Wertheimer and Leeper firstly reported an excess of cancer mortality among children living in homes located near power lines and presumably exposed to elevated magnetic fields. Subsequently, a large number of epidemiological studies investigated the possible association between residential or occupational exposure to ELF-EMF and cancer. Several in vivo and in vitro models have been investigated with the effort to determine a link, if any, between such fields and mutagenesis and to determine the possible mechanism of cancer risk. However, a causal relationship between exposure to ELF-EMF and cancer has been suggested but has not been unequivocally demonstrated. In 1998, following an analysis of the results retrieved in the literature, the U.S. National Institute of Environmental Health Sciences proposed to apply a "possible human carcinogen" category (Group 2B) to ELF-EMF. More recently, in 2002, the same classification for ELF-MF was proposed by the International Agency for Research on Cancer. In this in vitro approach, to test the genotoxic and/or co-genotoxic potency of ELF-MF, we used the alkaline single-cell microgel-electrophoresis (comet) assay and the cytokinesis block micronucleus test. Co-exposure assays were performed in the presence of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), 4-nitroquinoline N-oxide (4NQO), benzene, 1,4-benzenediol (1,4-BD), or 1,2,4-benzenetriol (1,2,4-BT). An ELF-MF (50 Hz, 5 mT) was obtained by a system composed of capsulated induction coils. ELF-MF alone was unable to cause direct primary DNA damage. Whereas, an increased extent of DNA damage was observed in cells co-exposed to ELF-MF and MNNG, 1,4-BD, or 1,2,4-BT. An opposite trend was observed in cells treated

  18. Genotoxic assessment of environmental tobacco smoke using bacterial bioassays

    SciTech Connect

    Claxton, L.D.; Morin, R.S.; Hughes, T.J.; Lewtas, J.

    1989-01-01

    The paper demonstrates that integrated chemical and bacterial mutagenicity information can be used to identify environmental tobacco smoke genotoxicants, monitor human exposure, and make comparative assessments. Approximately one-third of the environmental tobacco-smoke constituents for which there is quantitative analytical-chemistry information also have associated genotoxicity information. For example, 11 of the quantitated compounds are animal carcinogens. Work presented in this paper demonstrates that both the nonparticle-bound semi-volatile and the particulate-bound organic material contain bacterial mutagens. These environmental tobacco-smoke organics give an equivalent of about 86,000 revertants per cigarette. In addition, this article summarizes efforts to estimate environmental tobacco smoke bacterial mutagenicity, to use bacterial tests for the monitoring of environmental tobacco smoke-impacted indoor environments, and to use bacterial assays for the direct monitoring of human exposure.

  19. The potential for new methods to assess human reproductive genotoxicity

    SciTech Connect

    Mendelsohn, M.L.

    1987-09-01

    The immediate prospects are not good for practical methods for measuring the human heritable mutation rate. The methods discussed here range from speculative to impractical, and at best are sensitive enough only for large numbers of subjects. Given the rapid development of DNA methods and the current status of two-dimensional gel electrophoresis, there is some hope that the intermediate prospects may be better. In contrast, the prospects for useful cellular-based male germinal methods seem more promising and immediate. Effective specific locus methods for sperm are already conceivable and may be practical in a few years. Obviously such methods will not predict heritable effects definitively, but they will provide direct information on reproductive genotoxicity and should contribute significantly to many current medical and environmental situations where genetic damage is suspected. 22 refs.

  20. Cytotoxicity and genotoxicity of butyl cyclohexyl phthalate.

    PubMed

    Köksal, Çinel; Nalbantsoy, Ayse; Karabay Yavaşoğlu, N Ülkü

    2016-03-01

    Butyl cyclohexyl phthalate (BCP) is frequently used in personal care products, medical and household applications. The aim of this study is therefore to evaluate possible cytotoxicity and genotoxicity of BCP using in vitro and in vivo assays. The in vitro cytotoxic effect of BCP was investigated on mouse fibroblastic cell line (L929 cells) by MTT assay. The result showed that BCP inhibits cell proliferation in a concentration-dependent manner (IC50 value = 0.29 µg/mL). For genotoxicity assessment, tested concentrations of BCP demonstrated mutagenic activity in the presence of S9 mix with the Salmonella strain TA100 in the Ames test. Results showed that BCP is a secondary mutagenic substance even in low concentrations. The data obtained from 28-days repeated toxicity tests on mice revealed that BCP caused abnormalities of chromosome number, in a dose-dependent manner. Additionally, DNA damage, particularly DNA strand breaks, was assessed by Comet assay. The test result shows that BCP seemed to have genotoxic potential at a high level of exposure.

  1. Cytotoxicity and genotoxicity of biogenic silver nanoparticles

    NASA Astrophysics Data System (ADS)

    Lima, R.; Feitosa, L. O.; Ballottin, D.; Marcato, P. D.; Tasic, L.; Durán, N.

    2013-04-01

    Biogenic silver nanoparticles with 40.3 ± 3.5 nm size and negative surface charge (- 40 mV) were prepared with Fusarium oxysporum. The cytotoxicity of 3T3 cell and human lymphocyte were studied by a TaliTM image-based cytometer and the genotoxicity through Allium cepa and comet assay. The results of BioAg-w (washed) and BioAg-nw (unwashed) biogenic silver nanoparticles showed cytotoxicity exceeding 50 μg/mL with no significant differences of response in 5 and 10 μg/mL regarding viability. Results of genotoxicity at concentrations 5.0 and 10.0 ug/mL show some response, but at concentrations 0.5 and 1.0 μg/mL the washed and unwashed silver nanoparticles did not present any effect. This in an important result since in tests with different bacteria species and strains, including resistant, MIC (minimal inhibitory concentration) had good answers at concentrations less than 1.9 μg/mL. This work concludes that biogenic silver nanoparticles may be a promising option for antimicrobial use in the range where no cyto or genotoxic effect were observed. Furthermore, human cells were found to have a greater resistance to the toxic effects of silver nanoparticles in comparison with other cells.

  2. [Fibers glass induced cytotoxicity and genotoxicity].

    PubMed

    Proietti, L; Giallongo, A; Zakrzewska, A M; Ammoscato, I; Lombardo, L; Frasca, G; Cardile, V

    2007-01-01

    Man-made vitrous fibers, have been widely used as a substitute for asbestos, as an insulation material. However the fibrous morphology of MMVFs raises concern about potential health hazard. The aim of our study was to assess cytotoxic and genotoxic effects induced on a human alveolar cell line A549 by exposure to glass wool fibers (GW). Cells were exposed for 72 h to 5, 50, 100 microg/ml of glass wool, after incubation the cell viability was determined by a MTT reduction assay. The genotoxic effect was studies by Comet test. An undamaged cell appeared as a nucleoid and a cell with damaged DNA as a comet. Measurement of Comet parameters: % DNA in the tail, tail length and tail momente (the product of relative tail intensity and lenght, that provides a parameter of DNA damage) were obtained from the analysis. A MTT assay indicated that glass wool caused a decrease in cell viability and this decrease was concentration-dependent. The results of the Comet test for DNA damage detection indicated in cell exposed to glass wool fibers a significant increase of mean TM value. All these results provide that the glass wool fibers can induce cytotoxicity and genotoxicity

  3. Bioavailability of genotoxic mixtures in soil

    SciTech Connect

    Bordelon, N.; Washburn, K.; He, L.Y.; Donnelly, K.C.

    1996-12-31

    Contaminated media at Superfund sites typically consist of complex mixtures of organic and inorganic chemicals which are difficult to characterize, both analytically and toxicologically. The current EPA approach to risk assessment uses solvent extraction to remove chemicals from the soil as a basis for estimating risk to the human population. However, contaminants that can be recovered with a solvent extract may not represent the mixture of chemicals that are available for human exposure. A procedure using an aqueous extraction was investigated to provide a more realistic estimate of what chemicals are bioavailable. A study was conducted with two soil types: creosote-contaminated sandy soil and coal tar-contaminated clay soil spiked with benzo(a)pyrene [B(a)P], and trinitrotoluene (TNT). Samples were extracted with hexane:acetone and water titrated to pH2 and pH7. HPLC analysis demonstrated up to 35% and 29% recovery of contaminants using the aqueous extracts. The estimated cancer risk for the aqueous extract was one order of magnitude less than that for solvent extracts. Analysis using the Salmonella/microsome assay demonstrated that solvent extracts were genotoxic (133 revertants/mg) with metabolic activation while aqueous extracts of clay soil were not genotoxic. Sandy soil showed genotoxicity both with and without metabolic activation. These results suggest that solvent extraction techniques may overestimate the concentration of contaminants that are available for human exposure and, hence, the risk associated with the presence of the contaminants in soil.

  4. A further result on consensus problems of second-order multi-agent systems with directed graphs, a moving mode and multiple delays.

    PubMed

    Li, Xue; Gao, Kai; Lin, Peng; Mo, Lipo

    2017-07-03

    This paper considers a consensus problem of a class of second-order multi-agent systems with a moving mode and multiple delays on directed graphs. Using local information, a distributed algorithm is adopted to make all agents reach a consensus while moving together with a constant velocity in the presence of delays. To study the effects of the coexistence of the moving mode and delays on the consensus convergence, a frequency domain approach is employed through analyzing the relationship between the components of the eigenvector associated with the eigenvalue on imaginary axis. Then based on the continuity of the system function, an upper bound for the delays is given to ensure the consensus convergence of the system. A numerical example is included to illustrate the obtained theoretical results. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

  5. Multiphonon scattering of light with direct transitions between optical modes in uniaxial single crystals and its application to an all-optical computing

    NASA Astrophysics Data System (ADS)

    Shcherbakov, Alexandre S.; Tepichin Rodriguez, Eduardo; Aguirre Lopez, Arturo

    2004-11-01

    A specific case of a multi-phonon non-collinear light scattering in optically uniaxial media is presented. Compared to our previous studies, an innovation lies in the fact that now we consider passing just the quartet of incident light beams through a single crystal that is perturbed by the triplet of coherent acoustic waves. The exact and closed analytical model for describing this strongly nonlinear phenomenon is developed. In fact, specially designed regime of a four-order light scattering whit direct coupling of all the light modes, when transitions of four input light beams into four output light modes are allowed and electronically controlled, is examined. The feasibility of applying such an effect to an all-optical computing and performing an all-optical adder is analyzed.

  6. Transmission-mode direct analysis in real time and desorption electrospray ionization mass spectrometry of insecticide-treated bednets for malaria control.

    PubMed

    Pérez, José J; Harris, Glenn A; Chipuk, Joseph E; Brodbelt, Jennifer S; Green, Michael D; Hampton, Christina Y; Fernández, Facundo M

    2010-04-01

    Transmission-mode direct analysis in real time (TM-DART) is presented as an alternative sampling strategy to traditional methods of sample introduction for DART MS analysis. A custom-designed sample holder was fabricated to rapidly and reproducibly position insecticide-treated nets normal to the ionizing metastable gas stream, enabling transmission of desorbed analyte ions through the holder cavity and into the MS. Introduction of the sample at this fixed geometry eliminates the need for optimizing sample position and allows spectra based on factors such as metastable gas temperature and flow to be systematically evaluated. The results presented here, supported by computational fluid dynamic simulations, demonstrate the effects of these factors on the resulting mass spectra and the potential of this sampling strategy to be used for qualitative and quantitative analyses. Transmission-mode desorption electrospray ionization (TM-DESI) experiments on similar insecticide-treated nets were performed for comparison purposes.

  7. Genotoxicity of radiofrequency radiation. DNA/Genetox Expert Panel.

    PubMed

    Brusick, D; Albertini, R; McRee, D; Peterson, D; Williams, G; Hanawalt, P; Preston, J

    1998-01-01

    During the past several years, concerns have been raised regarding the potential adverse effects of exposures to nonionizing radiation, particularly in the extremely low frequency (ELF) range (50 to 60 MHz) and radiofrequency radiation (RFR) with frequencies ranging from 30 KHz to 30,000 MHz. One focus of concern has been potential DNA interactions. Publications reviewing the genotoxicity of ELF radiation [McCann et al. (1993): Mutat Res 297(1):61-95; Murphy et al. (1993): Mutat Res 296:221-240; NAS (1997)], have been uniform in concluding that the weight of evidence does not indicate any genotoxic risk from exposure to this type of radiation. Concern that RFR may be associated with adverse biological effects [WHO, 1993], including recent allegations that they may be involved in the production of brain tumors in humans [Elmer-Dewit (1993): Time, February 8:42], has resulted in the production of a large number of publications describing the effects of RFR on the integrity of nucleic acids. Data from studies conducted in a frequency range from 800 to 3,000 MHz were reviewed and subjected to a weight-of-evidence evaluation. The evaluation focused on direct toxicological effects of RFR as well as on studies addressing basic biological responses to RFR at the cellular and molecular level. The data from over 100 studies suggest that RFR is not directly mutagenic and that adverse effects from exposure of organisms to high frequencies and high power intensities of RFR are predominantly the result of hyperthermia; however, there may be some subtle indirect effects on the replication and/or transcription of genes under relatively restricted exposure conditions.

  8. Anti-genotoxic activity of the mushroom Lactarius vellereus extract in bacteria and in mammalian cells in vitro.

    PubMed

    Mlinaric, A; Kac, J; Fatur, T; Filipic, M

    2004-03-01

    In a previous study we screened a range of mushroom species growing in Slovenia for their anti-genotoxic potential and found Lactarius vellereus to be the most effective. In this study genotoxic and anti-genotoxic activities of methanol extracts of Lactarius vellereus (Fr.: Fr.) Fr. were evaluated in the bacterial reverse mutation test with Salmonella typhimurium TA98 and, in the mammalian cell test with human hepatoma (HepG2) cells, using the comet assay to measure DNA damage. The extract induced no mutations in S. typhimurium TA98 and no DNA damage in HepG2 cells. Against the indirect acting mutagen 2-amino-3-methylimidazo(4,5-f)quinoline (IQ) the extract showed significant, dose dependent antimutagenic activity, while it did not counteract the direct acting mutagen 4-nitroquinoline oxide (4-NQO). The extract also exerted a protective effect against IQ induced genotoxicity in mammalian cells of human origin. Treatment of HepG2 cells with the L. vellereus extract (125-500 microg/ml) together with IQ, reduced the genotoxic effect of the latter in a dose dependent manner. Our findings show that a methanol extract of L. vellereus is highly protective against IQ induced DNA damage in human derived cells and L. vellereus can be considered as a natural source of antimutagens with potential pharmacological applications in cancer prevention.

  9. Genotoxicity of nimesulide in Wistar rats.

    PubMed

    Borkotoky, Debojyoti; Panda, Sushen K; Sahoo, Gyana R; Parija, Subas C

    2014-04-01

    It is mandatory for all new drugs to be tested for their potential genotoxicity in addition to general toxicity testing. Some old drugs have not been tested adequately for their genotoxic effects because these were in use before the local regulations were enforced. According to the material safety database, the toxicological effect of nimesulide is not yet fully understood. The present study therefore aimed to explore the genotoxic potential of nimesulide in Wistar albino rats. Nimesulide at the dose level of 50 (Gr-50), 100 (Gr-100) and 200 (Gr-200) mg/kg body weight (b.w.) was given orally. Each rat in treated groups (Gr-50 to Gr-200; n = 10) and negative control group (Gr-NC; n = 10) were administered orally (p.o.) with nimesulide and normal saline, respectively, for 14 days. Similarly, rats of positive control (Gr-PC; n = 10) were administered with cyclophosphamide (CPA; 20 mg/kg b.w.) intraperitoneally. CPA served as positive control, whereas normal saline served as as negative control. Approximately 1-2 mL of blood was collected from retro-orbital sinus for comet assay and subsequently rats were sacrificed to aspirate the femoral bone marrow for the micronucleus test. Structural chromosomal aberration, micronucleated polychromatic erythrocytes (MnPCEs), polychromatic erythrocytes (PCEs) and comet tail length were calculated using micronucleus assay and comet assay, respectively, which served as markers of genotoxicity. In the present study, it was observed that a significant increase in (1) different classified structural chromosomal aberrations with increase in nimesulide dose, such as gaps (50 mg/kg), gaps, breaks and pulverizations (100 mg/kg) and gaps, breaks, fragments, rings and pulverizations (200 mg/kg) and (2) % MnPCE and comet tail length was observed in animals treated with CPA (p < 0.001) or 200 mg of nimesulide (p < 0.05), as compared to negative control. In conclusion, nimesulide (200 mg/kg b.w.) produced a

  10. Magnetoelastoelectric coupling in core-shell nanoparticles enabling directional and mode-selective magnetic control of THz beam propagation

    DOE PAGES

    Dutta, Moumita; Prasankumar, Rohit Prativadi; Natarajan, Kamaraju; ...

    2017-08-07

    Magnetoelastoelectric coupling in an engineered biphasic multiferroic nanocomposite enables a novel magnetic field direction-defined propagation control of terahertz (THz) waves. These core–shell nanoparticles are comprised of a ferromagnetic cobalt ferrite core and a ferroelectric barium titanate shell. Furthermore, an assembly of these nanoparticles, when operated in external magnetic fields, exhibits a controllable amplitude modulation when the magnetic field is applied antiparallel to the THz wave propagation direction; yet the same assembly displays an additional phase modulation when the magnetic field is applied along the propagation direction. And while field-induced magnetostriction of the core leads to amplitude modulation, phase modulation ismore » a result of stress-mediated piezoelectricity of the outer ferroelectric shell.« less

  11. Magnetoelastoelectric coupling in core-shell nanoparticles enabling directional and mode-selective magnetic control of THz beam propagation.

    PubMed

    Dutta, Moumita; Natarajan, Kamaraju; Betal, Soutik; Prasankumar, Rohit P; Bhalla, Amar S; Guo, Ruyan

    2017-09-14

    Magnetoelastoelectric coupling in an engineered biphasic multiferroic nanocomposite enables a novel magnetic field direction-defined propagation control of terahertz (THz) waves. These core-shell nanoparticles are comprised of a ferromagnetic cobalt ferrite core and a ferroelectric barium titanate shell. An assembly of these nanoparticles, when operated in external magnetic fields, exhibits a controllable amplitude modulation when the magnetic field is applied antiparallel to the THz wave propagation direction; yet the same assembly displays an additional phase modulation when the magnetic field is applied along the propagation direction. While field-induced magnetostriction of the core leads to amplitude modulation, phase modulation is a result of stress-mediated piezoelectricity of the outer ferroelectric shell.

  12. Femtosecond laser direct writing of single mode polymer micro ring laser with high stability and low pumping threshold.

    PubMed

    Parsanasab, Gholam-Mohammad; Moshkani, Mojtaba; Gharavi, Alireza

    2015-04-06

    We have demonstrated an optically pumped polymer microring laser fabricated by two photon polymerization (TPP) of SU-8. The gain medium is an organic dye (Rhodamine B) doped in SU-8, and the laser cavity is a double coupled microring structure. Single mode lasing was obtained from the two coupled rings each with 30 µm and 29 µm radii using Vernier effect. Low laser threshold of 0.4 µJ/mm(2) is achieved using 1 µm wide polymer waveguides and the quality factor is greater than 10(4) at 612.4 nm wavelength. The lasing remained stable with pump energies from threshold to energies as high as 125 times the threshold.

  13. Aroclor 1254 increases the genotoxicity of several carcinogens to liver primary cell cultures

    SciTech Connect

    Mendoza-Figueroa, T.; Lopez-Revilla, R.; Villa-Trevino, S.

    1985-01-01

    The genotoxicity of both direct-acting and precarcinogenic chemicals was evaluated in liver primary cell cultures (LPCC) from untreated and Aroclor 1254 (Ar) pretreated rats. Hepatocytes were isolated from partially hepatectomized rats and their DNA was labeled in vitro with (/sup 3/H) dThd; the molecular weight of single-stranded DNA was determined by alkaline sucrose sedimentation. Two parameters of DNA damage were defined: 1) the mean effective dose (ED50), i.e., the carcinogen concentration that decreased the DNA molecular weight to half the original, and 2) the DNA breaking potency (DBP), i.e., the number of breaks per DNA molecule produced by 2 h exposure to 1mM concentration of the chemical. Two hours exposure of LPCC from untreated rats to the direct-acting alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) (6.8-340..mu..M) and to the precarcinogens benzo(a)pyrene (BaP) (0.05-0.33 mM) and dimethylnitrosamine (DMN) (0.45-16 mM) produced a concentration-dependent decrease in the molecular weight of DNA. Pretreatment of rats with Ar decreased significantly the sedimentation velocity of DNA and increased five, three, and two times the DBP of MNNG, BaP, and DMN, respectively. These results show that Ar-pretreatment of rats increases the genotoxicity of both direct-acting and precarcinogenic chemicals and suggest that Ar might increase the genotoxicity of chemical carcinogens perhaps by enhancing their metabolic activation, by producing direct genotoxic effects, or both. Our results also emphasize the carcinogenic risk that the environmental pollution by polychlorinated biphenyls might represent to humans.

  14. Direct observation of the core/double-shell architecture of intense dual-mode luminescent tetragonal bipyramidal nanophosphors.

    PubMed

    Kim, Su Yeon; Jeong, Jong Seok; Mkhoyan, K Andre; Jang, Ho Seong

    2016-05-21

    Highly efficient downconversion (DC) green-emitting LiYF4:Ce,Tb nanophosphors have been synthesized for bright dual-mode upconversion (UC) and DC green-emitting core/double-shell (C/D-S) nanophosphors-Li(Gd,Y)F4:Yb(18%),Er(2%)/LiYF4:Ce(15%),Tb(15%)/LiYF4-and the C/D-S structure has been proved by extensive scanning transmission electron microscopy (STEM) analysis. Colloidal LiYF4:Ce,Tb nanophosphors with a tetragonal bipyramidal shape are synthesized for the first time and they show intense DC green light via energy transfer from Ce(3+) to Tb(3+) under illumination with ultraviolet (UV) light. The LiYF4:Ce,Tb nanophosphors show 65 times higher photoluminescence intensity than LiYF4:Tb nanophosphors under illumination with UV light and the LiYF4:Ce,Tb is adapted into a luminescent shell of the tetragonal bipyramidal C/D-S nanophosphors. The formation of the DC shell on the core significantly enhances UC luminescence from the UC core under irradiation of near infrared light and concurrently generates DC luminescence from the core/shell nanophosphors under UV light. Coating with an inert inorganic shell further enhances the UC-DC dual-mode luminescence by suppressing the surface quenching effect. The C/D-S nanophosphors show 3.8% UC quantum efficiency (QE) at 239 W cm(-2) and 73.0 ± 0.1% DC QE. The designed C/D-S architecture in tetragonal bipyramidal nanophosphors is rigorously verified by an energy dispersive X-ray spectroscopy (EDX) analysis, with the assistance of line profile simulation, using an aberration-corrected scanning transmission electron microscope equipped with a high-efficiency EDX. The feasibility of these C/D-S nanophosphors for transparent display devices is also considered.

  15. Direct stability-indicating method development and validation for analysis of etidronate disodium using a mixed-mode column and charged aerosol detector.

    PubMed

    Liu, Xiao-Keng; Fang, Jiang B; Cauchon, Nina; Zhou, Pengzu

    2008-03-13

    This paper describes the development and validation of a rapid, direct, and stability-indicating method for analysis of etidronate, a bisphosphonate compound without a UV chromophore. A mixed-mode column was used to separate etidronate from its impurities in an 8-min gradient method and a charged aerosol detector (CAD) was used for detection. The developed HPLC method was validated with respect to specificity, linearity, accuracy, precision, sensitivity, and stability. The method can be used for release and stability testing of etidronate and has applicability to other similar bisphosphonate compounds.

  16. Information Leakage in Efficient Bidirectional Quantum Secure Direct Communication with Single Photons in Both Polarization and Spatial-Mode Degrees of Freedom

    NASA Astrophysics Data System (ADS)

    Zhang, Cai; Situ, Haozhen

    2016-11-01

    Recently, Wang et al. presented a bidirectional quantum secure direct communication protocol with single photons in both polarization and spatial-mode degrees of freedom (Int. J. Theor. Phys. 54(10): 3443-3453, 2015). They claimed that their protocol was efficient and removed the drawback of information leakage. However, we found that the information leakage actually exists in their protocol. In this paper, we analyze Wang et al.'s protocol in detail. In addition, we propose an improvement to avoid the information leakage. The security of the improved protocol has also been discussed.

  17. Cytotoxicity and genotoxicity induced by photothermal effects of colloidal gold nanorods.

    PubMed

    Choi, Young Joo; Kim, Yang Jee; Lee, Joong Won; Lee, Younghyun; Lee, Sunyeong; Lim, Yong-Beom; Chung, Hai Won

    2013-06-01

    Gold nanorods (Au NRs) that absorb near-infrared (NIR) light have great potential in the field of nanomedicine. Photothermal therapy (PTT), a very attractive cancer therapy in nanomedicine, combines nanomaterials and light. The aim of this study was to elucidate the molecular mechanism involved in Au NR-mediated cytotoxic, genotoxic, and other biological responses, in the presence or absence of NIR irradiation. Specifically, cell death mode, generation of reactive oxygen species, DNA damage, apoptotic gene expression, and cell morphological changes induced by Au NRs under NIR irradiation were evaluated in cancer cells. In human lung adenocarcinoma epithelial cells (A549 cells), mild necrosis via DNA damage was induced by NIR responsive Au NRs. Unlike in the cancer cells, cell viability of normal human lymphocyte was not affected by the combined treatment of Au NRs and NIR irradiation. This study delineates differential cytotoxic and genotoxic susceptibility of cancer and normal cells during photothermal treatment of Au NRs. In conclusion, our results suggest that the photothermal cyto-/genotoxic activity of Au NRs is an effective method for cancer therapy in human lung cancer cells.

  18. Genotoxicity of Microcystin-LR in In Vitro and In Vivo Experimental Models

    PubMed Central

    Santos, Telma; Silva, Maria João

    2014-01-01

    Microcystin-LR (MCLR) is a cyanobacterial toxin known for its acute hepatotoxicity. Despite being recognized as tumour promoter, its genotoxicity is far from being completely clarified, particularly in organs other than liver. In this work, we used the comet and/or the micronucleus (MN) assays to study the genotoxicity of MCLR in kidney- (Vero-E6) and liver-derived (HepG2) cell lines and in blood cells from MCLR-exposed mice. MCLR treatment (5 and 20 μM) caused a significant induction in the MN frequency in both cell lines and, interestingly, a similar positive effect was observed in mouse reticulocytes (37.5 μg MCLR/kg, i.p. route). Moreover, the FISH-based analysis of the MN content (HepG2 cells) suggested that MCLR induces both chromosome breaks and loss. On the other hand, the comet assay results were negative in Vero-E6 cells and in mouse leukocytes, with the exception of a transient increase in the level of DNA damage 30 minutes after mice exposure. Overall, the present findings contributed to increase the weight of evidence in favour of MCLR genotoxicity, based on its capacity to induce permanent genetic damage either in vitro or in vivo. Moreover, they suggest a clastogenic and aneugenic mode of action that might underlie a carcinogenic effect. PMID:24955368

  19. Direct observation of the core/double-shell architecture of intense dual-mode luminescent tetragonal bipyramidal nanophosphors

    NASA Astrophysics Data System (ADS)

    Kim, Su Yeon; Jeong, Jong Seok; Mkhoyan, K. Andre; Jang, Ho Seong

    2016-05-01

    Highly efficient downconversion (DC) green-emitting LiYF4:Ce,Tb nanophosphors have been synthesized for bright dual-mode upconversion (UC) and DC green-emitting core/double-shell (C/D-S) nanophosphors--Li(Gd,Y)F4:Yb(18%),Er(2%)/LiYF4:Ce(15%),Tb(15%)/LiYF4--and the C/D-S structure has been proved by extensive scanning transmission electron microscopy (STEM) analysis. Colloidal LiYF4:Ce,Tb nanophosphors with a tetragonal bipyramidal shape are synthesized for the first time and they show intense DC green light via energy transfer from Ce3+ to Tb3+ under illumination with ultraviolet (UV) light. The LiYF4:Ce,Tb nanophosphors show 65 times higher photoluminescence intensity than LiYF4:Tb nanophosphors under illumination with UV light and the LiYF4:Ce,Tb is adapted into a luminescent shell of the tetragonal bipyramidal C/D-S nanophosphors. The formation of the DC shell on the core significantly enhances UC luminescence from the UC core under irradiation of near infrared light and concurrently generates DC luminescence from the core/shell nanophosphors under UV light. Coating with an inert inorganic shell further enhances the UC-DC dual-mode luminescence by suppressing the surface quenching effect. The C/D-S nanophosphors show 3.8% UC quantum efficiency (QE) at 239 W cm-2 and 73.0 +/- 0.1% DC QE. The designed C/D-S architecture in tetragonal bipyramidal nanophosphors is rigorously verified by an energy dispersive X-ray spectroscopy (EDX) analysis, with the assistance of line profile simulation, using an aberration-corrected scanning transmission electron microscope equipped with a high-efficiency EDX. The feasibility of these C/D-S nanophosphors for transparent display devices is also considered.Highly efficient downconversion (DC) green-emitting LiYF4:Ce,Tb nanophosphors have been synthesized for bright dual-mode upconversion (UC) and DC green-emitting core/double-shell (C/D-S) nanophosphors--Li(Gd,Y)F4:Yb(18%),Er(2%)/LiYF4:Ce(15%),Tb(15%)/LiYF4--and the C/D-S structure

  20. Genotoxicity testing: moving beyond qualitative "screen and bin" approach towards characterization of dose-response and thresholds.

    PubMed

    Pottenger, Lynn H; Gollapudi, B Bhaskar

    2010-01-01

    For more than 40+ years, genotoxicity data have been interpreted in a qualitative, binary mode; a chemical is considered either positive or negative for a response in the test system. Although dose-response information is sometimes used in this decision, it is not routine to obtain the amount of information needed to inform risk assessment, for example to determine no-observed-genotoxic-effect-levels, primarily due to the historical view of genotoxic responses as "linear, no-threshold." Only recently have researchers begun to address this issue through robust experimental designs and application of statistical models. A growing body-of-evidence supports the existence of response thresholds for a number of mutagenic agents, in vitro and in vivo. Clearly, simple observation of a "hockey-stick" dose-response curve is not sufficient to establish a threshold. Collection of robust empirical data must be supported with an analysis of biological plausibility for the observed threshold. In this context, a chemical-specific mode-of-action (MOA) approach, which identifies key events responsible for the observed mutagenic effect, is extremely valuable. Biomarkers of key events, providing qualitative and quantitative information, can be integrated in a weight-of-evidence-based assessment of genotoxicity data from multiple test systems and used to identify data gaps to resolve/reduce uncertainties during the risk assessment process. To this end, specific recommendations on study design and data analysis are proposed. As the Environmental Mutagen Society celebrates its 40th anniversary, the field of genetic toxicology is marking a milestone on the path to a new paradigm, using a MOA, data-driven approach to answer questions about thresholds for genotoxic agents.

  1. Genotoxicity biomarkers for airborne particulate matter (PM2.5) in an area under petrochemical influence.

    PubMed

    Lemos, Andréia Torres; Lemos, Clarice Torres de; Flores, Andressa Negreiros; Pantoja, Eduarda Ozório; Rocha, Jocelita Aparecida Vaz; Vargas, Vera Maria Ferrão

    2016-09-01

    The effects of fine inhalable particles (PM2.5) were evaluated in an area under the influence of a petrochemical industry, investigating the sensitivity of different genotoxicity biomarkers. Organic extracts were obtained from PM2.5 samples at two sites, positioned in the first and second preferential wind direction in the area. The extracts were evaluated with Salmonella/microsome assay, microsuspension method, strains TA98, YG1021 and YG1024. The mammalian metabolization fraction (S9) was used to evaluate metabolite mutagenicity. The Comet Assay (CA) and Micronuclei Test were used in a Chinese hamster lung cell line (V79). All extracts showed mutagenicity in Salmonella, and nitrogenated compounds were strongly present. Genotoxicity were found in CA in almost all extracts and the micronuclei induction at the Site in the first (Autumn 1, Winter 1), and in the second (Spring 2) wind direction. V79 showed cytotoxicity in all samples. The three biomarkers were concordant in characterization Site NO with worse quality, compatible with the greater pollutants dispersion in the first wind direction. All PM2.5 concentrations were lower than those recommended by air quality standards but genotoxic effects were detected in all samples, corroborating that these standards are inadequate as quality indicators. The Salmonella/microsome assay proved sensitive to PM2.5 mutagenicity, with an outstanding influence of nitroarenes and aromatic amines. Analyses using CA and the micronucleus test broadened the levels of response that involve different damage induction mechanisms. Results show that the complex PM2.5 composition can provoke various genotoxic effects and the use of different bioassays is essential to understand its effects.

  2. Chemical morphology of Areca nut characterized directly by Fourier transform near-infrared and mid-infrared microspectroscopic imaging in reflection modes.

    PubMed

    Chen, Jian-Bo; Sun, Su-Qin; Zhou, Qun

    2016-12-01

    Fourier transform near-infrared (NIR) and mid-infrared (MIR) imaging techniques are essential tools to characterize the chemical morphology of plant. The transmission imaging mode is mostly used to obtain easy-to-interpret spectra with high signal-to-noise ratio. However, the native chemical compositions and physical structures of plant samples may be altered when they are microtomed for the transmission tests. For the direct characterization of thick plant samples, the combination of the reflection NIR imaging and the attenuated total reflection (ATR) MIR imaging is proposed in this research. First, the reflection NIR imaging method can explore the whole sample quickly to find out typical regions in small sizes. Next, each small typical region can be measured by the ATR-MIR imaging method to reveal the molecular structures and spatial distributions of compounds of interest. As an example, the chemical morphology of Areca nut section is characterized directly by the above approach.

  3. Direction finding and suppression of vector-scalar sound signals in shallow water taking into account their correlation and mode structure

    NASA Astrophysics Data System (ADS)

    Belov, A. I.; Kuznetsov, G. N.

    2016-05-01

    The correlation of low-frequency sound signals from towed tonal low-frequency sources at the output of the scalar and vector channels is studied in shallow water. The correlation of the scalar field and signal received by a horizontally oriented vector receiver on average is 0.92-0.99; correlation with the signal received by a vertical vector receiver decreases to 0.66-85. When scalar fields or horizontal projections of the vibration velocity vector with application of the aperture synthesis algorithm are used, 3-5 normal waves are isolated; when the vertical component is used, 7-9 modes. It is demonstrated that the high signal correlation ensures direction-finding accuracy and suppression of strongly noise-emitting moving sources by 20-30 dB or more if the cardioid is directed at the source according to the zone of the minimum.

  4. Comet Assay on Daphnia magna in eco-genotoxicity testing.

    PubMed

    Pellegri, Valerio; Gorbi, Gessica; Buschini, Annamaria

    2014-10-01

    Detection of potentially hazardous compounds in water bodies is a priority in environmental risk assessment. For the evaluation and monitoring of water quality, a series of methodologies may be applied. Among them, the worldwide used toxicity tests with organisms of the genus Daphnia is one of the most powerful. In recent years, some attempts were made to utilize Daphnia magna in genotoxicity testing as many of the new environmental contaminants are described as DNA-damaging agents in aquatic organisms. The aim of this research was to develop a highly standardized protocol of the Comet Assay adapted for D. magna, especially regarding the isolation of cells derived from the same tissue (haemolymph) from newborn organisms exposed in vivo. Several methods for haemolymph extraction and different Comet Assay parameters were compared. Electrophoretic conditions were adapted in order to obtain minimum DNA migration in cells derived from untreated organisms and, at the same time, maximum sensitivity in specimens treated with known genotoxicants (CdCl2 and H2O2). Additional tests were performed to investigate if life-history traits of the cladoceran (such as the age of adult organisms that provide newborns, the clutch size of origin, the number of generations reared in standard conditions) and the water composition as well, might influence the response of the assay. This study confirms the potential application of the Comet Assay in D. magna for assessing genotoxic loads in aqueous solution. The newly developed protocol could integrate the acute toxicity bioassay, thus expanding the possibility of using this model species in freshwater monitoring (waters, sediment and soil elutriates) and is in line with the spirit of the EU Water Framework Directive in reducing the number of bioassays that involve medium-sized species.

  5. Cytotoxicity and genotoxicity of urban particulate matter in mammalian cells

    PubMed Central

    Dumax-Vorzet, Audrey F.; Tate, M.; Walmsley, Richard; Elder, Rhod H.; Povey, Andrew C.

    2015-01-01

    Ambient air particulate matter (PM)-associated reactive oxygen species (ROS) have been linked to a variety of altered cellular outcomes. In this study, three different PM samples from diesel exhaust particles (DEPs), urban dust standard reference material SRM1649a and air collected in Manchester have been tested for their ability to oxidise DNA in a cell-free assay, to increase intracellular ROS levels and to induce CYP1A1 gene expression in mammalian cells. In addition, the cytotoxicity and genotoxicity of PM were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and alkaline comet assay, respectively. All PM samples catalysed the Fenton reaction in a cell-free assay, but only DEP resulted in the generation of ROS as measured by dichlorodihydrofluorescein diacetate oxidation in mammalian cells. However, there was no evidence that increased ROS was a consequence of polycyclic aromatic hydrocarbon metabolism via CYP1A1 induction as urban dust, the Manchester dust samples but not DEP-induced CYP1A1 expression. Urban dust was more cytotoxic in murine embryonic fibroblasts (MEFs) than the other PM samples and also induced expression of GADD45a in the GreenScreen Human Cell assay without S9 activation suggesting the presence of a direct-acting genotoxicant. Urban dust and DEP produced comparable levels of DNA damage, as assessed by the alkaline comet assay, in MEFs at higher levels than those induced by Manchester PM. In conclusion, results from the cytotoxic and genotoxic assays are not consistent with ROS production being the sole determinant of PM-induced toxicity. This suggests that the organic component can contribute significantly to this toxicity and that further work is required to better characterise the extent to which ROS and organic components contribute to PM-induced toxicity. PMID:26113525

  6. N332-Directed Broadly Neutralizing Antibodies Use Diverse Modes of HIV-1 Recognition: Inferences from Heavy-Light Chain Complementation of Function

    PubMed Central

    Louder, Mark K.; Gorman, Jason; Lu, Gabriel; McLellan, Jason S.; Stuckey, Jonathan; Zhu, Jiang; Burton, Dennis R.; Koff, Wayne C.; Mascola, John R.; Kwong, Peter D.

    2013-01-01

    Dozens of broadly neutralizing HIV-1 antibodies have been isolated in the last few years from the sera of HIV-1-infected individuals. Only a limited number of regions on the HIV-1 spike, however, are recognized by these antibodies. One of these regions (N332) is characterized by an N-linked glycan at residue 332 on HIV-1 gp120 and is recognized by antibody 2G12 and by the recently reported antibodies PGT121-137, the latter isolated from three donors. To investigate the diversity in mode of antibody recognition at the N332 site, we used functional complementation between antibody heavy and light chains as a means of assessing similarity in mode of recognition. We examined a matrix of 12 PGT-heavy chains with each of 12 PGT-light chains. Expression in 96-well format for the 144 antibodies (132 chimeric and 12 wild-type) was generally consistent (58±10 µg/ml). In contrast, recognition of HIV-1 gp120 was bimodal: when the source of heavy and light chains was from the same donor, recognition was good; when sources of heavy and light chains were from different donors, recognition was poor. Moreover, neutralization of HIV-1 strains SF162.LS and TRO.11 generally followed patterns of gp120 recognition. These results are consistent with published sequence, mutational, and structural findings, all of which indicate that N332-directed neutralizing antibodies from different donors utilize different modes of recognition, and provide support for a correlation between functional complementation of antibody heavy and light chains and similarity in antibody mode of recognition. Overall, our results add to the growing body of evidence that the human immune system is capable of recognizing the N332-region of HIV-1 gp120 in diverse ways. PMID:23431362

  7. Directing the mode of nitrite binding to a copper-containing nitrite reductase from Alcaligenes faecalis S-6: characterization of an active site isoleucine.

    PubMed

    Boulanger, Martin J; Murphy, Michael E P

    2003-02-01

    Unlike the heme cd(1)-based nitrite reductase enzymes, the molecular mechanism of copper-containing nitrite reductases remains controversial. A key source of controversy is the productive binding mode of nitrite in the active site. To identify and characterize the molecular determinants associated with nitrite binding, we applied a combinatorial mutagenesis approach to generate a small library of six variants at position 257 in nitrite reductase from Alcaligenes faecalis S-6. The activities of these six variants span nearly two orders of magnitude with one variant, I257V, the only observed natural substitution for Ile257, showing greater activity than the native enzyme. High-resolution (> 1.8 A) nitrite-soaked crystal structures of these variants display different modes of nitrite binding that correlate well with the altered activities. These studies identify for the first time that the highly conserved Ile257 in the native enzyme is a key molecular determinant in directing a catalytically competent mode of nitrite binding in the active site. The O-coordinate bidentate binding mode of nitrite observed in native and mutant forms with high activity supports a catalytic model distinct from the heme cd(1) NiRs. (The atomic coordinates for I257V[NO(2)(-)], I257L[NO(2)(-)], I257A[NO(2)(-)], I257T[NO(2)(-)], I257M[NO(2)(-)] and I257G[NO(2)(-)] AfNiR have been deposited in the Protein Data Bank [PDB identification codes are listed in Table 2].)

  8. Spectral Discrimination of Fine and Coarse Mode Aerosol Optical Depth from AERONET Direct Sun Data of Singapore and South-East Asia

    NASA Astrophysics Data System (ADS)

    Salinas Cortijo, S.; Chew, B.; Liew, S.

    2009-12-01

    Aerosol optical depth combined with the Angstrom exponent and its derivative, are often used as a qualitative indicator of aerosol particle size, with Angstrom exp. values greater than 2 indicating small (fine mode) particles associated with urban pollution and bio-mass burning. Around this region, forest fires are a regular occurrence during the dry season, specially near the large land masses of Sumatra and Borneo. The practice of clearing land by burning the primary and sometimes secondary forest, results in a smog-like haze covering large areas of regional cities such as cities Singapore, Kuala Lumpur and sometimes the south of Thailand, often reducing visibility and increasing health problems for the local population. In Singapore, the sources of aerosols are mostly from fossil fuel burning (energy stations, incinerators, urban transport etc.) and from the industrial and urban areas. The proximity to the sea adds a possible oceanic source. However, as stated above and depending on the time of the year, there can be a strong bio-mass component coming from forest fires from various regions of the neighboring countries. Bio-mass related aerosol particles are typically characterized by showing a large optical depth and small, sub-micron particle size distributions. In this work, we analyze three years of direct Sun measurements performed with a multi-channel Cimel Sun-Photometer (part of the AERONET network) located at our site. In order to identify bio-mass burning events in this region, we perform a spectral discrimination between coarse and fine mode optical depth; subsequently, the fine mode parameters such as optical depth, optical ratio and fine mode Angstrom exponents (and its derivative) are used to identify possible bio-mass related events within the data set.

  9. A novel PWM control for a bi-directional full-bridge DC-DC converter with smooth conversion mode transitions

    NASA Astrophysics Data System (ADS)

    Lorentz, V. R. H.; Schwarzmann, H.; März, M.; Bauer, A. J.; Ryssel, H.; Frey, L.; Poure, P.; Braun, F.

    2011-08-01

    A novel CMOS integrated pulse-width modulation (PWM) control circuit allowing smooth transitions between conversion modes in full-bridge based bi-directional DC-DC converters operating at high switching frequencies is presented. The novel PWM control circuit is able to drive full-bridge based DC-DC converters performing step-down (i.e. buck) and step-up (i.e. boost) voltage conversion in both directions, thus allowing charging and discharging of the batteries in mobile systems. It provides smooth transitions between buck, buck-boost and boost modes. Additionally, the novel PWM control loop circuit uses a symmetrical triangular carrier, which overcomes the necessity of using an output phasing circuit previously required in PWM controllers based on sawtooth oscillators. The novel PWM control also enables to build bi-directional DC-DC converters operating at high switching frequencies (i.e. up to 10 MHz and above). Finally, the proposed PWM control circuit also allows the use of an average lossless inductor-current sensor for sensing the average load current even at very high switching frequencies. In this article, the proposed PWM control circuit is modelled and the integrated CMOS schematic is given. The corresponding theory is analysed and presented in detail. The circuit simulations realised in the Cadence Spectre software with a commercially available 0.18 µm mixed-signal CMOS technology from UMC are shown. The PWM control circuit was implemented in a monolithic integrated bi-directional CMOS DC-DC converter ASIC prototype. The fabricated prototype was tested experimentally and has shown performances in accordance with the theory.

  10. IWGT report on quantitative approaches to genotoxicity risk assessment II. Use of point-of-departure (PoD) metrics in defining acceptable exposure limits and assessing human risk.

    PubMed

    MacGregor, James T; Frötschl, Roland; White, Paul A; Crump, Kenny S; Eastmond, David A; Fukushima, Shoji; Guérard, Melanie; Hayashi, Makoto; Soeteman-Hernández, Lya G; Johnson, George E; Kasamatsu, Toshio; Levy, Dan D; Morita, Takeshi; Müller, Lutz; Schoeny, Rita; Schuler, Maik J; Thybaud, Véronique

    2015-05-01

    This is the second of two reports from the International Workshops on Genotoxicity Testing (IWGT) Working Group on Quantitative Approaches to Genetic Toxicology Risk Assessment (the QWG). The first report summarized the discussions and recommendations of the QWG related to the need for quantitative dose-response analysis of genetic toxicology data, the existence and appropriate evaluation of threshold responses, and methods to analyze exposure-response relationships and derive points of departure (PoDs) from which acceptable exposure levels could be determined. This report summarizes the QWG discussions and recommendations regarding appropriate approaches to evaluate exposure-related risks of genotoxic damage, including extrapolation below identified PoDs and across test systems and species. Recommendations include the selection of appropriate genetic endpoints and target tissues, uncertainty factors and extrapolation methods to be considered, the importance and use of information on mode of action, toxicokinetics, metabolism, and exposure biomarkers when using quantitative exposure-response data to determine acceptable exposure levels in human populations or to assess the risk associated with known or anticipated exposures. The empirical relationship between genetic damage (mutation and chromosomal aberration) and cancer in animal models was also examined. It was concluded that there is a general correlation between cancer induction and mutagenic and/or clastogenic damage for agents thought to act via a genotoxic mechanism, but that the correlation is limited due to an inadequate number of cases in which mutation and cancer can be compared at a sufficient number of doses in the same target tissues of the same species and strain exposed under directly comparable routes and experimental protocols. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  11. Synthesis and structure of duplex DNA containing the genotoxic nucleobase lesion N7-methylguanine

    SciTech Connect

    Lee, S.; Bowman, B.R.; Ueno, Y.; Wang, S.; Verdine, G.L.

    2008-11-03

    The predominant product of aberrant DNA methylation is the genotoxic lesion N7-methyl-2{prime}-deoxyguanosine (m{sup 7}dG). M{sup 7}dG is recognized and excised by lesion-specific DNA glycosylases, namely AlkA in E. coli and Aag in humans. Structural studies of m{sup 7}dG recognition and catalysis by these enzymes have been hampered due to a lack of efficient means by which to incorporate the chemically labile m{sup 7}dG moiety site-specifically into DNA on a preparative scale. Here we report a solution to this problem. We stabilized the lesion toward acid-catalyzed and glycosylase-catalyzed depurination by 2{prime}-fluorination and toward base-catalyzed degradation using mild, nonaqueous conditions in the DNA deprotection reaction. Duplex DNA containing 2{prime}-fluoro-m{sup 7}dG (Fm{sup 7}dG) cocrystallized with AlkA as a host-guest complex in which the lesion-containing segment of DNA was nearly devoid of protein contacts, thus enabling the first direct visualization of the N7-methylguanine lesion nucleobase in DNA. The structure reveals that the base-pairing mode of Fm{sup 7}dG:C is nearly identical to that of G:C, and Fm{sup 7}dG does not induce any apparent structural disturbance of the duplex structure. These observations suggest that AlkA and Aag must perform a structurally invasive interrogation of DNA in order to detect the presence of intrahelical m{sup 7}dG lesions.

  12. Development of a new sorptive extraction method based on simultaneous direct and headspace sampling modes for the screening of polycyclic aromatic hydrocarbons in water samples.

    PubMed

    Triñanes, Sara; Pena, Ma Teresa; Casais, Ma Carmen; Mejuto, Ma Carmen

    2015-01-01

    A new straightforward and inexpensive sample screening method for both EPA and EU priority polycyclic aromatic hydrocarbons (PAHs) in water has been developed. The method is based on combined direct immersion and headspace (DIHS) sorptive extraction, using low-cost disposable material, coupled to ultraperformance liquid chromatography with fluorescence and UV detection (UPLC-FD-UV). Extraction parameters, such as the sampling mode, extraction time and ionic strength were investigated in detail and optimized. Under optimized conditions, water samples (16 mL) were concentrated in silicone disks by headspace (HS) and direct immersion (DI) modes simultaneously, at room temperature for 9h for the majority of the 24 studied compounds. Ultrasound-assisted desorption of extracted analytes in acetonitrile was carried out also at room temperature. The optimized chromatographic method provided a good linearity (R≥0.9991) and a broad linear range for all studied PAHs. The proposed analytical procedure exhibited a good precision level with relative standard deviations below 15% for all analytes. Quantification limits between 0.7 and 2.3 µg L(-1) and 0.16 and 3.90 ng L(-1) were obtained for compounds analyzed by UV (acenaphtylene, cyclopenta[c,d]pyrene and benzo[j]fluoranthene) and fluorescence, respectively. Finally, the proposed method was applied to the determination of PAHs in different real tap, river and wastewater samples.

  13. On-line coupling of macroporous resin column chromatography with direct analysis in real time mass spectrometry utilizing a surface flowing mode sample holder.

    PubMed

    Zeng, Shanshan; Wang, Lu; Chen, Teng; Qu, Haibin

    2014-02-06

    A surface flowing mode sample holder was designed as an alternative sampling strategy for direct analysis in real time mass spectrometry (DART-MS). With the sample holder, the on-line coupling of macroporous resin column chromatography with DART-MS was explored and the new system was employed to monitor the column chromatography elution process of Panax notoginseng. The effluent from macroporous resin column was first diluted and mixed with a derivatization reagent on-line, and the mixture was then directly transferred into the ionization region of DART-MS by the sample holder. Notoginsenosides were methylated and ionized in a metastable helium gas stream, and was introduced into MS for detection. The on-line system showed reasonable repeatability with a relative standard deviation of 12.3% for the peak area. Three notoginsenosides, i.e. notoginsenoside R1, ginsenoside Rb1 and ginsenoside Rg1, were simultaneously determined during the eluting process. The alteration of the chemical composition in the effluent was accurately identified in 9 min, agreeing well with the off-line analysis. The presented technique is more convenient compared to the traditional UPLC method. These results suggest that the surface flowing mode DART-MS has a good potential for the on-line process monitoring in the pharmaceutical industry.

  14. Directly assessing uncertainty in designing the optimal operation of water resources systems by batch mode reinforcement learning

    NASA Astrophysics Data System (ADS)

    Biizzi, S.; Castelletti, A.; Pianosi, F.

    2012-04-01

    Optimal operating policies for water resources systems are obtained as the solution to a maximization/minimization problem, where the objective function is the operation target and the model of the physical system is the constraint set. Just as in any model-based analysis, the robustness and reliability of the result largely depend on the accuracy of the model. In water resource system applications this is a limitation since, despite the advances in data availability, systems understanding and computing facilities, still the characterization of most of these systems is affected by strong model uncertainties, including input, parameter and structural uncertainty. Traditionally, uncertainty estimation is evaluated via Monte Carlo methods: each source of uncertainty is given a statistical description (e.g. probability distribution function) and by random sampling from these distributions and repeated optimization and/or simulation uncertainty is propagated through the model. By doing so, the probability distribution of the objective function is derived for a given policy as well as a set of different policies, each one optimal for a different realization of the uncertain input. The approach is rather straightforward, though high resource demanding and then its effective application in real problems often unfeasible. In this paper we propose a novel optimization method that derives, just in one run, the set of optimal operating policies (and associated objective values) for all possible realizations of an uncertain variable in the model. The method is an extension of the Fitted-Q Iteration method, a model-free batch-mode reinforcement algorithm and it is demonstrated by application to a real water reservoir system. The case study is the Hoa Binh reservoir in Northern Vietnam, whose optimal operation is designed and assessed as a function of the uncertainty related to the evaporation rate of the reservoir model. It demonstrates the relevance of uncertainty in

  15. Direct observation of a propagating, planar-waveguide surface mode in a discontinuous film of metal nanoparticles.

    PubMed

    Soller, B J; Hall, D G

    2000-08-01

    We report the observation of p-polarized guided waves that propagate confined to the surface of a two-dimensional array of silver (Ag) nanoparticles of average particle diameter and film thickness of approximately 400 and 154 nm, respectively, and comparable interparticle spacing. We interpret resonant features in the attenuated total reflection angular spectrum as arising from the excitation of guided waves in our discontinuous samples. The excitation of these waves is a direct consequence of the interaction of the light field with the localized resonance of the conduction electrons in the individual metal nanoparticles.

  16. Genotoxicity of pyrroloquinoline quinone (PQQ) disodium salt (BioPQQ™).

    PubMed

    Nakano, Masahiko; Suzuki, Hiroshi; Imamura, Tadashi; Lau, Annette; Lynch, Barry

    2013-11-01

    The genotoxic potential of pyrroloquinoline quinone (PQQ) disodium salt (BioPQQ™) was evaluated in a battery of genotoxicity tests. The results of the bacterial mutation assay (Ames test) were negative. Weak positive results were obtained in 2 separate in vitro chromosomal aberration test in Chinese hamster lung (CHL) fibroblasts. Upon testing in an in vitro chromosomal aberration test in human peripheral blood lymphocytes, no genotoxic activity of PQQ was noted. In the in vivo micronucleus assay in mice, PQQ at doses up to 2,000 mg/kg body weight demonstrated that no genotoxic effects are expressed in vivo in bone marrow erythrocytes. The weak responses in the in vitro test CHL cells were considered of little relevance under conditions of likely human exposure. PQQ disodium was concluded to have no genotoxic activity in vivo. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Considerations on photochemical genotoxicity: report of the International Workshop on Genotoxicity Test Procedures Working Group.

    PubMed

    Gocke, E; Müller, L; Guzzie, P J; Brendler-Schwaab, S; Bulera, S; Chignell, C F; Henderson, L M; Jacobs, A; Murli, H; Snyder, R D; Tanaka, N

    2000-01-01

    Recent toxicological observations have caused concern regarding the need to test, for example, pharmaceuticals and cosmetic products for photochemical genotoxicity. The objective of this report is to give assistance on how to adapt existing test methods to investigate the potential of light-absorbing compounds to induce genotoxic effects on photoactivation. In general, the Organization for Economic Co-Operation & Economic Development (OECD) draft guideline on in vitro phototoxicity testing served as a basis for consideration. Concomitant exposure of the cells to the test compound and solar simulated light was considered appropriate as the initial, basic test condition. Optimization of the exposure scheme, e.g., a change of the irradiation spectrum, might be indicated depending on the initial test results. Selection of test compound concentrations should be based on results obtained with the dark version of the respective test system but might have to be modified if phototoxic effects are observed. Selection of the irradiation dose has to be performed individually for each test system based on dose-effect studies. The irradiation should induce per se a small, reproducible toxic or genotoxic effect. The report includes a specification of necessary controls, discusses factors that might have an impact on the irradiation characteristics, and gives a rationale for the omission of an external metabolic activation system. It also addresses the question that physicochemical and pharmacokinetic properties might trigger the need to test a chemical for photochemical genotoxicity. Relevant experimental observations are presented to back up the recommendations. The working group did not reach a consensus as to whether a single, adequately perfomed in vitro test for clastogenicity would be sufficient to exclude a photogenotoxic liability or whether a test battery including a gene mutation assay would be needed for product safety testing regarding photochemical genotoxicity.

  18. High speed direct imaging of thin metal film ablation by movie-mode dynamic transmission electron microscopy

    PubMed Central

    Hihath, Sahar; Santala, Melissa K.; Cen, Xi; Campbell, Geoffrey; van Benthem, Klaus

    2016-01-01

    Obliteration of matter by pulsed laser beams is not only prevalent in science fiction movies, but finds numerous technological applications ranging from additive manufacturing over machining of micro- and nanostructured features to health care. Pulse lengths ranging from femtoseconds to nanoseconds are utilized at varying laser beam energies and pulse lengths, and enable the removal of nanometric volumes of material. While the mechanisms for removal of material by laser irradiation, i.e., laser ablation, are well understood on the micrometer length scale, it was previously impossible to directly observe obliteration processes on smaller scales due to experimental limitations for the combination of nanometer spatial and nanosecond temporal resolution. Here, we report the direct observation of metal thin film ablation from a solid substrate through dynamic transmission electron microscopy. Quantitative analysis reveals liquid-phase dewetting of the thin-film, followed by hydrodynamic sputtering of nano- to submicron sized metal droplets. We discovered unexpected fracturing of the substrate due to evolving thermal stresses. This study confirms that hydrodynamic sputtering remains a valid mechanism for droplet expulsion on the nanoscale, while irradiation induced stress fields represent limit laser processing of nanostructured materials. Our results allow for improved safety during laser ablation in manufacturing and medical applications. PMID:26965073

  19. High speed direct imaging of thin metal film ablation by movie-mode dynamic transmission electron microscopy

    DOE PAGES

    Hihath, Sahar; Santala, Melissa K.; Cen, Xi; ...

    2016-03-11

    Obliteration of matter by pulsed laser beams is not only prevalent in science fiction movies, but finds numerous technological applications ranging from additive manufacturing over machining of micro- and nanostructured features to health care. Pulse lengths ranging from femtoseconds to nanoseconds are utilized at varying laser beam energies and pulse lengths, and enable the removal of nanometric volumes of material. While the mechanisms for removal of material by laser irradiation, i.e., laser ablation, are well understood on the micrometer length scale, it was previously impossible to directly observe obliteration processes on smaller scales due to experimental limitations for the combinationmore » of nanometer spatial and nanosecond temporal resolution. Here, we report the direct observation of metal thin film ablation from a solid substrate through dynamic transmission electron microscopy. Quantitative analysis reveals liquid-phase dewetting of the thin-film, followed by hydrodynamic sputtering of nano- to submicron sized metal droplets. We discovered unexpected fracturing of the substrate due to evolving thermal stresses. This study confirms that hydrodynamic sputtering remains a valid mechanism for droplet expulsion on the nanoscale, while irradiation induced stress fields represent limit laser processing of nanostructured materials. Ultimately, our results allow for improved safety during laser ablation in manufacturing and medical applications.« less

  20. High speed direct imaging of thin metal film ablation by movie-mode dynamic transmission electron microscopy

    SciTech Connect

    Hihath, Sahar; Santala, Melissa K.; Cen, Xi; Campbell, Geoffrey; van Benthem, Klaus

    2016-03-11

    Obliteration of matter by pulsed laser beams is not only prevalent in science fiction movies, but finds numerous technological applications ranging from additive manufacturing over machining of micro- and nanostructured features to health care. Pulse lengths ranging from femtoseconds to nanoseconds are utilized at varying laser beam energies and pulse lengths, and enable the removal of nanometric volumes of material. While the mechanisms for removal of material by laser irradiation, i.e., laser ablation, are well understood on the micrometer length scale, it was previously impossible to directly observe obliteration processes on smaller scales due to experimental limitations for the combination of nanometer spatial and nanosecond temporal resolution. Here, we report the direct observation of metal thin film ablation from a solid substrate through dynamic transmission electron microscopy. Quantitative analysis reveals liquid-phase dewetting of the thin-film, followed by hydrodynamic sputtering of nano- to submicron sized metal droplets. We discovered unexpected fracturing of the substrate due to evolving thermal stresses. This study confirms that hydrodynamic sputtering remains a valid mechanism for droplet expulsion on the nanoscale, while irradiation induced stress fields represent limit laser processing of nanostructured materials. Ultimately, our results allow for improved safety during laser ablation in manufacturing and medical applications.

  1. High speed direct imaging of thin metal film ablation by movie-mode dynamic transmission electron microscopy

    NASA Astrophysics Data System (ADS)

    Hihath, Sahar; Santala, Melissa K.; Cen, Xi; Campbell, Geoffrey; van Benthem, Klaus

    2016-03-01

    Obliteration of matter by pulsed laser beams is not only prevalent in science fiction movies, but finds numerous technological applications ranging from additive manufacturing over machining of micro- and nanostructured features to health care. Pulse lengths ranging from femtoseconds to nanoseconds are utilized at varying laser beam energies and pulse lengths, and enable the removal of nanometric volumes of material. While the mechanisms for removal of material by laser irradiation, i.e., laser ablation, are well understood on the micrometer length scale, it was previously impossible to directly observe obliteration processes on smaller scales due to experimental limitations for the combination of nanometer spatial and nanosecond temporal resolution. Here, we report the direct observation of metal thin film ablation from a solid substrate through dynamic transmission electron microscopy. Quantitative analysis reveals liquid-phase dewetting of the thin-film, followed by hydrodynamic sputtering of nano- to submicron sized metal droplets. We discovered unexpected fracturing of the substrate due to evolving thermal stresses. This study confirms that hydrodynamic sputtering remains a valid mechanism for droplet expulsion on the nanoscale, while irradiation induced stress fields represent limit laser processing of nanostructured materials. Our results allow for improved safety during laser ablation in manufacturing and medical applications.

  2. High speed direct imaging of thin metal film ablation by movie-mode dynamic transmission electron microscopy.

    PubMed

    Hihath, Sahar; Santala, Melissa K; Cen, Xi; Campbell, Geoffrey; van Benthem, Klaus

    2016-03-11

    Obliteration of matter by pulsed laser beams is not only prevalent in science fiction movies, but finds numerous technological applications ranging from additive manufacturing over machining of micro- and nanostructured features to health care. Pulse lengths ranging from femtoseconds to nanoseconds are utilized at varying laser beam energies and pulse lengths, and enable the removal of nanometric volumes of material. While the mechanisms for removal of material by laser irradiation, i.e., laser ablation, are well understood on the micrometer length scale, it was previously impossible to directly observe obliteration processes on smaller scales due to experimental limitations for the combination of nanometer spatial and nanosecond temporal resolution. Here, we report the direct observation of metal thin film ablation from a solid substrate through dynamic transmission electron microscopy. Quantitative analysis reveals liquid-phase dewetting of the thin-film, followed by hydrodynamic sputtering of nano- to submicron sized metal droplets. We discovered unexpected fracturing of the substrate due to evolving thermal stresses. This study confirms that hydrodynamic sputtering remains a valid mechanism for droplet expulsion on the nanoscale, while irradiation induced stress fields represent limit laser processing of nanostructured materials. Our results allow for improved safety during laser ablation in manufacturing and medical applications.

  3. Evaluation of the genotoxicity of cellulose nanofibers

    PubMed Central

    de Lima, Renata; Feitosa, Leandro Oliveira; Maruyama, Cintia Rodrigues; Barga, Mariana Abreu; Yamawaki, Patrícia Cristina; Vieira, Isolda Jesus; Teixeira, Eliangela M; Corrêa, Ana Carolina; Mattoso, Luiz Henrique Caparelli; Fraceto, Leonardo Fernandes

    2012-01-01

    Background Agricultural products and by products provide the primary materials for a variety of technological applications in diverse industrial sectors. Agro-industrial wastes, such as cotton and curaua fibers, are used to prepare nanofibers for use in thermoplastic films, where they are combined with polymeric matrices, and in biomedical applications such as tissue engineering, amongst other applications. The development of products containing nanofibers offers a promising alternative for the use of agricultural products, adding value to the chains of production. However, the emergence of new nanotechnological products demands that their risks to human health and the environment be evaluated. This has resulted in the creation of the new area of nanotoxicology, which addresses the toxicological aspects of these materials. Purpose and methods Contributing to these developments, the present work involved a genotoxicological study of different nanofibers, employing chromosomal aberration and comet assays, as well as cytogenetic and molecular analyses, to obtain preliminary information concerning nanofiber safety. The methodology consisted of exposure of Allium cepa roots, and animal cell cultures (lymphocytes and fibroblasts), to different types of nanofibers. Negative controls, without nanofibers present in the medium, were used for comparison. Results The nanofibers induced different responses according to the cell type used. In plant cells, the most genotoxic nanofibers were those derived from green, white, and brown cotton, and curaua, while genotoxicity in animal cells was observed using nanofibers from brown cotton and curaua. An important finding was that ruby cotton nanofibers did not cause any significant DNA breaks in the cell types employed. Conclusion This work demonstrates the feasibility of determining the genotoxic potential of nanofibers derived from plant cellulose to obtain information vital both for the future usage of these materials in

  4. Genotoxicity of Anesthetics Evaluated In Vivo (Animals)

    PubMed Central

    Braz, Mariana G.; Karahalil, Bensu

    2015-01-01

    The anesthesia has been improved all over the years. However, it can have impact on health, in both patients and animals anesthetized, as well as professionals exposed to inhaled anesthetics. There is continuing effort to understand the possible effects of anesthetics at molecular levels. Knowing the effects of anesthetic agents on genetic material could be a valuable basic support to better understand the possible mechanisms of these agents. Thus, the purpose of this review is to provide an overview on the genotoxic potential, evaluated in animal models, of many anesthetics that have already been used and those currently used in anesthesia. PMID:26199936

  5. In vitro genotoxicity assays to evaluate the role of vitamin A on arsenic in human lymphocytes.

    PubMed

    Avani, G; Rao, M V

    2009-02-01

    Ground water contamination of arsenic in drinking water is a burning problem worldwide; especially in West Bengal (India) and Bangladesh. The main endeavor in this study was to assess the role of vitamin A (2.72 microM/7 ml culture), a naturally occurring antioxidant upon arsenic-induced genotoxicity; with respect to chromosomal aberrations (structural and numerical) and micronuclei. Whole blood cultures set for 72 h were exposed to test chemicals for a period of 24 h ahead of harvesting. Arsenic concentrations tested in the present study are 0.36, 0.72 and 1.4 microM/7 ml culture. Mitomycin C (MMC), the direct acting mutagen was used as positive control. Our data indicates that at concentrations tested, arsenic-induced increase in the mean frequencies of these genotoxic indices were diminished by vitamin A, indicating its protective role towards cells from arsenic exerted injury.

  6. High-throughput sequencing in mutation detection: A new generation of genotoxicity tests?

    PubMed

    Maslov, Alexander Y; Quispe-Tintaya, Wilber; Gorbacheva, Tatyana; White, Ryan R; Vijg, Jan

    2015-06-01

    The advent of next generation sequencing (NGS) technology has provided the means to directly analyze the genetic material in primary cells or tissues of any species in a high throughput manner for mutagenic effects of potential genotoxic agents. In principle, direct, genome-wide sequencing of human primary cells and/or tissue biopsies would open up opportunities to identify individuals possibly exposed to mutagenic agents, thereby replacing current risk assessment procedures based on surrogate markers and extrapolations from animal studies. NGS-based tests can also precisely characterize the mutation spectra induced by genotoxic agents, improving our knowledge of their mechanism of action. Thus far, NGS has not been widely employed in genetic toxicology due to the difficulties in measuring low-abundant somatic mutations. Here, we review different strategies to employ NGS for the detection of somatic mutations in a cost-effective manner and discuss the potential applicability of these methods in testing the mutagenicity of genotoxic agents. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Genotoxicity Expert Panel review: weight of evidence evaluation of the genotoxicity of glyphosate, glyphosate-based formulations, and aminomethylphosphonic acid.

    PubMed

    Brusick, David; Aardema, Marilyn; Kier, Larry; Kirkland, David; Williams, Gary

    2016-09-01

    In 2015, the International Agency for Research on Cancer (IARC) published a monograph concluding there was strong evidence for genotoxicity of glyphosate and glyphosate formulations and moderate evidence for genotoxicity of the metabolite aminomethylphosphonic acid (AMPA). These conclusions contradicted earlier extensive reviews supporting the lack of genotoxicity of glyphosate and glyphosate formulations. The IARC Monograph concluded there was strong evidence of induction of oxidative stress by glyphosate, glyphosate formulations, and AMPA. The Expert Panel reviewed the genotoxicity and oxidative stress data considered in the IARC Monograph, together with other available data not considered by IARC. The Expert Panel defined and used a weight of evidence (WoE) approach that included ranking of studies and endpoints by the strength of their linkage to events associated with carcinogenic mechanisms. Importantly, the Expert Panel concluded that there was sufficient information available from a very large number of regulatory genotoxicity studies that should have been considered by IARC. The WoE approach, the inclusion of all relevant regulatory studies, and some differences in interpretation of individual studies led to significantly different conclusions by the Expert Panel compared with the IARC Monograph. The Expert Panel concluded that glyphosate, glyphosate formulations, and AMPA do not pose a genotoxic hazard and the data do not support the IARC Monograph genotoxicity evaluation. With respect to carcinogenicity classification and mechanism, the Expert Panel concluded that evidence relating to an oxidative stress mechanism of carcinogenicity was largely unconvincing and that the data profiles were not consistent with the characteristics of genotoxic carcinogens.

  8. Ultrafast direct modulation of transverse-mode coupled-cavity VCSELs far beyond the relaxation oscillation frequency

    NASA Astrophysics Data System (ADS)

    Dalir, Hamed; Koyama, Fumio

    2014-02-01

    A novel approach for bandwidth augmentation for direct modulation of VCSELs using transverse-coupled-cavity (TCC) scheme is raised, which enables us to tailor the modulation-transfer function. The base structure is similar to that of 3QW VCSELs with 980 nm wavelength operation. While the bandwidth of conventional VCSELs was limited by 9-10 GHz, the 3-dB bandwidth of TCC VCSEL with aperture diameters of 8.5×8.5μm2 and 3×3μm2 are increased by a factor of 3 far beyond the relaxation-oscillation frequency. Our current bandwidth achievement on the larger aperture size is 29 GHz which is limited by the used photo-detector. To the best of our knowledge this is the fastest 980 nm VCSEL.

  9. In situ assessment of genotoxicity using caged freshwater mussels

    SciTech Connect

    Black, M.C.; Westerfield, S.M.

    1995-12-31

    In recent years a decline in mussel populations has been documented in many areas, particularly in contaminated environments. Mussels are particularly vulnerable to exposure to xenobiotics in sediment and/or water because of their modes of feeding and respiration and close association with sediments. Because of this potential for exposure, their apparent sensitivity to xenobiotics, and their ease in collection and handling, mussels are an excellent species for in situ biomonitoring. Recently the authors have adapted an electrophoretic assay for detecting DNA strand breakage in freshwater mussels. Using this assay DNA damage was quantified in selected tissues in two mussel species, Quadrula quadrula and Anodonta grandis, following subchronic laboratory exposures to lead and benzo[a]pyrene. Current experiments involve exposing mussels in situ in polyethylene cages and exposure racks in several environments containing genotoxic agents, including a fly ash settling pond and a site contaminated with mercury. Mussels will be exposed for 1 week to 3 months and sampled at 2 to 4week intervals. Upon removal mussels will be dissected, and mantle, adductor muscle, and foot tissue will be analyzed for DNA strand breakage and xenobiotic residues. These data will be compared with laboratory exposures to single compounds conducted over the same exposure durations.

  10. Genotoxicity Studies Performed in the Ecuadorian Population

    PubMed Central

    Paz-y-Miño, César; Cumbal, Nadia; Sánchez, María Eugenia

    2012-01-01

    Genotoxicity studies in Ecuador have been carried out during the past two decades. The focuses of the research were mainly the area of environmental issues, where the populations have been accidentally exposed to contaminants and the area of occupational exposure of individuals at the workplace. This paper includes studies carried out in the population of the Amazon region, a zone known for its rich biodiversity as well as for the ecological damage caused by oil spills and chemical sprayings whose consequences continue to be controversial. Additionally, we show the results of studies comprised of individuals occupationally exposed to toxic agents in two very different settings: flower plantation workers exposed to pesticide mixtures and X-ray exposure of hospital workers. The results from these studies confirm that genotoxicity studies can help evaluate current conditions and prevent further damage in the populations exposed to contaminants. As such, they are evidence of the need for biomonitoring employers at risk, stricter law enforcement regarding the use of pesticides, and increasingly conscientious oil extraction activities. PMID:22496977

  11. Forskolin: genotoxicity assessment in Allium cepa.

    PubMed

    Mohammed, Khalid Pasha; Aarey, Archana; Tamkeen, Shayesta; Jahan, Parveen

    2015-01-01

    Forskolin, a diterpene, 7β-acetoxy-8,13-epoxy-1α,6β,9α-trihydroxy-labd-14-en-11-one (C22H34O7) isolated from Coleus forskohlii, exerts multiple physiological effects by stimulating the enzyme adenylate cyclase and increasing cyclic adenosine monophosphate (cAMP) concentrations. Forskolin is used in the treatment of hypertension, congestive heart failure, eczema, and other diseases. A cytogenetic assay was performed in Allium cepa to assess possible genotoxic effects of forskolin. Forskolin was tested at concentrations 5-100 μM for exposure periods of 24 or 48 h. Treated samples showed significant reductions in mitotic index (p < 0.05) and increases in the frequency of chromosome aberrations (p < 0.01) at both exposure times. The treated meristems showed chromosome aberrations including sticky metaphases, sticky anaphases, laggard, anaphase bridges, micronuclei, polyploidy, fragments, breaks, and C-mitosis. Forskolin may cause genotoxic effects and further toxicological evaluations should be conducted to ensure its safety.

  12. Genotoxicity of silver nanoparticles in Allium cepa.

    PubMed

    Kumari, Mamta; Mukherjee, A; Chandrasekaran, N

    2009-09-15

    Potential health and environmental effects of nanoparticles need to be thoroughly assessed before their widespread commercialization. Though there are few studies on cytotoxicity of nanoparticles on mammalian and human cell lines, there are hardly any reports on genotoxic and cytotoxic behavior of nanoparticles in plant cells. This study aims to investigate cytotoxic and genotoxic impacts of silver nanoparticles using root tip cells of Allium cepa as an indicator organism. A.cepa root tip cells were treated with four different concentrations (25, 20, 75, and 100 ppm) of engineered silver nanoparticles (below 100 nm size) dispersion, to study endpoints like mitotic index, distribution of cells in mitotic phases, different types of chromosomal aberrations, disturbed metaphase, sticky chromosome, cell wall disintegration, and breaks. For each concentration five sets of microscopic observations were carried out. No chromosomal aberration was observed in the control (untreated onion root tips) and the mitotic index (MI) value was 60.3%. With increasing concentration of the nanoparticles decrease in the mitotic index was noticed (60.30% to 27.62%). The different cytological effects including the chromosomal aberrations were studied in detail for the treated cells as well as control. We infer from this study that silver nanoparticles could penetrate plant system and may impair stages of cell division causing chromatin bridge, stickiness, disturbed metaphase, multiple chromosomal breaks and cell disintegration. The findings also suggest that plants as an important component of the ecosystems need to be included when evaluating the overall toxicological impact of the nanoparticles in the environment.

  13. Genotoxicity evaluation of sesamin and episesamin.

    PubMed

    Hori, Hisako; Takayanagi, Tomomi; Kamada, Yoko; Shimoyoshi, Satomi; Ono, Yoshiko; Kitagawa, Yoshinori; Shibata, Hiroshi; Nagao, Minako; Fujii, Wataru; Sakakibara, Yutaka

    2011-02-03

    Sesamin is a major lignan that is present in sesame seeds and oil. Sesamin is partially converted to its stereoisomer, episesamin, during the refining process of non-roasted sesame seed oil. We evaluated the genotoxicity of these substances through the following tests: a bacterial reverse mutation assay (Ames test), a chromosomal aberration test in cultured Chinese hamster lung cells (CHL/IU), a bone marrow micronucleus (MN) test in Crlj:CD1 (ICR) mice, and a comet assay using the liver of Sprague-Dawley (SD) rats. Episesamin showed negative results in the Ames test with and without S9 mix, in the in vitro chromosomal aberration test with and without S9 mix, and in the in vivo comet assay. Sesamin showed negative results in the Ames test with and without S9 mix. In the in vitro chromosomal aberration test, sesamin did not induce chromosomal aberrations in the absence of S9 mix, but induced structural abnormalities at cytotoxic concentrations in the presence of S9 mix. Oral administration of sesamin at doses up to 2.0g/kg did not cause a significant increase in either the percentage of micronucleated polychromatic erythrocytes in the in vivo bone marrow MN test or in the % DNA in the comet tails in the in vivo comet assay of liver cells. These findings indicate that sesamin does not damage DNA in vivo and that sesamin and episesamin have no genotoxic activity.

  14. Genotoxicity assessment of vaccine adjuvant squalene.

    PubMed

    Yüzbaşıoğlu, D; Ünal, F; Koç, F; Öztemel, S; Aksoy, H; Mamur, S; Demirtaş Korkmaz, F

    2013-06-01

    The genotoxic potential of the vaccine adjuvant Squalene was assessed by the chromosomal aberrations (CAs), sister chromatid exchanges (SCEs) and micronucleus (MNs) tests in human lymphocytes and comet assay in both human and rat lymphocytes. Five different concentrations of squalene (1250-20,000 μg/ml for human lymphocytes and 0.07-1.12 mg/kg for rat lymphocytes) were studied. Squalene did not affect the CAs and MN frequency, in all treatments in vitro. A significant increase in SCEs was observed in almost all concentrations at 24 h treatment. Squalene did not affect significantly the comet tail length (CTL) (except 2500 μg/ml) and comet tail intensity (CTI) at all treatments in vitro. In rats, squalene significantly increased and decreased CTL and CTI in some doses. Although there are increasing and reduction in the effect, squalene cannot be regarded as genotoxic in human lymphocytes. However, further in vivo studies are required to be sure on the effect. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Genotoxicity tests on D-tagatose.

    PubMed

    Kruger, C L; Whittaker, M H; Frankos, V H

    1999-04-01

    D-tagatose is a low-calorie sweetener that tastes like sucrose. Its genotoxic potential was examined in five standard assays: the Ames Salmonella typhimurium reverse mutation assay, the Escherichia coli/mammalian microsome assay, a chromosomal aberration assay in Chinese hamster ovary cells, a mouse lymphoma forward mutation assay, and an in vivo mouse micronucleus assay. D-tagatose was not found to increase the number of revertants per plate relative to vehicle controls in either the S. typhimurium tester strains or the WP2uvrA- tester strain with or without metabolic activation at doses up to 5000 microg/plate. No significant increase in Chinese hamster ovary cells with chromosomal aberrations was observed at concentrations up to 5000 microg/ml with or without metabolic activation. D-tagatose was not found to increase the mutant frequency in mouse lymphoma L5178Y cells with or without metabolic activation up to concentrations of 5000 microg/ml. D-tagatose caused no significant increase in micronuclei in bone marrow polychromatic erythrocytes at doses up to 5000 mg/kg. D-tagatose was not found to be genotoxic under the conditions of any of the assays described above. Copyright 1999 Academic Press.

  16. An Eco-Friendly Direct Injection HPLC Method for Methyldopa Determination in Serum by Mixed-Mode Chromatography Using a Single Protein-Coated Column.

    PubMed

    Emara, Samy; Masujima, Tsutomu; Zarad, Walaa; Kamal, Maha; Fouad, Marwa; El-Bagary, Ramzia

    2015-09-01

    A simple, rapid and environment-friendly direct injection HPLC method for the determination of methyldopa (MTD) in human serum has been developed and validated. The method was based on cleanup and separation of MTD from serum by mixed-mode liquid chromatography using a single protein-coated TSK gel ODS-80 TM analytical column (50 × 4.0 mm i.d., 5 µm). The protein-coated column exhibited excellent resolution, selectivity and functioned in two chromatographic modes: size-exclusion chromatography [i.e., solid-phase extraction (SPE) for serum proteins] and reversed-phase chromatography for the final separation of MTD. SPE and HPLC separation were carried out simultaneously with a green mobile phase consisting of acetate buffer (0.1 M, pH 2.4) at a flow rate of 1 mL/min and at room temperature (23 ± 1°C). The eluent was monitored at emission and excitation wavelengths of 320 and 270 nm, respectively. A calibration curve was linear over the range of 0.1-30 µg/mL with a detection limit of 0.027 µg/mL. This online SPE method was successfully applied to real samples obtained from patients receiving MTD therapy. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Structure of Bacillus subtilis γ-glutamyltranspeptidase in complex with acivicin: diversity of the binding mode of a classical and electrophilic active-site-directed glutamate analogue

    SciTech Connect

    Ida, Tomoyo; Suzuki, Hideyuki; Fukuyama, Keiichi; Hiratake, Jun; Wada, Kei

    2014-02-01

    The binding modes of acivicin, a classical and an electrophilic active-site-directed glutamate analogue, to bacterial γ-glutamyltranspeptidases were found to be diverse. γ-Glutamyltranspeptidase (GGT) is an enzyme that plays a central role in glutathione metabolism, and acivicin is a classical inhibitor of GGT. Here, the structure of acivicin bound to Bacillus subtilis GGT determined by X-ray crystallography to 1.8 Å resolution is presented, in which it binds to the active site in a similar manner to that in Helicobacter pylori GGT, but in a different binding mode to that in Escherichia coli GGT. In B. subtilis GGT, acivicin is bound covalently through its C3 atom with sp{sup 2} hybridization to Thr403 O{sup γ}, the catalytic nucleophile of the enzyme. The results show that acivicin-binding sites are common, but the binding manners and orientations of its five-membered dihydroisoxazole ring are diverse in the binding pockets of GGTs.

  18. Steviol glycoside safety: is the genotoxicity database sufficient?

    PubMed

    Urban, J D; Carakostas, M C; Brusick, D J

    2013-01-01

    The safety of steviol glycoside sweeteners has been extensively reviewed in the literature. National and international food safety agencies and approximately 20 expert panels have concluded that steviol glycosides, including the widely used sweeteners stevioside and rebaudioside A, are not genotoxic. However, concern has been expressed in recent publications that steviol glycosides may be mutagenic based on select studies representing a small fraction of the overall database, and it has been suggested that further in vivo genotoxicity studies are required to complete their safety profiles. To address the utility of conducting additional in vivo genotoxicity studies, this review evaluates the specific genotoxicity studies that are the sources of concern, and evaluates the adequacy of the database including more recent genotoxicity data not mentioned in those publications. The current database of in vitro and in vivo studies for steviol glycosides is robust and does not indicate that either stevioside or rebaudioside A are genotoxic. This, combined with a lack of evidence for neoplasm development in rat bioassays, establish the safety of all steviol glycosides with respect to their genotoxic/carcinogenic potential. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Genotoxicity of sludges, wastewater and effluents from three different industries.

    PubMed

    Krishnamurthi, K; Saravana Devi, S; Hengstler, J G; Hermes, Matthias; Kumar, Koel; Dutta, Dipanwita; Muhil Vannan, S; Subin, T S; Yadav, R R; Chakrabarti, T

    2008-12-01

    Many surface waters in Europe, Asia and South America have been reported to be contaminated with genotoxic substances. Therefore, it is important to establish strategies for identification of the most critical sources. In this study, we used a battery of four genotoxicity assays namely chromosomal aberration, DNA strand break, DNA laddering and P53 accumulation tests in mononuclear blood cells. Before cleaning of wastewater high levels of genotoxic contamination could be observed. For instance, we observed an increase in chromosomal aberrations from 2.6 +/- 1.1 (aberrant cells in %; control), to 33.6 +/- 6.6 in a petrochemical plant, 29.4 +/- 3.3 in a petroleum refinery and 14.4 +/- 1.8 in a coke plant of steel industry. A good correlation between the four assays was found. The most sensitive and reproducible results were obtained with the chromosomal aberration assay. Interestingly, clear differences in the efficiency of wastewater cleaning in three different treatment plants were observed. The first and second treatment plants in petrochemical industry and coke plant of steel industry completely eliminated genotoxicity of the wastewater. However, the third plant in petroleum refinery could achieve a reduction in genotoxicity but significant genotoxic contaminations were still present. In conclusion, our battery of genotoxicity tests allows the identification of critical sources contributing to contamination of surface waters.

  20. Autofocus technique for three-dimensional imaging, direct-detection laser radar using Geiger-mode avalanche photodiode focal-plane array.

    PubMed

    Oh, Min Seok; Kong, Hong Jin; Kim, Tae Hoon; Jo, Sung Eun

    2010-12-15

    An autofocus technique is proposed for a three-dimensional imaging, direct-detection laser radar system that uses a Geiger-mode avalanche photodiode focal plane array (GmAPD-FPA). This technique is implemented by pointing laser pulses on a target of interest and observing its scattered photon distribution on a GmAPD-FPA. Measuring the standard deviation of the photon distribution on a GmAPD-FPA enables the best focus condition to be found. The feasibility of this technique is demonstrated experimentally by employing a 1 × 8 pixel GmAPD-FPA. It is shown that the spatial resolution improves when the GmAPD-FPA is located in the best focus position found by the autofocus technique.

  1. Rapid fingerprinting of sterols and related compounds in vegetable and animal oils and phytosterol enriched- margarines by transmission mode direct analysis in real time mass spectrometry.

    PubMed

    Alberici, Rosana M; Fernandes, Gabriel D; Porcari, Andréia M; Eberlin, Marcos N; Barrera-Arellano, Daniel; Fernández, Facundo M

    2016-11-15

    Plant-derived sterols, often referred to as phytosterols, are important constituents of plant membranes where they assist in maintaining phospholipid bilayer stability. Consumption of phytosterols has been suggested to positively affect human health by reducing cholesterol levels in blood via inhibition of its absorption in the small intestine, thus protecting against heart attack and stroke. Sterols are challenging analytes for mass spectrometry, since their low polarity makes them difficult to ionize by both electrospray ionization (ESI) and matrix-assisted laser desorption ionization (MALDI), typically requiring derivatization steps to overcome their low ionization efficiencies. We present a fast and reliable method to characterize the composition of phytosterols in vegetable oils and enriched margarines. The method requires no derivatization steps or sample extraction procedures thanks to the use of transmission mode direct analysis in real time mass spectrometry (TM-DART-MS).

  2. Direct chemical-analysis of uv laser-ablation products of organic polymers by using selective ion monitoring mode in gas-chromatography mass-spectrometry

    USGS Publications Warehouse

    Cho, Yirang; Lee, H.W.; Fountain, S.T.; Lubman, D.M.

    1994-01-01

    Trace quantities of laser ablated organic polymers were analyzed by using commercial capillary column gas chromatography/mass spectrometry; the instrument was modified so that the laser ablation products could be introduced into the capillary column directly and the constituents of each peak in the chromatogram were identified by using a mass spectrometer. The present study takes advantage of the selective ion monitoring mode for significantly improving the sensitivity of the mass spectrometer as a detector, which is critical in analyzing the trace quantities and confirming the presence or absence of the species of interest in laser ablated polymers. The initial composition of the laser ablated polymers was obtained by using an electron impact reflectron time-of-flight mass spectrometer and the possible structure of the fragments observed in the spectra was proposed based on the structure of the polymers.

  3. A 250 MHz, high power mode-locked Nd:GdVO4 oscillator with low timing jitter under 879 nm direct pumping

    NASA Astrophysics Data System (ADS)

    Zhang, F. F.; Zuo, J. W.; Wang, Z. M.; Yang, J.; Cheng, H. L.; Zong, N.; Yang, F.; Peng, Q. J.; Xu, Z. Y.

    2013-04-01

    We developed a high power mode-locked Nd:GdVO4 oscillator with low timing jitter directly pumped by an 879 nm diode. Under the absorbed pump power of 13.8 W, a maximum output power of 5.68 W at 1063 nm was obtained with a repetition rate of ˜250 MHz, corresponding to a slope efficiency of 78.7%. The measured pulse width and root mean square timing jitter at the output power of 5.35 W were 7.4 ps and 286 fs, respectively. To the best of our knowledge, this is the highest output power for a picosecond Nd:GdVO4 oscillator with low timing jitter.

  4. Genotoxicity assessment of five tremorgenic mycotoxins (fumitremorgen B, paxilline, penitrem A, verruculogen, and verrucosidin) produced by molds isolated from fermented meats.

    PubMed

    Sabater-Vilar, Monica; Nijmeijer, Sandra; Fink-Gremmels, Johanna

    2003-11-01

    A number of toxinogenic fungal species, particularly producers of tremorgenic mycotoxins, have been isolated from traditional fermented meats. Tremorgenic mycotoxins are a group of fungal metabolites known to act on the central nervous system, causing sustained tremors, convulsions, and death in animals. However, the mode of action of these mycotoxins has not been elucidated in detail, and their genotoxic capacity has hardly been investigated. Because genotoxicity is one of the most prominent toxicological end points in food safety testing, we assessed the genotoxicity of five tremorgenic mycotoxins (fumitremorgen B, paxilline, penitrem A, verrucosidin, and verruculogen) associated with molds found in fermented meats. The mycotoxins were tested in two short-term in vitro assays with the use of different genotoxic end points in different phylogenetic systems (the Ames Salmonella/mammalian-microsome assay and the single-cell gel electrophoresis assay of human lymphocytes). According to the results obtained in this study, all of the investigated mycotoxins except penitrem A exhibited a certain degree of genotoxicity. Verrucosidin appeared to have the highest toxic potential, testing positive in both assays. Verruculogen tested positive in the Salmonella/mammalian-microsome assay, and paxilline and fumitremorgen B caused DNA damage in human lymphocytes. The use of fungal starter cultures to avoid tremorgen contamination in fermented meats is recommended.

  5. Multigenerational demographic responses of sexual and asexual Artemia to chronic genotoxicity by a reference mutagen.

    PubMed

    Sukumaran, Sandhya; Grant, Alastair

    2013-11-15

    parthenogenetic phase in their life cycle, may be particularly vulnerable to the effects of environmental mutagens. Ecological risk assessments should include information from multigenerational studies, as responses to genotoxicity may vary depending on the life history strategies and reproductive modes of the species under consideration. Single generation studies may under or over-estimate risks. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Evidence of the in vitro genotoxicity of methyl-pyrazole pesticides in human cells.

    PubMed

    Graillot, Vanessa; Tomasetig, Florence; Cravedi, Jean-Pierre; Audebert, Marc

    2012-10-09

    Consumers are exposed daily to several pesticide residues in food, which can be of potential concern for human health. Based on a previous study dealing with exposure of the French population to pesticide residues via the food, we selected 14 pesticides frequently found in foodstuffs, on the basis of their persistence in the environment or their bioaccumulation in the food chain. In a first step, the objective of this study was to investigate if the 14 selected pesticides were potentially cytotoxic and genotoxic. For this purpose, we used a new and sensitive genotoxicity assay (the γH2AX test, involving phosphorylation of histone H2AX) with four human cell lines (ACHN, SH-SY5Y, LS-174T and HepG2), each originating from a potential target tissue of food contaminants (kidney, nervous system, colon, and liver, respectively). Tebufenpyrad was the only compound identified as genotoxic and the effect was only observed in the SH-SY5Y neuroblastoma cell-line. A time-course study showed that DNA damage appeared early after treatment (1h), suggesting that oxidative stress could be responsible for the induction of γH2AX. In a second step, three other pesticides were studied, i.e. bixafen, fenpyroximate and tolfenpyrad, which - like tebufenpad - also had a methyl-pyrazole structure. All these compounds demonstrated genotoxic activity in SH-SY5Y cells at low concentration (nanomolar range). Complementary experiments demonstrated that the same compounds show genotoxicity in a human T-cell leukemia cell line (Jurkat). Moreover, we observed an increased production of reactive oxygen species in Jurkat cells in the presence of the four methyl-pyrazoles. These results demonstrate that tebufenpyrad, bixafen, fenpyroximat and tolfenpyrad induce DNA damage in human cell lines, very likely by a mode of action that involves oxidative stress. Nonetheless, additional in vivo data are required before a definitive conclusion can be drawn regarding hazard prediction to humans. © 2012

  7. Anti-genotoxic and free-radical scavenging activities of extracts from (Tunisian) Myrtus communis.

    PubMed

    Hayder, N; Abdelwahed, A; Kilani, S; Ammar, R Ben; Mahmoud, A; Ghedira, K; Chekir-Ghedira, L

    2004-11-14

    The effect of extracts from leaves of Myrtus communis on the SOS reponse induced by Aflatoxin B1 (AFB1) and Nifuroxazide was investigated in a bacterial assay system, i.e. the SOS chromotest with Escherichia coli PQ37. Aqueous extract, the total flavonoids oligomer fraction (TOF), hexane, chloroform, ethyl acetate and methanol extracts and essential oil obtained from M. communis significantly decreased the SOS response induced by AFB1 (10 microg/assay) and Nifuroxazide (20 microg/assay). Ethyl acetate and methanol extracts showed the strongest inhibition of the induction of the SOS response by the indirectly genotoxic AFB1. The methanol and aqueous extracts exhibited the highest level of protection towards the SOS-induced response by the directly genotoxic Nifuroxazide. In addition to anti-genotoxic activity, the aqueous extract, the TOF, and the ethyl acetate and methanol extracts showed an important free-radical scavenging activity towards the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical. These results suggest the future utilization of these extracts as additives in chemoprevention studies.

  8. Cyto- and genotoxic profile of groundwater used as drinking water supply before and after disinfection.

    PubMed

    Pellacani, C; Cassoni, F; Bocchi, C; Martino, A; Pinto, G; Fontana, F; Furlini, M; Buschini, A

    2016-12-01

    The assessment of the toxicological properties of raw groundwater may be useful to predict the type and quality of tap water. Contaminants in groundwater are known to be able to affect the disinfection process, resulting in the formation of substances that are cytotoxic and/or genotoxic. Though the European directive (98/83/EC, which establishes maximum levels for contaminants in raw water (RW)) provides threshold levels for acute exposure to toxic compounds, the law does not take into account chronic exposure at low doses of pollutants present in complex mixture. The purpose of this study was to evaluate the cyto- and genotoxic load in the groundwater of two water treatment plants in Northern Italy. Water samples induced cytotoxic effects, mainly observed when human cells were treated with RW. Moreover, results indicated that the disinfection process reduced cell toxicity, independent of the biocidal used. The induction of genotoxic effects was found, in particular, when the micronucleus assay was carried out on raw groundwater. These results suggest that it is important to include bio-toxicological assays as additional parameters in water quality monitoring programs, as their use would allow the evaluation of the potential risk of groundwater for humans.

  9. [Evaluation of genotoxicity of sodium hypochlorite, chlorine dioxide and peracetic acid using plant tests].

    PubMed

    Feretti, D; Zani, C; Alberti, A; Copetta, L; Nardi, G; Monarca, S

    2003-01-01

    The aim of this research was to evaluate the potential genotoxic effects of three drinking water disinfectants by means of in vivo short-term mutagenicity tests using plants. The study was carried out in laboratory using distilled water disinfected with sodium hypochlorite (NaClO), chlorine dioxide (ClO2) and peracetic acid (PAA) at different concentrations both in neutral and acid conditions. Untreated distilled water was used as a negative control. Micronuclei test in Tradescantia pollen cells and chromosomal aberration test in root cells of Allium cepa were the bioassays performed by exposing directly plant bioindicators to treated and untreated distilled water. The Tradescantia/micronuclei test gave positive results in most of the ClO2-treated water samples but only at acid pH. The Allium cepa test showed genotoxicity in NaClO-treated samples at acid pH and in a ClO2-treated sample at pH 7. PAA-treated samples were always nongenotoxic. Since the concentrations tested of free disinfectants are usually present in drinking water for biocidal purposes, genotoxicity of these compounds could be a public health problem.

  10. Eco-genotoxicity of six anticancer drugs using comet assay in daphnids.

    PubMed

    Parrella, Alfredo; Lavorgna, Margherita; Criscuolo, Emma; Russo, Chiara; Isidori, Marina

    2015-04-09

    The eco-genotoxicity of six anti-neoplastic drugs, 5-fluorouracil, capecitabine, cisplatin, doxorubicin, etoposide, and imatinib, belonging to five classes of anatomical therapeutic classification (ATC), was studied applying the in vivo comet assay on cells from whole organisms of Daphnia magna and Ceriodaphnia dubia. For the first time, this test was performed in C. dubia. In addition, to have a wider genotoxic/mutagenic profile of the anticancer drugs selected, SOS chromotest and Salmonella mutagenicity assay were performed. The comet results showed that all drugs induced DNA damage, in both Cladocerans, with environmental concern; indeed Doxorubicin induced DNA damage in the order of tens of ng L(-1) in both crustaceans, as well as 5-flurouracil in C. dubia and cisplatin in D. magna. In the SOS Chromotest all drugs, except imatinib, were able to activate the repair system in Escherichia coli PQ37 while in the Salmonella mutagenicity assay, doxorubicin was the only drug able to cause direct and indirect frameshift and base-pair substitution mutations. Comet assay was the most sensitive tool of genotoxic exposure assessment, able to detect in vivo the adverse effects at concentration lower than those evaluated in vitro by bacterial assays.

  11. Detection of genotoxicity of the gaseous agents emitted from two industrial sites with Tradescantia bioassays

    SciTech Connect

    Fomin, A.; Hafner, C.; Schachner, J.; Sallenave, R.M.

    1995-12-31

    The Tradescantia-Micronucleus (Trad-MCN) assay was used to determine the genotoxicity of gaseous agents emitted from a car painting factory and from an incinerator. The fumigation chambers consisted of small greenhouses placed on the roofs of the factory and incinerator, into which mixtures of flue gases and clean air could be directly pumped. Plant cuttings bearing young flower buds were exposed to various concentrations of the emissions for 8 or 24 hours. The treated and control flower buds were fixed in aceto-ethanol (1:3 ratio) and slides of the early tetrads were prepared to score the micronuclei frequencies. The genotoxicity of fumes emitted from two paint formulations (P1, P2) used at the paint factory were compared, The average MCN frequencies of the groups exposed to P2 fumes increased with increasing concentration, and were as high as 6 times those of the control groups at full strength. Average MCN frequencies of groups exposed to full strength P1 fumes were 3.6 times higher than those of the control groups. Although the results of the incinerator trials were more variable, the average MCN frequencies of groups exposed to 1:1,000 diluted incinerator emissions were significantly higher than those in the control groups, on most dates. The results of the study demonstrated the potential genotoxicity of the emissions, and the usefulness of in-situ monitoring of gaseous emissions from incinerators and industrial sources.

  12. Evidence for oxidative metabolism in the genotoxicity of 2-nitronaphthalene and 2-nitrodibenzopyranone

    SciTech Connect

    Sasaki, J.C.; Arey, J.; Eastmond, D.A.

    1997-10-01

    Previous studies of atmospheric reaction products of naphthalene and phenanthrene in metabolically competent human cells (MCL-5), identified 2-nitronaphthalene (2NN) and 2-nitrodibenzopyranone (2NDBP) as genotoxic species. This work investigated if transfected enzymatic activities were required for activation of these compounds, and if a single enzyme could be sufficient for metabolic activation. Three directly related cell lines with multiple (MCL-5), single (AHH-1 1A1), or no (L3) transfected cytochrome P450 genes were used. AHH-1 is additionally distinguished by elevated mutagenic response at the tk locus, p53 status and apoptosis capacity. The effect of these differences on genotoxicity of 2NN, 2NDBP and {beta}-naphthylamine ({beta}NA) was also investigated. The results suggest that 2NN and 2NDBP are not activated to genotoxic species through nitroreduction pathways. Mutagenicity induced at the tk locus is dependent on oxidative metabolism, provided by transfected cytochrome P450 enzymes in MCL-5 and AHH-1 1A1. Mutagenicity was not observed in the L3 cell line, which does not carry transfected cytochrome P450 activities. The negative response of {beta}NA are not activated by similar metabolic pathways in these human cell lines.

  13. Assessment of the genotoxic risk from laxative senna products.

    PubMed

    Brusick, D; Mengs, U

    1997-01-01

    Laxative senna products and several of their specific components have been submitted to a large number of genetic tests. While most studies gave negative responses, results from some of the studies suggest that components of senna products, particularly emodin and aloe-emodin, have genotoxic activity. Assessment of the genotoxicity profile of these substances, in light of other data from animal and human metabolism or kinetic studies, human clinical trials and rodent carcinogenicity studies do not support concerns that senna laxatives pose a genotoxic risk to humans when consumed under prescribed use conditions.

  14. Large-scale genotoxicity assessments in the marine environment.

    PubMed

    Hose, J E

    1994-12-01

    There are a number of techniques for detecting genotoxicity in the marine environment, and many are applicable to large-scale field assessments. Certain tests can be used to evaluate responses in target organisms in situ while others utilize surrogate organisms exposed to field samples in short-term laboratory bioassays. Genotoxicity endpoints appear distinct from traditional toxicity endpoints, but some have chemical or ecotoxicologic correlates. One versatile end point, the frequency of anaphase aberrations, has been used in several large marine assessments to evaluate genotoxicity in the New York Bight, in sediment from San Francisco Bay, and following the Exxon Valdez oil spill.

  15. Large-scale genotoxicity assessments in the marine environment.

    PubMed Central

    Hose, J E

    1994-01-01

    There are a number of techniques for detecting genotoxicity in the marine environment, and many are applicable to large-scale field assessments. Certain tests can be used to evaluate responses in target organisms in situ while others utilize surrogate organisms exposed to field samples in short-term laboratory bioassays. Genotoxicity endpoints appear distinct from traditional toxicity endpoints, but some have chemical or ecotoxicologic correlates. One versatile end point, the frequency of anaphase aberrations, has been used in several large marine assessments to evaluate genotoxicity in the New York Bight, in sediment from San Francisco Bay, and following the Exxon Valdez oil spill. PMID:7713029

  16. Large-scale genotoxicity assessments in the marine environment

    SciTech Connect

    Hose, J.E.

    1994-12-01

    There are a number of techniques for detecting genotoxicity in the marine environment, and many are applicable to large-scale field assessments. Certain tests can be used to evaluate responses in target organisms in situ while others utilize surrogate organisms exposed to field samples in short-term laboratory bioassays. Genotoxicity endpoints appear distinct from traditional toxicity endpoints, but some have chemical or ecotoxicologic correlates. One versatile end point, the frequency of anaphase aberrations, has been used in several large marine assessments to evaluate genotoxicity in the New York Bight, in sediment from San Francisco Bay, and following the Exxon Valdez oil spill. 31 refs., 2 tabs.

  17. Evaluating microRNA profiles reveals discriminative responses following genotoxic or non-genotoxic carcinogen exposure in primary mouse hepatocytes.

    PubMed

    Rieswijk, Linda; Brauers, Karen J J; Coonen, Maarten L J; van Breda, Simone G J; Jennen, Danyel G J; Kleinjans, Jos C S

    2015-11-01

    Chemical carcinogenesis can be induced by genotoxic (GTX) or non-genotoxic (NGTX) carcinogens. GTX carcinogens have a well-described mode of action. However, the complex mechanisms by which NGTX carcinogens act are less clear and may result in conflicting results between species [e.g. Wy-14,643 (Wy)]. We hypothesise that common microRNA response pathways exist for each class of carcinogenic agents. Therefore, this study compares and integrates mRNA and microRNA expression profiles following short term acute exposure (24 and 48h) to three GTX [aflatoxin B1 (AFB1), benzo[a]pyrene (BaP) and cisplatin (CisPl)] or three NGTX (2,3,7,8-tetrachloordibenzodioxine (TCDD), cyclosporine A (CsA) and Wy) carcinogens in primary mouse hepatocytes. Discriminative gene sets, microRNAs (not for 24h) and processes were identified following 24 and 48h of exposure. From the three discriminative microRNAs found following 48h of exposure, mmu-miR-503-5p revealed to have an interaction with mRNA target gene cyclin D2 (Ccnd2 - 12444) which was involved in the discriminative process of p53 signalling and metabolism. Following exposure to NGTX carcinogens Mmu-miR-503-5p may have an oncogenic function by stimulating Ccnd2 possibly leading to a tumourigenic cell cycle progression. By contrast, after GTX carcinogen exposure it may have a tumour-suppressive function (repressing Ccnd2) leading to cell cycle arrest and to increased DNA repair activities. In addition, compound-specific microRNA-mRNA interactions [mmu-miR-301b-3p-Papss2 (for AFB1), as well as mmu-miR-29b-3p-Col4a2 and mmu-miR-24-3p-Flna (for BaP)] were found to contribute to a better understanding of microRNAs in cell cycle arrest and the impairment of the DNA damage repair, an important hallmark of GTX-induced carcinogenesis. Overall, our results indicate that microRNAs represent yet another relevant intracellular regulatory level in chemical carcinogenesis. © The Author 2015. Published by Oxford University Press on behalf of the

  18. Radio frequency electromagnetic fields: cancer, mutagenesis, and genotoxicity.

    PubMed

    Heynick, Louis N; Johnston, Sheila A; Mason, Patrick A

    2003-01-01

    We present critiques of epidemiologic studies and experimental investigations, published mostly in peer-reviewed journals, on cancer and related effects from exposure to nonionizing electromagnetic fields in the nominal frequency range of 3 kHz to 300 GHz of interest to Subcommittee 4 (SC4) of the International Committee on Electromagnetic Safety (ICES). The major topics discussed are presented under the headings Epidemiologic and Other Findings on Human Exposure, Mammals Exposed In Vivo, Mammalian Live Tissues and Cell Preparations Exposed In Vitro, and Mutagenesis and Genotoxicity in Microorganisms and Fruit Flies. Under each major topic, we present minireviews of papers on various specific endpoints investigated. The section on Epidemiologic and Other Findings on Human Exposure is divided into two subsections, the first on possible carcinogenic effects of exposure from emitters not in physical contact with the populations studied, for example, transmitting antennas and other devices. Discussed in the second subsection are studies of postulated carcinogenic effects from use of mobile phones, with prominence given to brain tumors from use of cellular and cordless telephones in direct physical contact with an ear of each subject. In both subsections, some investigations yielded positive findings, others had negative findings, including papers directed toward experimentally verifying positive findings, and both were reported in a few instances. Further research on various important aspects may resolve such differences. Overall, however, the preponderance of published epidemiologic and experimental findings do not support the supposition that in vivo or in vitro exposures to such fields are carcinogenic.

  19. Monitoring genotoxic exposure in uranium mines

    SciTech Connect

    Sram, R.J.; Vesela, D.; Vesely, D.

    1993-10-01

    Recent data from deep uranium mines in Czechoslovakia indicated that miners are exposed to other mutagenic factors in addition to radon daughter products. Mycotoxins were identified as a possible source of mutagens in these mines. Mycotoxins were examined in 38 samples from mines and in throat swabs taken from 116 miners and 78 controls. The following mycotoxins were identified from mines samples: aflatoxins B{sub 1} and G1, citrinin, citreoviridin, mycophenolic acid, and sterigmatocystin. Some mold strains isolated from mines and throat swabs were investigated for mutagenic activity by the SOS chromotest and Salmonella assay with strains TA100 and TA98. Mutagenicity was observed, especially with metabolic activation in citro. These data suggest that mycotoxins produced by molds in uranium mines are a new genotoxic factor im uranium miners. 17 refs., 4 tabs.

  20. The absence of genotoxicity of sucralose.

    PubMed

    Brusick, D; Grotz, V L; Slesinski, R; Kruger, C L; Hayes, A W

    2010-11-01

    Sucralose is a non-nutritive sweetener that is approximately 600 times sweeter than table sugar. It is currently approved for use in over 80 countries. Evidence from chronic studies demonstrates that this compound is not carcinogenic. This report summarizes the results of genotoxicity studies that were part of the original safety assessment of sucralose-conducted early in the safety investigation and shared with regulatory agencies around the world. Studies included the Ames (Salmonella typhimurium) reverse mutation test, the Escherichia coli pol A+/A- test, an in vitro chromosome damage assay in human lymphocytes, mutation in TK +/- mouse lymphoma cells, an in vivo chromosome aberration test in rats and two separate micronucleus tests in mice. All results were evaluated as negative. These results support the overall conclusion by regulatory and heath agencies that sucralose is safe for its intended use. Copyright © 2010 Elsevier Ltd. All rights reserved.

  1. Monitoring genotoxic exposure in uranium mines.

    PubMed Central

    Srám, R J; Dobiás, L; Rössner, P; Veselá, D; Veselý, D; Rakusová, R; Rericha, V

    1993-01-01

    Recent data from deep uranium mines in Czechoslovakia indicated that mines are exposed to other mutagenic factors in addition to radon daughter products. Mycotoxins were identified as a possible source of mutagens in these mines. Mycotoxins were examined in 38 samples from mines and in throat swabs taken from 116 miners and 78 controls. The following mycotoxins were identified from mines samples: aflatoxins B1 and G1, citrinin, citreoviridin, mycophenolic acid, and sterigmatocystin. Some mold strains isolated from mines and throat swabs were investigated for mutagenic activity by the SOS chromotest and Salmonella assay with strains TA100 and TA98. Mutagenicity was observed, especially with metabolic activation in vitro. These data suggest that mycotoxins produced by molds in uranium mines are a new genotoxic factor for uranium miners. PMID:8143610

  2. Genotoxicity evaluation of Isaria sinclairii (ISE) extract.

    PubMed

    Ahn, Mi Young; Ryu, Kang Sun; Jee, Sang Duck; Kim, Iksoo; Kim, Jin Won; Kim, Yeong Shik; Kim, Hyung Sik; Kim, In Sun; Kang, Se C; Koo, Hyun Jung; Park, Yo An; Choi, Sul Min; Yoo, Eun Jeong; Kwack, Seung Jun; Yoo, Sun Dong; Lee, Byung Mu

    2004-12-01

    The mutagenic potential Isaria sinclairii, a traditional Chinese medicine composed of the fruiting bodies of I. sinclairii and its parasitic host larva, was evaluated using short-term genotoxicity tests, namely, the Ames test, chromosome aberration (CA), and micronuclei (MN) tests. In a Salmonella typhimurium assay, I. sinclairii extract (ISE) did not produce any mutagenic response in the absence or presence of 59 mix with TA98, TA100, TA1535, and TA1537. In the chromosome aberration (CA) test, ISE induced no significant effect on Chinese hamster ovary (CHO) cells compared with control. In the MN test, no significant change in the occurrence of micronucleated polychromatic erythrocytes was observed in male ICR mice intraperitoneally administered ISE at doses of 15, 150, or 1500 mg/kg. These results indicate that ISE has no mutagenic potential in these in vitro and in vivo systems.

  3. Methylation of Lysine 9 in Histone H3 Directs Alternative Modes of Highly Dynamic Interaction of Heterochromatin Protein hHP1β with the Nucleosome*

    PubMed Central

    Munari, Francesca; Soeroes, Szabolcs; Zenn, Hans Michael; Schomburg, Adrian; Kost, Nils; Schröder, Sabrina; Klingberg, Rebecca; Rezaei-Ghaleh, Nasrollah; Stützer, Alexandra; Gelato, Kathy Ann; Walla, Peter Jomo; Becker, Stefan; Schwarzer, Dirk; Zimmermann, Bastian; Fischle, Wolfgang; Zweckstetter, Markus

    2012-01-01

    Binding of heterochromatin protein 1 (HP1) to the histone H3 lysine 9 trimethylation (H3K9me3) mark is a hallmark of establishment and maintenance of heterochromatin. Although genetic and cell biological aspects have been elucidated, the molecular details of HP1 binding to H3K9me3 nucleosomes are unknown. Using a combination of NMR spectroscopy and biophysical measurements on fully defined recombinant experimental systems, we demonstrate that H3K9me3 works as an on/off switch regulating distinct binding modes of hHP1β to the nucleosome. The methyl-mark determines a highly flexible and very dynamic interaction of the chromodomain of hHP1β with the H3-tail. There are no other constraints of interaction or additional multimerization interfaces. In contrast, in the absence of methylation, the hinge region and the N-terminal tail form weak nucleosome contacts mainly with DNA. In agreement with the high flexibility within the hHP1β-H3K9me3 nucleosome complex, the chromoshadow domain does not provide a direct binding interface. Our results report the first detailed structural analysis of a dynamic protein-nucleosome complex directed by a histone modification and provide a conceptual framework for understanding similar interactions in the context of chromatin. PMID:22815475

  4. Chromium genotoxicity: a double-edged sword

    PubMed Central

    Nickens, Kristen P.; Patierno, Steven R.; Ceryak, Susan

    2010-01-01

    Certain forms of hexavalent chromium [Cr(VI)] are known respiratory carcinogens that induce a broad spectrum of DNA damage. Cr(VI)-carcinogenesis may be initiated or promoted through several mechanistic processes including, the intracellular metabolic reduction of Cr(VI) producing chromium species capable of interacting with DNA to yield genotoxic and mutagenic effects, Cr(VI)-induced inflammatory/immunological responses, and alteration of survival signaling pathways. Cr(VI) enters the cell through nonspecific anion channels, and is metabolically reduced by agents including ascorbate, glutathione, and cysteine to Cr(V), Cr(IV), and Cr(III). Cr(III) has a weak membrane permeability capacity and is unable to cross the cell membrane, thereby trapping it within the cell where it can bind to DNA and produce genetic damage leading to genomic instability. Structural genetic lesions produced by the intracellular reduction of Cr(VI) include DNA adducts, DNA strand breaks, DNA-protein crosslinks, oxidized bases, abasic sites, and DNA inter- and intrastrand crosslinks. The damage induced by Cr(VI) can lead to dysfunctional DNA replication and transcription, aberrant cell cycle checkpoints, dysregulated DNA repair mechanisms, microsatelite instability, inflammatory responses, and the disruption of key regulatory gene networks responsible for the balance of cell survival and cell death, which may all play an important role in Cr(VI) carcinogenesis. Several lines of evidence have indicated that neoplastic progression is a result of consecutive genetic/epigenetic changes that provide cellular survival advantages, and ultimately lead to the conversion of normal human cells to malignant cancer cells. This review is based on studies that provide a glimpse into Cr(VI) carcinogenicity via mechanisms including Cr(VI)-induced death-resistance, the involvement of DNA repair mechanisms in survival after chromium exposure, and the activation of survival signaling cascades in response to Cr

  5. Monitoring of genotoxicity in marine zooplankton induced by toxic metals in Ennore estuary, Southeast coast of India.

    PubMed

    Goswami, Prasun; Thirunavukkarasu, Subramani; Godhantaraman, Nallamuthu; Munuswamy, Natesan

    2014-11-15

    The present study provides preliminary in-situ data on genetic integrity of marine zooplankton. Paracalanus parvus, Oithona rigida and Euterpina acutifrons were collected during four different seasons (summer, pre-monsoon, monsoon and post-monsoon) from 2011 to 2012 in Ennore and Kovalum estuaries. DNA damage levels in different zooplankton were analyzed by comet assay and were correlated with different environmental stressors. Spatial and temporal variations in DNA damage was observed in all the species. Zooplankton from Ennore estuary showed significantly lower genetic integrity. Particulate, sediment, and zooplankton fractions of Pb, Ni, Cu, Cr and Co were associated with high DNA damage during the period of lowest pH, salinity and dissolved oxygen. Zn and Cd showed lower genotoxic impact than the other metals. Feeding modes strongly influenced the genetic integrity in the zooplankton species studied. These results support the use of comet assay as a tool in effectively monitoring genotoxicity in marine plankton communities.

  6. Academic Travel: Modes and Directions

    ERIC Educational Resources Information Center

    Barnett, Ronald; Phipps, Alison

    2005-01-01

    The Great Khan's atlas contains also the maps of the promised lands visited in thought but not yet discovered or founded: New Atlantis, Utopia, the City of the Sun, Oceana, Tamoe, New Harmony, New Lanark, Icaria. Kublai asked Marco: "You, who go about exploring and who see signs, can you tell me towards which of these futures the favouring winds…

  7. Academic Travel: Modes and Directions

    ERIC Educational Resources Information Center

    Barnett, Ronald; Phipps, Alison

    2005-01-01

    The Great Khan's atlas contains also the maps of the promised lands visited in thought but not yet discovered or founded: New Atlantis, Utopia, the City of the Sun, Oceana, Tamoe, New Harmony, New Lanark, Icaria. Kublai asked Marco: "You, who go about exploring and who see signs, can you tell me towards which of these futures the favouring winds…

  8. Titanium dioxide nanoparticles cause genotoxicity in human lung epithelial cells

    EPA Science Inventory

    The use of engineered nanoparticles in consumer products is steadily increasing. However, the health effects of exposure to these nanoparticles are not thoroughly understood. This study investigated the genotoxicity of six titanium dioxide and two cerium oxide nanoparticles of va...

  9. Genotoxicity Induced by Dental Materials: A Comprehensive Review.

    PubMed

    Ribeiro, Daniel Araki; Yujra, Veronica Quispe; DE Moura, Carolina Foot Gomes; Handan, Bianca Andrade; DE Barros Viana, Milena; Yamauchi, Liria Yuri; Castelo, Paula Midori; Aguiar, Odair

    2017-08-01

    Genotoxicity is the capacity of an agent to produce damage in the DNA molecule. Considering the strong evidence for a relationship between genetic damage and carcinogenesis, evaluation of genotoxicity induced by dental materials is necessary for elucidating the true health risks to patients and professionals. The purpose of this article was to provide a comprehensive review of genotoxicity induced by dental materials. All published data showed some evidence of genotoxicity, especially related to dental bleaching, restorative materials and endodontic compounds. Certainly, such information will be added to that already established for regulatory purposes as a safe way to promote oral healthcare and prevent oral carcinogenesis. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  10. Genotoxicity guidelines recommended by International Conference of Harmonization (ICH).

    PubMed

    Kamath, Gireesh H; Rao, K S

    2013-01-01

    Genotoxicity tests are designed to detect the genetic damage by various mechanisms. Several guidelines have provided various tests to be conducted for testing the genotoxicity and each of the regulatory agencies around the world have developed their own requirements for mutagenicity, without realizing that the products developed or registered in one country are also going to be registered and marketed around the world. The ICH guideline of genotoxicity helps to optimize the standard battery for genetic toxicology and to provide guidance on interpretation of results. These suggested standard set of tests does not imply that other genotoxicity tests are inadequate or inappropriate, but they help in improving risk characterization for carcinogenic effects that have their basis in changes in the genetic material.

  11. THE GENOTOXICITY OF AMBIENT OUTDOOR AIR, A REVIEW: SALMONELLA MUTAGENICITY

    EPA Science Inventory

    The genotoxicity of ambient outdoor air, a review: Salmonella mutagenicity

    Abstract
    Mutagens in urban air pollution come from anthropogenic sources (especially combustion sources) and are products of airborne chemical reactions. Bacterial mutation tests have been used ...

  12. Titanium dioxide nanoparticles cause genotoxicity in human lung epithelial cells

    EPA Science Inventory

    The use of engineered nanoparticles in consumer products is steadily increasing. However, the health effects of exposure to these nanoparticles are not thoroughly understood. This study investigated the genotoxicity of six titanium dioxide and two cerium oxide nanoparticles of va...

  13. Combining the in vivo comet and micronucleus assays: a practical approach to genotoxicity testing and data interpretation.

    PubMed

    Vasquez, Marie Z

    2010-03-01

    Despite regulatory directives requiring the reduction of animal use in safety testing, recent modifications to genotoxicity testing guidelines now propose the use of two in vivo genotoxicity assays as a follow-up to an in vitro positive (International Conference on Harmonization Consensus Draft Guidance S2[R1] released March, 2008). To address both goals, the in vivo comet and micronucleus (MN) assays can be successfully combined into one informative study. Combining these two assays with such differences in sensitivity, endpoints measured and the type of data generated significantly improves upon the current standard capabilities for detecting genotoxicity without requiring additional animals. But to take full advantage of the benefits of incorporating the comet assay in safety testing, these same differences must be recognized and considered. Developed from over 15 years experience using the in vivo comet and MN assays in genotoxicity testing of chemicals and pharmaceuticals, this paper presents guidelines for the appropriate experimental design, dose selection and data interpretation for combined in vivo comet/MN assay studies. To illustrate the approach, data from combined assay studies are presented and discussed.

  14. SB202190 affects cell response to hydroxyurea-induced genotoxic stress in root meristems of Vicia faba.

    PubMed

    Winnicki, Konrad; Maszewski, Janusz

    2012-11-01

    Genotoxic stress caused by a variety of chemical and physical agents may lead to DNA breaks and genome instability. Response to DNA damage depends on ATM/ATR sensor kinases and their downstream proteins, which arrange cell cycle checkpoints. Activation of ATM (ataxia-telangiectasia-mutated)/ATR (ATM and Rad 3-related) signaling pathway triggers cell cycle arrest (by keeping cyclin-Cdk complexes inactive), combined with gamma-phosphorylation of histone H2A.X and induction of DNA repair processes. However, genotoxic stress activates also mitogen-activated protein kinases (MAPKs) which may control the functions of checkpoint proteins both directly, by post-translational modifications, or indirectly, by regulation of their expression. Our results indicate that in root meristem cells of Vicia faba, MAP kinase signaling pathway takes part in response to hydroxyurea-induced genotoxic stress. It is shown that SB202190, an inhibitor of p38 MAP kinase, triggers PCC (premature chromosome condensation) more rapidly, but only if cell cycle checkpoints are alleviated by caffeine. Since SB202190 and, independently, caffeine reduces HU-mediated histone H4 Lys5 acetylation, it may be that there is a cooperation of MAP kinase signaling pathways and ATM/ATR-dependent checkpoints during response to genotoxic stress.

  15. Temporally distinct roles of ATM and ROS in genotoxic-stress-dependent induction and maintenance of cellular senescence.

    PubMed

    Nair, Raji R; Bagheri, Meisam; Saini, Deepak Kumar

    2015-01-15

    Cells exposed to genotoxic stress induce cellular senescence through a DNA damage response (DDR) pathway regulated by ATM kinase and reactive oxygen species (ROS). Here, we show that the regulatory roles for ATM kinase and ROS differ during induction and maintenance of cellular senescence. Cells treated with different genotoxic agents were analyzed using specific pathway markers and inhibitors to determine that ATM kinase activation is directly proportional to the dose of the genotoxic stress and that senescence initiation is not dependent on ROS or the p53 status of cells. Cells in which ROS was quenched still activated ATM and initiated the DDR when insulted, and progressed normally to senescence. By contrast, maintenance of a viable senescent state required the presence of ROS as well as activated ATM. Inhibition or removal of either of the components caused cell death in senescent cells, through a deregulated ATM-ROS axis. Overall, our work demonstrates existence of an intricate temporal hierarchy between genotoxic stress, DDR and ROS in cellular senescence. Our model reports the existence of different stages of cellular senescence with distinct regulatory networks.

  16. Assessment of the genotoxicity of three cryoprotectants used for human oocyte vitrification: dimethyl sulfoxide, ethylene glycol and propylene glycol.

    PubMed

    Aye, M; Di Giorgio, C; De Mo, M; Botta, A; Perrin, J; Courbiere, B

    2010-07-01

    Vitrification requires high concentrations of cryoprotectants that may induce long-term toxic effects on cells. The aim of this study was to evaluate the possible genotoxicity of three cryoprotectants extensively used for oocyte vitrification: dimethyl sulfoxide (DMSO), ethylene glycol (EG) and propylene glycol (PROH). For this purpose, a Chinese Hamster Ovary cell line (CHO), commonly used in genetic toxicology, was selected as an in vitro biological model to assess both the induction of DNA strand-breaks as identifiable by the alkaline comet assay and the persistence of chromosomal damages (micronuclei) as analyzed by the micronucleus assay. Results showed that DMSO was not genotoxic. EG did not exert direct genotoxic activity, however EG exhibited significant genotoxic and clastogenic activities in the presence of an external cytochrome-based P450 oxidation system (S9 Mix). PrOH produced in vitro DNA-damage leading to chromosome mutations in the presence and absence of the S9 Mix. These results showed that high concentrations of EG and PrOH could induce in vitro chromosomal damage in eukaryotic cells.

  17. Are genotoxic carcinogens more potent than nongenotoxic carcinogens?

    PubMed Central

    Parodi, S; Malacarne, D; Romano, P; Taningher, M

    1991-01-01

    In this report we have raised the question whether genotoxic carcinogens are more potent than nongenotoxic carcinogens when studied in long-term carcinogenicity assays in rodents. To build a large database of compounds for which both carcinogenicity and genotoxicity had been investigated, we have used a database produced by Gold and co-workers for carcinogenic potency data (975 chemicals) and a database produced by Würgler for genotoxicity data (2834 chemicals). Considering compounds positive or negative in at least three short-term tests and in at least 75% of available tests, we could define 67 genotoxic carcinogens and 46 nongenotoxic carcinogens. Carcinogenic potency of genotoxic carcinogens was about 50 times higher than carcinogenic potency of nongenotoxic carcinogens. Our results are different from the results of Tennant et al.; their database (24 genotoxic carcinogens and 12 nongenotoxic carcinogens compatible with our definition) seems to suggest that there is practically no difference in potency between genotoxic and nongenotoxic carcinogens. The two databases have only four compounds in common and are also different in terms of number of elements for different chemical classes. Nitrosocompounds, nitrogen mustards, hydrazine derivatives, and polycyclic aromatic hydrocarbons are not represented in the database of Tennant. The overall impression from our analysis is that the usefulness of short-term tests of genotoxicity could be significantly better than what has been suggested by the previous work of Tennant et al. because these tests tend to detect, at least for many important chemical classes, the most potent carcinogens. This consideration may not be valid for certain classes of chemicals. PMID:1821372

  18. Genotoxicity of the fungicide dichlofluanide in seven assays

    SciTech Connect

    Heil, J.; Reifferscheid, G.; Hellmich, D.; Hergenroeder, M.; Zahn, R.K. )

    1991-01-01

    Seven different endpoints for detection of genotoxicity have been used to demonstrate the DNA-altering properties of Dichlofluanid, a fungicide commonly used in viticulture pest control. Each endpoint (DNA synthesis inhibition test, alkaline viscosimetry, umu-test, alkaline filter elution, FADU-test, {sup 32}P-postlabeling, and electron microscopy) shows clear evidence of genotoxicity. These data indicate that application of the fungicide dichlofluanid may be mutagenic and/or carcinogenic for exposed humans.

  19. First examples of stable arenium ions from large methylene-bridged polycyclic aromatic hydrocarbons (PAHs). Directive effects and charge delocalization mode.

    PubMed

    Laali, K K; Okazaki, T; Harvey, R G

    2001-06-01

    In connection to a growing interest in developing structure/activity trends in nonalternant polyarenes, we report on the generation and NMR studies of the first series of persistent arenium ions from large methylene-bridged PAHs (mostly 22pi six-fused ring systems). Low-temperature protonation (FSO(3)H/SO(2)ClF) and model nitration (with HNO(3)/HOAc or NO(2)(+) BF(4)(-)) were used as mimic reactions for generation of biological electrophiles. The site(s) of protonation (and nitration) were determined as a function of PAH structure. Charge delocalization mode in the resulting arenium ions of protonation are assessed based on detailed low-temperature NMR studies at 500 MHz. Systems studied were 1-methylcyclopenta[def]phenanthrene 2, 11H-benz[bc]aceanthrylene 8, 5H-benzo[b]cyclopenta[def]chrysene 9, 13H-dibenzo-[bc,l]aceanthrylene 10, 13H-cyclopenta[rst]pentaphene 11, 4H-benzo[b]cyclopenta[mno]chrysene 12, 6H-cyclopenta[ghi]picene 13, 4H-cyclopenta[pqr]picene 14, 4H-cyclopenta[def]dibenz[a,c]anthracene 15. For comparison, dibenzo[a,c]anthracene 16 and dibenzo[a,h]anthracene 17 were also included (Figures 1 and 2). It is shown that the methano-bridge exerts a strong directive effect which diminishes as the bridge moves from the more central "inner" positions to more peripheral "outer" positions. Charge delocalization mode in the resulting carbocations are discussed based on the magnitude of Deltadelta (13)C values. Possible relationships with biological electrophiles formed by epoxide ring opening in the putative metabolites are also considered.

  20. Direct comparison of GaN-based e-mode architectures (recessed MISHEMT and p-GaN HEMTs) processed on 200mm GaN-on-Si with Au-free technology

    NASA Astrophysics Data System (ADS)

    Marcon, Denis; Van Hove, Marleen; De Jaeger, Brice; Posthuma, Niels; Wellekens, Dirk; You, Shuzhen; Kang, Xuanwu; Wu, Tian-Li; Willems, Maarten; Stoffels, Steve; Decoutere, Stefaan

    2015-03-01

    Gallium nitride transistors are going to dominate the power semiconductor market in the coming years. The natural form of GaN-based devices is "normally-on" or depletion mode (d-mode). Despite these type of devices can be used in power semiconductor systems by means of special drivers or in a cascode package solution, yet the market demands for normally-off or enhancement mode (e-mode) devices. In this work, we directly compare and analyze the two most common approaches to obtain GaN-based e-mode devices: recessed gate MISHEMTs and p-GaN HEMTs. Both approaches have their pro's and con's as well as their critical process steps.

  1. Evaluation of protective effect of amifostine on dacarbazine induced genotoxicity

    PubMed Central

    Etebari, M.; Jafarian-Dehkordi, A.; Lame, V.

    2015-01-01

    Anticancer therapy with alkylating agents has been used for many years. Dacarbazine (DTIC) as an alkylating agent is used alone or in combination with other chemotherapy drugs. In order to inhibit the formation of secondary cancers resulting from chemotherapy with DTIC, preventional strategies is necessary. The present study was undertaken to evaluate the genoprotective effect of amifostine on the genotoxic effects of DTIC in cell culture condition. To determine the optimum genotoxic concentration of DTIC, HepG2 cells were incubated with various DTIC concentrations including 5, 10 and 20 μg/ml for 2 h and the genotoxic effects were evaluated by the comet assay. The result of this part of the study showed that incubation of HepG2 cells with DTIC at 5 μg/ml was sufficient to produce genotoxic effect. In order to determine the protective effects of amifostine on genotoxicity induced by DTIC, HepG2 cells were incubated with different concentrations of amifostine (2, 3 and 5 mg/ml) for 1 h which was followed by incubation with DTIC at 5 μg/ml for 2 h. One hour incubation of cells with different concentrations of amifostine before incubation with DITC indicated that at least 5 mg/ml concentration of amifostine can prevent genotoxic effects induced by DTIC on HepG2 cells under described condition. In conclusion amifostine could prevent DNA damage induced by DTIC on HepG2 cells. PMID:26430459

  2. Update on the genotoxicity and carcinogenicity of cobalt compounds

    PubMed Central

    Lison, D; De Boeck, M; Verougstraete, V; Kirsch-Volders, M

    2001-01-01

    OBJECTIVE—To integrate recent understandings of the mechanisms of genotoxicity and carcinogenicity of the different cobalt compounds.
METHOD—A narrative review of the studies published since the last IARC assessment in 1991 (genotoxicity, experimental carcinogenesis, and epidemiology).
RESULTS—Two different mechanisms of genotoxicity, DNA breakage induced by cobalt metal and especially hard metal particles, and inhibition of DNA repair by cobalt (II) ions contribute to the carcinogenic potential of cobalt compounds. There is evidence that soluble cobalt (II) cations exert a genotoxic and carcinogenic activity in vitro and in vivo in experimental systems but evidence in humans is lacking. Experimental data indicate some evidence of a genotoxic potential for cobalt metal in vitro in human lymphocytes but there is no evidence available of a carcinogenic potential. There is evidence that hard metal particles exert a genotoxic and carcinogenic activity in vitro and in human studies, respectively. There is insufficient information for cobalt oxides and other compounds.
CONCLUSION—Although many areas of uncertainty remain, an assessment of the carcinogenicity of cobalt and its compounds requires a clear distinction between the different compounds of the element and needs to take into account the different mechanisms involved.


Keywords: cobalt; DNA breakage; inhibition of DNA repair PMID:11555681

  3. Evaluation of protective effect of amifostine on dacarbazine induced genotoxicity.

    PubMed

    Etebari, M; Jafarian-Dehkordi, A; Lame, V

    2015-01-01

    Anticancer therapy with alkylating agents has been used for many years. Dacarbazine (DTIC) as an alkylating agent is used alone or in combination with other chemotherapy drugs. In order to inhibit the formation of secondary cancers resulting from chemotherapy with DTIC, preventional strategies is necessary. The present study was undertaken to evaluate the genoprotective effect of amifostine on the genotoxic effects of DTIC in cell culture condition. To determine the optimum genotoxic concentration of DTIC, HepG2 cells were incubated with various DTIC concentrations including 5, 10 and 20 μg/ml for 2 h and the genotoxic effects were evaluated by the comet assay. The result of this part of the study showed that incubation of HepG2 cells with DTIC at 5 μg/ml was sufficient to produce genotoxic effect. In order to determine the protective effects of amifostine on genotoxicity induced by DTIC, HepG2 cells were incubated with different concentrations of amifostine (2, 3 and 5 mg/ml) for 1 h which was followed by incubation with DTIC at 5 μg/ml for 2 h. One hour incubation of cells with different concentrations of amifostine before incubation with DITC indicated that at least 5 mg/ml concentration of amifostine can prevent genotoxic effects induced by DTIC on HepG2 cells under described condition. In conclusion amifostine could prevent DNA damage induced by DTIC on HepG2 cells.

  4. Cytotoxicity and genotoxicity of superporous hydrogel containing interpenetrating polymer networks.

    PubMed

    Yin, Lichen; Zhao, Xin; Cui, Liming; Ding, Jieying; He, Miao; Tang, Cui; Yin, Chunhua

    2009-06-01

    The superporous hydrogel containing poly(acrylic acid-co-acrylamide)/O-carboxymethyl chitosan (O-CMC) interpenetrating polymer networks (SPH-IPN) that had been developed as an oral delivery vehicle for protein drugs was subject to cytotoxicity and genotoxicity testing, thus evaluating its biological safety in use. In a battery of cytotoxicity assays on RBL-2H3 and Caco-2 cells, the SPH-IPN caused minimal damage towards cell viability, lysosomal activity, and metabolic activity following both direct and indirect treatment. The SPH-IPN did not induce cell apoptosis or DNA breakage in the above cell lines; it did not increase micronucleus (MN) incidence in mouse bone marrow, either. Therefore, the SPH-IPN was preliminarily considered to be biocompatible and might be a safe carrier for protein drugs. In addition, using the HPLC method, residual acrylic acid, acrylamide, and glutaraldehyde in the SPH-IPN were quantified to be 1.4, 2.0, and below 0.2 ppm, respectively. Lack of these low molecular monomers and crosslinker that were mainly responsible for the toxicity provided evidence for the good biocompatibility of the SPH-IPN.

  5. The carcinogenic action of crystalline silica: a review of the evidence supporting secondary inflammation-driven genotoxicity as a principal mechanism.

    PubMed

    Borm, Paul J A; Tran, Lang; Donaldson, Ken

    2011-10-01

    In 1987 the International Agency for Research on Cancer (IARC) classified crystalline silica (CS) as a probable carcinogen and in 1997 reclassified it as a Group 1 carcinogen, i.e., that there was sufficient evidence for carcinogenicity in experimental animals and sufficient evidence for carcinogenicity in humans. The Working Group noted that "carcinogenicity in humans was not detected in all industrial circumstances studied, carcinogenicity may be dependent on inherent characteristics of the crystalline silica or on external factors affecting its biological activity or distribution of its polymorphs." This unusual statement that the physicochemical form of the CS influences its carcinogenicity is well understood at the toxicological level and arises as a consequence of the fact that CS activity depends on the reactivity of the CS surface, which can be blocked by a number of agents. We reviewed the literature on CS genotoxicity that has been published since the 1997 monograph, with special reference to the mechanism of CS genotoxicity. The mechanism of CS genotoxicity can be primary, a result of direct interaction of CS with target cells, or indirect, as a consequence of inflammation elicited by quartz, where the inflammatory cell-derived oxidants cause the genotoxicity. The review revealed a number of papers supporting the hypothesis that the CS genotoxic and inflammatory hazard is a variable one. In an attempt to attain a quantitative basis for the potential mechanism, we carried out analysis of published data and noted a 5-fold greater dose required to reach a threshold for genotoxic effects than for proinflammatory effects in the same cell line in vitro. When we related the calculated threshold dose at the proximal alveolar region for inflammation in a published study with the threshold dose for genotoxicity in vitro, we noted that a 60-120-fold greater dose was required for direct genotoxic effects in vitro. These data strongly suggests that inflammation is

  6. Inhalation of formaldehyde does not induce systemic genotoxic effects in rats.

    PubMed

    Speit, Günter; Zeller, Jasmin; Schmid, Oliver; Elhajouji, Azeddine; Ma-Hock, Lan; Neuss, Simone

    2009-01-01

    Male Fischer-344 rats were exposed to formaldehyde (FA) by inhalation for 4 weeks (6 h/day, 5 days/week). Groups of six rats each were exposed to the target concentrations of 0, 0.5, 1, 2, 6, 10 and 15 ppm. Potential systemic genotoxic effects were investigated as part of a comprehensive study on local and systemic toxic and genotoxic effects. For this purpose, peripheral blood samples were obtained by puncturing the retro-orbital venous plexus at the end of the exposure period. Blood sampling was carried out in a randomized sequence and samples were coded by sequence number to ensure blind evaluation. Blood samples were used for the comet assay, the sister chromatid exchange test (SCE test) and the micronucleus test (MNT). DNA migration in the comet assay was measured both directly and after irradiation of the blood samples with 2 Gy gamma-radiation. The latter modification of the comet assay was included to increase its sensitivity for the detection of DNA-protein cross-links (DPX). The following positive control groups were included: one group (six animals) was treated with 50mg/kg methyl methanesulfonate (MMS) once by gavage 4h before blood sampling. Another group (six animals) was treated twice orally with 10mg/kg cyclophosphamide (CP) with an interval of 24 h. The last application of CP was 24h before blood sampling. For the comet assay, four slides were analysed from each blood sample, two without and two with irradiation. From each slide, 50 randomly selected cells were measured by image analysis, and tail intensity (% tail DNA) and tail moment were evaluated. For the SCE test, blood was cultured for 56 h in the presence of BrdU (10 microg/ml for the last 35 h) and SCE were counted in 30 second-division metaphases per sample. The MNT with peripheral blood was performed according to the instructions for the micronucleus analysis kit MICROFLOW (Litron Laboratories). Approximately 20,000 cells per sample were analysed by flow cytometry and the percentage of

  7. Cyto-genotoxic effects of smoke from commercial filter and non-filter cigarettes on human bronchial and pulmonary cells.

    PubMed

    Cavallo, Delia; Ursini, Cinzia L; Fresegna, Anna M; Maiello, Raffaele; Ciervo, Aureliano; Ferrante, Riccardo; Buresti, Giuliana; Iavicoli, Sergio

    2013-01-20

    Cigarette smoke is a complex mixture of chemicals, some of which are known as carcinogens. The cyto-genotoxic effects of cigarette-smoke extract (CSE) from commercial cigarettes without (A and B) and with filter (C and D) were evaluated at different CSE concentrations on A549 and BEAS-2B cells. The particle content of the cigarette smoke and the metal composition of the CSE were also analyzed. The cells were exposed to 1-10% of the CSE from one cigarette per experiment. Cytotoxicity was evaluated by use of the MTT assay after 24h, and the lactate dehydrogenase (LDH) assay after 30min and 24h. The Fpg-modified comet assay was used to evaluate direct-oxidative DNA damage on cells exposed for 30min. As expected, unfiltered cigarette smoke (particularly from the B cigarette) contained a higher number of particles than filtered smoke. With smoke extract from the B cigarette we found a decrease in cell viability only in BEAS-2B cells. The results of the LDH test showed membrane damage for B-cigarette smoke extract, particularly in BEAS-2B cells. Extracts from unfiltered cigarette smoke induced significant direct DNA damage, to a larger extent in A549 cells. Filtered cigarette-smoke extract induced a significant direct DNA damage at 5-10%. A significant induction of oxidative DNA damage was found at the highest CSE concentration in both cell types (by smoke extracts from B and C cigarettes in A549 cells, and from A and D cigarettes in BEAS-2B cells). Smoke extracts from filter cigarettes induced less direct DNA damage than those from unfiltered cigarettes in A549 cells, probably due to a protective effect of filter. In BEAS-2B cells the smoke extract from the B-cigarette showed the highest genotoxic effect, with a concentration-dependent trend. These findings show a higher cyto-genotoxicity for smoke extracts from the B-cigarette and oxidative effects for those from the A and D cigarettes, particularly in BEAS-2B cells. Moreover, there was a higher responsiveness of A549

  8. Assessment of genotoxicity of Lannate-90® and its plant and animal metabolites in human lymphocyte cultures.

    PubMed

    Valencia-Quintana, Rafael; Gómez-Arroyo, Sandra; Sánchez-Alarcón, Juana; Milić, Mirta; Olivares, José Luis Gómez; Waliszewski, Stefan M; Cortés-Eslava, Josefina; Villalobos-Pietrini, Rafael; Calderón-Segura, María Elena

    2016-06-01

    This study evaluated direct and metabolic genotoxic effects caused by Lannate-90®, a methomyl-based formulation (90 % active ingredient), in human lymphocyte cultures using sister chromatid exchange assay (SCE). Two processes were used for the plant promutagens evaluation: in vivo activation, applying the insecticide systemically in plants for 4 h and subsequently adding plant metabolites containing extracts to lymphocyte cultures; and in vitro activation, where the insecticide was incubated with Vicia faba S10 mix plus human lymphocyte culture. Direct treatment with the insecticide significantly increased SCE frequency in human lymphocytes (250-750 mgL-1), with cellular death observed at 1000 mgL-1 concentration. Using the extracts of Vicia faba treated with Lannate-90® to treat human lymphocytes, a dose-response relationship was observed. In lymphocyte cultures treated directly with the insecticide for 2 h, a negative response was obtained. When S10 mix was added, SCE frequency did not change significantly. Meanwhile, a mixture of S9 mammalian metabolic mix and Lannate-90® increased the SCE frequency, with an observed concentration-dependent response. Although Lannate-90® induced cellular death at the highest concentrations, it did not cause a delay in cell proliferation in any of the treatments, confirming its genotoxic action. This study is one of the first to evaluate and compare the direct effect of Lannate-90® in two bioassays, animal and vegetal, and the effect of plant and animal metabolism on its genotoxic potential.

  9. Vinyl acetate monomer (VAM) genotoxicity profile: relevance for carcinogenicity.

    PubMed

    Albertini, Richard J

    2013-09-01

    Vinyl acetate monomer (VAM) is a site-of-contact carcinogen in rodents. It is also DNA reactive and mutagenic, but only after its carboxylesterase mediated conversion to acetaldehyde (AA), a metabolic reaction that also produces acetic acid and protons. As VAM's mutagenic metabolite, AA is normally produced endogenously; detoxification by aldehyde dehydrogenase (ALDH) is required to maintain intra-cellular AA homeostasis. This review examines VAM's overall genotoxicity, which is due to and limited by AA, and the processes leading to mutation induction. VAM and AA have both been universally negative in mutation studies in bacteria but both have tested positive in several in vitro studies in higher organisms that usually employed high concentrations of test agents. Recently however, in vitro studies evaluating submillimolar concentrations of VAM or AA have shown threshold dose-responses for mutagenicity in human cultured cells. Neither VAM nor AA induced systemic mutagenicity in in vivo studies in metabolically competent mice when tested at non-lethal doses while treatments of animals deficient in aldehyde dehydrogenase (Aldh in animals) did induce both gene and chromosome level mutations. The results of several studies have reinforced the critical role for aldehyde dehydrogenase 2 (ALDH2 in humans) in limiting AA's (and therefore VAM's) mutagenicity. The overall aim of this review of VAM's mutagenic potential through its AA metabolite is to propose a mode of action (MOA) for VAM's site-of-contact carcinogenesis that incorporates the overall process of mutation induction that includes both background mutations due to endogenous AA and those resulting from exogenous exposures.

  10. Type-1 and Type-2 Fuzzy Logic and Sliding-Mode Based Speed Control of Direct Torque and Flux Control Induction Motor Drives - A Comparative Study

    NASA Astrophysics Data System (ADS)

    Ramesh, Tejavathu; Panda, A. K.; Kumar, S. Shiva

    2013-08-01

    In this research study, the performance of direct torque and flux control induction motor drive (IMD) is presented using five different speed control techniques. The performance of IMD mainly depends on the design of speed controller. The PI speed controller requires precise mathematical model, continuous and appropriate gain values. Therefore, adaptive control based speed controller is desirable to achieve high-performance drive. The sliding-mode speed controller (SMSC) is developed to achieve continuous control of motor speed and torque. Furthermore, the type-1 fuzzy logic speed controller (T1FLSC), type-1 fuzzy SMSC and a new type-2 fuzzy logic speed controller are designed to obtain high performance, dynamic tracking behaviour, speed accuracy and also robustness to parameter variations. The performance of each control technique has been tested for its robustness to parameter uncertainties and load disturbances. The detailed comparison of different control schemes are carried out in a MATALB/Simulink environment at different speed operating conditions, such as, forward and reversal motoring under no-load, load and sudden change in speed.

  11. Measurements of the ablation-front trajectory and low-mode nonuniformity in direct-drive implosions using x-ray self-emission shadowgraphy

    DOE PAGES

    Michel, D. T.; Davis, A. K.; Armstrong, W.; ...

    2015-07-08

    Self-emission x-ray shadowgraphy provides a method to measure the ablation-front trajectory and low-mode nonuniformity of a target imploded by directly illuminating a fusion capsule with laser beams. The technique uses time-resolved images of soft x-rays (> 1 keV) emitted from the coronal plasma of the target imaged onto an x-ray framing camera to determine the position of the ablation front. Methods used to accurately measure the ablation-front radius (more » $${\\it\\delta}R=\\pm 1.15~{\\rm\\mu}\\text{m}$$), image-to-image timing ($${\\it\\delta}({\\rm\\Delta}t)=\\pm 2.5$$ ps) and absolute timing ($${\\it\\delta}t=\\pm 10$$ ps) are presented. Angular averaging of the images provides an average radius measurement of$${\\it\\delta}(R_{\\text{av}})=\\pm 0.15~{\\rm\\mu}\\text{m}$$and an error in velocity of$${\\it\\delta}V/V=\\pm 3\\%$$. This technique was applied on the Omega Laser Facility and the National Ignition Facility.« less

  12. [Study on genotoxicity of aldicarb and methomyl].

    PubMed

    Sun, Xiao-Yu; Jin, Yong-Tang; Wu, Bin; Wang, Wei-Qin; Pang, Xiao-Lu; Wang, Jing

    2010-12-01

    Genotoxicity of aldicarb and methomyl was explored. The aldicarb and methomyl were diluted by the deionized water respectively, and then five concentrations of aldicarb were generated as 0.002, 0.02, 0.2, 2, 20 microg/L, methomyl as 0.02, 0.2, 2, 20, 200 microg/L. The micronucleus of carp erythrocyte was counted by micronucleus test. The mutation of bacteria was assessed by Ames test. The DNA damage of human lymphocytes was tested by comet assay. The genotoxicity of aldicarb and methomyl was estimated by the three toxicology tests mentioned above. The results showed that, in the micronucleus test, both any concentration of two pesticides were not able to induce higher frequency of micronucleus in carp erythrocyte (p > 0.05). Under condition of metabolic inactivation, although the number of colony with back mutation in any concentration of two pesticides did not exceed the double number of those with spontaneous mutation, the revertants of TA97 strains in the aldicarb 2-20 microg/L and the methomyl 20-200 microg/L were (129.17 +/- 17.00), (129.50 +/- 18.28), (109.83 +/- 10.80) and (114.17 +/- 9.37) entries/plate, respectively, they were significantly greater than those in spontaneous mutation (p < 0.05, p < 0.01). In the methomyl 200 microg/L group, the revertants of TA100 and TA102 strains were (147.83 +/- 23.29) and (275.83 +/- 20.63) entries/plate, respectively, they are significantly higher than that of the control group under condition of metabolic activation (p < 0.05). In comet assay, both the high concentration groups of aldicarb and methomyl resulted in different degrees of DNA damage of human peripheral blood lymphocytes. Compared with deionized water group, all of three indexes of comet assay in the aldicarb 20 microg/L groups and the methomyl 200 microg/L groups were significantly higher (p < 0.01). Despite that both aldicarb and methomyl did not results in damaging chromosome carp erythrocyte and producing apparent mutagenicity, the effect of

  13. A tiered approach to the use of alternatives to animal testing for the safety assessment of cosmetics: genotoxicity. A COLIPA analysis.

    PubMed

    Pfuhler, Stefan; Kirst, Annette; Aardema, Marilyn; Banduhn, Norbert; Goebel, Carsten; Araki, Daisuke; Costabel-Farkas, Margit; Dufour, Eric; Fautz, Rolf; Harvey, James; Hewitt, Nicola J; Hibatallah, Jalila; Carmichael, Paul; Macfarlane, Martin; Reisinger, Kerstin; Rowland, Joanna; Schellauf, Florian; Schepky, Andreas; Scheel, Julia

    2010-01-01

    For the assessment of genotoxic effects of cosmetic ingredients, a number of well-established and regulatory accepted in vitro assays are in place. A caveat to the use of these assays is their relatively low specificity and high rate of false or misleading positive results. Due to the 7th amendment to the EU Cosmetics Directive ban on in vivo genotoxicity testing for cosmetics that was enacted March 2009, it is no longer possible to conduct follow-up in vivo genotoxicity tests for cosmetic ingredients positive in in vitro genotoxicity tests to further assess the relevance of the in vitro findings. COLIPA, the European Cosmetics Association, has initiated a research programme to improve existing and develop new in vitro methods. A COLIPA workshop was held in Brussels in April 2008 to analyse the best possible use of available methods and approaches to enable a sound assessment of the genotoxic hazard of cosmetic ingredients. Common approaches of cosmetic companies are described, with recommendations for evaluating in vitro genotoxins using non-animal approaches. A weight of evidence approach was employed to set up a decision-tree for the integration of alternative methods into tiered testing strategies.

  14. Silver nanoparticles: correlating nanoparticle size and cellular uptake with genotoxicity

    PubMed Central

    Butler, Kimberly S.; Peeler, David J.; Casey, Brendan J.; Dair, Benita J.; Elespuru, Rosalie K.

    2015-01-01

    The focus of this research was to develop a better understanding of the pertinent physico-chemical properties of silver nanoparticles (AgNPs) that affect genotoxicity, specifically how cellular uptake influences a genotoxic cell response. The genotoxicity of AgNPs was assessed for three potential mechanisms: mutagenicity, clastogenicity and DNA strand-break-based DNA damage. Mutagenicity (reverse mutation assay) was assessed in five bacterial strains of Salmonella typhimurium and Echerichia coli, including TA102 that is sensitive to oxidative DNA damage. AgNPs of all sizes tested (10, 20, 50 and 100nm), along with silver nitrate (AgNO3), were negative for mutagenicity in bacteria. No AgNPs could be identified within the bacteria cells using transmission electron microscopy (TEM), indicating these bacteria lack the ability to actively uptake AgNPs 10nm or larger. Clastogenicity (flow cytometry-based micronucleus assay) and intermediate DNA damage (DNA strand breaks as measured in the Comet assay) were assessed in two mammalian white blood cell lines: Jurkat Clone E6-1 and THP-1. It was observed that micronucleus and Comet assay end points were inversely correlated with AgNP size, with smaller NPs inducing a more genotoxic response. TEM results indicated that AgNPs were confined within intracellular vesicles of mammalian cells and did not penetrate the nucleus. The genotoxicity test results and the effect of AgNO3 controls suggest that silver ions may be the primary, and perhaps only, cause of genotoxicity. Furthermore, since AgNO3 was not mutagenic in the gram-negative bacterial Ames strains tested, the lack of bacterial uptake of the AgNPs may not be the major reason for the lack of genotoxicity observed. PMID:25964273

  15. Silver nanoparticles: correlating nanoparticle size and cellular uptake with genotoxicity.

    PubMed

    Butler, Kimberly S; Peeler, David J; Casey, Brendan J; Dair, Benita J; Elespuru, Rosalie K

    2015-07-01

    The focus of this research was to develop a better understanding of the pertinent physico-chemical properties of silver nanoparticles (AgNPs) that affect genotoxicity, specifically how cellular uptake influences a genotoxic cell response. The genotoxicity of AgNPs was assessed for three potential mechanisms: mutagenicity, clastogenicity and DNA strand-break-based DNA damage. Mutagenicity (reverse mutation assay) was assessed in five bacterial strains of Salmonella typhimurium and Echerichia coli, including TA102 that is sensitive to oxidative DNA damage. AgNPs of all sizes tested (10, 20, 50 and 100nm), along with silver nitrate (AgNO3), were negative for mutagenicity in bacteria. No AgNPs could be identified within the bacteria cells using transmission electron microscopy (TEM), indicating these bacteria lack the ability to actively uptake AgNPs 10nm or larger. Clastogenicity (flow cytometry-based micronucleus assay) and intermediate DNA damage (DNA strand breaks as measured in the Comet assay) were assessed in two mammalian white blood cell lines: Jurkat Clone E6-1 and THP-1. It was observed that micronucleus and Comet assay end points were inversely correlated with AgNP size, with smaller NPs inducing a more genotoxic response. TEM results indicated that AgNPs were confined within intracellular vesicles of mammalian cells and did not penetrate the nucleus. The genotoxicity test results and the effect of AgNO3 controls suggest that silver ions may be the primary, and perhaps only, cause of genotoxicity. Furthermore, since AgNO3 was not mutagenic in the gram-negative bacterial Ames strains tested, the lack of bacterial uptake of the AgNPs may not be the major reason for the lack of genotoxicity observed.

  16. Three-Dimensional, Transgenic Cell Models to Quantify Space Genotoxic Effects

    NASA Technical Reports Server (NTRS)

    Gonda, S. R.; Sognier, M. A.; Wu, H.; Pingerelli, P. L.; Glickman, B. W.; Dawson, David L. (Technical Monitor)

    1999-01-01

    ; and iii,, mitotic cells located throughout the spheroids. Spheroidal integrity and cell viability were retained for the 30-day test period after removal of spheroids from the bioreactor. Potential utility of this three-dimensional, transgenic model for genotoxicity was initially assessed by exposure of spheroids to 0-2 Gy neon at dose rates of 0.3 to 1.5 Gy/min (National Institute of Radiological Sciences, Chiba, Japan). Quantification of mutation at the lacl gene revealed a linear dose response for mutation induction. Limited sequencing analysis of mutant clones revealed higher frequencies of deletions and multiple base sequence changes with increasing dose. These results suggest that our three-dimensional, transgenic model is applicable to a wide variety of studies involving the quantification, identification, and characterization of genotoxicity incurred in space and on Earth. This model uniquely allows investigation of the interaction of relevant factors, namely cell-to-cell interactions and the mechanistic interaction of microgravity with radiation insults and DNA repair. Using this three-dimensional model will allow us to obtain dual genotoxic information (i.e., mutation rate plus chromosome aberration data) from the same system so that one endpoint can be used to reference the other, thereby increasing the fidelity of the data set. Moreover, the tissue-equivalent nature of the three-dimensional model provides high confidence for relevance of risk assessment, i.e., the establishment of quality factors directly applicable to the microgravity environment.

  17. Three-Dimensional, Transgenic Cell Models to Quantify Space Genotoxic Effects

    NASA Technical Reports Server (NTRS)

    Gonda, S. R.; Sognier, M. A.; Wu, H.; Pingerelli, P. L.; Glickman, B. W.; Dawson, David L. (Technical Monitor)

    1999-01-01

    ; and iii,, mitotic cells located throughout the spheroids. Spheroidal integrity and cell viability were retained for the 30-day test period after removal of spheroids from the bioreactor. Potential utility of this three-dimensional, transgenic model for genotoxicity was initially assessed by exposure of spheroids to 0-2 Gy neon at dose rates of 0.3 to 1.5 Gy/min (National Institute of Radiological Sciences, Chiba, Japan). Quantification of mutation at the lacl gene revealed a linear dose response for mutation induction. Limited sequencing analysis of mutant clones revealed higher frequencies of deletions and multiple base sequence changes with increasing dose. These results suggest that our three-dimensional, transgenic model is applicable to a wide variety of studies involving the quantification, identification, and characterization of genotoxicity incurred in space and on Earth. This model uniquely allows investigation of the interaction of relevant factors, namely cell-to-cell interactions and the mechanistic interaction of microgravity with radiation insults and DNA repair. Using this three-dimensional model will allow us to obtain dual genotoxic information (i.e., mutation rate plus chromosome aberration data) from the same system so that one endpoint can be used to reference the other, thereby increasing the fidelity of the data set. Moreover, the tissue-equivalent nature of the three-dimensional model provides high confidence for relevance of risk assessment, i.e., the establishment of quality factors directly applicable to the microgravity environment.

  18. Genotoxic and epigenetic mechanisms in arsenic carcinogenicity.

    PubMed

    Bustaffa, Elisa; Stoccoro, Andrea; Bianchi, Fabrizio; Migliore, Lucia

    2014-05-01

    Arsenic is a human carcinogen with weak mutagenic properties that induces tumors through mechanisms not yet completely understood. People worldwide are exposed to arsenic-contaminated drinking water, and epidemiological studies showed a high percentage of lung, bladder, liver, and kidney cancer in these populations. Several mechanisms by which arsenical compounds induce tumorigenesis were proposed including genotoxic damage and chromosomal abnormalities. Over the past decade, a growing body of evidence indicated that epigenetic modifications have a role in arsenic-inducing adverse effects on human health. The main epigenetic mechanisms are DNA methylation in gene promoter regions that regulate gene expression, histone tail modifications that regulate the accessibility of transcriptional machinery to genes, and microRNA activity (noncoding RNA able to modulate mRNA translation). The "double capacity" of arsenic to induce mutations and epimutations could be the main cause of arsenic-induced carcinogenesis. The aim of this review is to better clarify the mechanisms of the initiation and/or the promotion of arsenic-induced carcinogenesis in order to understand the best way to perform an early diagnosis and a prompt prevention that is the key point for protecting arsenic-exposed population. Studies on arsenic-exposed population should be designed in order to examine more comprehensively the presence and consequences of these genetic/epigenetic alterations.

  19. DNA Dosimetry Assessment for Sunscreen Genotoxic Photoprotection

    PubMed Central

    Schuch, André Passaglia; Lago, Juliana Carvalhães; Yagura, Teiti; Menck, Carlos Frederico Martins

    2012-01-01

    Background Due to the increase of solar ultraviolet radiation (UV) incidence over the last few decades, the use of sunscreen has been widely adopted for skin protection. However, considering the high efficiency of sunlight-induced DNA lesions, it is critical to improve upon the current approaches that are used to evaluate protection factors. An alternative approach to evaluate the photoprotection provided by sunscreens against daily UV radiation-induced DNA damage is provided by the systematic use of a DNA dosimeter. Methodology/Principal Findings The Sun Protection Factor for DNA (DNA-SPF) is calculated by using specific DNA repair enzymes, and it is defined as the capacity for inhibiting the generation of cyclobutane pyrimidine dimers (CPD) and oxidised DNA bases compared with unprotected control samples. Five different commercial brands of sunscreen were initially evaluated, and further studies extended the analysis to include 17 other products representing various formulations and Sun Protection Factors (SPF). Overall, all of the commercial brands of SPF 30 sunscreens provided sufficient protection against simulated sunlight genotoxicity. In addition, this DNA biosensor was useful for rapidly screening the biological protection properties of the various sunscreen formulations. Conclusions/Significance The application of the DNA dosimeter is demonstrated as an alternative, complementary, and reliable method for the quantification of sunscreen photoprotection at the level of DNA damage. PMID:22768281

  20. Genotoxic effects of zinc oxide nanoparticles

    NASA Astrophysics Data System (ADS)

    Heim, Julia; Felder, Eva; Tahir, Muhammad Nawaz; Kaltbeitzel, Anke; Heinrich, Ulf Ruediger; Brochhausen, Christoph; Mailänder, Volker; Tremel, Wolfgang; Brieger, Juergen

    2015-05-01

    The potential toxicity of nanoparticles has currently provoked public and scientific discussions, and attempts to develop generally accepted handling procedures for nanoparticles are under way. The investigation of the impact of nanoparticles on human health is overdue and reliable test systems accounting for the special properties of nanomaterials must be developed. Nanoparticular zinc oxide (ZnO) may be internalised through ambient air or the topical application of cosmetics, only to name a few, with unpredictable health effects. Therefore, we analysed the determinants of ZnO nanoparticle (NP) genotoxicity. ZnO NPs (15-18 nm in diameter) were investigated at concentrations of 0.1, 10 and 100 μg mL-1 using the cell line A549. Internalised NPs were only infrequently detectable by TEM, but strongly increased Zn2+ levels in the cytoplasm and even more in the nuclear fraction, as measured by atom absorption spectroscopy, indicative of an internalised zinc and nuclear accumulation. We observed a time and dosage dependent reduction of cellular viability after ZnO NP exposure. ZnCl2 exposure to cells induced similar impairments of cellular viability. Complexation of Zn2+ with diethylene triamine pentaacetic acid (DTPA) resulted in the loss of toxicity of NPs, indicating the relevant role of Zn2+ for ZnO NP toxicity. Foci analyses showed the induction of DNA double strand breaks (DSBs) by ZnO NPs and increased intracellular reactive oxygen species (ROS) levels. Treatment of the cells with the ROS scavenger N-acetyl-l-cysteine (NAC) resulted in strongly decreased intracellular ROS levels and reduced DNA damage. However, a slow increase of ROS after ZnO NP exposure and reduced but not quashed DSBs after NAC-treatment suggest that Zn2+ may exert genotoxic activities without the necessity of preceding ROS-induction. Our data indicate that ZnO NP toxicity is a result of cellular Zn2+ intake. Subsequently increased ROS-levels cause DNA damage. However, we found evidence for

  1. Monitoring genotoxic exposure in uranium miners

    SciTech Connect

    Sram, R.J.; Binkova, B.; Dobias, L.; Roessner, P.T.; Topinka, J.; Vesela, D.; Vesely, D.; Stejskalova, J.; Bavorova, H.; Rericha, V. )

    1993-03-01

    Recent data from deep uranium mines in Czechoslovakia indicated that in addition to radon daughter products, miners are also exposed to chemical mutagens. Mycotoxins were identified as a possible source of mutagenicity present in the mines. Various methods of biomonitoring were used to examine three groups of miners from different uranium mines. Cytogenetic analysis of peripheral lymphocytes, unscheduled DNA synthesis (UDS) in lymphocytes, and lipid peroxidation (LPO) in both plasma and lymphocytes were studied on 66 exposed miners and 56 controls. Throat swabs were taken from 116 miners and 78 controls. Significantly increased numbers of aberrant cells were found in all groups of miners, as well as decreased UDS values in lymphocytes and increased LPO plasma levels in comparison to controls. Molds were detected in throat swabs from 27% of miners, and 58% of these molds were embryotoxic. Only 5% of the control samples contained molds and none of them was embryotoxic. The following mycotoxins were isolated from miners' throat swab samples: rugulosin, sterigmatocystin, mycophenolic acid, brevianamid A, citreoviridin, citrinin, penicilic acid, and secalonic acid. These data suggest that mycotoxins are a genotoxic factor affecting uranium miners.

  2. Cells behaviors and genotoxicity on topological surface.

    PubMed

    Yang, N; Yang, M K; Bi, S X; Chen, L; Zhu, Z Y; Gao, Y T; Du, Z

    2013-08-01

    To investigate different cells behaviors and genotoxicity, which were driven by specific microenvironments, three patterned surfaces (pillars, wide grooves and narrow grooves) and one smooth surface were prepared by template-based technique. Vinculin is a membrane-cytoskeletal protein in focal adhesion plaques and associates with cell-cell and cell-matrix junctions, which can promote cell adhesion and spreading. The immunofluorescence staining of vinculin revealed that the narrow grooves patterned substrate was favorable for L929 cell adhesion. For cell multiplication, the narrow grooves surface was fitted for the proliferation of L929, L02 and MSC cells, the pillars surface was only in favor of L929 cells to proliferate during 7 days of cell cultivation. Cell genetic toxicity was evaluated by cellular micronuclei test (MNT). The results indicated that topological surfaces were more suitable for L929 cells to proliferate and maintain the stability of genome. On the contrary, the narrow grooves surface induced higher micronuclei ratio of L02 and MSC cells than other surfaces. With the comprehensive results of cell multiplication and MNT, it was concluded that the wide grooves surface was best fitted for L02 cells to proliferate and have less DNA damages, and the smooth surface was optimum for the research of MSC cells in vitro.

  3. Genotoxicity and carcinogenicity risk of carbon nanotubes.

    PubMed

    Toyokuni, Shinya

    2013-12-01

    Novel materials are often commercialized without a complete assessment of the risks they pose to human health because such assessments are costly and time-consuming; additionally, sometimes the methodology needed for such an assessment does not exist. Carbon nanotubes have the potential for widespread application in engineering, materials science and medicine. However, due to the needle-like shape and high durability of multiwalled carbon nanotubes (MWCNTs), concerns have been raised that they may induce asbestos-like pathogenicity when inhaled. Indeed, experiments in rodents supported this hypothesis. Notably, the genetic alterations in MWCNT-induced rat malignant mesothelioma were similar to those induced by asbestos. Single-walled CNTs (SWCNTs) cause mitotic disturbances in cultured cells, but thus far, there has been no report that SWCNTs are carcinogenic. This review summarizes the recent noteworthy publications on the genotoxicity and carcinogenicity of CNTs and explains the possible molecular mechanisms responsible for this carcinogenicity. The nanoscale size and needle-like rigid structure of CNTs appear to be associated with their pathogenicity in mammalian cells, where carbon atoms are major components in the backbone of many biomolecules. Publishing adverse events associated with novel materials is critically important for alerting people exposed to such materials. CNTs still have a bright future with superb economic and medical merits. However, appropriate regulation of the production, distribution and secondary manufacturing processes is required, at least to protect the workers.

  4. Assessment of hazardous wastes for genotoxicity

    SciTech Connect

    DeMarini, D.M.; Houk, V.S.

    1987-09-01

    The authors have evaluated a group of short-term bioassays to identify those that may be suitable for screening large numbers of diverse hazardous industrial wastes for genotoxicity. Fifteen wastes (and dichloromethane extracts of these wastes) from a variety of manufacturing processes were tested for mutagenicity in Salmonella typhimurium strains TA98 and TA100 with and without Aroclor 1254-induced rat-liver S9. Ten of these wastes were fed by gavage to F-344 male rats, and the raw urines were assayed for mutagenicity in the presence of beta-glucuronidase in strain TA98 with S9. Six of these urines were extracted by C18/methanol elution, incubated with beta-glucuronidase, and evaluated in strain TA98 with S9 and beta-glucuronidase. Fourteen of the wastes were examined for their ability to induce prophage lambda in Escherichia coli in a microsuspension assay. A second set of wastes, consisting of four industrial wastes, were evaluated in Salmonella and in a series of mammalian cell assays to measure mutagenicity, cytogenetic effects, and transformation.

  5. Genotoxicity of Graphene in Escherichia coli

    NASA Astrophysics Data System (ADS)

    Sharma, Ananya

    Rapid advances in nanotechnology necessitate assessment of the safety of nanomaterials in the resulting products and applications. One key nanomaterial attracting much interest in many areas of science and technology is graphene. Graphene is a one atom thick carbon allotrope arranged in a two-dimensional honeycomb lattice. In addition to being extremely thin, graphene has several extraordinary physical properties such as its exceptional mechanical strength, thermal stability, and high electrical conductivity. Graphene itself is relatively chemically inert and therefore pristine graphene must undergo a process called functionalization, which is combination of chemical and physical treatments that change the properties of graphene, to make it chemically active. Functionalization of graphene is of crucial importance as the end application of graphene depends on proper functionalization. In the field of medicine, graphene is currently a nanomaterial of high interest for building biosensors, DNA transistors, and probes for cancer detection. Despite the promising applications of graphene in several areas of biomedicine, there have been only few studies in recent years that focus on evaluating cytotoxicity of graphene on cells, and almost no studies that investigate how graphene exposure affects cellular genetic material. Therefore, in this study we used a novel approach to evaluate the genotoxicity, i.e., the effects of graphene on DNA, using Escherichia coli as a prokaryotic model organism.

  6. Mutagenicity and genotoxicity assessment of industrial wastewaters.

    PubMed

    Masood, Farhana; Malik, Abdul

    2013-10-01

    The genotoxicity of industrial wastewaters from Jajmau (Kanpur), was carried out by Ames Salmonella/microsome test, DNA repair-defective mutants, and Allium cepa anaphase-telophase test. Test samples showed maximum response with TA98 strain with and without metabolic activation. Amberlite resins concentrated wastewater samples were found to be more mutagenic as compared to those of liquid-liquid extracts (hexane and dichloromethane extracts). The damage in the DNA repair defective mutants in the presence of Amberlite resins concentrated water samples were found to be higher to that of liquid-liquid-extracted water samples at the dose level of 20 μl/ml culture. Among all the mutants, polA exhibited maximum decline with test samples. Mitotic index (MI) of root tip meristematic cells of A. cepa treated with 5, 10, 25, 50, and 100 % (v/v) wastewaters were significantly lower than the control. Complementary to the lower levels of MI, the wastewaters showed higher chromosomal aberration levels in all cases investigated.

  7. Genotoxicity of drinking water from Chao Lake

    SciTech Connect

    Liu, Q.; Jiao, Q.C.; Huang, X.M.; Jiang, J.P.; Cui, S.Q.; Yao, G.H.; Jiang, Z.R.; Zhao, H.K.; Wang, N.Y.

    1999-02-01

    Genotoxic activity appears to originate primarily from reactions of chlorine with humic substances in the source waters. Comparisons of extracts of settled versus chlorinated water have confirmed that chlorinating during water treatment produces mutagenic activity in the mutagenicity tests. Present work on XAD-2 extracts of raw, chlorinated (treated), and settled water from the Chao Lake region of China has involved a battery of mutagenicity assays for various genetic endpoints: the Salmonella test, the sister-chromatid exchange (SCE) induction in Chinese hamster lung (CHL) cells, and the micronucleus (MN) induction in the peripheral blood erythrocytes of silver carp. Extracts of raw and treated water but not the settled water are mutagenic in the Salmonella assay. On the other hand, extracts of three water samples show activity in the SCE and MN assays, especially the raw and treated water. These data show that contamination and chlorinating contribute mutagens to drinking water and suggest that the mammalian assays may be more sensitive for detecting mutagenicity in aquatic environment than the Salmonella test.

  8. Toxicity and genotoxicity of organic and inorganic nanoparticles to the bacteria Vibrio fischeri and Salmonella typhimurium.

    PubMed

    Lopes, I; Ribeiro, R; Antunes, F E; Rocha-Santos, T A P; Rasteiro, M G; Soares, A M V M; Gonçalves, F; Pereira, R

    2012-04-01

    The present work aimed at evaluating the toxicity and genotoxicity of two organic (vesicles composed of sodium dodecyl sulphate/didodecyl dimethylammonium bromide-SDS/DDAB and of monoolein and sodium oelate-Mo/NaO) and four inorganic (titanium oxide-TiO₂, silicon titanium-TiSiO₄, Lumidot-CdSe/ZnS, and gold nanorods) nanoparticles (NP), suspended in two aqueous media (Milli Q water and American Society for Testing and Materials (ASTM) hardwater), to the bacteria Vibrio fischeri (Microtox test) and Salmonella typhimurium-his⁻ (Ames test with strains TA98 and TA100). Aiming a better understanding of these biological responses physical and chemical characterization of the studied NP suspensions was carried out. Results denoted a high aggregation state of the NP in the aqueous suspensions, with the exception of SDS/DDAB and Mo/NaO vesicles, and of nanogold suspended in Milli Q water. This higher aggregation was consistent with the low values of zeta potential, revealing the instability of the suspensions. Regarding toxicity data, except for nano TiO₂, the tested NP significantly inhibited bioluminescence of V. fischeri. Genotoxic effects were only induced by SDS/DDAB and TiO₂ for the strain TA98. A wide range of toxicity responses was observed for the six tested NP, differing by more than 5 orders of magnitude, and suggesting different modes of action of the tested NP.

  9. METHYLATED ASIII COMPOUNDS AS POTENTIAL PROXIMATE/ULTIMATE GENOTOXIC METABOLITES OF INORGANIC ARSENIC

    EPA Science Inventory

    METHYLATED Asm COMPOUNDS AS POTENTIAL PROXIMATE/ULTIMATE GENOTOXIC METABOLITES OF INORGANIC ARSENIC.

    The methylation of inorganic arsenic has typically been viewed as a detoxification process. Genotoxicity tests have generally shown that arsenite has greater mutagenic p...

  10. METHYLATED ASIII COMPOUNDS AS POTENTIAL PROXIMATE/ULTIMATE GENOTOXIC METABOLITES OF INORGANIC ARSENIC

    EPA Science Inventory

    METHYLATED Asm COMPOUNDS AS POTENTIAL PROXIMATE/ULTIMATE GENOTOXIC METABOLITES OF INORGANIC ARSENIC.

    The methylation of inorganic arsenic has typically been viewed as a detoxification process. Genotoxicity tests have generally shown that arsenite has greater mutagenic p...

  11. Revision of OECD Guidelines for Genotoxicity Testing: Current Status and Next Steps

    EPA Science Inventory

    Over the past 30 years, assays have been developed to evaluate chemical genotoxicity. OECD Genotoxicity Test Guidelines (TG) describe assay procedures for regulatory safety testing. Since the last OECD TG revision (1997), there has been tremendous scientific and technological pro...

  12. Revision of OECD Guidelines for Genotoxicity Testing: Current Status and Next Steps

    EPA Science Inventory

    Over the past 30 years, assays have been developed to evaluate chemical genotoxicity. OECD Genotoxicity Test Guidelines (TG) describe assay procedures for regulatory safety testing. Since the last OECD TG revision (1997), there has been tremendous scientific and technological pro...

  13. Genotoxic and immunotoxic potential effects of selected psychotropic drugs and antibiotics on blue mussel (Mytilus edulis) hemocytes.

    PubMed

    Lacaze, Emilie; Pédelucq, Julie; Fortier, Marlène; Brousseau, Pauline; Auffret, Michel; Budzinski, Hélène; Fournier, Michel

    2015-07-01

    The potential toxicity of pharmaceuticals towards aquatic invertebrates is still poorly understood and sometimes controversial. This study aims to document the in vitro genotoxicity and immunotoxicity of psychotropic drugs and antibiotics on Mytilus edulis. Mussel hemocytes were exposed to fluoxetine, paroxetine, venlafaxine, carbamazepine, sulfamethoxazole, trimethoprim and erythromycin, at concentrations ranging from μg/L to mg/L. Paroxetine at 1.5 μg/L led to DNA damage while the same concentration of venlafaxine caused immunomodulation. Fluoxetine exposure resulted in genotoxicity, immunotoxicity and cytotoxicity. In the case of antibiotics, trimethoprim was genotoxic at 200 μg/L and immunotoxic at 20 mg/L whereas erythromycin elicited same detrimental effects at higher concentrations. DNA metabolism seems to be a highly sensitive target for psychotropic drugs and antibiotics. Furthermore, these compounds affect the immune system of bivalves, with varying intensity. This attests the relevance of these endpoints to assess the toxic mode of action of pharmaceuticals in the aquatic environment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Evaluation of Cytotoxicity and Genotoxicity of Acacia aroma Leaf Extracts

    PubMed Central

    Mattana, C. M.; Cangiano, M. A.; Alcaráz, L. E.; Sosa, A.; Escobar, F.; Sabini, C.; Sabini, L.; Laciar, A. L.

    2014-01-01

    Acacia aroma, native plant from San Luis, Argentina, is commonly used as antiseptic and for healing of wounds. The present study was conducted to investigate the in vitro cytotoxicity and genotoxicity of hot aqueous extract (HAE) and ethanolic extract (EE) of A. aroma. The cytotoxic activity was assayed by neutral red uptake assay on Vero cell. Cell treatment with a range from 100 to 5000 μg/mL of HAE and EE showed that 500 μg/mL and 100 μg/mL were the maximum noncytotoxic concentrations, respectively. The CC50 was 658 μg/mL for EE and 1020 μg/mL for HAE. The genotoxicity was tested by the single-cell gel electrophoresis comet assay. The results obtained in the evaluation of DNA cellular damage exposed to varied concentrations of the HAE showed no significant genotoxic effect at range of 1–20 mg/mL. The EE at 20 mg/mL showed moderate genotoxic effect related to the increase of the DNA percentage contained in tail of the comet; DNA was classified in category 2. At concentrations below 5 mg/mL, the results of cytotoxicity and genotoxicity of aqueous and ethanolic extracts of Acacia aroma guarantee the safety at cell and genomic level. However further studies are needed for longer periods including animal models to confirm the findings. PMID:25530999

  15. The influence of thermal desorption on genotoxicity of multipolluted soil.

    PubMed

    Bonnard, M; Devin, S; Leyval, C; Morel, J-L; Vasseur, P

    2010-07-01

    A multipolluted soil sampled from a former coking plant in Lorraine (France) was evaluated for its genotoxic effects on coelomocytes of the Eisenia fetida earthworm using the comet assay. The biological efficiency of thermal desorption of the contaminated soil was also investigated. The untreated polluted soil was shown to be genotoxic to earthworms. Although thermal desorption reduced the concentration of PAHs by 94% (Sigma(16 PAHs)=1846 and 101 mg/kg before and after thermal desorption, respectively), the treatment did not eliminate the genotoxicity of soil pollutants to earthworms but increased it. The concentration of non-volatile metals did not change after thermal desorption. Among metals found in the treated soil, cadmium, chromium and nickel could explain the genotoxicity of the contaminated soil after thermal desorption. The treatment could increase the bioavailability and genotoxicity of heavy metals, through a modification of the soil's organic matter, the speciation of heavy metals and their binding to organic matter. This study underlines the importance of measuring biological effects, in order to evaluate the risk associated with formerly contaminated soils and the efficiency of remediation.

  16. Combined genotoxicity of chlorinated products from tyrosine and benzophenone-4.

    PubMed

    Chang, Yangyang; Bai, Yaohui; Ji, Qinghua; Huo, Yang; Liu, Huijuan; Crittenden, John C; Qu, Jiuhui

    2017-01-15

    The toxicity of disinfection by-products (DBPs) from a single precursor was studied intensively. Here we examined the genotoxicity when two precursors (tyrosine (Tyr) and benzophenone-4 (BP-4)) were chlorinated together and separately. We sought to examine whether the genotoxicity of the mixture (GCM) could be estimated from the sum of the genotoxicities of the individual precursors (GCI), which were chlorinated separately. We determined the genotoxicity using the SOS/umu test. The results revealed that GCM was not identical to GCI. The difference in genotoxicity between GCM and GCI (GΔ) was observed to decrease with increasing pH. GCM was higher than GCI (GΔ>0) at pH 5.0-6.1, and lower than GCI (GΔ<0) at pH 6.3-8.0. We found that nitrogen-containing DBPs played a dominant role in determining GCM and GCI. We propose that the total organic nitrogen (TON) ratio, TON(chlorinatedmixture)/TON(thesumofchlorinatedindividuals), is useful to estimate GΔ.

  17. Genotoxic risk in rubber manufacturing industry: a systematic review.

    PubMed

    Bolognesi, Claudia; Moretto, Angelo

    2014-10-15

    A large body of evidence from epidemiological studies among workers employed in the rubber manufacturing industry has indicated a significant excess cancer risk in a variety of sites. The International Agency for Research on Cancer has recently classified the "Occupational exposures in the rubber-manufacturing industry" as carcinogenic to humans (Group 1). A genotoxic mechanism for the increased cancer risk was suggested on the basis of the evidence from the scientific literature. Exposure assessment studies have shown that workers in the rubber manufacturing industry may be exposed to different airborne carcinogenic and/or genotoxic chemicals, such as certain aromatic amines, polycyclic aromatic hydrocarbons, N-nitrosamines, although the available information does not allow to establish a causal association of cancer or genotoxic risk with particular substances/classes of chemicals or specific jobs. The aim of this paper is to critically evaluate, by conducting a systematic review, the available biomonitoring studies using genotoxicity biomarkers in rubber manufacturing industry. This systematic review suggests that a genotoxic hazard may still be present in certain rubber manufacturing industries. A quantitative risk assessment needs further studies addressing the different, processes and chemicals in the rubber manufacturing industries.

  18. Measurements of the ablation-front trajectory and low-mode nonuniformity in direct-drive implosions using x-ray self-emission shadowgraphy

    SciTech Connect

    Michel, D. T.; Davis, A. K.; Armstrong, W.; Bahr, R.; Epstein, R.; Goncharov, V. N.; Hohenberger, M.; Igumenshchev, I. V.; Jungquist, R.; Meyerhofer, D. D.; Radha, P. B.; Sangster, T. C.; Sorce, C.; Froula, D. H.

    2015-07-08

    Self-emission x-ray shadowgraphy provides a method to measure the ablation-front trajectory and low-mode nonuniformity of a target imploded by directly illuminating a fusion capsule with laser beams. The technique uses time-resolved images of soft x-rays (> 1 keV) emitted from the coronal plasma of the target imaged onto an x-ray framing camera to determine the position of the ablation front. Methods used to accurately measure the ablation-front radius (${\\it\\delta}R=\\pm 1.15~{\\rm\\mu}\\text{m}$), image-to-image timing (${\\it\\delta}({\\rm\\Delta}t)=\\pm 2.5$ ps) and absolute timing (${\\it\\delta}t=\\pm 10$ ps) are presented. Angular averaging of the images provides an average radius measurement of${\\it\\delta}(R_{\\text{av}})=\\pm 0.15~{\\rm\\mu}\\text{m}$and an error in velocity of${\\it\\delta}V/V=\\pm 3\\%$. This technique was applied on the Omega Laser Facility and the National Ignition Facility.

  19. Direct aqueous determination of glyphosate and related compounds by liquid chromatography/tandem mass spectrometry using reversed-phase and weak anion-exchange mixed-mode column.

    PubMed

    Hao, Chunyan; Morse, David; Morra, Franca; Zhao, Xiaoming; Yang, Paul; Nunn, Brian

    2011-08-19

    Analysis of the broad-spectrum herbicide glyphosate and its related compounds is quite challenging. Tedious and time-consuming derivatization is often required for these substances due to their high polarity, high water solubility, low volatility and molecular structure which lacks either a chromophore or fluorophore. A novel liquid chromatography/tandem mass spectrometry (LC/MS-MS) method has been developed for the determination of glyphosate, aminomethylphosphonic acid (AMPA) and glufosinate using a reversed-phase and weak anion-exchange mixed-mode Acclaim® WAX-1 column. Aqueous environmental samples are directly injected and analyzed in 12 min with no sample concentration or derivatization steps. Two multiple reaction monitoring (MRM) channels are monitored in the method for each target compound to achieve true positive identification, and ¹³C, ¹⁵N-glyphosate is used as an internal standard to carry out isotope dilution mass spectrometric (IDMS) measurement for glyphosate. The instrument detection limits (IDLs) for glyphosate, AMPA and glufosinate are 1, 2 and 0.9 μg/L, respectively. Linearity of the detector response with a minimum coefficient of determination (R² value (R² > 0.995) was demonstrated in the range of ∼10 to 10³ μg/L for each analytes. Spiked drinking water, surface water and groundwater samples were analyzed using this method and the average recoveries of analytes in three matrices ranged from 77.0 to 102%, 62.1 to 101%, 66.1 to 93.7% while relative standard deviation ranged from 6.3 to 10.2%, 2.7 to 14.8%, 2.9 to 10.7%, respectively. Factors that may affect method performance, such as metal ions, sample preservation, and storage time, are also discussed. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

  20. Cost Analysis of Direct versus Indirect and Individual versus Group Modes of Manual-Based Speech-and-Language Therapy for Primary School-Age Children with Primary Language Impairment

    ERIC Educational Resources Information Center

    Dickson, Kirstin; Marshall, Marjorie; Boyle, James; McCartney, Elspeth; O'Hare, Anne; Forbes, John

    2009-01-01

    Background: The study is the first within trial cost analysis of direct versus indirect and individual versus group modes of speech-and-language therapy for children with primary language impairment. Aims: To compare the short-run resource consequences of the four interventions alongside the effects achieved measured by standardized scores on a…

  1. Cost Analysis of Direct versus Indirect and Individual versus Group Modes of Manual-Based Speech-and-Language Therapy for Primary School-Age Children with Primary Language Impairment

    ERIC Educational Resources Information Center

    Dickson, Kirstin; Marshall, Marjorie; Boyle, James; McCartney, Elspeth; O'Hare, Anne; Forbes, John

    2009-01-01

    Background: The study is the first within trial cost analysis of direct versus indirect and individual versus group modes of speech-and-language therapy for children with primary language impairment. Aims: To compare the short-run resource consequences of the four interventions alongside the effects achieved measured by standardized scores on a…

  2. In vivo genotoxic interactions among three phenolic benzene metabolites.

    PubMed

    Marrazzini, A; Chelotti, L; Barrai, I; Loprieno, N; Barale, R

    1994-11-01

    Three benzene metabolites, hydroquinone (HQ), cathecol (CAT) and phenol (PHE) were studied to define their possible interaction in inducing micronuclei (Mn) in mouse bone marrow polychromatic erythrocytes (PCEs). HQ and CAT, administered separately, induced Mn while PHE showed no genotoxic effects. Binary and ternary mixtures of two or three metabolites gave different results, causing considerable increase or decrease in Mn induction. HQ and PHE, in binary mixtures, as well as PHE and CAT, increased Mn synergistically, while HQ and CAT interacted negatively. The genotoxicity of ternary mixtures was mainly the consequence of two metabolites: HQ and CAT. The maximal effect obtained is far below the induction of Mn consequent to benzene treatment. These data suggest that toxic and genotoxic effects of benzene alone could be the result of more complex interactions among these and other metabolites.

  3. Review of the genotoxic properties of chlorpromazine and related phenothiazines.

    PubMed

    Gocke, E

    1996-10-01

    Chlorpromazine and related phenothiazine drugs have been used in human and veterinary medications for more than 40 years, predominantly as psychotropic agents. Genotoxicity reports are in many cases of relatively antiquated test design. Overall there appears to be no genotoxic activity associated with these drugs when tested under standard conditions. Limited evidence for the potential to form mutagenic nitrosation products and some indication for the ability to modulate the genotoxic action of various mutagens have been presented in the literature. UV irradiation of chlorpromazine and other chlorinated derivatives produces reactive free radicals which possess DNA damaging properties. Induction of gene mutation and chromosomal aberrations have been observed in appropriately designed photomutagenesis experiments. Enhancement but also reduction of UV induced skin tumour formation by chlorpromazine have been found. The decisive factor for the discrepant actions has not been recognized. It is clearly advisable to avoid extensive UV exposure during therapy with these drugs.

  4. Genotoxicity of Superparamagnetic Iron Oxide Nanoparticles in Granulosa Cells

    PubMed Central

    Pöttler, Marina; Staicu, Andreas; Zaloga, Jan; Unterweger, Harald; Weigel, Bianca; Schreiber, Eveline; Hofmann, Simone; Wiest, Irmi; Jeschke, Udo; Alexiou, Christoph; Janko, Christina

    2015-01-01

    Nanoparticles that are aimed at targeting cancer cells, but sparing healthy tissue provide an attractive platform of implementation for hyperthermia or as carriers of chemotherapeutics. According to the literature, diverse effects of nanoparticles relating to mammalian reproductive tissue are described. To address the impact of nanoparticles on cyto- and genotoxicity concerning the reproductive system, we examined the effect of superparamagnetic iron oxide nanoparticles (SPIONs) on granulosa cells, which are very important for ovarian function and female fertility. Human granulosa cells (HLG-5) were treated with SPIONs, either coated with lauric acid (SEONLA) only, or additionally with a protein corona of bovine serum albumin (BSA; SEONLA-BSA), or with dextran (SEONDEX). Both micronuclei testing and the detection of γH2A.X revealed no genotoxic effects of SEONLA-BSA, SEONDEX or SEONLA. Thus, it was demonstrated that different coatings of SPIONs improve biocompatibility, especially in terms of genotoxicity towards cells of the reproductive system. PMID:26540051

  5. Evaluation of subchronic genotoxic potential of Swarna Makshika Bhasma.

    PubMed

    Savalgi, Pavan B; Patgiri, Biswajyoti; Thakkar, Jalaram H; Ravishankar, B; Gupta, Varun B

    2012-07-01

    Extremely diminutive published information is available on the mutagenic activity of Ayurvedic Bhasmas. Genotoxicity of few Bhasmas were reported on single maximum dose, but no reference is available on the sub-chronic level. Hence the present study was carried to generate and evaluate genotoxic potentials of Swarna Makshika Bhasma (mineral preparation) administered at therapeutic dose for 14 days. Chromosomal aberrations and abnormal sperm assay parameters were taken in this study. Cyclophosphamide (CP) was taken as positive group and results were compared. The results revealed a lack of generation of structural deformity in above parameters by tested drugs compared to CP treated group. Observed data indicate that the Bhasmas tested were non-genotoxic under the experimental conditions.

  6. 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.

  7. Ecotoxicity and genotoxicity of cyclophosphamide, ifosfamide, their metabolites/transformation products and their mixtures.

    PubMed

    Česen, Marjeta; Eleršek, Tina; Novak, Matjaž; Žegura, Bojana; Kosjek, Tina; Filipič, Metka; Heath, Ester

    2016-03-01

    Cyclophosphamide (CP) and ifosfamide (IF) are commonly used cytostatic drugs that repress cell division by interaction with DNA. The present study investigates the ecotoxicity and genotoxicity of CP, IF, their human metabolites/transformation products (TPs) carboxy-cyclophosphamide (CPCOOH), keto-cyclophosphamide (ketoCP) and N-dechloroethyl-cyclophosphamide (NdCP) as individual compounds and as mixture. The two parent compounds (CP and IF), at concentrations up to 320 mg L(-1), were non-toxic towards the alga Pseudokirchneriella subcapitata and cyanobacterium Synecococcus leopoliensis. Further ecotoxicity studies of metabolites/TPs and a mixture of parent compounds and metabolites/TPs performed in cyanobacteria S. leopoliensis, showed that only CPCOOH (EC50 = 17.1 mg L(-1)) was toxic. The measured toxicity (EC50 = 11.5 mg L(-1)) of the mixture was lower from the toxicity predicted by concentration addition model (EC50 = 21.1 mg L(-1)) indicating potentiating effects of the CPCOOH toxicity. The SOS/umuC assay with Salmonella typhimurium revealed genotoxic activity of CP, CPCOOH and the mixture in the presence of S9 metabolic activation. Only CPCOOH was genotoxic also in the absence of metabolic activation indicating that this compound is a direct acting genotoxin. This finding is of particular importance as in the environment such compounds can directly affect DNA of non-target organisms and also explains toxicity of CPCOOH against cyanobacteria S. leopoliensis. The degradation study with UV irradiation of samples containing CP and IF showed efficient degradation of both compounds and remained non-toxic towards S. leopoliensis, suggesting that no stable TPs with adverse effects were formed. To our knowledge, this is the first study describing the ecotoxicity and genotoxicity of the commonly used cytostatics CP and IF, their known metabolites/TPs and their mixture. The results indicate the importance of toxicological evaluation and monitoring of

  8. Single phase bi-directional AC-DC converter with reduced passive components size and common mode electro-magnetic interference

    DOEpatents

    Mi, Chris; Li, Siqi

    2017-01-31

    A bidirectional AC-DC converter is presented with reduced passive component size and common mode electro-magnetic interference. The converter includes an improved input stage formed by two coupled differential inductors, two coupled common and differential inductors, one differential capacitor and two common mode capacitors. With this input structure, the volume, weight and cost of the input stage can be reduced greatly. Additionally, the input current ripple and common mode electro-magnetic interference can be greatly attenuated, so lower switching frequency can be adopted to achieve higher efficiency.

  9. Genotoxicity and cytotoxicity of 2-hydroxyethyl methacrylate.

    PubMed

    Pawlowska, Elzbieta; Poplawski, Tomasz; Ksiazek, Dominika; Szczepanska, Joanna; Blasiak, Janusz

    2010-02-01

    Resin-based methacrylate materials are widely used in restorative dentistry. They are viscous substances that are converted into solid material via polymerization. This process, however, may be incomplete, leading to the release of monomers into the oral cavity and the pulp, which can be reached through the dentin micro-channels. This opens the opportunity for the monomers to reach the bloodstream. Monomers can reach concentrations in the millimolar range, high enough to cause cellular damage, so it is justified to study their potential toxic effects. In the present work we investigated the cytotoxicity and genotoxicity of 2-hydroxyethyl methacrylate (HEMA) in human peripheral blood lymphocytes and A549 lung-tumour cells. HEMA at concentrations up to 10mM neither affected the viability of the cells nor interacted with isolated plasmid DNA during a 1h exposure. However, HEMA induced concentration-dependent DNA damage in lymphocytes, as assessed by alkaline and pH 12.1 versions of the comet assay. HEMA did not cause double-strand breaks, as assessed by the neutral version of the comet assay and pulsed-field gel electrophoresis. The use of DNA repair enzymes, spin traps and vitamin C produced results suggesting that HEMA induced oxidative modifications to DNA bases. DNA damage caused by HEMA at 10mM was removed within 120min. HEMA induced apoptosis in a concentration-dependent manner and caused cell-cycle delay at the G0/G1-checkpoint. Methylglycol chitosan displayed a protective effect against the DNA-damaging action of HEMA. The results obtained in this study suggest that HEMA induces adverse biological effects, mainly via reactive oxygen species, which can lead to DNA damage, apoptosis and cell-cycle delay. Chitosan and its derivatives can be considered as additional components of dental restoration to decrease the harmful potency of HEMA.

  10. Single Low-Dose Ionizing Radiation Induces Genotoxicity in Adult Zebrafish and its Non-Irradiated Progeny.

    PubMed

    Lemos, J; Neuparth, T; Trigo, M; Costa, P; Vieira, D; Cunha, L; Ponte, F; Costa, P S; Metello, L F; Carvalho, A P

    2017-02-01

    This study investigated to what extent a single exposure to low doses of ionizing radiation can induce genotoxic damage in irradiated adult zebrafish (Danio rerio) and its non-irradiated F1 progeny. Four groups of adult zebrafish were irradiated with a single dose of X-rays at 0 (control), 100, 500 and 1000 mGy, respectively, and couples of each group were allowed to reproduce following irradiation. Blood of parental fish and whole-body offspring were analysed by the comet assay for detection of DNA damage. The level of DNA damage in irradiated parental fish increased in a radiation dose-dependent manner at day 1 post-irradiation, but returned to the control level thereafter. The level of DNA damage in the progeny was directly correlated with the parental irradiation dose. Results highlight the genotoxic risk of a single exposure to low-dose ionizing radiation in irradiated individuals and also in its non-irradiated progeny.

  11. The Cytotoxicity and Genotoxicity of Hexavalent Chromium in Steller Sea Lion Lung Fibroblasts Compared to Human Lung Fibroblasts

    PubMed Central

    Wise, John Pierce; Wise, Sandra S.; Holmes, Amie L.; LaCerte, Carolyne; Shaffiey, Fariba; Aboueissa, AbouEl-Makarim

    2010-01-01

    In this study we directly compared soluble and particulate chromate cytotoxicity and genotoxicity in human (Homo sapiens) and sea lion (Eumetopias jubatus) lung fibroblasts. Our results show that hexavalent chromium induces increased cell death and chromosome damage in both human and sea lion cells with increasing intracellular chromium ion levels. The data further indicate that both sodium chromate and lead chromate are less cytotoxic and genotoxic to sea lion cells than human cells, based on administered dose. Differences in chromium ion uptake explained some but not all of the reduced amounts of sodium chromate-induced cell death. By contrast, uptake differences could explain the differences in sodium chromate-induced chromosome damage and particulate chromate-induced toxicity. Altogether they indicate that while hexavalent chromium induces similar toxic effects in sea lion and human cells, there are different mechanisms underlying the toxic outcomes. PMID:20211760

  12. DNA adductomics to study the genotoxic effects of red meat consumption with and without added animal fat in rats.

    PubMed

    Hemeryck, Lieselot Y; Van Hecke, Thomas; Vossen, Els; De Smet, Stefaan; Vanhaecke, Lynn

    2017-09-01

    Digestion of red and processed meat has been linked to the formation of genotoxic N-nitroso compounds (NOCs) and lipid peroxidation products (LPOs) in the gut. In this study, rats were fed a meat based diet to compare the possible genotoxic effects of red vs. white meat, and the interfering role of dietary fat. To this purpose, liver, duodenum and colon DNA adductomes were analyzed with UHPLC-HRMS. The results demonstrate that the consumed meat type alters the DNA adductome; the levels of 22 different DNA adduct types significantly increased upon the consumption of beef (compared to chicken) and/or lard supplemented beef or chicken. Furthermore, the chemical constitution of the retrieved DNA adducts hint at a direct link with an increase in NOCs and LPOs upon red (and processed) meat digestion, supporting the current hypotheses on the causal link between red and processed meat consumption and the development of colorectal cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Antimutagenic Effect of Dioscorea Pentaphylla on Genotoxic Effect Induced By Methyl Methanesulfonate in the Drosophila Wing Spot Test

    PubMed Central

    Prakash, G.; Hosetti, B. B.; Dhananjaya, B. L.

    2014-01-01

    Objectives: Plants as dietary sources are known to have several chemoprotective agents. Dioscorea pentaphylla is an important medicinal plant, which is often used as edible food. This study was undertaken to evaluate the antigenotoxic potential of D. pentaphylla extracts on the genotoxic effect induced by methyl methanesulfonate (MMS) in the Drosophila wing spot test. Materials and Methods: The somatic mutation and recombination test (SMART) was carried out in Drosophila melanogaster. In transheterogyous larvae, multiple wing hair (mwh 3-0.3) and flare (flr3-38.8) genes were used as markers of the extent of mutagenicity. Results: It was observed thatall the three extracts (petroleum ether, choloroform, and ethyl alcohol) in the combined treatment had significantly inhibited the effect of MMS-induced genotoxic effects. When compared to others, the ethanol extract showed a very significant antimutagenic activity. Conclusion: The compounds that are present in the extracts may directly interact with the methyl radical groups of MMS and inactivate them by chemical reaction. It is also possible that the compounds in the extract compete to interact with the nucleophilic sites in deoxyribonucleic acid (DNA), thus altering the binding of the mutagen to these sites. Although our results indicate that the compounds present in the extracts may directly interact with the methyl radical groups of MMS and inactivate them by chemical reaction, it may also be quite interesting to investigate through the other different mechanisms by which D. pentaphylla could interfere in vivo on the effect of genotoxic agents. PMID:25948963

  14. Genetic toxicity assessment: employing the best science for human safety evaluation part VI: when salt and sugar and vegetables are positive, how can genotoxicity data serve to inform risk assessment?

    PubMed

    Pottenger, Lynn H; Bus, James S; Gollapudi, B Bhaskar

    2007-08-01

    This opinion piece examines the current approaches in the design and evaluation of genotoxicity data and recommends an alternative that would provide information that could be more useful to human risk assessment. It is suggested that genotoxicity studies, both in vitro and in vivo, be designed similar to other traditional toxicology studies, such that a dose-response relationship is characterized, including identification of a "no-observed-adverse-effect-level" dose. It is further suggested that genotoxicity tests should no longer be designed or interpreted in isolation but should be examined in the context of other available data including toxicokinetics, mechanism of genotoxicity, and relevant exposure information. The answer to improving genetic toxicology testing does not lie in coming up with better, "more sensitive" genotoxicity test systems but rather in the incorporation of contextual improvements in both the experimental design and the interpretation of data collected using the current models. Such a strategy will better position the toxicology and risk assessment communities to cope with the current intellectually uncomfortable dichotomy that directs disproportionate scientific resource to addressing genetic toxicity findings of anthropogenic substances, regardless of dose-exposure context, while at the same time ignoring the plethora and comparatively large amounts of genotoxic and toxic substances that are inescapably present in what are otherwise regarded as healthy foods (salt, sugar, and vegetables).

  15. An evaluation of the genotoxic potential of glyphosate.

    PubMed

    Li, A P; Long, T J

    1988-04-01

    The potential genotoxicity of glyphosate, the active ingredient in Roundup herbicide, was tested in a variety of well-established in vitro and in vivo assays including the Salmonella typhimurium and Escherichia coli WP-2 reversion assays, recombination (rec-assay) with Bacillus subtilis. Chinese hamster ovary cell gene mutation assay at the hypoxanthine/guanine phosphoribosyl transferase gene locus, hepatocyte primary culture/DNA repair assay, and in vivo cytogenetics assay in rat bone marrow. No genotoxic activity was observed in the assays performed. The data suggest that glyphosate should not pose a genetic risk to man.

  16. Genotoxicity of ibuprofen in mouse bone marrow cells in vivo.

    PubMed

    Tripathi, Rina; Pancholi, Shyam S; Tripathi, Pankaj

    2012-10-01

    Genotoxicity of ibuprofen was evaluated by employing the mouse in vivo chromosomal aberration (CA) test. Ibuprofen administered orally at doses of 10, 20, 40, and 60 mg/kg body weight to mice resulted in mitotic depression and induction of CAs. A dose-related decrease in mitotic index (MI) and an increase in the frequencies of chromosomal aberrations per cell (CAs/cell) were recorded in bone marrow cells. However, a statistically significant reduction in MI and an increase in CAs/cell were found for both the higher doses. The results obtained indicate that ibuprofen is capable of inducing dose-dependent genotoxicity in bone marrow cells of mice.

  17. Is the Comet Assay a Sensitive Procedure for Detecting Genotoxicity?

    PubMed Central

    Kawaguchi, Satomi; Nakamura, Takanori; Yamamoto, Ayumi; Honda, Gisho; Sasaki, Yu F.

    2010-01-01

    Although the Comet assay, a procedure for quantitating DNA damage in mammalian cells, is considered sensitive, it has never been ascertained that its sensitivity is higher than the sensitivity of other genotoxicity assays in mammalian cells. To determine whether the power of the Comet assay to detect a low level of genotoxic potential is superior to those of other genotoxicity assays in mammalian cells, we compared the results of Comet assay with those of micronucleus test (MN test). WTK1 human lymphoblastoid cells were exposed to methyl nitrosourea (MNU), ethyl nitrosourea (ENU), methyl methanesulfonate (MMS), ethyl methanesulfonate (EMS), bleomycin (BLM), or UVC. In Comet assay, cells were exposed to each mutagen with (Comet assay/araC) and without (Comet assay) DNA repair inhibitors (araC and hydroxyurea). Furthermore, acellular Comet assay (acellular assay) was performed to determine how single-strand breaks (SSBs) as the initial damage contributes to DNA migration and/or to micronucleus formation. The lowest genotoxic dose (LGD), which is defined as the lowest dose at which each mutagen causes a positive response on each genotoxicity assay, was used to compare the power of the Comet assay to detect a low level of genotoxic potential and that of MN test; that is, a low LGD indicates a high power. Results are summarized as follows: (1) for all mutagens studied, LGDs were MN test ≦ Comet assay; (2) except for BLM, LGDs were Comet assay/araC ≦ MN test; (3) except for UVC and MNU, LGDs were acellular assay ≦ Comet assay/araC ≦ MN test ≦ Comet assay. The following is suggested by the present findings: (1) LGD in the Comet assay is higher than that in MN test, which suggests that the power of the MN test to detect a low level of genotoxic potential is superior to that of the Comet assay; (2) for the studied mutagens, all assays were able to detect all mutagens correctly, which suggests that the sensitivity of the Comet assay and that of the MN test were

  18. Current Studies into the Genotoxic Effects of Nanomaterials

    PubMed Central

    Ng, Cheng-Teng; Li, Jasmine J.; Bay, Boon-Huat; Yung, Lin-Yue Lanry

    2010-01-01

    Nanotechnology has created opportunities for engineers to manufacture superior and more efficient devices and products. Nanomaterials (NMs) are now widely used in consumer products as well as for research applications. However, while the lists of known toxic effects of nanomaterials and nanoparticles (NPs) continue to grow, there is still a vast gap in our knowledge about the genotoxicity of NMs. In this paper, we highlight some NMs of interest and discuss the current in vivo and in vitro studies into genotoxic effects of NMs. PMID:20936181

  19. Narrow linewidth, single mode 3 kW average power from a directly diode pumped ytterbium-doped low NA fiber amplifier.

    PubMed

    Beier, F; Hupel, C; Nold, J; Kuhn, S; Hein, S; Ihring, J; Sattler, B; Haarlammert, N; Schreiber, T; Eberhardt, R; Tünnermann, A

    2016-03-21

    We report on a newly designed and fabricated ytterbium-doped large mode area fiber with an extremely low NA (~0.04) and related systematic investigations on fiber parameters that crucially influence the mode instability threshold. The fiber is used to demonstrate a narrow linewidth, continuous wave, single mode fiber laser amplifier emitting a maximum output power of 3 kW at a wavelength of 1070 nm without reaching the mode-instability threshold. A high slope efficiency of 90 %, excellent beam quality, high temporal stability, and an ASE suppression of 70 dB could be reached with a signal linewidth of only 170 pm.

  20. Genotoxicity and cytotoxicity of cisplatin treatment combined with anaesthetics on EAT cells in vivo.

    PubMed

    Brozovic, Gordana; Orsolic, Nada; Knezevic, Fabijan; Horvat Knezevic, Anica; Benkovic, Vesna; Sakic, Katarina; Hrgovic, Zlatko; Bendelja, Kreso; Fassbender, Walter J

    2009-06-01

    In this study, DNA damage in tumour cells, as well as irreversible cell damage leading to apoptosis induced in vivo by the combined application of cisplatin and inhalation anaesthetics, was investigated. The genotoxicity of anaesthetics on Ehrlich ascites tumour (EAT) cells of mice, alone or in combined application with cisplatin, was estimated by using the alkaline comet assay. The percentage of EAT cell apoptosis was quantified by flow cytometry. Groups of EAT-bearing mice were (i) treated intraperitoneally with cisplatin, (ii) exposed to repeated anaesthesia with inhalation anaesthetic, and (iii) subjected to combined treatment of exposure to anaesthetics after cisplatin for 3 days. Sevoflurane, halothane and isoflurane caused strong genotoxic effects on tumour cells in vivo. The tested anaesthetics alone showed no direct effect on programmed cell death although sevoflurane and especially halothane decreased the number of living EAT cells in peritoneal cavity lavage. Repeated anaesthesia with isoflurane had stimulatory effects on EAT cell proliferation and inhibited tumour cell apoptosis (6.11%), compared to the control group (10.26%). Cisplatin caused massive apoptosis of EAT cells (41.14%) and decreased the number of living EAT cells in the peritoneal cavity. Combined cisplatin and isoflurane treatment additionally increased EAT cell apoptosis to 51.32%. Combined treatment of mice with cisplatin and all anaesthetics increased the number of living tumour cells in the peritoneal cavity compared to cisplatin treatment of mice alone. These results suggest that the inhalation of anaesthetics may protect tumour cells from the cisplatin-induced genotoxic and cytotoxic effects. Copyright 2009 S. Karger AG, Basel.

  1. Genotoxic properties of cyclopentenone prostaglandins and the onset of glutathione depletion.

    PubMed

    Solecki, Gergely Morten; Groh, Isabel Anna Maria; Kajzar, Julia; Haushofer, Carolin; Scherhag, Anne; Schrenk, Dieter; Esselen, Melanie

    2013-02-18

    Prostaglandins are endogenous mediators formed from arachidonic acid by cyclooxygenases and prostaglandin synthases during inflammatory processes. The five-membered ring can be dehydrated, and α,β-unsaturated cyclopentenone PGs (cyPGs) are generated. Recent studies have been focused on their potential pharmacological use against inflammation and cancer. However, little is known so far about possible adverse health effects of cyPGs. We addressed the question whether selected cyPGs at a concentration range of 0.1-10 μM exhibit mutagenic and genotoxic properties in the hamster lung fibroblast V79 cell line and whether these effects are accompanied by a depletion of intracellular glutathione (GSH). The cyPGs 15-deoxy-Δ12,14-prostaglandin J2 (15dPGJ2) and prostaglandin A2 (PGA2) significantly induced DNA damage in V79 cells after 1 h of incubation. Furthermore, a more pronounced increase in formamidopyrimidine-DNA glycosylase (FPG) sensitive sites, indicative of oxidative DNA-damage, was observed. The findings on DNA-damaging properties were supported by our results that 15dPGJ(2) acts as an aneugenic agent which induces the amount of kinetochore positive micronuclei associated with an increase of apoptosis. The strong potency of cyPGs to rapidly bind GSH measured in a chemical assay and to significantly reduce the GSH level after only 1 h of incubation may contribute to the observed oxidative DNA strand breaks, whereas directly induced oxidative stress via reactive oxygen species could be excluded. However, after an extended incubation time of 24 h no genotoxicity could be measured, this may contribute to the lack of mutagenicity in the hypoxanthine phosphorybosyltransferase (HPRT) assay. In conclusion, potential in vitro genotoxicity of cyPG and a strong impact on GSH homeostasis have been demonstrated, which may be involved in carcinogenesis mediated by chronic inflammation.

  2. Genotoxicity induced by monomethylarsonous acid (MMA(+3)) in mouse thymic developing T cells.

    PubMed

    Xu, Huan; Medina, Sebastian; Lauer, Fredine T; Douillet, Christelle; Liu, Ke Jian; Stýblo, Miroslav; Burchiel, Scott W

    2017-09-05

    Drinking water exposure to arsenic is known to cause immunotoxicity. Our previous studies demonstrated that monomethylarsonous acid (MMA(+3)) was the major arsenical species presented in mouse thymus cells after a 30 d drinking water exposure to arsenite (As(+3)). MMA(+3) was also showed to be ten times more toxic than As(+3) on the suppression of IL-7/STAT5 signaling in the double negative (DN) thymic T cells. In order to examine the genotoxicity induced by low to moderate doses of MMA(+3), isolated mouse thymus cells were treated with 5, 50 and 500nMMMA(+3) for 18h in vitro. MMA(+3) suppressed the proliferation of thymus cells in a dose dependent manner. MMA(+3) at 5nM induced DNA damage in DN not double positive (DP) cells. Differential sensitivity to double strand breaks and reactive oxygen species generation was noticed between DN and DP cells at 50nM, but the effects were not seen at the high dose (500nM). A stronger apoptotic effect induced by MMA(+3) was noticed in DN cells than DP cells at low doses (5 and 50nM), which was negated by the strong apoptosis induction at the high dose (500nM). Analysis of intracellular MMA(+3) concentrations in DN and DP cells, revealed that more MMA(+3) accumulated in the DN cells after the in vitro treatment. Collectively, these results suggested that MMA(+3) could directly induce strong genotoxicity in the early developing T cells in the thymus. The DN cells were much more sensitive to MMA(+3) induced genotoxicity and apoptosis than DP cells, probably due to the higher intracellular levels of MMA(+3). Copyright © 2017 Elsevier B.V. All rights reserved.

  3. In vitro gene expression data supporting a DNA non-reactive genotoxic mechanism for ochratoxin A

    SciTech Connect

    Arbillaga, Leire; Lopez de Cerain, Adela . E-mail: acerain@unav.es

    2007-04-15

    Ochratoxin A (OTA) is a mycotoxin often found in cereals and agricultural products. There is unequivocal evidence of renal carcinogenicity of OTA in male rats, although the mechanism of action is unknown. At present, available data support an epigenetic mechanism (DNA non-reactive) resulting from oxidative stress and cytotoxicity, because a direct OTA interaction with DNA has not been demonstrated. Genotoxic mechanism (DNA-reactive vs. DNA non-reactive) may have implications on human risk assessment. Therefore, the aim of the present work was to identify biological pathways modulated by OTA in vitro in a human renal cell line (HK-2) to contribute to the elucidation of the mechanism of OTA toxicity. For that purpose, cells were exposed to 50 {mu}M OTA during 6 and 24 h, and gene expression profiles were analyzed using Affymetrix Human Genome U133 A 2.0 Gene Chips. Under the same experimental conditions, genotoxicity was evaluated by the modified comet assay using FPG and Endo III to detect oxidative DNA damage, and intracellular ROS level by the H{sub 2}DCF assay. After 6 h, with slight cytotoxicity (83% survival), genes involved in mitochondrial electron transport chain were up-regulated; and after 24 h, with a more pronounced cytotoxicity (51% survival), genes implicated in oxidative stress response were also up-regulated. Increase in intracellular ROS level and oxidative DNA damage was evident at both exposure times being more pronounced with high cytotoxicity. On the contrary, up-regulation of genes implicated in DNA damage response, as cell cycle control or apoptosis, was not detected at any exposure time. In conclusion, these results support a DNA non-reactive mechanism of OTA genotoxicity.

  4. In silico studies with human DNA topoisomerase-II alpha to unravel the mechanism of in vitro genotoxicity of benzene and its metabolites.

    PubMed

    Pandey, Alok Kumar; Gurbani, Deepak; Bajpayee, Mahima; Parmar, Devendra; Ajmani, Subhash; Dhawan, Alok

    2009-02-10

    Exposure of humans to benzene present in environment may lead to adverse chronic effects-even at the genetic level. However, the mechanism of its genotoxicity is not well understood. In the present study, in vitro genotoxicity of benzene (BZ) and its major metabolites [p-benzoquinone (BQ), hydroquinone (HQ), catechol (CT), 1,2,4-benzenetriol (BT) and trans-trans muconic acid (MA)] at concentrations 0.5-50 microM, was assessed in Chinese hamster ovary (CHO) cells employing the alkaline Comet assay, cytokinesis blocked micronucleus (CBMN) assay, flow cytometric analysis of micronucleus (flow MN) and chromosome aberration (CA) test. The data revealed significant (P<0.05) concentration-dependent response in all end points. HQ was found to be the most potent DNA damaging metabolite in the Comet assay followed by BQ>BT>CT>BZ>MA. Both CBMN and flow MN assays revealed a good correlation in their results, where BQ and MA exhibited maximum and minimum micronucleus induction respectively. Significant chromosomal aberrations were induced mainly by BQ, BT and HQ, with moderate response shown by CT and BZ and least by MA. The results demonstrated the utility of sensitive techniques like Comet assay and flow cytometry for determination of MN, to quantify in vitro genotoxicity at low levels and also suggested that partly non-repaired DNA damage could cause adverse health effects in human population exposed to benzene. In silico studies using different endpoints of genotoxicity and molecular docking studies with human topoisomerase-II alpha, a major DNA repair enzyme were also conducted. These corroborated the results obtained from the in vitro data, pointing to a direct relationship of the observed genotoxicity with the structural properties and various interactions of metabolites with the enzyme. This comprehensive study demonstrated that genotoxicity of benzene in mammalian cells is mainly due to the inhibition of topoisomerase by the metabolites.

  5. Genotoxic and mutagenic effects of guarana (Paullinia cupana) in prokaryotic organisms.

    PubMed

    da Fonseca, C A; Leal, J; Costa, S S; Leitão, A C

    1994-05-01

    Aqueous extracts of Paullinia cupana (guarana), a species that belongs to the Sapindaceae family, were analyzed for the presence of genotoxic activities in bacterial cells. The extracts of guarana were genotoxic as assessed by lysogenic induction in Escherichia coli and they were also able to induce mutagenesis in Salmonella typhimurium. Addition of S9 microsomal fraction, catalase, superoxide dismutase or thiourea counteracted the genotoxic activity of guarana, suggesting that oxygen reactive species play an essential role in the genotoxicity of aqueous guarana extracts. The genotoxic activity in the extracts was related to the presence of a molecular complex formed by caffeine and a flavonoid (catechin or epicatechin) in the presence of potassium.

  6. Strategy for genotoxicity testing: hazard identification and risk assessment in relation to in vitro testing.

    PubMed

    Thybaud, V; Aardema, M; Clements, J; Dearfield, K; Galloway, S; Hayashi, M; Jacobson-Kram, D; Kirkland, D; MacGregor, J T; Marzin, D; Ohyama, W; Schuler, M; Suzuki, H; Zeiger, E

    2007-02-03

    studies based on actual test results that illustrated common situations encountered, and consensus opinions were developed based on group analysis of these cases. The Working Group defined circumstances in which the pattern and magnitude of positive results was such that there was very low or no concern (e.g., non-reproducible or marginal responses), and no further testing would be needed. This included a discussion of the importance of the use of historical control data. The criteria for determining when follow-up testing is needed included factors, such as evidence of reproducibility, level of cytotoxicity at which an increased DNA damage or mutation frequency is observed, relationship of results to the historical control range of values, and total weight of evidence across assays. When the initial battery is negative, further testing might be required based on information from the published literature, structure activity considerations, or the potential for significant human metabolites not generated in the test systems. Additional testing might also be needed retrospectively when increase in tumors or evidence of pre-neoplastic change is seen. When follow-up testing is needed, it should be based on knowledge about the mode of action, based on reports in the literature or learned from the nature of the responses observed in the initial tests. The initial findings, and available information about the biochemical and pharmacological nature of the agent, are generally sufficient to conclude that the responses observed are consistent with certain molecular mechanisms and inconsistent with others. Follow-up tests should be sensitive to the types of genetic damage known to be capable of inducing the response observed initially. It was recognized that genotoxic events might arise from processes other than direct reactivity with DNA, that these mechanisms may have a non-linear, or threshold, dose-response relationship, and that in such cases it may be possible to determine an

  7. Detection of genotoxic and non-genotoxic carcinogens in Xpc{sup −/−}p53{sup +/−} mice

    SciTech Connect

    Melis, Joost P.M.; Speksnijder, Ewoud N.; Kuiper, Raoul V.; Salvatori, Daniela C.F.; Schaap, Mirjam M.; Maas, Saskia; Robinson, Joke; Verhoef, Aart; Benthem, Jan van; Luijten, Mirjam; Steeg, Harry van

    2013-01-15

    An accurate assessment of the carcinogenic potential of chemicals and pharmaceutical drugs is essential to protect humans and the environment. Therefore, substances are extensively tested before they are marketed to the public. Currently, the rodent two-year bioassay is still routinely used to assess the carcinogenic potential of substances. However, over time it has become clear that this assay yields false positive results and also has several economic and ethical drawbacks including the use of large numbers of animals, the long duration, and the high cost. The need for a suitable alternative assay is therefore high. Previously, we have proposed the Xpa*p53 mouse model as a very suitable alternative to the two-year bioassay. We now show that the Xpc*p53 mouse model preserves all the beneficial traits of the Xpa*p53 model for sub-chronic carcinogen identification and can identify both genotoxic and non-genotoxic carcinogens. Moreover, Xpc*p53 mice appear to be more responsive than Xpa*p53 mice towards several genotoxic and non-genotoxic carcinogens. Furthermore, Xpc*p53 mice are far less sensitive than Xpa*p53 mice for the toxic activity of DNA damaging agents and as such clearly respond in a similar way as wild type mice do. These advantageous traits of the Xpc*p53 model make it a better alternative for in vivo carcinogen testing than Xpa*p53. This pilot study suggests that Xpc*p53 mice are suited for routine sub-chronic testing of both genotoxic and non-genotoxic carcinogens and as such represent a suitable alternative to possibly replace the murine life time cancer bioassay. Highlights: ► The Xpc*p53 mouse model is able to identify genotoxic and non-genotoxic carcinogens. ► Time, animals and cost can be significantly reduced compared to the 2-year bioassay. ► Xpc*p53 mice are more advantageous for carcinogen identification than Xpa*p53 mice. ► Xpc*p53 mice exhibit a wild type response upon exposure to genotoxicants.

  8. SIGNALING TO THE P53 TUMOR SUPPRESSOR THROUGH PATHWAYS ACTIVATED BY GENOTOXIC AND NON-GENOTOXIC STRESSES.

    SciTech Connect

    ANDERSON,C.W.APPELLA,E.

    2002-07-01

    The p53 tumor suppressor is a tetrameric transcription factor that is post-translational modified at {approx}18 different sites by phosphorylation, acetylation, or sumoylation in response to various cellular stress conditions. Specific posttranslational modifications, or groups of modifications, that result from the activation of different stress-induced signaling pathways are thought to modulate p53 activity to regulate cell fate by inducing cell cycle arrest, apoptosis, or cellular senescence. Here we review the posttranslational modifications to p53 and the pathways that produce them in response to both genotoxic and non-genotoxic stresses.

  9. Genotoxic potential of organic extracts from particle emissions of diesel and rapeseed oil powered engines.

    PubMed

    Topinka, Jan; Milcova, Alena; Schmuczerova, Jana; Mazac, Martin; Pechout, Martin; Vojtisek-Lom, Michal

    2012-07-07

    The present study was performed to identify possible genotoxicity induced by organic extracts from particulate matter in the exhaust of two typical diesel engines run on diesel fuel and neat heated fuel-grade rapeseed oil: a Cummins ISBe4 engine tested using the World Harmonized Steady State Test Cycle (WHSC) and modified Engine Steady Cycle (ESC) and a Zetor 1505 engine tested using the Non-Road Steady State Cycle (NRSC). In addition, biodiesel B-100 (neat methylester of rapeseed oil) was tested in the Cummins engine run on the modified ESC. Diluted exhaust was sampled with high-volume samplers on Teflon coated filters. Filters were extracted with dichlormethane (DCM) and DNA adduct levels induced by extractable organic matter (EOM) in an acellular assay of calf thymus DNA coupled with (32)P-postlabeling in the presence and absence of rat liver microsomal S9 fraction were employed. Simultaneously, the chemical analysis of 12 priority PAHs in EOM, including 7 carcinogenic PAHs (c-PAHs) was performed. The results suggest that diesel emissions contain substantially more total PAHs than rapeseed oil emissions (for the ESC) or that these concentrations were comparable (for the WHSC and NRSC), while c-PAHs levels were comparable (for the ESC) or significantly higher (for the WHSC and NRSC) for rapeseed oil emissions. DNA adduct levels induced by diesel and rapeseed oil derived EOM were comparable, but consistently slightly higher for diesel than for rapeseed oil. Highly significant correlations were found between 12 priority PAHs concentrations and DNA adduct levels (0.980; p<0.001) and these correlations were even stronger for c-PAHs (0.990; p<0.001). Metabolic activation by the microsomal S9 fraction resulted in several fold higher genotoxicity, suggesting a major contribution of PAHs to genotoxicity. Directly acting compounds, other than c-PAHs, and not requiring S9 to exhibit DNA reactivity were also significant. Generally, DNA adduct levels were more dependent on

  10. Genotoxic effects of fumes from asphalt modified with waste plastic and tall oil pitch.

    PubMed

    Lindberg, Hanna K; Väänänen, Virpi; Järventaus, Hilkka; Suhonen, Satu; Nygren, Jonas; Hämeilä, Mervi; Valtonen, Jarkko; Heikkilä, Pirjo; Norppa, Hannu

    2008-05-31

    results indicate that fumes from SMA and SMA-WPT contain direct-acting genotoxic components.

  11. Sall2 is required for proapoptotic Noxa expression and genotoxic stress-induced apoptosis by doxorubicin

    PubMed Central

    Escobar, D; Hepp, M I; Farkas, C; Campos, T; Sodir, N M; Morales, M; Álvarez, C I; Swigart, L; Evan, G I; Gutiérrez, J L; Nishinakamura, R; Castro, A F; Pincheira, R

    2015-01-01

    The Sall2 transcription factor is deregulated in several cancers; however, little is known about its cellular functions, including its target genes. Recently, we demonstrated that p53 directly regulates Sall2 expression under genotoxic stress. Here, we investigated the role of Sall2 in the context of cellular response to genotoxic stress. In addition, we further examined the Sall2-p53 relationship during genotoxic stress in primary mouse embryo fibroblasts (MEFs), which are derived from Sall2 knockout mice separately, or in combination with the p53ERTAM knock-in mice. We found that the levels of Sall2 mRNA and protein are dynamically modulated in response to doxorubicin. At early times of stress, Sall2 is downregulated, but increases under extension of the stress in a p53-independent manner. Based on caspase-3/7 activities, expression of cleaved poly (ADP-ribose) polymerase, expression of cleaved caspase-3 and induction of proapoptotic proteins, Sall2 expression was correlated with cellular apoptosis. Consequently, Sall2−/− MEFs have decreased apoptosis, which relates with increased cell viability in response to doxorubicin. Importantly, Sall2 was required for apoptosis even in the presence of fully activated p53. Searching for putative Sall2 targets that could mediate its role in apoptosis, we identified proapoptotic NOXA/PMAIP1 (phorbol-12-myristate-13-acetate-induced protein 1). We demonstrated that Sall2 positively regulates Noxa promoter activity. Conserved putative Sall2-binding sites at the NOXA promoter were validated in vitro by electrophoretic mobility shift assay and in vivo by ChIP experiments, identifying NOXA as a novel Sall2 target. In agreement, induction of Noxa protein and mRNA in response to doxorubicin was significantly decreased in Sall2−/− MEFs. In addition, studies in leukemia Jurkat T cells support the existence of the Sall2/Noxa axis, and the significance of this axis on the apoptotic response to doxorubicin in cancer cells. Our

  12. Genotoxicity studies of organically grown broccoli (Brassica oleracea var. italica) and its interactions with urethane, methyl methanesulfonate and 4-nitroquinoline-1-oxide genotoxicity in the wing spot test of Drosophila melanogaster.

    PubMed

    Heres-Pulido, María Eugenia; Dueñas-García, Irma; Castañeda-Partida, Laura; Santos-Cruz, Luis Felipe; Vega-Contreras, Viridiana; Rebollar-Vega, Rosa; Gómez-Luna, Juan Carlos; Durán-Díaz, Angel

    2010-01-01

    Broccoli (Brassica oleracea var. italica) has been defined as a cancer preventive food. Nevertheless, broccoli contains potentially genotoxic compounds as well. We performed the wing spot test of Drosophila melanogaster in treatments with organically grown broccoli (OGB) and co-treatments with the promutagen urethane (URE), the direct alkylating agent methyl methanesulfonate (MMS) and the carcinogen 4-nitroquinoline-1-oxide (4-NQO) in the standard (ST) and high bioactivation (HB) crosses with inducible and high levels of cytochrome P450s (CYPs), respectively. Larvae of both crosses were chronically fed with OGB or fresh market broccoli (FMB) as a non-organically grown control, added with solvents or mutagens solutions. In both crosses, the OGB added with Tween-ethanol yielded the expected reduction in the genotoxicity spontaneous rate. OGB co-treatments did not affect the URE effect, MMS showed synergy and 4-NQO damage was modulated in both crosses. In contrast, FMB controls produced damage increase; co-treatments modulated URE genotoxicity, diminished MMS damage, and did not change the 4-NQO damage. The high dietary consumption of both types of broccoli and its protective effects in D. melanogaster are discussed.

  13. Fruits and vegetables protect against the genotoxicity of heterocyclic aromatic amines activated by human xenobiotic-metabolizing enzymes expressed in immortal mammalian cells.

    PubMed

    Platt, K L; Edenharder, R; Aderhold, S; Muckel, E; Glatt, H

    2010-12-21

    ineffective. In most cases, fruits and vegetables inhibited PhIP genotoxicity less strongly than IQ genotoxicity. As one possible mechanism of antigenotoxicity, the inhibition of activating enzymes was studied either indirectly with diagnostic substrates or directly by measuring CYP1A2 inhibition. Only sour cherry, blueberry, and black currant juices suppressed the first step of HAA enzymatic activation, whereas most plant-derived beverages inhibited the second step. 2010 Elsevier B.V. All rights reserved.

  14. Assessment of genotoxicity of herbal medicinal products: application of the "bracketing and matrixing" concept using the example of Valerianae radix (valerian root).

    PubMed

    Kelber, Olaf; Wegener, Tankred; Steinhoff, Barbara; Staiger, Christiane; Wiesner, Jacqueline; Knöss, Werner; Kraft, Karin

    2014-01-01

    An assessment of genotoxicity is a precondition for marketing authorization respectively registration of herbal medicinal products (HMPs), as well as for inclusion into the 'Community list of herbal substances, preparations and combinations thereof for use in traditional herbal medicinal products' established by the European Commission in accordance with Directive 2001/83/EC as amended, and based on proposals from the Committee on Herbal Medicinal Products (HMPC). In the 'Guideline on the assessment of genotoxicity of herbal substances/preparations' (EMEA/HMPC/107079/2007) HMPC has described a stepwise approach for genotoxicity testing, according to which the Ames test is a sufficient base for the assessment of genotoxicity in case of an unequivocally negative result. For reducing efforts for testing of individual herbal substances/preparations, HMPC has also developed the 'guideline on selection of test materials for genotoxicity testing for traditional herbal medicinal products/herbal medicinal products' (EMEA/HMPC/67644/2009) with the aim to allow testing of a standard range of test materials which could be considered representative of the commonly used preparations from a specific herbal drug according to a 'bracketing/matrixing' approach. The purpose of this paper is to provide data on the practical application of this bracketing and matrixing concept using the example of Valerianae radix, with the intention of facilitating its inclusion in the "Community list". Five extraction solvents, representing the extremes of the polarity range and including also mid-range extraction solvents, were used, covering the entire spectrum of phytochemical constituents of Valerianae radix, thereby including polar and non-polar constituents. Extracts were tested in the Ames test according to all relevant guidelines. Results were unequivocally negative for all extracts. A review of the literature showed that this result is in accordance with the available data, thus

  15. THE GENOTOXICITY OF PRIORITY POLYCYCLIC AROMATIC HYDROCARBONS IN COMPLEX MIXTURES

    EPA Science Inventory

    Risk assessment of complex environmental samples suffers from difficulty in identifying toxic components, inadequacy of available toxicity data, and a paucity of knowledge about the behavior of geno(toxic) substances in complex mixtures. Lack of information about the behavior of ...

  16. Linking genotoxic responses and reproductive success in ecotoxicology

    SciTech Connect

    Anderson, S.L.; Wild, G.C.

    1994-12-01

    The potential of genotoxicity biomarkers as predictors of detrimental environmental effects, such as altered reproductive success of wild organisms, must be rigorously determined. Recent research to evaluate relationships between genotoxic responses and indicators of reproductive success in model animals is described from an ecotoxicological perspective. Genotoxicity can be correlated with reproductive effects such as gamete loss due to cell death; embryonic mortality; and heritable mutations in a range of model animals including polychaete worms, nematodes, sea urchins, amphibians, and fish. In preliminary studies, the polychaete worm, Neanthes arenaceodentata, and the nematode, Caenorhabditis elegans, have also shown the potential for cumulative DNA damage in gametes. If DNA repair capacity is limited in gametes, then selected life history traits such as long and synchronous periods of gametogenesis may confer vulnerability to genotoxic substances in chronic exposures. Recommendations for future research include strategic development of animal models that can be used to elucidate multiple mechanisms of effect (multiend point) at varying levels of biological organization (multilevel). 27 refs., 2 tabs.

  17. Evaluation of Genotoxic Pressure along the Sava River

    PubMed Central

    Kračun-Kolarević, Margareta; Kostić, Jovana; Simonović, Predrag; Simić, Vladica; Milošković, Aleksandra; Reischer, Georg; Farnleitner, Andreas; Gačić, Zoran; Milačič, Radmila; Zuliani, Tea; Vidmar, Janja; Pergal, Marija; Piria, Marina; Paunović, Momir; Vuković-Gačić, Branka

    2016-01-01

    In this study we have performed a comprehensive genotoxicological survey along the 900 rkm of the Sava River. In total, 12 sites were chosen in compliance with the goals of GLOBAQUA project dealing with the effects of multiple stressors on biodiversity and functioning of aquatic ecosystems. The genotoxic potential was assessed using a complex battery of bioassays performed in prokaryotes and aquatic eukaryotes (freshwater fish). Battery comprised evaluation of mutagenicity by SOS/umuC test in Salmonella typhimurium TA1535/pSK1002. The level of DNA damage as a biomarker of exposure (comet assay) and biomarker of effect (micronucleus assay) and the level of oxidative stress as well (Fpg—modified comet assay) was studied in blood cells of bleak and spirlin (Alburnus alburnus/Alburnoides bipunctatus respectively). Result indicated differential sensitivity of applied bioassays in detection of genotoxic pressure. The standard and Fpg—modified comet assay showed higher potential in differentiation of the sites based on genotoxic potential in comparison with micronucleus assay and SOS/umuC test. Our data represent snapshot of the current status of the river which indicates the presence of genotoxic potential along the river which can be traced to the deterioration of quality of the Sava River by communal and industrial wastewaters. The major highlight of the study is that we have provided complex set of data obtained from a single source (homogeneity of analyses for all samples). PMID:27631093

  18. GENOTOXICITY STUDIES OF SODIUM DICHLOROACETATE AND SODIUM TRICHLOROACETATE

    EPA Science Inventory

    The genotoxic properties of sodium dichloroacetate (DCA) and sodium trichloroacetate (TCA)were evaluated in several short-term in vitro and in vivo assays. Neither compound was mutagenic in tester strain TA102 in the Salmonella mutagenicity assay. Both DCA and TCA were weak induc...

  19. Genotoxicity of pesticide waste contaminated soil and its leachate.

    PubMed

    Sivanesan, S D; Krishnamurthi, K; Wachasunder, S D; Chakrabarti, T

    2004-09-01

    Improper land disposal of hazardous waste can result in leaching of hazardous constituents which may contaminate ground and surface water leading to adverse impact on human health and environment consequences. The present study utilized mammalian cell culture for the genotoxicity assessment of waste and its leachate. Genotoxic potential and chemical analysis of pesticide derived tarry waste contaminated soil extract and its leachate was assessed using in vitro human lymphocyte cultures and GC-MS. The investigation revealed that the soil extract could cause significant to highly significant genotoxicity in the form of DNA strand break at 25 microL (P < 0.01), 50 microL, 100 microL and 200 microL (P < 0.001) and chromosomal aberration at 25 microL (P < 0.01) and 50 microL and 100 microL (P < 0.001). The leachate could cause significant DNA strand break and chromosomal aberration only at 100 microL and 200 microL (P < 0.01) dose levels. The genotoxicity observed is attributed to carbaril and tetra methyl naphthyl carbamate, the major ingredients of the extracts, as revealed by GC-MS.

  20. Review of genotoxicity biomonitoring studies of glyphosate-based formulations

    PubMed Central

    Kier, Larry D.

    2015-01-01

    Abstract Human and environmental genotoxicity biomonitoring studies involving exposure to glyphosate-based formulations (GBFs) were reviewed to complement an earlier review of experimental genotoxicity studies of glyphosate and GBFs. The environmental and most of the human biomonitoring studies were not informative because there was either a very low frequency of GBF exposure or exposure to a large number of pesticides without analysis of specific pesticide effects. One pesticide sprayer biomonitoring study indicated there was not a statistically significant relationship between frequency of GBF exposure reported for the last spraying season and oxidative DNA damage. There were three studies of human populations in regions of GBF aerial spraying. One study found increases for the cytokinesis-block micronucleus endpoint but these increases did not show statistically significant associations with self-reported spray exposure and were not consistent with application rates. A second study found increases for the blood cell comet endpoint at high exposures causing toxicity. However, a follow-up to this study 2 years after spraying did not indicate chromosomal effects. The results of the biomonitoring studies do not contradict an earlier conclusion derived from experimental genotoxicity studies that typical GBFs do not appear to present significant genotoxic risk under normal conditions of human or environmental exposures. PMID:25687244

  1. Mercury-induced genotoxicity in marine diatom (Chaetoceros tenuissimus).

    PubMed

    Sarker, Subhodeep; Desai, Somashekhar R; Verlecar, Xivanand N; Sarker, Munmun Saha; Sarkar, A

    2016-02-01

    In this paper, we present an evaluation of genotoxic responses in marine diatom, Chaetoceros tenuissimus, isolated from Kandla Creek (lat 23.03° N, long 70.22° E), Gujarat, India, in terms of impairment of DNA integrity as a function of their exposure to elevated levels of mercury (Hg) under laboratory conditions. DNA integrity in C. tenuissimus was determined by partial alkaline unwinding assay. To our knowledge, this is the first such genotoxicity study to be conducted on marine diatom cultures towards understanding the relationship between Hg toxicity and DNA damage. Furthermore, we studied the impact of Hg on the growth of C. tenuissimus as a function of their exposure to enhanced levels of Hg in terms of decreasing chlorophyll a (chl a) concentrations. The data show the genotoxic effect of Hg on the growth of C. tenuissimus as well as DNA integrity to a great extent. Based on the results of our investigations, it is suggested that C. tenuissimus can be used as sentinel species for bio-monitoring of pollution due to genotoxic contaminants.

  2. Genotoxicity of refinery waste assessed by some DNA damage tests.

    PubMed

    Gupta, Amit Kumar; Ahmad, Irshad; Ahmad, Masood

    2015-04-01

    Refinery waste effluent is well known to contain polycyclic aromatic hydrocarbons, phenols and heavy metals as potentially genotoxic substances. The aim of the present study was to assess the genotoxic potential of Mathura refinery wastewater (MRWW) by various in vitro tests including the single cell gel electrophoresis, plasmid nicking assay and S1 nuclease assay. Treatment of human lymphocytes to different MRWW concentrations (0.15×, 0.3×, 0.5× and 0.78×) caused the formation of comets of which the mean tail lengths increased proportionately and differed significantly from those of unexposed controls. The toxic effect of MRWW on DNA was also studied by plasmid nicking assay and S1 nuclease assay. Strand breaks formation in the MRWW treated pBR322 plasmid confirmed its genotoxic effect. Moreover, a dose dependent increase in cleavage of calf thymus DNA in S1 nuclease assay was also suggestive of the DNA damaging potential of MRWW. A higher level of ROS generation in the test water sample was recorded which might be contributing to its genotoxicity. Interaction between the constituents of MRWW and calf thymus DNA was also ascertained by UV-visible spectroscopy. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Genotoxicity of Swimming Pool Water and Carcinogenicity of Drinking Water**

    EPA Science Inventory

    Among the 11 disinfection by-products (DBPs) in drinking water that are regulated by the U.S. EPA, (a) 2 DBPs (chloroaceticacid and chlorite) are not carcinogenic-in either of2 species; (b) chlorite is not carcinogenic in 3 rodent assays and has never been tested for genotoxicity...

  4. Genotoxicity of Swimming Pool Water and Carcinogenicity of Drinking Water

    EPA Science Inventory

    Among the 11 disinfection by-products (DBPs) in drinking water that are regulated by the U.S. EPA, (a) 2 DBPs (chloroaceticacid and chlorite) are not carcinogenic-in either of2 species; (b) chlorite is not carcinogenic in 3 rodent assays and has never been tested for genotoxicity...

  5. Intracellular STING inactivation sensitizes breast cancer cells to genotoxic agents

    PubMed Central

    Gaston, Julie; Cheradame, Laura; Yvonnet, Vanessa; Deas, Olivier; Poupon, Marie-France; Judde, Jean-Gabriel

    2016-01-01

    Activation of the IFN/STAT1 pathway is closely associated with drug response and recurrence of breast cancer treated by chemotherapy. The aim of the current study was to elucidate the molecular mechanisms involved upstream and downstream of this pathway in order to identify distinct entities that might be manipulated to improve treatment efficacy. Four breast cancer cell lines (T-47D, MCF7, MDA-MB-231 and HBCx-19 established from the eponymous PDX) were treated in vitro with mafosfamide, a DNA damage inducer. In two of these cell lines (MCF7 and HBCx-19), genotoxic treatment upregulated type I IFN expression leading to paracrine activation of IFN/STAT1 signaling pathway after 6–8 days. We show that STING, a well-characterized inducer of IFN in immune cells, is rapidly triggered in MCF7 cells under genotoxic stress and forms nuclear foci that co-localize with phosphorylated IRF-3 and γH2AX. STING silencing abrogated chemotherapy-induced type I IFN production and signaling and potentiated genotoxic treatment efficacy as it promoted cell death extent and delayed cell colony regrowth. Similar results were obtained after silencing PARP12, one selected gene of the IFN/STAT1 pathway fingerprint. In summary, this study provides the first demonstration of STING activation in breast cancer cells. Our data suggest that genotoxic-induced, STING-mediated type I IFN signaling is a cell-intrinsic mechanism of breast cancer cell survival and regrowth. PMID:27791205

  6. THE GENOTOXICITY OF PRIORITY POLYCYCLIC AROMATIC HYDROCARBONS IN COMPLEX MIXTURES

    EPA Science Inventory

    Risk assessment of complex environmental samples suffers from difficulty in identifying toxic components, inadequacy of available toxicity data, and a paucity of knowledge about the behavior of geno(toxic) substances in complex mixtures. Lack of information about the behavior of ...

  7. Boron compounds reduce vanadium tetraoxide genotoxicity in human lymphocytes.

    PubMed

    Geyikoglu, Fatime; Turkez, Hasan

    2008-11-01

    Vanadium has potential medical and pharmacological uses although it may also show genotoxic effects. Biological effects of boron are defined, but its interaction with vanadium is not known for therapeutic uses. The objective of present study was especially to determine whether boron compounds (boric acid and borax) conferred the protection against vanadium(IV) tetraoxide genotoxicity. After the application of vanadium (5, 10 and 20mg/l) and boron compounds (5 and 10mg/l), blood cultures were assessed by genetic endpoints and total antioxidant capacity (TAC). According to our results, vanadium(IV) tetraoxide induced a reduction in proliferation index (PI). Besides, the frequencies of sister-chromatid exchanges (SCEs), micronuclei (MN) rates and chromosomal aberrations (CAs) in peripheral lymphocytes were significantly increased by vanadium(IV) tetraoxide (10 and 20mg/l) compared to controls. On the other hand, boric acid and borax did not show cytotoxic and genotoxic effects at the concentrations tested. Moreover, these compounds elevated TAC in erythrocytes. The order of anti-genotoxicity efficacy against vanadium was boric acid and borax, respectively. In conclusion, boron compounds have been shown to protect vanadium-induced DNA damage in vitro for the first time. Copyright © 2008 Elsevier B.V. All rights reserved.

  8. Genotoxicity of Swimming Pool Water and Carcinogenicity of Drinking Water**

    EPA Science Inventory

    Among the 11 disinfection by-products (DBPs) in drinking water that are regulated by the U.S. EPA, (a) 2 DBPs (chloroaceticacid and chlorite) are not carcinogenic-in either of2 species; (b) chlorite is not carcinogenic in 3 rodent assays and has never been tested for genotoxicity...

  9. Genotoxicity of Swimming Pool Water and Carcinogenicity of Drinking Water

    EPA Science Inventory

    Among the 11 disinfection by-products (DBPs) in drinking water that are regulated by the U.S. EPA, (a) 2 DBPs (chloroaceticacid and chlorite) are not carcinogenic-in either of2 species; (b) chlorite is not carcinogenic in 3 rodent assays and has never been tested for genotoxicity...

  10. Genistein genotoxicity: critical considerations of in vitro exposure dose.

    PubMed

    Klein, Catherine B; King, Audrey A

    2007-10-01

    The potential health benefits of soy-derived phytoestrogens include their reported utility as anticarcinogens, cardioprotectants and as hormone replacement alternatives in menopause. Although there is increasing popularity of dietary phytoestrogen supplementation and of vegetarian and vegan diets among adolescents and adults, concerns about potential detrimental or other genotoxic effects persist. While a variety of genotoxic effects of phytoestrogens have been reported in vitro, the concentrations at which such effects occurred were often much higher than the physiologically relevant doses achievable by dietary or pharmacologic intake of soy foods or supplements. This review focuses on in vitro studies of the most abundant soy phytoestrogen, genistein, critically examining dose as a crucial determinant of cellular effects. In consideration of levels of dietary genistein uptake and bioavailability we have defined in vitro concentrations of genistein >5 microM as non-physiological, and thus "high" doses, in contrast to much of the previous literature. In doing so, many of the often-cited genotoxic effects of genistein, including apoptosis, cell growth inhibition, topoisomerase inhibition and others become less obvious. Recent cellular, epigenetic and microarray studies are beginning to decipher genistein effects that occur at dietarily relevant low concentrations. In toxicology, the well accepted principle of "the dose defines the poison" applies to many toxicants and can be invoked, as herein, to distinguish genotoxic versus potentially beneficial in vitro effects of natural dietary products such as genistein.

  11. Genotoxicity hazard assessment of Caramel Colours III and IV.

    PubMed

    Brusick, D J; Jagannath, D R; Galloway, S M; Nestmann, E R

    1992-05-01

    Results from a battery of short-term tests in vitro and in vivo used to assess the genotoxicity of caramel colours are presented and discussed in relation to reports from the literature. No evidence of genotoxicity was found in the Salmonella plate incorporation test using five standard strains or in the Saccharomyces cerevisiae gene conversion assay using strain D4, either with or without S-9 for activation. A weak clastogenic effect for a sample of Caramel Colour III in CHO cells was abolished in the presence of S-9. Two samples of Caramel Colour IV were not clastogenic in CHO cells. Salmonella pre-incubation tests without S-9 also failed to reveal any mutagenic activity for any of the caramel colours tested. The Caramel Colour III sample that showed clastogenic activity in CHO cells in vitro did not induce micronuclei when evaluated in a mouse bone marrow assay. These results are in general agreement with reports in the literature regarding the genotoxicity of caramel colours, and support the conclusion that caramel colours do not pose a genotoxic hazard to humans.

  12. Review of genotoxicity biomonitoring studies of glyphosate-based formulations.

    PubMed

    Kier, Larry D

    2015-03-01

    Abstract Human and environmental genotoxicity biomonitoring studies involving exposure to glyphosate-based formulations (GBFs) were reviewed to complement an earlier review of experimental genotoxicity studies of glyphosate and GBFs. The environmental and most of the human biomonitoring studies were not informative because there was either a very low frequency of GBF exposure or exposure to a large number of pesticides without analysis of specific pesticide effects. One pesticide sprayer biomonitoring study indicated there was not a statistically significant relationship between frequency of GBF exposure reported for the last spraying season and oxidative DNA damage. There were three studies of human populations in regions of GBF aerial spraying. One study found increases for the cytokinesis-block micronucleus endpoint but these increases did not show statistically significant associations with self-reported spray exposure and were not consistent with application rates. A second study found increases for the blood cell comet endpoint at high exposures causing toxicity. However, a follow-up to this study 2 years after spraying did not indicate chromosomal effects. The results of the biomonitoring studies do not contradict an earlier conclusion derived from experimental genotoxicity studies that typical GBFs do not appear to present significant genotoxic risk under normal conditions of human or environmental exposures.

  13. Comparative genotoxicity of aluminium and cadmium in embryonic zebrafish cells.

    PubMed

    Pereira, Sandrine; Cavalie, Isabelle; Camilleri, Virginie; Gilbin, Rodolphe; Adam-Guillermin, Christelle

    2013-01-20

    Aluminium is a toxic metal whose genotoxicity has been scarcely studied in aquatic species and more generally in mammals. Recently, human and ecological disaster caused by the discharge of red mud in Hungary has revived questions about the toxicity of this metal particularly for the environment. On the contrary, cadmium is a highly toxic metal whose genotoxicity has been well characterized in various mammalian cells. However on non-human cells, little is known about its impact on DNA damage and repair. In this study, the genotoxic potential of both metals on embryonic zebrafish cells ZF4 was analyzed and particularly the impairment of the major DNA double strand breaks (DSB)-repair pathway, i.e. non-homologous end-joining (NHEJ). To this aim, DNA single strand breaks (SSB) and DSB were evaluated using the comet assay and the immunodetection of γ-H2AX proteins, respectively, in AlCl(3) or CdCl(2) exposed ZF4 cells. These exposures result in the production of DSBs a few hours after incubation. The DNA-PK kinase activity, essential for NHEJ, is more affected by the presence of aluminium than cadmium. Altogether our data provide evidence of the high toxicity induced by aluminium in zebrafish and indicates the pertinence of genotoxicity evaluation in organisms living in contaminated water.

  14. GENOTOXICITY STUDIES OF SODIUM DICHLOROACETATE AND SODIUM TRICHLOROACETATE

    EPA Science Inventory

    The genotoxic properties of sodium dichloroacetate (DCA) and sodium trichloroacetate (TCA)were evaluated in several short-term in vitro and in vivo assays. Neither compound was mutagenic in tester strain TA102 in the Salmonella mutagenicity assay. Both DCA and TCA were weak induc...

  15. Genistein genotoxicity: Critical considerations of in vitro exposure dose

    SciTech Connect

    Klein, Catherine B. King, Audrey A.

    2007-10-01

    The potential health benefits of soy-derived phytoestrogens include their reported utility as anticarcinogens, cardioprotectants and as hormone replacement alternatives in menopause. Although there is increasing popularity of dietary phytoestrogen supplementation and of vegetarian and vegan diets among adolescents and adults, concerns about potential detrimental or other genotoxic effects persist. While a variety of genotoxic effects of phytoestrogens have been reported in vitro, the concentrations at which such effects occurred were often much higher than the physiologically relevant doses achievable by dietary or pharmacologic intake of soy foods or supplements. This review focuses on in vitro studies of the most abundant soy phytoestrogen, genistein, critically examining dose as a crucial determinant of cellular effects. In consideration of levels of dietary genistein uptake and bioavailability we have defined in vitro concentrations of genistein > 5 {mu}M as non-physiological, and thus 'high' doses, in contrast to much of the previous literature. In doing so, many of the often-cited genotoxic effects of genistein, including apoptosis, cell growth inhibition, topoisomerase inhibition and others become less obvious. Recent cellular, epigenetic and microarray studies are beginning to decipher genistein effects that occur at dietarily relevant low concentrations. In toxicology, the well accepted principle of 'the dose defines the poison' applies to many toxicants and can be invoked, as herein, to distinguish genotoxic versus potentially beneficial in vitro effects of natural dietary products such as genistein.

  16. Relevance of the mouse spot test as a genotoxicity indicator

    SciTech Connect

    Russell, L.B.

    1982-01-01

    This paper examined the mammalian spat test as an indicator of genotoxicity and evaluated the weight that may be given to results from this test with respect to their predictiveness for human health hazards. The evaluation was based on theoretical considerations and the performance of the test to date. (PSB)

  17. Toxicity and genotoxicity of water and sediment from streams on dotted duckweed (Landoltia punctata).

    PubMed

    Factori, R; Leles, S M; Novakowski, G C; Rocha, C L S C; Thomaz, S M

    2014-11-01

    Most rivers are used as a source to supply entire cities; the quality of water is directly related to the quality of tributaries. Unfortunately men have neglected the importance of streams, which receive domestic and industrial effluents and transport nutrients and pesticides from rural areas. Given the complexity of the mixtures discharged into these water bodies, this study aimed to evaluate the quality of water and sediment of ten tributaries of Pirapó River, in Maringá, Paraná State, Brazil. To this end, the free-floating macrophyte Landoltia punctata (G. Meyer) Les & D.J.Crawford was used as test organism in microcosm, and the toxicity of water and sediment samples was evaluated by the relative growth rate, dry/fresh biomass ratio, and genotoxic effects (comet assay). Samples of water and sediment of each stream were arranged in microcosms with L. punctata. Seven days later, plants were collected for analysis. Nutrient levels were higher than the reference location, indicating eutrophication, but the results indicated a toxic effect for only three streams, and a genotoxic effect for all streams.

  18. Photochemical fate and eco-genotoxicity assessment of the drug etodolac.

    PubMed

    Passananti, Monica; Lavorgna, Margherita; Iesce, Maria Rosaria; DellaGreca, Marina; Brigante, Marcello; Criscuolo, Emma; Cermola, Flavio; Isidori, Marina

    2015-06-15

    The photochemical behavior of etodolac was investigated under various irradiation conditions. Kinetic data were obtained after irradiation of 10(-4) M aqueous solutions by UVB, UVA and direct exposure to sunlight. The Xenon lamp irradiation was used in order to determine the photodegradation quantum yield under sun-simulated condition (ϕsun). The value was determined to be=0.10±0.01. In order to obtain photoproducts and for mechanistic purposes, experiments were carried out on more concentrated solutions by exposure to sunlight and to UVA and UVB lamps. The drug underwent photooxidative processes following an initial oxygen addition to the double bond of the five membered ring and was mainly converted into a spiro compound and a macrolactam. Ecotoxicity tests were performed on etodolac, its photostable spiro derivative and its sunlight irradiation mixture on two different aquatic trophic levels, plants (algae) and invertebrates (rotifers and crustaceans). Mutagenesis and genotoxicity were detected on bacterial strains. The results showed that only etodolac had long term effects on rotifers although at concentrations far from environmental detection values. A mutagenic and genotoxic potential was found for its derivative. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Genotoxicity testing of two lead-compounds in somatic cells of Drosophila melanogaster.

    PubMed

    Carmona, Erico R; Creus, Amadeu; Marcos, Ricard

    2011-09-18

    The in vivo genotoxic activity of two inorganic lead compounds was studied in Drosophila melanogaster by measurement of two different genetic endpoints. We used the wing-spot test and the comet assay. The comet assay was conducted with larval haemocytes. The results from the wing-spot test showed that neither lead chloride, PbCl(2), nor lead nitrate, Pb(NO(3))(2), were able to induce significant increases in the frequency of mutant spots. In addition, the combined treatments with gamma-radiation and PbCl(2) or Pb(NO(3))(2) did not show significant variations in the frequency of the three categories of mutant spots recorded, compared with the frequency induced by gamma-radiation alone. This seems to indicate that the lead compounds tested do not interact with the repair of the genetic damage induced by ionizing radiation. When the lead compounds were evaluated in the in vivo comet assay with haemocytes, Pb(NO(3))(2) was effective in inducing significant increases of DNA damage with a direct dose-response pattern. These results confirm the usefulness of the comet assay with haemocytes as an in vivo model and support the assumption that there is a genotoxic risk associated with lead exposure.

  20. Evaluation of vinyl laurate in a battery of in vitro and in vivo tests for genotoxicity.

    PubMed

    van Acker, Frédérique; Messinger, Horst; Bär, Albert

    2015-06-01

    Vinyl laurate is a potential residual monomer in chewing gum base formulated with polyvinyl acetate vinyl laurate copolymer (PVAcVL). The genotoxic potential of vinyl laurate was examined in a battery of in vitro and in vivo genotoxicity tests. Vinyl laurate was not mutagenic in Ames tests. In addition, it was not mutagenic in the HPRT mutation assay in L5178Y cells. An in vitro mammalian chromosome aberration assay performed in CHO cells was equivocal. Vinyl laurate and/or its metabolites were not clastogenic in the mouse bone marrow micronucleus test. Kinetic data indicate that VL is metabolised to acetaldehyde and lauric acid. Both metabolites are well known and have been studied previously. Model calculations show, that any exposure to acetaldehyde from the consumption of PVAcVL containing chewing gum will remain far below levels of acetaldehyde exposure from food in which acetaldehyde occurs naturally. Direct exposure to VL will primarily be at the site of entry. The lack of toxicity in a 90-day repeated dose toxicity test, performed with VL doses up to approximately 3000 times higher than the maximal VL intake from the consumption of a typical piece of chewing gum, demonstrates a high safety margin.

  1. Histopathological findings on Carassius auratus hepatopancreas upon exposure to acrylamide: correlation with genotoxicity and metabolic alterations.

    PubMed

    Larguinho, Miguel; Costa, Pedro M; Sousa, Gonçalo; Costa, Maria H; Diniz, Mário S; Baptista, Pedro V

    2014-12-01

    Acrylamide is an amide used in several industrial applications making it easily discharged to aquatic ecosystems. The toxicity of acrylamide to aquatic organisms is scarcely known, although previous studies with murine models provided evidence for deleterious effects. To assess the effects of acrylamide to freshwater fish, goldfish (Carassius auratus L.) were exposed to several concentrations of waterborne acrylamide and analysed for genotoxic damage, alterations to detoxifying enzymes and histopathology. Results revealed a dose-dependent increase in total DNA strand breakage, the formation of erythrocytic nuclear abnormalities and in the levels of hepatic cytochrome P4501A (CYP1A) and glutathione S-transferase (GST) activity. In addition, acrylamide induced more histopathological changes to pancreatic acini than to the hepatic parenchyma, regardless of exposure concentration, whereas hepatic tissue only endured significant alterations at higher concentrations of exposure. Thus, results confirm the genotoxic potential of acrylamide to fish and its ability to induce CYP1A, probably as a direct primary defence mechanism. This strongly suggests the substance's pro-mutagenic potential in fish, similarly to what is known for rodents. However, the deleterious effects observed in the pancreatic acini, more severe than in the liver, could indicate a specific, albeit unknown toxic mechanism of acrylamide to fish that overran the organism's metabolic defences against a chemical agent rather than causing a general systemic failure. Copyright © 2013 John Wiley & Sons, Ltd.

  2. p53 induction and cell viability modulation by genotoxic individual chemicals and mixtures.

    PubMed

    Di Paolo, Carolina; Müller, Yvonne; Thalmann, Beat; Hollert, Henner; Seiler, Thomas-Benjamin

    2017-03-16

    The binding of the p53 tumor suppression protein to DNA response elements after genotoxic stress can be quantified by cell-based reporter gene assays as a DNA damage endpoint. Currently, bioassay evaluation of environmental samples requires further knowledge on p53 induction by chemical mixtures and on cytotoxicity interference with p53 induction analysis for proper interpretation of results. We investigated the effects of genotoxic pharmaceuticals (actinomycin D, cyclophosphamide) and nitroaromatic compounds (4-nitroquinoline 1-oxide, 3-nitrobenzanthrone) on p53 induction and cell viability using a reporter gene and a colorimetric assay, respectively. Individual exposures were conducted in the absence or presence of metabolic activation system, while binary and tertiary mixtures were tested in its absence only. Cell viability reduction tended to present direct correlation with p53 induction, and induction peaks occurred mainly at chemical concentrations causing cell viability below 80%. Mixtures presented in general good agreement between predicted and measured p53 induction factors at lower concentrations, while higher chemical concentrations gave lower values than expected. Cytotoxicity evaluation supported the selection of concentration ranges for the p53 assay and the interpretation of its results. The often used 80% viability threshold as a basis to select the maximum test concentration for cell-based assays was not adequate for p53 induction assessment. Instead, concentrations causing up to 50% cell viability reduction should be evaluated in order to identify the lowest observed effect concentration and peak values following meaningful p53 induction.

  3. Gold-nanobeacons for gene therapy: evaluation of genotoxicity, cell toxicity and proteome profiling analysis.

    PubMed

    Conde, João; Larguinho, Miguel; Cordeiro, Ana; Raposo, Luís R; Costa, Pedro M; Santos, Susana; Diniz, Mário S; Fernandes, Alexandra R; Baptista, Pedro V

    2014-08-01

    Antisense therapy is a powerful tool for post-transcriptional gene silencing suitable for down-regulating target genes associated to disease. Gold nanoparticles have been described as effective intracellular delivery vehicles for antisense oligonucleotides providing increased protection against nucleases and targeting capability via simple surface modification. We constructed an antisense gold-nanobeacon consisting of a stem-looped oligonucleotide double-labelled with 3'-Cy3 and 5'-Thiol-C6 and tested for the effective blocking of gene expression in colorectal cancer cells. Due to the beacon conformation, gene silencing was directly detected as fluorescence increases with hybridisation to target, which can be used to assess the level of silencing. Moreover, this system was extensively evaluated for the genotoxic, cytotoxic and proteomic effects of gold-nanobeacon exposure to cancer cells. The exposure was evaluated by two-dimensional protein electrophoresis followed by mass spectrometry to perform a proteomic profile and 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay, glutathione-S-transferase assay, micronucleus test and comet assay to assess the genotoxicity. This integrated toxicology evaluation showed that the proposed nanotheranostics strategy does not exhibit significant toxicity, which is extremely relevant when translating into in vivo systems.

  4. p53 suppresses muscle differentiation at the myogenin step in response to genotoxic stress

    PubMed Central

    Yang, Z J P; Kenzelmann Broz, D; Noderer, W L; Ferreira, J P; Overton, K W; Spencer, S L; Meyer, T; Tapscott, S J; Attardi, L D; Wang, C L

    2015-01-01

    Acute muscle injury and physiological stress from chronic muscle diseases and aging lead to impairment of skeletal muscle function. This raises the question of whether p53, a cellular stress sensor, regulates muscle tissue repair under stress conditions. By investigating muscle differentiation in the presence of genotoxic stress, we discovered that p53 binds directly to the myogenin promoter and represses transcription of myogenin, a member of the MyoD family of transcription factors that plays a critical role in driving terminal muscle differentiation. This reduction of myogenin protein is observed in G1-arrested cells and leads to decreased expression of late but not early differentiation markers. In response to acute genotoxic stress, p53-mediated repression of myogenin reduces post-mitotic nuclear abnormalities in terminally differentiated cells. This study reveals a mechanistic link previously unknown between p53 and muscle differentiation, and suggests new avenues for managing p53-mediated stress responses in chronic muscle diseases or during muscle aging. PMID:25501595

  5. Genotoxicity of volatile and secondary reactive oxygen species generated by photosensitization

    SciTech Connect

    Camoirano, A.; De Flora, S.; Dahl, T.A. Tufts Univ. Veterinary, Boston, MA )

    1993-01-01

    Reactive oxygen species were generated in the gas phase by photosensitization involving illumination of Rose Bengal. Depending on whether the chromophore is dry or solubilized, this system produces either energy-transfer reactions leading to generation of singlet oxygen specifically, or a combination of energy-transfer and electron-transfer reactions, providing both singlet oxygen and reduced forms of oxygen, such as superoxide anion and hydrogen peroxide. In neither case were the reactive species mutagenic in strain TA104 of Salmonella typhimurium, which had been previously shown to be reverted by oxygen species generated by the hypoxanthine-xanthine oxidase system in aqueous medium. However, mixed oxygen species induced an increased lethality in a variety of DNA repair-deficient Escherichia coli strains. This genotoxic effect, mainly reparable by the uvrA and recA mechanisms, was efficiently prevented by the thiol N-acetyl-L-cysteine. Singlet oxygen itself failed to exert direct genotoxic effects, although secondary reactants produced by its reaction with cell components enhanced lethality in some repair-deficient bacteria. Distance-dependence analyses provided measurements of the lifetimes of the oxygen species generated in the gas phase. 35 refs., 7 figs., 2 tabs.

  6. Curcumin attenuates acrylamide-induced cytotoxicity and genotoxicity in HepG2 cells by ROS scavenging.

    PubMed

    Cao, Jun; Liu, Yong; Jia, Li; Jiang, Li-Ping; Geng, Cheng-Yan; Yao, Xiao-Feng; Kong, Ying; Jiang, Bao-Na; Zhong, Lai-Fu

    2008-12-24

    Acrylamide (AA), a proven rodent carcinogen, has recently been discovered in foods heated at high temperatures. This finding raises public health concerns. In our previous study, we found that AA caused DNA fragments and increase of reactive oxygen species (ROS) formation and induced genotoxicity and weak cytotoxicity in HepG2 cells. Presently, curcumin, a natural antioxidant compound present in turmeric was evaluated for its protective effects. The results showed that curcumin at the concentration of 2.5 microg/mL significantly reduced AA-induced ROS production, DNA fragments, micronuclei formation, and cytotoxicity in HepG2 cells. The effect of PEG-catalase on protecting against AA-induced cytotoxicity suggests that AA-induced cytotoxicity is directly dependent on hydrogen peroxide production. These data suggest that curcumin could attenuate the cytotoxicity and genotoxicity induced by AA in HepG2 cells. The protection is probably mediated by an antioxidant protective mechanism. Consumption of curcumin may be a plausible way to prevent AA-mediated genotoxicity.

  7. A new approach for the oocyte genotoxicity assay: adaptation of comet assay on mouse cumulus-oocyte complexes.

    PubMed

    Greco, F; Perrin, J; Auffan, M; Tassistro, V; Orsière, T; Courbiere, B

    2015-07-01

    Conventional genotoxicity tests are technically difficult to apply to oocytes, and results obtained on somatic cells cannot be extrapolated to gametes. We have previously described a comet assay (original-CA) on denuded mouse oocytes, but, in vivo, oocytes are not isolated from their surrounding follicular cells. Our objective was to develop a comet assay on cumulus-oocyte complexes (COC-CA) for a more physiological approach to study the genotoxicity of environmental factors on oocytes. For COC-CA, whole COC were exposed directly to exogenous agents after ovulation and removal from oviducts. Three conditions were studied: a negative control group, and two positive control groups, one of which was exposed to hydrogen peroxide (H2O2) and the other group was incubated with cerium dioxide nanoparticles (CeO2 NPs). With both tests, DNA damage was significant in the presence of both H2O2 and CeO2 NPs compared with the negative control. COC-CA offers an interesting tool for assaying the genotoxicity of environmental agents towards germinal cells. Furthermore, COC-CA is less time-consuming and simplifies the protocol of the original-CA, because COC-CA is easier to perform without the washing-out procedure.

  8. Evaluation of the water genotoxicity from Santos Estuary (Brazil) in relation to the sediment contamination and effluent discharges.

    PubMed

    Umbuzeiro, Gisela de A; Kummrow, Fábio; Roubicek, Deborah A; Tominaga, Maria Y

    2006-04-01

    The genotoxic activity of water samples collected in 9 different sites within the area of the Santos estuary was preliminary evaluated, and related to previous data on the genotoxicity of sediments and the contents of PAHs in both water and sediment samples. The liquid discharge of a steel mill (coke plant), known to be mutagenic, was chemically analyzed to determine its PAH content. For the water evaluation we employed the Salmonella/microsome assay with the strains TA98 and TA100 with and without S9 mix in the plate incorporation method. The water was filtered with an AP20 membrane before being extracted with XAD4 at natural and acidic pH. The industrial effluent was filtered in 0.45 microm membranes before being extracted with the liquid/liquid method. Both membranes containing the particulate material were extracted using ultrasonication. PAHs were found associated with the suspended particles present in the industrial effluent in accordance with mutagenicity data previously reported. In relation to the estuarine waters, sites 1 and 5 presented low levels of mutagenic activity only in the filtered water (liquid fraction) extracts. At site 3, both the filtered water and particulate solids presented also low mutagenicity. Results show that the mutagenic activity observed in water could not be directly related to the genotoxic activity and PAHs contents of the bottom sediments.

  9. Genome-wide redistribution of H3K27me3 is linked to genotoxic stress and defective growth

    PubMed Central

    Basenko, Evelina Y.; Sasaki, Takahiko; Ji, Lexiang; Prybol, Cameron J.; Burckhardt, Rachel M.; Schmitz, Robert J.; Lewis, Zachary A.

    2015-01-01

    H3K9 methylation directs heterochromatin formation by recruiting multiple heterochromatin protein 1 (HP1)-containing complexes that deacetylate histones and methylate cytosine bases in DNA. In Neurospora crassa, a single H3K9 methyltransferase complex, called the DIM-5,-7,-9, CUL4, DDB1 Complex (DCDC), is required for normal growth and development. DCDC-deficient mutants are hypersensitive to the genotoxic agent methyl methanesulfonate (MMS), but the molecular basis of genotoxic stress is unclear. We found that both the MMS sensitivity and growth phenotypes of DCDC-deficient strains are suppressed by mutation of embryonic ectoderm development or Su-(var)3-9; E(z); Trithorax (set)-7, encoding components of the H3K27 methyltransferase Polycomb repressive complex-2 (PRC2). Trimethylated histone H3K27 (H3K27me3) undergoes genome-wide redistribution to constitutive heterochromatin in DCDC- or HP1-deficient mutants, and introduction of an H3K27 missense mutation is sufficient to rescue phenotypes of DCDC-deficient strains. Accumulation of H3K27me3 in heterochromatin does not compensate for silencing; rather, strains deficient for both DCDC and PRC2 exhibit synthetic sensitivity to the topoisomerase I in