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Sample records for direct genotoxic mode

  1. 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.

  2. 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. PMID:27085472

  3. 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. Bioelectromagnetics. 37:234-243, 2016. © 2016 Wiley Periodicals, Inc. PMID:27018544

  4. Genotoxic mode of action predictions from a multiplexed flow cytometric assay and a machine learning approach.

    PubMed

    Bryce, Steven M; Bernacki, Derek T; Bemis, Jeffrey C; Dertinger, Stephen D

    2016-04-01

    Several endpoints associated with cellular responses to DNA damage as well as overt cytotoxicity were multiplexed into a miniaturized, "add and read" type flow cytometric assay. Reagents included a detergent to liberate nuclei, RNase and propidium iodide to serve as a pan-DNA dye, fluorescent antibodies against γH2AX, phospho-histone H3, and p53, and fluorescent microspheres for absolute nuclei counts. The assay was applied to TK6 cells and 67 diverse reference chemicals that served as a training set. Exposure was for 24 hrs in 96-well plates, and unless precipitation or foreknowledge about cytotoxicity suggested otherwise, the highest concentration was 1 mM. At 4- and 24-hrs aliquots were removed and added to microtiter plates containing the reagent mix. Following a brief incubation period robotic sampling facilitated walk-away data acquisition. Univariate analyses identified biomarkers and time points that were valuable for classifying agents into one of three groups: clastogenic, aneugenic, or non-genotoxic. These mode of action predictions were optimized with a forward-stepping process that considered Wald test p-values, receiver operator characteristic curves, and pseudo R(2) values, among others. A particularly high performing multinomial logistic regression model was comprised of four factors: 4 hr γH2AX and phospho-histone H3 values, and 24 hr p53 and polyploidy values. For the training set chemicals, the four-factor model resulted in 94% concordance with our a priori classifications. Cross validation occurred via a leave-one-out approach, and in this case 91% concordance was observed. A test set of 17 chemicals that were not used to construct the model were evaluated, some of which utilized a short-term treatment in the presence of a metabolic activation system, and in 16 cases mode of action was correctly predicted. These initial results are encouraging as they suggest a machine learning strategy can be used to rapidly and reliably predict new chemicals

  5. 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.

  6. 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

  7. Considering mutagenicity and genotoxicity in the cancer mode of action for naphthalene, styrene, and ethylbenzene

    EPA Science Inventory

    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 throug...

  8. 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...

  9. Sensitivity of Allium and Nicotiana in cellular and acellular comet assays to assess differential genotoxicity of direct and indirect acting mutagens.

    PubMed

    Bandyopadhyay, Atrayee; Mukherjee, Anita

    2011-05-01

    We have evaluated the extent of DNA damage induced by direct and indirect mutagens by cellular and acellular comet assays in two plant systems, Nicotiana tabacum (wild type tobacco) and Allium cepa (common onion). The objectives of this study were: (1) to generate dose-response curves for DNA migration values from root and shoot nuclei of A. cepa and N. tabacum treated with the direct acting mutagens, ethyl methanesulphonate (EMS), hydrogen peroxide (H(2)O(2)) and the indirect acting mutagen, cadmium chloride (CdCl(2)), (2) to assess the differential response between isolated nuclei and nuclei of root and shoot and of both plants and (3) to examine the differences of sensitivity between direct and indirect acting mutagens by cellular and acellular comet assays. Similar sensitivities were evident in both plant systems to direct and indirect acting mutagens. The combination of cellular and acellular comet assays provided valuable insight to the mode of action of the genotoxicants used. The data obtained demonstrated the estimable capacity of the two plant systems to evaluate genotoxicity under different stress conditions and suggests Allium is a more desirable test system for rapid monitoring of genotoxicity. PMID:21237510

  10. 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

  11. Genotoxicity of tri- and hexavalent chromium compounds in vivo and their modes of action on DNA damage in vitro.

    PubMed

    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

  12. 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...

  13. 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

  14. Mode characteristics and directional emission for square microcavity lasers

    NASA Astrophysics Data System (ADS)

    Yang, Yue-De; Huang, Yong-Zhen

    2016-06-01

    Square microcavities with high quality factor whispering-gallery-like modes have a series of novel optical properties and can be employed as compact-size laser resonators. In this paper, the mode characteristics of square optical microcavities and the lasing properties of directional-emission square semiconductor microlasers are reviewed for the realization of potential light sources in the photonic integrated circuits and optical interconnects. A quasi-analytical model is introduced to describe the confined modes in square microcavities, and high quality factor whispering-gallery-like modes are predicted by the mode-coupling theory and confirmed by the numerical simulation. An output waveguide directly coupled to the position with weak mode field is used to achieve directional emission and control the lasing mode. Electrically-pumped InP-based directional-emission square microlasers are realized at room temperature, and the lasing spectra agree well with the mode analysis. Different kinds of square microcavity lasers, including dual-mode laser with a tunable interval, single-mode laser with a wide tunable wavelength range, and high-speed direct-modulated laser are also demonstrated experimentally.

  15. 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.

  16. 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.

  17. A metabolomics investigation of non genotoxic carcinogenicity in the rat

    PubMed Central

    Ament, Zsuzsanna; Waterman, Claire L; West, James A; Waterfield, Catherine; Currie, Richard A; Wright, Jayne; Griffin, Julian L

    2014-01-01

    Non-genotoxic carcinogens (NGCs) promote tumour growth by altering gene expression which ultimately leads to cancer without directly causing a change in DNA sequence. As a result NGCs are not detected in mutagenesis assays. Whilst there are proposed biomarkers of carcinogenic potential, the definitive identification of non-genotoxic carcinogens still rests with the rat and mouse long term bioassay. Such assays are expensive, time consuming, require a large number of animals and their relevance to human health risk assessments is debatable. Metabolomics and lipidomics in combination with pathology and clinical chemistry were used to profile perturbations produced by 10 compounds which represented a range of rat non-genotoxic hepatocarcinogens (NGC), non-genotoxic non-hepatocarcinogens (non-NGC) and a genotoxic hepatocarcinogen. Each compound was administered at its maximum tolerated dose level for 7, 28 and 91 days to male Fisher 344 rats. Changes in liver metabolite concentration differentiated the treated groups across different time points. The most significant differences were driven by pharmacological mode of action, specifically by the peroxisome proliferator activated receptor alpha (PPAR-α) agonists. Despite these dominant effects, good predictions could be made when differentiating NGCs from non-NGCs. Predictive ability measured by leave one out cross validation was 87% and 77% after 28 days of dosing for NGCs and non-NGCs, respectively. Amongst the discriminatory metabolites we identified free fatty acids, phospholipids, triacylglycerols, as well as precursors of eicosanoid and the products of reactive oxygen species linked to processes of inflammation, proliferation and oxidative stress. Thus, metabolic profiling is able to identify changes due to the pharmacological mode of action of xenobiotics and contribute to early screening for non-genotoxic potential. PMID:24161236

  18. 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

  19. Chiral modes and directional lasing at exceptional points.

    PubMed

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

    2016-06-21

    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

  20. 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

  1. Direct Optical Probing of Transverse Electric Mode in Graphene

    NASA Astrophysics Data System (ADS)

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

    2016-02-01

    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.

  2. Transient mode competition in directly modulated DFB semiconductor laser

    NASA Astrophysics Data System (ADS)

    Xiao, RuLei; Shi, YueChun; Zheng, JiLin; Zhang, YunShan; Zheng, JunShou; Chen, XiangFei

    2015-12-01

    A new effect of transient mode competition in directly modulated DFB laser based on equivalent phase-shift (EPS) technique is presented and studied. Since there are multi-order reflections in EPS structure and if the 0th order subgrating is properly designed, the transient lasing of 0th order will occur during the rising time of the injection current. As a result, transient mode competition between -1st order (main mode) and 0th order will occur accordingly. This can consume redundant carrier and suppress the transient relaxation oscillation, which may be applied in some areas like on-off switching modulation of DFB semiconductor lasers. As an example, an equivalent π phase shift (π-EPS) is carefully designed to realize the effect. In such a laser the 0th order wavelength is in the margin of the material gain region and the -1st order wavelength is around the gain peak, while the stable single longitudinal mode (SLM) operation of the -1st order is guaranteed. The simulation investigation is performed. Good results with suppressed relaxation oscillation and 1.25 Gb/s directly on-off modulation (32 dB extinction ratio) are demonstrated. We believe it provides a new kind of method for on-off switching with high extinction ratio and weak relaxation oscillation.

  3. Comparing Direct and Semi-Direct Modes for Speaking Assessment: Affective Effects on Test Takers

    ERIC Educational Resources Information Center

    Qian, David D.

    2009-01-01

    In recent decades, with an increasing application of computer technology to the delivery of oral language proficiency assessment, there have been renewed debates over the appropriateness of two different testing modes, namely, (a) face-to-face, or direct, testing, and (b) person-to-machine, or semi-direct, testing. Previous research conducted in…

  4. 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...

  5. SOS Chromotest, a Direct Assay of Induction of an SOS Function in Escherichia coli K-12 to Measure Genotoxicity

    NASA Astrophysics Data System (ADS)

    Quillardet, Philippe; Huisman, Olivier; D'Ari, Richard; Hofnung, Maurice

    1982-10-01

    We present and evaluate the SOS chromotest, a bacterial test for detecting DNA-damaging agents. It is a colorimetric assay based on the induction by these agents of the SOS function sfiA, whose level of expression is monitored by means of a sfiA::lacZ operon fusion. The response is rapid (a few hours), and does not require survival of the tester strain. Dose-response curves for various chemicals include a linear region. The slope of this region is taken as a measure of the SOS inducing potency. Comparison for a number of substances of known genotoxicity of the SOS inducing potency determined in the SOS chromotest with the mutagenic potency determined in the Salmonella assay (mutatest) revealed a striking quantitative correlation over more than 7 orders of magnitude. The sensitivity of the SOS chromotest (lowest amount detected) is equal to that of the mutatest and generally 4-40 times higher than that of a phage induction assay (inductest). From a practical point of view our observations contribute to the validation of the SOS chromotest as a test for detecting genotoxins and in particular genotoxic carcinogens. From a theoretical standpoint the results suggest that mutagenic potency measured in the mutatest reflects the level of induction of an SOS function and that most genotoxins are inducers of the SOS response in bacteria.

  6. SOS chromotest, a direct assay of induction of an SOS function in Escherichia coli K-12 to measure genotoxicity.

    PubMed Central

    Quillardet, P; Huisman, O; D'Ari, R; Hofnung, M

    1982-01-01

    We present and evaluate the SOS chromotest, a bacterial test for detecting DNA-damaging agents. It is a colorimetric assay based on the induction by these agents of the SOS function sfiA, whose level of expression is monitored by means of a sfiA::lacZ operon fusion. The response is rapid (a few hours), and does not require survival of the tester strain. Dose-response curves for various chemicals include a linear region. The slope of this region is taken as a measure of the SOS inducing potency. Comparison for a number of substances of known genotoxicity of the SOS inducing potency determined in the SOS chromotest with the mutagenic potency determined in the Salmonella assay (mutatest) revealed a striking quantitative correlation over more than 7 orders of magnitude. The sensitivity of the SOS chromotest (lowest amount detected) is equal to that of the mutatest and generally 4-40 times higher than that of a phage induction assay (inductest). From a practical point of view our observations contribute to the validation of the SOS chromotest as a test for detecting genotoxins and in particular genotoxic carcinogens. From a theoretical standpoint the results suggest that mutagenic potency measured in the mutatest reflects the level of induction of an SOS function and that most genotoxins are inducers of the SOS response in bacteria. PMID:6821127

  7. 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

  8. Robustness of superconducting quantum modes against direct quasiparticle injection

    NASA Astrophysics Data System (ADS)

    Patel, U.; Nsanzineza, I.; Vavilov, M. G.; Plourde, B. L. T.; McDermott, R.

    Classical Josephson digital logic based on Single Flux Quantum (SFQ) pulses offers a path to high-fidelity coherent control of large-scale superconducting quantum machines. However, an SFQ pulse driver generates nonequilibrium quasiparticles that contribute to qubit relaxation, and steps must be taken to protect the qubit from this decoherence channel. Here we describe experiments to characterize the robustness of high-Q superconducting linear resonators and qubits against direct quasiparticle injection. We use NIS junctions and SFQ elements to controllably inject quasiparticles into the groundplane of superconducting resonator and qubit chips, and we characterize the quasiparticle contribution to dissipation. We examine the effectiveness of groundplane cuts, normal metal quasiparticle traps, and spatially-varying superconducting gaps at protecting the quantum modes against quasiparticle loss. Finally, we discuss strategies for the integration of multiqubit circuits with on-chip SFQ control elements.

  9. 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. PMID:20370163

  10. Convenient, multi-well plate-based DNA damage response analysis using DT40 mutants is applicable to a high-throughput genotoxicity assay with characterization of modes of action

    PubMed Central

    Ridpath, John R.; Takeda, Shunichi; Swenberg, James A.; Nakamura, Jun

    2012-01-01

    Chemists continually synthesize myriad new chemicals (~2000/yr), some of which make their way into the environment or otherwise pose possible threats to humans who potentially become exposed to the compounds. Regulators must determine whether these, along with the glut (~80,000) of existing, chemicals are toxic and at what exposure levels. An important component of this determination is to ascertain the mode of action (MOA) of each compound as it relates to the pathway the compound uses to induce genotoxicity. Several assays have traditionally been used to reveal these effects to the genome: the Ames test, tests with yeast and mammalian cell lines, and animal studies. Previously, we described a new multi-well plate-based method which makes use of the DT40 isogenic cell line and its dozens of available mutants knocked out in DNA repair and cell cycle pathways and we now provide a detailed protocol of the further improvement of the assay. Although the DT40 line has existed for some time and has been used in numerous studies of DNA repair pathways, little use has been made of this valuable resource for toxicological investigations. Our method introduces the XTT dye scheme determination of cell survival in a manner that greatly increases throughput and reduces cost while maintaining reasonable sensitivity. Although this new genotoxicity assay requires validation with many more mutagens before becoming an established, regulatory decision-making analysis tool, we believe that this method will be very advantageous if eventually added to the repertoire of those investigating MOAs of potentially genotoxic substances. PMID:20839229

  11. 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.

  12. Influence of anoxia and respiratory deficiency on the genotoxicity of some direct-acting alkylating agents in yeast.

    PubMed

    Deorukhakar, V V; Murthy, M S

    1991-01-01

    We have studied the influence of anoxia and respiratory deficiency (RD) in yeast on the cytotoxic and recombinogenic effects of 5 direct-acting alkylating agents, namely N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), methylnitrosourea (MNU), ethylnitrosourea (ENU), methyl methanesulphonate (MMS) and ethyl methanesulphonate (EMS). We found that the effects of both conditions parallel each other for MMS, MNNG, MNU and ENU. Both anoxia and RD did not modify the effects of MMS to any significant extent. On the other hand, anoxic and respiratory-deficient cells were found to be more resistant than euoxic and respiratory-proficient cells respectively for MNNG, MNU and ENU. In the case of EMS, which is similar to MMS in its chemical reaction with DNA, the respiratory-deficient cells were found to be more sensitive than the respiratory-proficient ones. These studies indicate that the response of anoxic and respiratory-deficient cells cannot be predicted solely on the basis of the chemical reactivity pattern of the alkylating agents. The physiological state which exists under these conditions may exert considerable influence on the cellular response. PMID:1846028

  13. 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.

  14. Numerical Simulation of Direct Exitation of the TE11 Mode in a Coaxial Vircator

    NASA Astrophysics Data System (ADS)

    Möller, Cecilia; Hurtig, Tomas; Larsson, Anders; Nyholm, Sten E.

    Studies of the concept of direct excitation of the TE11 mode in a coaxial vircator using three-dimensional particle-in-cell simulations is presented. The excitation of the TE11 mode is made possible by sectioning the emitting surface of the cathode, thus creating two interacting virtual cathodes. It is shown that the two virtual cathodes formed oscillate in push-pull mode as previously has been described for a planar geometry.

  15. Spurious Modes in Spectral Collocation Methods with Two Non-Periodic Directions

    NASA Technical Reports Server (NTRS)

    Balachandar, S.; Madabhushi, Ravi K.

    1992-01-01

    Collocation implementation of the Kleiser-Schumann's method in geometries with two non-periodic directions is shown to suffer from three spurious modes - line, column and checkerboard - contaminating the computed pressure field. The corner spurious modes are also present but they do not affect evaluation of pressure related quantities. A simple methodology in the inversion of the influence matrix will efficiently filter out these spurious modes.

  16. Directional couplers for detecting the TE sub 11 and TE sub 12 circular waveguide modes

    NASA Technical Reports Server (NTRS)

    Hoppe, D.

    1987-01-01

    The theoretical and experimental results for a pair of mode-selective directional couplers designed to detect the TE sub 11 and TE sub 12 modes in a multimode circular wavelength are described. A brief description of the design of the couplers is presented, followed by a comparison of their measured and calculated parameters. The couplers were used to measure the characteristics of a circular waveguide mode converter. The results of these measurements are described.

  17. Integrated dual-mode 3 dB power coupler based on tapered directional coupler

    PubMed Central

    Luo, Yuchan; Yu, Yu; Ye, Mengyuan; Sun, Chunlei; Zhang, Xinliang

    2016-01-01

    A dual-mode 3 dB power coupler based on silicon-on-insulator platform for mode division multiplexing system is proposed and demonstrated. The device, which consists of a tapered directional coupler and two output bend waveguides, has a 50:50 coupling ratio around the wavelength of 1550 nm for both fundamental and first order transverse magnetic (TM0 and TM1) modes. Based on asymmetrical tapered structure, a short common coupling length of ~15.2 μm for both modes is realized by optimizing the width of the tapered waveguide. The measured insertion loss for both modes is less than 0.7 dB. The crosstalks are about −14.3 dB for TM0 mode and −18.1 dB for TM1 mode. PMID:27002747

  18. Integrated dual-mode 3 dB power coupler based on tapered directional coupler.

    PubMed

    Luo, Yuchan; Yu, Yu; Ye, Mengyuan; Sun, Chunlei; Zhang, Xinliang

    2016-01-01

    A dual-mode 3 dB power coupler based on silicon-on-insulator platform for mode division multiplexing system is proposed and demonstrated. The device, which consists of a tapered directional coupler and two output bend waveguides, has a 50:50 coupling ratio around the wavelength of 1550 nm for both fundamental and first order transverse magnetic (TM0 and TM1) modes. Based on asymmetrical tapered structure, a short common coupling length of ~15.2 μm for both modes is realized by optimizing the width of the tapered waveguide. The measured insertion loss for both modes is less than 0.7 dB. The crosstalks are about -14.3 dB for TM0 mode and -18.1 dB for TM1 mode. PMID:27002747

  19. Direct coupling of photonic modes and surface plasmon polaritons observed in 2-photon PEEM.

    PubMed

    Word, Robert C; Fitzgerald, Joseph P S; Könenkamp, Rolf

    2013-12-16

    We report the direct microscopic observation of optical energy transfer from guided photonic modes in an indium tin oxide (ITO) thin film to surface plasmon polaritons (SPP) at the surfaces of a single crystalline gold platelet. The photonic and SPP modes appear as an interference pattern in the photoelectron emission yield across the surface of the specimen. We explore the momentum match between the photonic and SPP modes in terms of simple waveguide theory and the three-layer slab model for bound SPP modes of thin metal films. We show that because the gold is thin (30-40 nm), two SPP modes exist and that momentum of the spatially confined asymmetric field mode coincides with the dominant mode of the ITO waveguide. The results demonstrate that photoemission electron microscopy (PEEM) can be an important tool for the observation of photonic to SPP interactions in the study of integrated photonic circuits. PMID:24514628

  20. Direct determination of the number of transverse modes of a light beam.

    PubMed

    Karny, Z; Lavi, S; Kafri, O

    1983-07-01

    A method based on moiré deflectometry for direct determination of the number of transverse modes of radiation of a light beam is presented. An expression for the number of transverse modes of a light beam, as a function of the beam divergence, is derived. We demonstrate the method for a Cu-vapor laser-beam analysis. PMID:19718131

  1. 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. PMID:26766727

  2. Direct Estimation of Fine and Coarse Mode Particle Parameters from Multiwavelength Lidar Measurements

    NASA Astrophysics Data System (ADS)

    Kolgotin, Alexei; Korenskiy, Mikhail; Veselovskii, Igor; Whiteman, David N.

    2016-06-01

    An approach for the direct estimation (DE) of particle parameters in the fine and coarse mode from multiwavelength lidar measurements is presented. Particle size distributions in both modes are approximated by rectangular functions, so the particle density is estimated directly without solving the inverse problem. The numerical simulation demonstrates that the particle volume in both modes can be estimated from 3β+2α lidar measurements with uncertainty of ~25% for a wide range of size distributions. The technique developed was applied to the observations of NASA GSFC Raman lidar. Comparison of the results obtained with DE and regularization approach applied to the same set of data demonstrates agreement between these two techniques.

  3. 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. PMID:26686458

  4. 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 ...

  5. Tapered acoustical directional couplers for integrated acousto-optical mode converters with weighted coupling

    NASA Astrophysics Data System (ADS)

    Herrmann, Harald; Rust, Ulrich; Schafer, Klaus

    1995-03-01

    Weighted coupling for strong sidelobe suppression of integrated acoustooptical mode converters in LiNbO3 using acoustical directional couplers has been studied theoretically and experimentally. A parameter free model for the propagation of surface acoustic waves in guiding structures has been developed based on a step-like variation of the acoustic velocity. Comparisons of theoretical results with experimental ones for acoustic waveguides and directional coupler structures confirm the applicability of the model. A coupled mode description of the acousto-optical polarization conversion in converters with acoustical directional couplers has been developed and applied to several tapered acoustical directional couplers. The model reveals that the conversion characteristics are usually strongly asymmetric. If the directional coupler is appropriately designed, a sidelobe suppression of about 30 dB can be achieved. First experimental results with tapered directional couplers confirm within some limits the theoretical predictions.

  6. Genotoxicity of phthalates.

    PubMed

    Erkekoglu, Pınar; Kocer-Gumusel, Belma

    2014-12-01

    Many of the environmental, occupational and industrial chemicals are able to generate reactive oxygen species (ROS) and cause oxidative stress. ROS may lead to genotoxicity, which is suggested to contribute to the pathophysiology of many human diseases, including inflammatory diseases and cancer. Phthalates are ubiquitous environmental chemicals and are well-known peroxisome proliferators (PPs) and endocrine disruptors. Several in vivo and in vitro studies have been conducted concerning the carcinogenic and mutagenic effects of phthalates. Di(2-ethylhexyl)-phthalate (DEHP) and several other phthalates are shown to be hepatocarcinogenic in rodents. The underlying factor in the hepatocarcinogenesis is suggested to be their ability to generate ROS and cause genotoxicity. Several methods, including chromosomal aberration test, Ames test, micronucleus assay and hypoxanthine guanine phosphoribosyl transferase (HPRT) mutation test and Comet assay, have been used to determine genotoxic properties of phthalates. Comet assay has been an important tool in the measurement of the genotoxic potential of many chemicals, including phthalates. In this review, we will mainly focus on the studies, which were conducted on the DNA damage caused by different phthalate esters and protection studies against the genotoxicity of these chemicals. PMID:25174766

  7. A relativistic backward wave oscillator for directly generating circularly polarized TE11 mode

    NASA Astrophysics Data System (ADS)

    Xiao, Renzhen; Zhang, Zhiqiang; Liang, Tiezhu; Deng, Yuqun; Li, Jiawei; Zhang, Qingyuan

    2016-03-01

    A relativistic backward wave oscillator for directly generating circularly polarized TE11 mode is proposed. In the device, the electrodynamics structures are divided into two groups in azimuth, each group consisting of two opposite 90 ° sectors, to produce two orthogonal TE11 modes. The axial position of the two groups is shifted to each other with a quarter of slow wave structure period to achieve a 90 ° phase difference between the two orthogonal TE11 modes. In particle-in-cell simulation, a circularly polarized TE11 mode with 1.5 GW power has been demonstrated. The amplitude ratio between the two orthogonal TE11 modes is smaller than 0.5 dB, and the phase difference is close to 90 ° .

  8. Direct diode-pumped Kerr-lens mode-locked Ti:sapphire laser.

    PubMed

    Durfee, Charles G; Storz, Tristan; Garlick, Jonathan; Hill, Steven; Squier, Jeff A; Kirchner, Matthew; Taft, Greg; Shea, Kevin; Kapteyn, Henry; Murnane, Margaret; Backus, Sterling

    2012-06-18

    We describe a Ti:sapphire laser pumped directly with a pair of 1.2 W 445 nm laser diodes. With over 30 mW average power at 800 nm and a measured pulsewidth of 15 fs, Kerr-lens-modelocked pulses are available with dramatically decreased pump cost. We propose a simple model to explain the observed highly stable Kerr-lens modelocking in spite of the fact that both the mode-locked and continuous-wave modes are smaller than the pump mode in the crystal. PMID:22714433

  9. Direct diode-pumped Kerr-lens mode-locked Ti:sapphire laser

    PubMed Central

    Durfee, Charles G.; Storz, Tristan; Garlick, Jonathan; Hill, Steven; Squier, Jeff A.; Kirchner, Matthew; Taft, Greg; Shea, Kevin; Kapteyn, Henry; Murnane, Margaret; Backus, Sterling

    2012-01-01

    We describe a Ti:sapphire laser pumped directly with a pair of 1.2W 445nm laser diodes. With over 30mW average power at 800 nm and a measured pulsewidth of 15fs, Kerr-lens-modelocked pulses are available with dramatically decreased pump cost. We propose a simple model to explain the observed highly stable Kerr-lens modelocking in spite of the fact that both the mode-locked and continuous-wave modes are smaller than the pump mode in the crystal. PMID:22714433

  10. 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.

  11. The Direction Cosine Method of Scatterer Location Extended to Spotlight-Mode IFSAR

    SciTech Connect

    EICHEL,PAUL H.

    2000-10-26

    In this paper we have shown how the direction cosine method of stripmap-mode IFSAR maybe modified for use in the spotlight-mode case. Spotlight-mode IFSAR geometry dictates a common aperture phase center, velocity vector, and baseline vector for every pixel in an image. Angle with respect to the velocity vector is the same for every pixel in a given column and can be computed from the column index, the Doppler of the motion compensation point and the Doppler column sample spacing used in image formation. With these modifications, the direction cosines and length of the line of sight vector to every scatterer in the scene may be computed directly from the raw radar measurements of range, Doppler, and interferometric phase.

  12. 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.

  13. 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.

  14. Direct excitation of TE11 mode in a relativistic backward wave oscillator

    NASA Astrophysics Data System (ADS)

    Xiao, Renzhen; Zhang, Yuchuan; Li, Jiawei; Song, Zhimin; Sun, Jun

    2016-02-01

    A relativistic backward wave oscillator for directly generating TE11 mode is proposed. An axially asymmetric slow wave structure and a sectioned annular cathode are introduced to suppress the TM01 mode and excite the TE11 mode. A pre-modulation dual-cavity, which allows part of the backward power to propagate into the diode region, is adopted to optimize the electron beam bunch, indicating that the conventional design principle that the diode region and the beam-wave interaction region should be isolated can be broken to increase the interaction efficiency. Particle-in-cell simulations show that when the diode voltage is 780 kV, and beam current is 6.1 kA, a microwave with power of 2.0 GW, and frequency of 9.25 GHz can be obtained, corresponding to an efficiency of 42%. Furthermore, the main output mode is TE11 mode, and the power of the cross-polarized mode is less than 10% within the calculation time of 50 ns.

  15. Laser direct writing of complex radially varying single-mode polymer waveguide structures

    NASA Astrophysics Data System (ADS)

    Kruse, Kevin; Peng, Jie; Middlebrook, Christopher T.

    2015-07-01

    Increasing board-to-board and chip-to-chip computational data rates beyond 12.5 Gbs will require the use of single-mode polymer waveguides (WGs) that have high bandwidths and are able to be wavelength division multiplexed. Laser direct writing (LDW) of polymer WGs provides a scalable and reconfigurable maskless procedure compared to common photolithography fabrication. LDW of straights and radial curves are readily achieved using predefined drive commands of the two-axis direct drive linear stage system. Using the laser direct write process for advanced WG structures requires stage-drive programming techniques that account for specified polymer material exposure durations. Creating advanced structures such as WG S-bends into single-mode polymer WG builds provides designers with the ability to affect pitch control, optical coupling, and reduce footprint requirements. Fabrication of single-mode polymer WG segmented radial arcs is achieved through a smooth radial arc user-programmed defined mathematical algorithm. Cosine and raised-sine S-bends are realized through a segmentation method where the optimal incremental step length and bend dimensions are controlled to achieve minimal structure loss. Laser direct written S-bends are compared with previously published photolithographic S-bend results using theoretical bend loss models. Fabrication results show that LDW is a viable method in the fabrication of advanced polymer WG structures.

  16. Direct imaging of radio-frequency modes via traveling wave magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Tonyushkin, A.; Deelchand, D. K.; Van de Moortele, P.-F.; Adriany, G.; Kiruluta, A.

    2016-01-01

    We demonstrate an experimental method for direct 2D and 3D imaging of magnetic radio-frequency (rf) field distribution in metal-dielectric structures based on traveling wave (TW) magnetic resonance imaging (MRI) at ultra-high field (>7 T). The typical apparatus would include an ultra-high field whole body or small bore MRI scanner, waveguide elements filled with MRI active dielectrics with predefined electric and magnetic properties, and TW rf transmit-receive probes. We validated the technique by obtaining TW MR images of the magnetic field distribution of the rf modes of circular waveguide filled with deionized water in a 16.4 T small-bore MRI scanner and compared the MR images with numerical simulations. Our MRI technique opens up a practical non-perturbed way of imaging of previously inaccessible rf field distribution of modes inside various shapes metal waveguides with inserted dielectric objects, including waveguide mode converters and transformers.

  17. Direct observation of collective modes coupled to molecular orbital-driven charge transfer

    NASA Astrophysics Data System (ADS)

    Ishikawa, Tadahiko; Hayes, Stuart A.; Keskin, Sercan; Corthey, Gastón; Hada, Masaki; Pichugin, Kostyantyn; Marx, Alexander; Hirscht, Julian; Shionuma, Kenta; Onda, Ken; Okimoto, Yoichi; Koshihara, Shin-ya; Yamamoto, Takashi; Cui, Hengbo; Nomura, Mitsushiro; Oshima, Yugo; Abdel-Jawad, Majed; Kato, Reizo; Miller, R. J. Dwayne

    2015-12-01

    Correlated electron systems can undergo ultrafast photoinduced phase transitions involving concerted transformations of electronic and lattice structure. Understanding these phenomena requires identifying the key structural modes that couple to the electronic states. We report the ultrafast photoresponse of the molecular crystal Me4P[Pt(dmit)2]2, which exhibits a photoinduced charge transfer similar to transitions between thermally accessible states, and demonstrate how femtosecond electron diffraction can be applied to directly observe the associated molecular motions. Even for such a complex system, the key large-amplitude modes can be identified by eye and involve a dimer expansion and a librational mode. The dynamics are consistent with the time-resolved optical study, revealing how the electronic, molecular, and lattice structures together facilitate ultrafast switching of the state.

  18. 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. PMID:26929995

  19. 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 -}.

  20. Mode Locking of Spin Waves Excited by Direct Currents in Microwave Nano-oscillators

    NASA Astrophysics Data System (ADS)

    Rezende, S. M.; de Aguiar, F. M.; Rodríguez-Suárez, R. L.; Azevedo, A.

    2007-02-01

    A spin-wave theory is presented which explains the frequency pulling and mode locking observed when two closely spaced spin-transfer nanometer-scale oscillators with slightly different frequencies are separately driven in the same magnetic thin film by spin-polarized carriers at high direct-current densities. The theory confirms recent experimental evidence that the origin of the phenomena lies in the nonlinear interaction between two overlapping spin waves excited in the magnetic nanostructure.

  1. Local mode excitation and direct unimolecular reaction rate measurements in tetramethyldioxetane

    SciTech Connect

    Cannon, B.D.; Crim, F.F.

    1981-08-15

    Direct excitation of overtone vibrations combined with time-resolved detection of product chemiluminescence produces both overtone vibration excitation spectra and directly measured unimolecular decay rates of tetramethyldioxetane. The spectra show increasingly pure local mode character in higher vibrational levels and exhibit splittings which arise from nonequivalent sites occupied by methyl hydrogens. The temporal evolution of the signal reflects the unimolecular decomposition rate of the highly vibrationally excited molecule, and comparing the observed behavior to Rice--Ramsperger--Kassel--Marcus theory calculations shows that they adequately describe the decomposition if properly averaged over the thermal vibrational energy content of the molecule.

  2. 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. PMID:25410580

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

    NASA Astrophysics Data System (ADS)

    Lo, An-Ya; Liu, Shang-Bin; Kuo, Cheng-Tzu

    2010-09-01

    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 Δ T, 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 Δ T 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 Δ T > 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 Δ T to obtain the desired growth mode of CNTs by thermal or plasma-enhanced CVD systems for different applications.

  4. 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

  5. 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

  6. 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.

  7. 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

    2016-01-01

    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/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. PMID:27297267

  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. Single-Mode Fiber-Optic Directional Couplers For Narrow Spectral Linewidth Analyser

    NASA Astrophysics Data System (ADS)

    Belovolov, , M. I.; Dianov, E. M.; Krjukov, A. P.; Pencheva, V. H.

    1988-02-01

    A new design of Y-type end-fused single-mode fiber directional couplers has been suggest ed, and its optimum parameters with which it is possible to obtain losses of 0,5-1 dB have been determined. Cross-talk attenuation between reverse channels exceeds 60 dB. It has been found by experiments that transmission coefficients of the developed couplers are stable at wavelength variations. Furthermore, Y-type directional couplers maintain polarization state of the propagating radiation. Simple Michelson interferometer based on Y-type fiber optic directional couplers with a new optical fringe visibility registration system for the narrow linewidth( ▵V) = 10 kHz - 1 MHz) analysis of the single-frequency lasers has been created.

  10. Genotoxicity of glycol ethers.

    PubMed Central

    McGregor, D B

    1984-01-01

    The genetic toxicology of glycol ethers is reviewed. Ethylene glycol monomethyl ether (EGME) and diglyme have been more extensively studied than other members of this series. Most results indicate a lack of genotoxic potential, but certain tests have yielded positive responses with certain compounds. Ethylene glycol monoethyl ether (EGEE) induced sister chromatid exchanges and chromosomal aberrations in cultured cells. Both EGME and diglyme induced mouse sperm head morphological changes, male rat weak dominant lethal mutations and marked, but reversible, loss of male rat fertility. PMID:6541999

  11. 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 research dealt with direct geolocation of spaceborne high-resolution SAR image. The TerraSAR-X spotlight mode image was chosen as the study object. The mathematical model of SAR geolocation is Range-Doppler (RD) model. Its resolving algorithms had been studied and the ASF algorithm was chosen because of its high accuracy. The focus of this research laid on the error sources and their correction method which could affect the geolocation accuracy, such as the orbit errors, azimuth timing errors and range timing errors. At last, the accuracy of this method was verified by the experiment results.

  12. Indirect mechanisms of genotoxicity.

    PubMed

    Kirsch-Volders, Micheline; Vanhauwaert, Annelies; Eichenlaub-Ritter, Ursula; Decordier, Ilse

    2003-04-11

    Indirect mechanisms of genotoxicity correspond to interactions of mutagens with non-DNA targets, and are expected to show threshold concentration-effect response curves. If these thresholds can be proven experimentally they may provide a third alternative for risk assessment, besides the No Effect Level/Safety Factor approach and the low dose linear extrapolation method. We contributed significantly to the in vitro assessment of thresholds in human lymphocytes exposed to the spindle inhibitors nocodazole and carbendazim showing dose dependency and existence of lower thresholds for induction of non-disjunction as compared to chromosome loss. Micronuclei correlated with p53-independent or p53-dependent apoptosis and elimination of aneuploid cells. Extrapolation from in vitro threshold values to the in vivo situation remains unsolved. Comparing the in vitro threshold values for griseofulvin in human and rat lymphocytes with in vivo NOAEL/LOAEL in bone marrow/gut/erythrocytes suggests that the in vitro human system is the most sensitive. The threshold for induction of non-disjunction in in vitro maturing, nocodazole-exposed mouse oocytes was in the same low range. Regulators (UK Committee on Mutagenicity, http://www.doh.gov.uk/com/com.htm) considered the importance of thresholds for indirect mechanisms of genotoxicity. Acceptance of a non-linear extrapolation for mutagens requires mechanistic studies identifying the mutagen/target interactions. Moreover appropriate risk evaluation will require additional studies on individual susceptibility for indirect mutagenic effects and on interactions of aneugens in complex mixtures. PMID:12676452

  13. Two modes of a plasma jet excited by a direct current voltage

    NASA Astrophysics Data System (ADS)

    Li, Xuechen; Zhang, Panpan; Bao, Wenting; Jia, Pengying; Chu, Jingdi

    2016-04-01

    A plasma jet excited by a direct current voltage is developed to generate a diffuse plasma plume by blowing atmospheric pressure argon. Results show that the plume discharge operates in a single-pulsed mode or a continuous one depending on the applied voltage. For the single-pulsed mode, the discharge frequency increases with increasing the applied voltage or the air concentration, while it keeps almost constant with increasing the argon flow rate. The discharge dynamics at the breakdown stage indicate that the light emission propagates along the gas flow at a velocity in the order of 104 m s-1. The spatially resolved emission intensity at the afterglow stage of the pulsed discharge manifests a stratification into dark and bright luminous regions along the gas flow. For the continuous mode, however, the emission intensity gradually decreases along the gas flow. It is found that the continuous discharge is in a Townsend discharge regime judged from both the positive slope of the voltage-current curve and the small current density on the cathode surface. Based on optical emission spectroscopy, excited electron temperature and gas temperature of the plasma plume are obtained by a Boltzmann plot and fitting the spectra of OH radicals, respectively.

  14. 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.

  15. Laser direct micro-machining with top-hat-converted single mode lasers

    NASA Astrophysics Data System (ADS)

    Homburg, O.; Toennissen, F.; Mitra, T.; Lissotschenko, V.

    2008-02-01

    Laser direct micro-machining processes are used in a variety of industries like inkjet printing, semiconductor processing, solar technology, flat-panel display production and medicine. Various kinds of materials, e.g. ceramics, metals, isolators, oxides, organics and semiconductors are being structured. In most cases pulsed single mode solid state lasers with an inhomogeneous Gaussian beam profile are employed, like YAG lasers and their harmonics. However, the quality and functionality of the generated structures and micro-systems as well as the speed of the process can be improved by the utilization of homogeneous top hat profiles. The beam shaping principle of refractive Gaussian-to-top-hat converters is shown. Compact beam shaper modules based on this principle have been developed - supporting most direct laser micro-machining applications. The resulting process advantages are demonstrated by selected application results, namely the drilling of holes and patterning of trenches for different kinds of materials.

  16. 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.

  17. 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.

  18. The genotoxicity of selenium.

    PubMed

    Shamberger, R J

    1985-07-01

    Selenium at nutritional levels has been shown to have numerous anticarcinogenic or preventative effects against carcinogen-induced breast, colon, liver and skin cancer in animals. Many of these anticarcinogenic effects have been summarized. In addition, numerous mutagenic and antimutagenic effects of selenium compounds have been reported. Some of the selenium compounds frequently tested for mutagenicity are listed in Table 1. Because of the numerous reported anticarcinogenic and preventative effects of selenium, many individuals are supplementing their diets with amounts of selenium that are greater than the recommended daily requirement. Selenium is also used widely in industrial products such as selenium rectifiers, photoelectric batteries, alloys and paints. Because selenium at higher levels is known to be toxic, there should be a greater understanding about its genotoxic as well as its beneficial effect. The object of this review is to summarize experimental evidence both for the antimutagenic and the mutagenic effect of selenium. PMID:3923345

  19. 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

  20. Burst-mode-operated, sub-nanosecond fiber MOPA system incorporating direct seed-packet shaping.

    PubMed

    Chen, Tao; Liu, Hao; Kong, Wei; Shu, Rong

    2016-09-01

    We report a novel burst-mode-operated sub-nanosecond fiber Master Oscillator, Power Amplifier (MOPA) system incorporating direct seed-packet shaping without external modulators. A fast digital-to-analog converter with 1 Gsps sampling rate and 16 bit resolution was developed to control the pulse amplitudes and sequences of a distributed feedback semiconductor seed laser to realize packet-shaped burst mode operation. Optical pulses with durations as short as 700 ps and peak power as high as 1 W can be generated from the seed by applying proper reverse voltages after positive electrical pulses to the laser driver to cancel the residual charges at its gate electrode. The average power of the laser can be amplified to nearly 40 W with FWHM spectral linewidth of ~0.12 nm after three stages of polarization maintaining fiber amplifiers. Different packet shapes including ramp-off, Gaussian, square and double rectangle can be produced from the fiber MOPA by finely pre-shaping the seed pulse bursts. It is believed that such a laser has provided a cost-effective solution to the generation of pulse bursts with arbitrary packet shapes for different practical applications including material micromachining and nonlinear frequency conversion. PMID:27607699

  1. Non-destructive Patterning of Carbon Electrodes by Using the Direct Mode of Scanning Electrochemical Microscopy.

    PubMed

    Stratmann, Lutz; Clausmeyer, Jan; Schuhmann, Wolfgang

    2015-11-16

    Patterning of glassy carbon surfaces grafted with a layer of nitrophenyl moieties was achieved by using the direct mode of scanning electrochemical microscopy (SECM) to locally reduce the nitro groups to hydroxylamine and amino functionalities. SECM and atomic force microscopy (AFM) revealed that potentiostatic pulses applied to the working electrode lead to local destruction of the glassy carbon surface, most likely caused by etchants generated at the positioned SECM tip used as the counter electrode. By applying galvanostatic pulses, and thus, limiting the current during structuring, corrosion of the carbon surface was substantially suppressed. After galvanostatic patterning, unambiguous proof of the formation of the anticipated amino moieties was possible by modulation of the pH value during the feedback mode of SECM imaging. This patterning strategy is suitable for the further bio-modification of microstructured surfaces. Alkaline phosphatase, as a model enzyme, was locally bound to the modified areas, thus showing that the technique can be used for the development of protein microarrays. PMID:26316379

  2. 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.

  3. 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.

  4. 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

  5. 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. PMID:26774663

  6. Genotoxicity of pyrrolizidine alkaloids.

    PubMed

    Chen, Tao; Mei, Nan; Fu, Peter P

    2010-04-01

    Pyrrolizidine alkaloids (PAs) are common constituents of many plant species around the world. PA-containing plants are probably the most common poisonous plants affecting livestock and wildlife. They can inflict harm to humans through contaminated food sources, herbal medicines and dietary supplements. Half of the identified PAs are genotoxic and many of them are tumorigenic. The mutagenicity of PAs has been extensively studied in different biological systems. Upon metabolic activation, PAs produce DNA adducts, DNA cross-linking, DNA breaks, sister chromatid exchange, micronuclei, chromosomal aberrations, gene mutations and chromosome mutations in vivo and in vitro. PAs induced mutations in the cII gene of rat liver and in the p53 and K-ras genes of mouse liver tumors. It has been suggested that all PAs produce a set of (+/-)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine-derived DNA adducts and similar types of gene mutations. The signature types of mutations are G : C --> T : A transversion and tandem base substitutions. Overall, PAs are mutagenic in vivo and in vitro and their mutagenicity appears to be responsible for the carcinogenesis of PAs. PMID:20112250

  7. 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. PMID:16005256

  8. Genotoxicity of Endodontic Materials: A Critical Review.

    PubMed

    Mohammadi, Zahed; Shalavi, Sousan; Jafarzadeh, Hamid; Bhandi, Shilpa; Patil, Shankargouda

    2015-08-01

    Genotoxicity is an action on cell's genetic material which may affect its integrity. This includes certain types of radiations and also certain chemical compounds. Genotoxic materials are those with affinity to interact with DNA but render them potentially carcinogenic or mutagenic. This review will address the genotoxicity of endodontic irrigants, medicaments and sealers. PMID:26423507

  9. Coupled-mode analysis of power-transfer characteristics in a three-waveguide nonlinear directional coupler

    NASA Astrophysics Data System (ADS)

    Yasumoto, K.; Mitsunaga, N.; Maeda, H.

    1996-03-01

    A planar three-waveguide nonlinear directional coupler (NLDC) is analyzed by the use of a coupled-mode approach based on the singular perturbation technique. The self-consistent first-order coupled-mode equations are derived in an analytically closed form, which demonstrates that the power transfer in three-waveguide NLDC is described by linear-coupling terms and nonlinear self-modulation terms. The optical switching characteristics predicted by the coupled-mode theory are discussed and shown to be in good agreement with those obtained from a numerical analysis with the finite-difference beam-propagation method.

  10. Polarization-dependent continuous change in the propagation direction of Dirac-cone modes in photonic-crystal slabs

    NASA Astrophysics Data System (ADS)

    Sakoda, Kazuaki

    2014-07-01

    We show that the propagation direction of the Dirac-cone modes of photonic-crystal slabs can be continuously controlled by the polarization of the incident wave. This property is realized by their isotropic dispersion relation and anisotropic mixture of two dipolar wave functions. To clarify these features, we formulate a Green-function method to describe the excitation process of the Dirac-cone modes and analyze the coupling strength with the incident wave by group theory. This angular dependence of the intensity distribution of the excited wave can be used for experimentally detecting the Dirac cones and distinguishing their mode symmetry.

  11. 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.

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

    DOE PAGESBeta

    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 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

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

    PubMed

    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

  14. Fractional fuzzy adaptive sliding-mode control of a 2-DOF direct-drive robot arm.

    PubMed

    Efe, Mehmet Onder

    2008-12-01

    This paper presents a novel parameter adjustment scheme to improve the robustness of fuzzy sliding-mode control achieved by the use of an adaptive neuro-fuzzy inference system (ANFIS) architecture. The proposed scheme utilizes fractional-order integration in the parameter tuning stage. The controller parameters are tuned such that the system under control is driven toward the sliding regime in the traditional sense. After a comparison with the classical integer-order counterpart, it is seen that the control system with the proposed adaptation scheme displays better tracking performance, and a very high degree of robustness and insensitivity to disturbances are observed. The claims are justified through some simulations utilizing the dynamic model of a 2-DOF direct-drive robot arm. Overall, the contribution of this paper is to demonstrate that the response of the system under control is significantly better for the fractional-order integration exploited in the parameter adaptation stage than that for the classical integer-order integration. PMID:19022726

  15. 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. PMID:22589056

  16. 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

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

    NASA Astrophysics Data System (ADS)

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

    2015-11-01

    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.

  18. Efficient forward and adjoint calculations of normal mode spectra in laterally heterogeneous earth models using an iterative direct solution method

    NASA Astrophysics Data System (ADS)

    Al-Attar, D.; Woodhouse, J. H.

    2011-12-01

    Normal mode spectra provide a valuable data set for global seismic tomography, and, notably, are amongst the few geophysical observables that are sensitive to lateral variations in density structure within the Earth. Nonetheless, the effects of lateral density variations on mode spectra are rather subtle. In order, therefore, to reliably determine density variations with in the earth, it is necessary to make use of sufficiently accurate methods for calculating synthetic mode spectra. In particular, recent work has highlighted the need to perform 'full-coupling calculations' that take into account the interaction of large numbers of spherical earth multiplets. However, present methods for performing such full-coupling calculations require diagonalization of large coupling matrices, and so become computationally inefficient as the number of coupled modes is increased. In order to perform full-coupling calculations more efficiently, we describe a new implementation of the direct solution method for calculating synthetic spectra in laterally heterogeneous earth models. This approach is based on the solution of the inhomogeneous mode coupling equations in the frequency domain, and does not require the diagonalization of large matrices. Early implementations of the direct solution method used LU-decomposition to solve the mode coupling equations. However, as the number of coupled modes is increased, this method becomes impractically slow. To circumvent this problem, we solve the mode coupling equations iteratively using the preconditioned biconjugate gradient algorithm. We present a number of numerical tests to display the accuracy and efficiency of this method for performing large full-coupling calculations. In addition, we describe a frequency-domain formulation of the adjoint method for the calculation of Frechet kernels that show the sensitivity of normal mode observations to variations in earth structure. The calculation of such Frechet kernels involves one solution

  19. 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

  20. Mode-specific tunneling splittings in 9-hydroxyphenalenone: Comparison of two methods for direct tunneling dynamics

    NASA Astrophysics Data System (ADS)

    Fernández-Ramos, Antonio; Smedarchina, Zorka; Zgierski, Marek Z.; Siebrand, Willem

    1998-07-01

    A benchmark comparison is presented of two direct dynamics methods for proton tunneling, namely variational transition-state theory with semiclassical tunneling corrections (VTST/ST) and the instanton method. The molecules chosen for the comparison are 9-hydroxyphenalenone-d0 and -d1, which have 64 vibrational degrees of freedom and show large tunneling splittings for the zero-point level and several vibrationally excited levels of the electronic ground state. Some of the excited-level splittings are larger and some smaller than the zero-level splitting, illustrating the multidimensional nature of the tunneling. Ab initio structure and force field calculations at the Hartree-Fock/6-31G** level are carried out for the two stationary points of the tunneling potential, viz. the equilibrium configuration and the transition state. The VTST/ST calculations are based on both the small- and the large-curvature approximation; the additional quantum-chemical calculations required at intermediate points of the potential are performed at the semiempirical modified neglect of differential overlap (MNDO)/H2 level. The VTST/ST computations use the MORATE 6.5 code developed by Truhlar and co-workers. The instanton dynamics calculations are based on the method we previously developed and applied to tropolone, among others. It uses the transition state rather than the equilibrium configuration as reference structure and approximates the least action analytically. The computations use our "dynamics of instanton tunneling" (DOIT) code. It is found that the large-curvature approximation and the instanton method both reproduce the observed zero-level splitting of the d0 isotopomer if the calculated barrier is reduced by a factor 0.87. With this adjusted barrier, the instanton method also reproduces the zero-level and excited-level splittings of the d1 isotopomer. However, both the small- and the large-curvature approximations severely underestimate all these splittings. These methods

  1. 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.

  2. Periodic Radiation Patterns and Circulating Direction of Lasing Light by Quasi Whispering Gallery Mode in Hexagonal GaN Microdisk

    NASA Astrophysics Data System (ADS)

    Kouno, Tetsuya; Suzuki, Sho; Sakai, Masaru; Kishino, Katsumi; Hara, Kazuhiko

    2016-05-01

    We have experimentally elucidated the periodic radiation patterns and circulating direction of the lasing light generated by the quasi-whispering-gallery mode (QWGM) in a hexagonal GaN microdisk. The radiated lasing light from the microdisk is highly directional, with the high intensities of the obtained radiated lasing light having a periodic spacing of 120° in the planar direction. The results show that the QWGM-generated lasing light circulates in a single direction in the microdisk, namely, either clockwise or counter-clockwise.

  3. 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.

  4. Quantitative and Direct Near-Field Analysis of Plasmonic-Induced Transparency and the Observation of a Plasmonic Breathing Mode.

    PubMed

    Khunsin, Worawut; Dorfmüller, Jens; Esslinger, Moritz; Vogelgesang, Ralf; Rockstuhl, Carsten; Etrich, Christoph; Kern, Klaus

    2016-02-23

    We investigated experimentally and numerically in the optical near-field a plasmonic model system similar to a dolmen-type structure for phenomena such as plasmon-induced transparency. Through engineering of coupling strength, structure orientation, and incident angle and phase of the excitation source it was possible to control near-field excitation of the dark modes. We showed that quantitative analysis of near-field amplitude and excitation strength provided essential information that allowed identifying the interaction between the bright and the dark mode and how it causes the formation of plasmon-induced transparency features and a Fano resonance. In addition, we introduced a mechanism to excite field distributions in plasmonic structures that cannot be accessed directly using far-field illumination and demonstrated the excitation of a dark mode akin to a symmetry-forbidden plasmonic breathing mode using a linearly polarized far-field source. PMID:26789080

  5. Studies of H-Mode Plasmas Produced Directly by Pellet Injection in the DIII-D Tokamak

    SciTech Connect

    P. Gohil; L.R. Baylor; T.C. Jernigan; K.H. Burrell; T.N. Carlstrom; G.R. McKee; T.L. Rhodes

    2000-08-01

    A key issue for the physics of H-mode plasmas is to determine which plasma quantities are critical for the formation of the edge transport barrier. One approach is to directly perturb the edge plasma and observe the subsequent changes. In DIII-D, pellet injection has been used to directly change the edge plasma conditions and produce H-mode transitions. One hypothesis for the H-mode transition is that the attainment of a critical edge electron temperature is required for the transition [1-3]. This hypothesis is disproved in this paper. H-mode transitions were produced by injecting frozen deuterium pellets of diameter 2.7 mm from the inner wall of the DIII-D vessel into the high toroidal field side (HFS) and from the outer wall into the low field side (LFS) of the plasma. Both the HFS and LFS pellets produced significant increases in the edge electron density, which led to substantial reductions in the edge electron and ion temperatures. However, H-mode transitions were still produced with the lowered edge temperatures, implying that a critical edge temperature is not necessary for H-mode transitions. The pellet induced H-mode plasma exhibited clear pedestals in electron density and electron and ion temperatures at the plasma edge and persisted for the duration of the applied neutral beam power. The HFS pellet's penetration and deposition profiles were substantially deeper (up to {rho} {approx} 0.2) than that of the LFS pellet (up to {rho} {approx} 0.7). However, since both HFS and LFS pellets produced H-mode transitions, this implies that pellet penetration depth is not important the important factor is the large increase in the electron density right at the plasma edge produced by both types of pellets. The values of the edge plasma quantities at the H-mode transition were expressed in the parametric terms described in several theories and models of the H-mode transitions [4-6]. On comparison, the experimentally determined parameters at the H-mode transition were

  6. Saturable absorbers incorporating carbon nanotubes directly synthesized onto substrates and fibers and their application to mode-locked fiber lasers

    NASA Astrophysics Data System (ADS)

    Yamashita, S.; Inoue, Y.; Maruyama, S.; Murakami, Y.; Yaguchi, H.; Jablonski, M.; Set, S. Y.

    2004-07-01

    We present novel carbon-nanotube-based saturable absorbers. Using the low-temperature alcohol catalytic chemical-vapor deposition method, high-quality single-walled carbon nanotubes (SWNTs) were directly synthesized on quartz substrates and fiber ends. We successfully applied the SWNTs to mode lock a fiber laser producing subpicosecond pulses at a 50-MHz repetition rate.

  7. 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

  8. 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. PMID:24673907

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

    PubMed

    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

  10. 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

  11. 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. PMID:25597956

  12. 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.

  13. Mechanism of genotoxicity induced by targeted cytoplasmic irradiation

    PubMed Central

    Hong, M; Xu, A; Zhou, H; Wu, L; Randers-Pehrson, G; Santella, R M; Yu, Z; Hei, T K

    2010-01-01

    Background: Direct damage to DNA is generally accepted as the main initiator of mutation and cancer induced by environmental carcinogens or ionising radiation. However, there is accumulating evidence suggesting that extracellular/extranuclear targets may also have a key role in mediating the genotoxic effects of ionising radiation. As the possibility of a particle traversal through the cytoplasm is much higher than through the nuclei in environmental radiation exposure, the contribution to genotoxic damage from cytoplasmic irradiation should not be ignored in radiation risk estimation. Although targeted cytoplasmic irradiation has been shown to induce mutations in mammalian cells, the precise mechanism(s) underlying the mutagenic process is largely unknown. Methods: A microbeam that can target the cytoplasm of cells with high precision was used to study mechanisms involved in mediating the genotoxic effects in irradiated human–hamster hybrid (AL) cells. Results: Targeted cytoplasmic irradiation induces oxidative DNA damages and reactive nitrogen species (RNS) in AL cells. Lipid peroxidation, as determined by the induction of 4-hydroxynonenal was enhanced in irradiated cells, which could be suppressed by butylated hydroxyl toluene treatment. Moreover, cytoplasmic irradiation of AL cells increased expression of cyclooxygenase-2 (COX-2) and activation of extracellular signal-related kinase (ERK) pathway. Conclusion: We herein proposed a possible signalling pathway involving reactive oxygen/nitrogen species and COX-2 in the cytoplasmic irradiation-induced genotoxicity effect. PMID:20842121

  14. 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.

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

    PubMed Central

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

    2015-01-01

    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 500mg/kg/day) or EC (250mg/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. PMID:25833916

  16. 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. PMID:18447065

  17. 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.

  18. Parity time-symmetric vertical cavities: intrinsically single-mode regime in longitudinal direction.

    PubMed

    Jones, Hugh F; Kulishov, Mykola; Kress, Bernard

    2016-07-25

    We explore a new class of distributed feedback (DFB) structures that employ the recently-developed concept of parity-time (PT) symmetry in optics. We show that, based on PT-symmetric pure reflective volume gratings, a vertical surface-emitting cavity can be constructed. We provide a detailed analysis of the threshold conditions as well as the wavelength and angular spectral characteristics using the Kogelnik coupled-wave approximation, backed up by an exact solution of the Helmholtz equation. We show that such a PT-symmetric cavity can be configured to support one and only one longitudinal mode, leading to inherently single-mode lasing. PMID:27464163

  19. 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.

  20. 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

  1. 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.

  2. Experimental and theoretical analysis of THz-frequency, direction-dependent, phonon polariton modes in a subwavelength, anisotropic slab waveguide.

    PubMed

    Yang, Chengliang; Wu, Qiang; Xu, Jingjun; Nelson, Keith A; Werley, Christopher A

    2010-12-01

    Femtosecond optical pulses were used to generate THz-frequency phonon polariton waves in a 50 micrometer lithium niobate slab, which acts as a subwavelength, anisotropic planar waveguide. The spatial and temporal electric field profiles of the THz waves were recorded for different propagation directions using a polarization gating imaging system, and experimental dispersion curves were determined via a two-dimensional Fourier transform. Dispersion relations for an anisotropic slab waveguide were derived via analytical analysis and found to be in excellent agreement with all observed experimental modes. From the dispersion relations, we analyze the propagation-direction-dependent behavior, effective refractive index values, and generation efficiencies for THz-frequency modes in the subwavelength, anisotropic slab waveguide. PMID:21164986

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

    PubMed

    Fry-Petit, A M; Rebola, A F; Mourigal, M; Valentine, M; Drichko, N; Sheckelton, J P; Fennie, C J; McQueen, T M

    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, LiZn2Mo3O8, this approach allows direct assignment of the constrained rotational mode of Mo3O13 clusters and internal modes of MoO6 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. PMID:26429001

  4. 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].

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

    PubMed

    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. PMID:22507867

  6. 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

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

    NASA Astrophysics Data System (ADS)

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

    2016-04-01

    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.

  8. 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

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

    PubMed

    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

  10. 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

  11. Biomonitoring of genotoxic effects for human exposure to nanomaterials: The challenge ahead.

    PubMed

    Gonzalez, Laetitia; Kirsch-Volders, Micheline

    2016-01-01

    Exposures to nanomaterials (NMs), with their specific physico-chemical characteristics, are likely to increase over the next years, as their production for industrial, consumer and medical applications is steadily rising. Therefore, there is an urgent need for the implementation of human biomonitoring studies of genotoxic effects after NM exposures in order to monitor and assure safety for workers and the general population. In this review, most commonly used biomarkers of early genetic effects were analyzed for their adequacy after NM exposures. A more in depth analysis of the ex vivo/in vitro lymphocyte MN assay was performed, although, in literature no studies are available using this assay for NM exposures. Therefore, the known factors determining the NMs tissue/cellular targets and the multiplicity of modes of action of NMs were summarized. The main pending questions are whether (1) lymphocytes are a NM target or an adequate surrogate tissue, (2) whether the buccal MN assay might be more suitable for NM exposures via inhalation or ingestion, as buccal cells might be exposed more directly. While the current state-of-the-art does not allow for drawing firm conclusions, major research gaps are identified and some cautious recommendations can be formulated. Therefore in vitro and in vivo studies should be conducted comparing methodologies side-by-side in the same subjects and for different types of NMs. The ex vivo/in vitro MN assay in its automated version, allowing objective analysis of large cohorts and detection of direct and indirect genotoxic effects, remains a valuable candidate for human biomonitoring to NM exposure. Considering the potential cancer risk from exposure to NMs and previous dramatic experiences with too late surveillance of occupational exposures to similar substances (e.g. to asbestos), there is an urgent need to define and implement adequate scientifically sound biomonitoring methods and programme for exposure to NMs. PMID:27234560

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

    NASA Astrophysics Data System (ADS)

    Wang, L. L.; Ma, W. P.; Shen, D. S.; Wang, M. L.

    2015-10-01

    With single photos in both polarization and spatial-mode degrees of freedom,we present an efficient bidirectional quantum secure direct communication (QSDC) protocol is proposed. The participants' secret messages can be transmitted directly in a quantum channel through performing different local unitary operations, which are chosen by the two participants separately from the Pauli operations and Hadamard operations, on the polarization states and the spatial-mode states of single photons. Each single photon in two degrees of freedom can carry two bits of information. Thus the capacity of quantum communication of our protocol is improved. Moreover, we discuss the security of our QSDC network protocol comprehensively. It is showed that the proposed scheme not only can defend several outsider eavesdropper's attacks but also can remove the drawback of information leakage, which prevents the secret messages being leaked out to other people through the public information. In addition, our protocol is practical since the preparation and the measurement of single photon quantum states in both the polarization and the spatial-mode degrees of freedom are available with current quantum techniques.

  13. Direct generation of genuine single-longitudinal-mode narrowband photon pairs

    NASA Astrophysics Data System (ADS)

    Luo, Kai-Hong; Herrmann, Harald; Krapick, Stephan; Brecht, Benjamin; Ricken, Raimund; Quiring, Viktor; Suche, Hubertus; Sohler, Wolfgang; Silberhorn, Christine

    2015-07-01

    The practical prospect of quantum communication and information processing relies on sophisticated single-photon pairs, which feature a controllable waveform, narrow spectrum, excellent purity, fiber compatibility, and miniaturized design. For practical realizations, stable, miniaturized, low-cost devices are required. Sources with one or some of the above characteristics have already been demonstrated, but it is quite challenging to obtain a source with all of the described characteristics simultaneously. Here we report on an integrated single-longitudinal-mode, non-degenerate, narrowband photon pair source that exhibits all the requirements needed for quantum applications. The device is composed of a periodically poled, Ti-indiffused, lithium niobate waveguide with high reflective dielectric mirror coatings deposited on the waveguide end-faces. Photon pairs with wavelengths around 890 and 1320 nm are generated via type II phase-matched parametric down-conversion (PDC). Clustering in this dispersive cavity restricts the whole conversion spectrum to one single-longitudinal mode in a single cluster, yielding a narrow bandwidth of only 60 MHz. The high conversion efficiency in the waveguide, together with the spectral clustering in the doubly resonant waveguide, leads to a high brightness of 3× {10}4 pairs/(s mW MHz). This source exhibits prominent single-longitudinal-mode purity and remarkable temporal shaping capability. In particular, due to temporal broadening, we can observe that the coherence time of the two-photon component of the PDC state is actually longer than that of the single-photon states. The miniaturized monolithic design enables this source to have various fiber communication applications.

  14. 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

  15. 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. PMID:26643763

  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. Distinct ETA receptor binding mode of macitentan as determined by site directed mutagenesis.

    PubMed

    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 ET(A) 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 ET(A) 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 ET(A) 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 ET(A) receptor-antagonist interaction modes, we performed functional studies using ET(A) receptor variants harboring amino acid point mutations in the presumed ERA interaction site. Three ET(A) 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-ET(A) 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

  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. Genotoxicity of streptonigrin: a review.

    PubMed

    Bolzán, A D; Bianchi, M S

    2001-03-01

    Streptonigrin (SN, CAS no. 3930-19-6) is an aminoquinone antitumor antibiotic isolated from cultures of Streptomyces flocculus. This compound is a member of a group of antitumor agents which possess the aminoquinone moiety and that includes also mitomycin C, porfiromycin, actinomycin, rifamycin and geldanamycin. Because of the potential use of SN in clinical chemotherapy, the study of its genotoxicity has considerable practical significance.SN inhibits the synthesis of DNA and RNA, causes DNA strand breaks after reduction with NADH, induces unscheduled DNA synthesis and DNA adducts and inhibits topoisomerase II. At the chromosome level, this antibiotic causes chromosome damage and increases the frequency of sister-chromatid exchanges.SN cleaves DNA in cell-free systems by a mechanism that involves complexing with metal ions and autoxidation of the quinone moiety to semiquinone in the presence of NADH with production of oxygen-derived reactive species. Recent evidence strongly suggests that the clastogenic action of this compound is partially mediated by free radicals. The present review aims at summarizing past and current knowledge concerning the genotoxic effects of SN. PMID:11223403

  20. 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.

  1. Comparison of epoxy- and siloxane-based single-mode optical waveguides defined by direct-write lithography

    NASA Astrophysics Data System (ADS)

    Elmogi, Ahmed; Bosman, Erwin; Missinne, Jeroen; Van Steenberge, Geert

    2016-02-01

    This paper reports on the fabrication and characterization of single-mode polymer optical waveguides at telecom and SOI compatible wavelengths; by making a comparison between an epoxy and a siloxane polymer waveguide material system (both commercially-available). The proposed waveguides can be used in short-reach optical interconnects targeting chip-to-chip communication on the interposer level or providing a coupling interface between single-mode optical fibers and photonic integrated circuits (PICs). This technology enables the integration of optoelectronic chips for photonic packaging purposes. First, the single-mode dimensions (4 × 4 μm2 and 5 × 5 μm2) for both materials at selected wavelengths (1.31 μm and 1.55 μm) were determined based on the refractive index measurements. Then, the waveguides were patterned by a direct-write lithography method. The fabricated waveguides show a high-quality surface with smooth sidewalls. The optical propagation losses were measured using the cut-back method. For the siloxane-based waveguides, the propagation losses were found to be 0.34 dB/cm and 1.36 dB/cm at 1.31 μm and 1.55 μm respectively while for the epoxy-based waveguides the losses were 0.49 dB/cm and 2.23 dB/cm at 1.31 μm and 1.55 μm respectively.

  2. Three-party Quantum Secure Direct Communication with Single Photons in both Polarization and Spatial-mode Degrees of Freedom

    NASA Astrophysics Data System (ADS)

    Wang, LiLi; Ma, WenPing; Wang, MeiLing; Shen, DongSu

    2016-05-01

    We present an efficient three-party quantum secure direct communication (QSDC) protocol with single photos in both polarization and spatial-mode degrees of freedom. The three legal parties' messages can be encoded on the polarization and the spatial-mode states of single photons independently with desired unitary operations. A party can obtain the other two parties' messages simultaneously through a quantum channel. Because no extra public information is transmitted in the classical channels, the drawback of information leakage or classical correlation does not exist in the proposed scheme. Moreover, the comprehensive security analysis shows that the presented QSDC network protocol can defend the outsider eavesdropper's several sorts of attacks. Compared with the single photons with only one degree of freedom, our protocol based on the single photons in two degrees of freedom has higher capacity. Since the preparation and the measurement of single photon quantum states in both the polarization and the spatial-mode degrees of freedom are available with current quantum techniques, the proposed protocol is practical.

  3. Histaminergic nerves demonstrated in the skin. A new direct mode of neurogenic inflammation?

    PubMed

    Johansson, O; Virtanen, M; Hilliges, M

    1995-04-01

    An intradermal administration of histamine into human skin results in a local erythema, edema and often also the sensations of itch and/or pain. These effects have classically been attributed to the presence of histamine-containing mast cells. However, in the present investigation, we report the observation of histamine-immunoreactive nerves in the skin of Sprague-Dawley rats using a new and highly sensitive immunohistochemical approach. These data suggest a more direct route of cutaneous histamine effects, mediated exclusively by the peripheral nervous system. The findings could also give a new basis for explaining histamine-related issues, such as itch. PMID:7543795

  4. 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. PMID:23443534

  5. Direct single-mode fibre-coupled miniature White cell for laser absorption spectroscopy

    NASA Astrophysics Data System (ADS)

    Kühnreich, Benjamin; Höh, Matthias; Wagner, Steven; Ebert, Volker

    2016-02-01

    We present the design, setup, and characterization of a new lens-free fibre-coupled miniature White cell for extractive gas analysis using direct tunable diode laser absorption spectroscopy (dTDLAS). The construction of this cell is based on a modified White cell design and allows for an easy variation of the absorption length in the range from 29 cm to 146 cm. The design avoids parasitic absorption paths outside the cell by using direct, lensless fibre coupling and allows small physical cell dimensions and cell volumes. To characterize the cell performance, different H2O and CH4 concentration levels were measured using dTDLAS. Detection limits of 2.5 ppm ṡ m for CH4 (at 1.65 μm) and 1.3 ppm ṡ m for H2O (at 1.37 μm) were achieved. In addition, the gas exchange time and its flow-rate dependence were determined for both species and found to be less than 15 s for CH4 and up to a factor of thirteen longer for H2O.

  6. METABOLISM AND GENOTOXICITY OF 1-NITROPYRENE

    EPA Science Inventory

    1-Nitropyrene (NP), a nitrated polycyclic aromatic hydrocarbon and a potent bacterial mutagen, has been identified in combustion emissions and may contribute to the burden of genotoxicity associated with air pollution. NP undergoes rapid metabolism by rat hepatic subcellular frac...

  7. 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. PMID:24525378

  8. Ameliorative effect of certain antioxidants against mercury induced genotoxicity in peripheral blood lymphocytes.

    PubMed

    Patel, Tapan A; Rao, Mandava V

    2015-10-01

    Various antioxidants play an important role in reducing the reactive oxygen species (ROS) by scavenging them directly or indirectly. Mercury (Hg) is one of the known hazardous genotoxicant, induces the genotoxicity by enhancing the ROS. In the present study, three structurally different bioactive compounds such as melatonin (0.2 mM), curcumin (3.87 µM) and andrographolide (0.4 µM) were evaluated against the genotoxic effect of mercury. All the experiments were conducted using the peripheral blood lymphocytes In Vitro. The cultures were exposed to different doses (2.63 µM; 6.57 µM; 10.52 µM) of mercury salt (HgCl2) for studying various genotoxic indices. All three antioxidant compounds, alone and in combination with high dose of mercury, were added to the cultures with controls. For ascertaining genotoxicity, sister chromatid exchanges (SCEs), cell cycle proliferative index/replicative index (CCPI/RI), average generation time (AGT), population doubling time (PDT), %M1, %M2 and %M3 were assessed and analyzed using suitable statistical analysis. The results revealed a dose dependent increase in SCEs, AGT and PDT, with a concomitant reduction in CCPI values after treatment of mercury. Supplementation of these three antioxidant compounds effectively negated these genotoxic endpoints in treated cultures with improvement in the cell cycle kinetics i.e. CCPI. The antimutagenic activity of these compounds on mercury induced genotoxicity was in the following order: melatonin > curcumin > andrographolide. In conclusion, these compounds have ameliorated mercury induced increase in genotoxic indices due to their excellent antioxidant properties and the combination seems to be effective. PMID:25645230

  9. Based on interval type-2 fuzzy-neural network direct adaptive sliding mode control for SISO nonlinear systems

    NASA Astrophysics Data System (ADS)

    Lin, Tsung-Chih

    2010-12-01

    In this paper, a novel direct adaptive interval type-2 fuzzy-neural tracking control equipped with sliding mode and Lyapunov synthesis approach is proposed to handle the training data corrupted by noise or rule uncertainties for nonlinear SISO nonlinear systems involving external disturbances. By employing adaptive fuzzy-neural control theory, the update laws will be derived for approximating the uncertain nonlinear dynamical system. In the meantime, the sliding mode control method and the Lyapunov stability criterion are incorporated into the adaptive fuzzy-neural control scheme such that the derived controller is robust with respect to unmodeled dynamics, external disturbance and approximation errors. In comparison with conventional methods, the advocated approach not only guarantees closed-loop stability but also the output tracking error of the overall system will converge to zero asymptotically without prior knowledge on the upper bound of the lumped uncertainty. Furthermore, chattering effect of the control input will be substantially reduced by the proposed technique. To illustrate the performance of the proposed method, finally simulation example will be given.

  10. Study of a dual mode SWIR active imaging system for direct imaging and non-line-of-sight vision

    NASA Astrophysics Data System (ADS)

    Laurenzis, Martin; Christnacher, Frank; Velten, Andreas

    2015-05-01

    The application of non-line of sight vision and see around a corner has been demonstrated in the recent past on laboratory level with round trip path lengths on the scale of 1 m as well as 10 m. This method uses a computational imaging approach to analyze the scattered information of objects which are hidden from the direct sensors field of view. Recent demonstrator systems were driven at laser wavelengths (800 nm and 532 nm) which are far from the eye-safe shortwave infrared (SWIR) wavelength band i.e. between 1.4 μm and 2 μm. Therefore, the application in public or inhabited areas is difficult with respect to international laser safety conventions. In the present work, the authors evaluate the application of recent eye safe laser sources and sensor devices for non-line of sight sensing and give predictions on range and resolution. Further, the realization of a dual mode concept is studied enabling both, the direct view on a scene and the indirect view on a hidden scene. While recent laser gated viewing sensors have high spatial resolution, their application in non-line of sight imaging suffer from a too low temporal resolution due to minimal sensor gate width of around 150 ns. On the other hand, Geiger-mode single photon counting devices have high temporal resolution, but their spatial resolution is (until now) limited to array sizes of some thousand sensor elements. In this publication the authors present detailed theoretical and experimental evaluations.

  11. 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.

  12. Genotoxicity of organic extracts of airborne particles in somatic cells of Drosophila melanogaster.

    PubMed

    Delgado-Rodríguez, A; Ortíz-Marttelo, R; Villalobos-Pietrini, R; Gómez-Arroyo, S; Graf, U

    1999-07-01

    Complex mixtures extracted from air filters exposed for 24 h in two sessions (27 July and 02 August 1991) and at two locations (Merced, downtown, and Pedregal de San Angel, south-west) in Mexico City were analysed. The organic extracts were from airborne particles equal or smaller than 10 microns (PM10), and from total suspended particles (TSP). These organic extracts were assayed in the somatic mutation and recombination test (SMART) in wings of Drosophila melanogaster using two different crosses as well as in the Salmonella/microsome assay using strain TA98 with and without S9 fraction. The presence of polycyclic aromatic hydrocarbons (PAH) in the extracts was determined by gas chromatography. The genotoxic activities observed in the two test systems were comparable with the indirect mutagens producing greater response than the direct mutagens. The quantities of particulate matter as well as the genotoxic activities were higher on 02 August than on 27 July 1991 for both locations. The amounts of airborne particles and the resulting genotoxic activities were higher at Merced than at Pedregal. In both biological systems, PM10 were more genotoxic than TSP. These results demonstrate the sensitivity of the Drosophila wing SMART-which is an in vivo eukaryotic genotoxicity assay-as a biological monitor of environmental pollution related to airborne particles. PMID:10377966

  13. 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

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

    SciTech Connect

    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.

  15. 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.

  16. Acrolein genotoxicity in Drosophila melanogaster. III. Effects of metabolism modification.

    PubMed

    Barros, A R; Sierra, L M; Comendador, M A

    1994-05-01

    In order to investigate the role of metabolism in acrolein genotoxicity in D. melanogaster, the action of several metabolism modifiers, namely phenobarbital, an inducer of xenobiotic metabolism, phenylimidazole and iproniazid, inhibitors of oxidative activities of cytochrome P450, and diethyl maleate, a glutathione-depleting agent, have been assayed using the sex-linked recessive lethal (SLRL) test, with two different administration routes (feeding and injection). The results support the hypothesis that acrolein is not only a direct mutagen but is also transformed, by oxidative activities of cytochrome P450 after glutathione conjugation, into an active metabolite, possibly glycidaldehyde. Moreover, acrolein is deactivated by an enzymatic activity induced by phenobarbital. PMID:7513061

  17. 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.

  18. 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...

  19. 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

  20. 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. PMID:26891274

  1. Insecticidal, mutagenic and genotoxic evaluation of annonaceous acetogenins.

    PubMed

    Alvarez Colom, Olga; Salvatore, Analia; Willink, Eduardo; Ordóñez, Roxana; Isla, María I; Neske, Adriana; Bardón, Alicia

    2010-03-01

    Annonaceous acetogenins represent a class of bioactive compounds whose primary mode of action is the inhibition of NADH-ubiquinone oxidoreductase (Mitochondrial Complex I). Given the potential pesticidal use of these compounds, we evaluated the effects of seven acetogenins: squamocin (1), molvizarin (2), itrabin (3), almuñequin (4), cherimolin-1 (5), cherimolin-2 (6), and tucumanin (7) isolated from Annona cherimolia Mill. against Ceratitis capitata Wiedemann (Tephritidae). These acetogenins did not display insecticidal action at 250 microg of treatment per g of adult diet. However, the oviposition capacity of C. capitata females was significantly altered by some of the acetogenins at this concentration. The most potent compounds were itrabin, molvizarin and squamocin. Moreover, significant differences were detected in the preference of oviposition sites when itrabin and squamocin were spread on the surface of artificial fruits at doses of 30 microg/cm2. Additionally, we investigated the mutagenic effects displayed by itrabin, as well as the phytotoxic and genotoxic action of squamocin and itrabin. Both compounds displayed slight phytotoxic and genotoxic effects on roots of Allium cepa at 2.5 microg/mL though no mutagenic effects were detected at 0.25, 0.5 and 2.5 microg/mL on Salmonella typhimurium strains TA98 and TA100. PMID:20420314

  2. Genotoxic sensitivity of the developing hematopoietic system.

    PubMed

    Udroiu, Ion; Sgura, Antonella

    2016-01-01

    Genotoxic sensitivity seems to vary during ontogenetic development. Animal studies have shown that the spontaneous mutation rate is higher during pregnancy and infancy than in adulthood. Human and animal studies have found higher levels of DNA damage and mutations induced by mutagens in fetuses/newborns than in adults. This greater susceptibility could be due to reduced DNA repair capacity. In fact, several studies indicated that some DNA repair pathways seem to be deficient during ontogenesis. This has been demonstrated also in murine hematopoietic stem cells. Genotoxicity in the hematopoietic system has been widely studied for several reasons: it is easy to assess, deals with populations cycling also in the adults and may be relevant for leukemogenesis. Reviewing the literature concerning the application of the micronucleus test (a validated assay to assess genotoxicity) in fetus/newborns and adults, we found that the former show almost always higher values than the latter, both in animals treated with genotoxic substances and in those untreated. Therefore, we draw the conclusion that the genotoxic sensitivity of the hematopoietic system is more pronounced during fetal life and decreases during ontogenic development. PMID:27036061

  3. 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...

  4. Identification of the direction and value of the wave length of each mode for a rotating tire using the phase difference method

    NASA Astrophysics Data System (ADS)

    Lee, Jongsuh; Wang, Semyung; Kindt, Peter; Pluymers, Bert; Desmet, Wim

    2016-02-01

    Natural frequencies, mode shapes and modal damping values are the most important parameters to describe the noise and vibration behavior of a mechanical system. For rotating machinery, however, the directivity of the propagation wave and the wave length of each mode should also be taken into account. Generally, the information on directivity and wave length is obtained on the basis of the mode shape result, which is estimated from several measurements measured at different locations. In this research, the accurate directivity and wave length results will be observed by calculating the phase difference at two different locations. The limitation of the proposed method, which arises from the difference between the assumed ring model and the real tire, will be explained, and a method to address the limitation is introduced. The proposed method is verified by applying it to experimental measurements, and a brief explanation of the obtained results is provided.

  5. 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.

  6. Mechanisms of non-genotoxic carcinogenesis.

    PubMed

    Shaw, I C; Jones, H B

    1994-03-01

    Until recently, the mechanism of carcinogenesis has been regarded as a two-stage phenomenon involving damage to the genetic material, which initiates the process, followed by a cell-division stimulus, which promotes the development of the tumour. However, exposure to some chemicals has been shown to result in carcinogenesis without involvement of the initiation step. The mechanism of non-genotoxic carcinogenesis is not fully understood, but is believed to involve stimulation of cell division with a consequent increased probability of a mutation occurring spontaneously. In this article, Ian Shaw and Huw Jones review the theories of non-genotoxic carcinogenesis with reference to specific examples of known non-genotoxic carcinogens. PMID:8184492

  7. 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.

  8. Evaluation of the genotoxic potential of alkylalkanolamines.

    PubMed

    Leung, H W; Ballantyne, B

    1997-09-18

    Three alkylalkanolamines, N,N-dimethylethanolamine, N-methyldiethanolamine, and tert-butyldiethanolamine, were evaluated for potential genotoxic activity using the Salmonella/microsome reverse gene mutation test, the CHO/HGPRT forward gene mutation test, a sister chromatid exchange test in cultured CHO cells, and an in vivo peripheral blood micronucleus test in Swiss-Webster mice. None of the three alkylalkanolamines produced any significant or dose-related increases in the frequencies of mutations, sister chromatid exchanges or micronuclei. These results indicate that N,N-dimethylethanolamine, N-methyldiethanolamine, and tert-butyldiethanolamine are not genotoxic in the tests conducted. PMID:9357557

  9. 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

  10. 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

    2016-06-01

    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.

  11. GENOTOXICITY STUDIES OF BENZ(1)ACEANTHRYLENE

    EPA Science Inventory

    The genotoxicity of the cyclopenta-fused polycyclic aromatic hydrocarbon, benz(1)aceanthrylene (B(1)A),was evaluated in vitro using the L5178Y/T (K sup +/-) mouse lymphoma assay and in vivo using the mouse peripheral blood lymphocyte (PBL) culture system. The mutagenicity and sis...

  12. 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.

  13. 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.

  14. ASSESSMENT OF HAZARDOUS WASTES FOR GENOTOXICITY

    EPA Science Inventory

    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 pro...

  15. "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. PMID:26321723

  16. 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

  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. 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. PMID:21499398

  19. 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

  20. 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

  1. Genomic and gene expression responses to genotoxic stress in PAC2 zebrafish embryonic cell line.

    PubMed

    Šrut, Maja; Bourdineaud, Jean-Paul; Štambuk, Anamaria; Klobučar, Göran I V

    2015-11-01

    PAC2 cell line is, along most of the developed zebrafish cell lines, poorly characterized concerning its response to genotoxicants. To define the PAC2 cell line response to different forms of genotoxic stress, we exposed the cells to model genotoxic agents (benzo[a]pyrene, B[a]P, and ethyl methanesulfonate) and subsequently monitored DNA damage and alterations by using the battery of tests, including the Comet assay, quantitative random-amplified polymorphic DNA and amplified fragment length polymorphism. The expression of several DNA repair (xpc, xpd, hr23b, rad51, msh2) and oxidative stress response (sod (Cu/Zn)) genes was monitored as well. To obtain an indication of the PAC2 cell line metabolizing capacity, the expression of genes belonging to cyp1, cyp2 and cyp3 families was assessed upon exposure to B[a]P. Genotoxic responses were observed in all the used methods, and quantitative random-amplified polymorphic DNA and amplified fragment length polymorphism proved to be more sensitive by revealing DNA alterations even when the Comet assay indicated lack of significant damage. The PAC2 cell line demonstrated basal and B[a]P-induced expression of several cyp genes, suggesting its ability to metabolize indirect acting xenobiotics to a certain point. Based on these results, PAC2 cells seem to be sensitive zebrafish in vitro model in the genotoxicity assessment of the direct acting genotoxicant; however, they are less sensitive toward the indirect acting genotoxicant due to their limited metabolizing properties. PMID:25612249

  2. 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

  3. 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. PMID:26212309

  4. Development of a Quantitative Model Incorporating Key Events in a Hepatoxic Mode of Action to Predict Tumor Incidence

    EPA Science Inventory

    Biologically-Based Dose Response (BBDR) modeling of environmental pollutants can be utilized to inform the mode of action (MOA) by which compounds elicit adverse health effects. Chemicals that produce tumors are typically described as either genotoxic or non-genotoxic. One common...

  5. Production of multicharged ions and behavior of microwave modes in an electron cyclotron resonance ion source directly excited in a circular cavity resonator

    SciTech Connect

    Kato, Yushi; Furuki, Hideyuki; Asaji, Toyohisa; Sato, Fuminobu; Iida, Toshiyuki

    2006-03-15

    Electron cyclotron resonance ion sources (ECRIS) have been widely used for production of high-intensity multicharged ion beams. Making good use of microwave modes is proposed for enhancing the efficiency of ECR for production of multicharged ions (TAIKO II). We can assign the peak position of the electric field of the standing waves to the ECR zone in the directly excited cavity resonator, i.e., the vacuum chamber with the fixed and the mobile plates for selecting and tuning the modes. Periodicity of the extracted multicharged ion currents and plasma parameters is observed as the position of the mobile plate moves. We measure the intensity of the electric field in the ECR plasma by using the insulated semidipole probe and the standing waves are observed. The correlation between the production of multicharged ions and the microwave modes is clarified by measuring the electric field and plasma parameters in the circular cavity resonator.

  6. Mutagenic and Genotoxic Effect of Hydroxyurea

    PubMed Central

    Santos, Jean L.; Bosquesi, Priscila L.; Almeida, Adélia E.; Chin, Chung Man; Varanda, Eliana A.

    2011-01-01

    The hydroxyurea, a cytotoxic drug, is the mainly available therapeutical strategy for the treatment of sickle cell disease. This study aimed to evaluate the mutagenic and genotoxic potential of the hydroxyurea through the Salmonella/Microsome assay and micronucleus test in peripheral blood of mice. The doses were evaluated at 29.25-468 μmol/plate in Salmonella/Microsome assay in presence and absence of metabolic activation the drug. In the micronucleus test the doses were evaluated at 12.5; 25; 50; 75 and 100 mg/kg. The results show that hydroxyurea present mutagenic activity in TA98 and TA100 in doses above 117 μmol/plate and 234 μmol/plate respectively. The drug induced a significant increase in the frequency of micronuclei in reticulocytes of mice at concentrations of 50, 75 and 100 mg/kg, compared to negative control (water). These results demonstrated the mutagenic and genotoxic potential of hydroxyurea. PMID:23675245

  7. Electrochemical Genotoxicity Assay Based on a SOS/umu Test Using Hydrodynamic Voltammetry in a Droplet

    PubMed Central

    Kuramitz, Hideki; Sazawa, Kazuto; Nanayama, Yasuaki; Hata, Noriko; Taguchi, Shigeru; Sugawara, Kazuharu; Fukushima, Masami

    2012-01-01

    The SOS/umu genotoxicity assay evaluates the primary DNA damage caused by chemicals from the β-galactosidase activity of S. typhimurium. One of the weaknesses of the common umu test system based on spectrophotometric detection is that it is unable to measure samples containing a high concentration of colored dissolved organic matters, sediment, and suspended solids. However, umu tests with electrochemical detection techniques prove to be a better strategy because it causes less interference, enables the analysis of turbid samples and allows detection even in small volumes without loss of sensitivity. Based on this understanding, we aim to develop a new umu test system with hydrodynamic chronoamperometry using a rotating disk electrode (RDE) in a microliter droplet. PAPG when used as a substrate is not electroactive at the potential at which PAP is oxidized to p-quinone imine (PQI), so the current response of chronoamperometry resulting from the oxidation of PAP to PQI is directly proportional to the enzymatic activity of S. typhimurium. This was achieved by performing genotoxicity tests for 2-(2-furyl)-3-(5-nitro-2-furyl)-acrylamide (AF-2) and 2-aminoanthracene (2-AA) as model genotoxic compounds. The results obtained in this study indicated that the signal detection in the genotoxicity assay based on hydrodynamic voltammetry was less influenced by the presence of colored components and sediment particles in the samples when compared to the usual colorimetric signal detection. The influence caused by the presence of humic acids (HAs) and artificial sediment on the genotoxic property of selected model compounds such as 4-nitroquinoline-N-oxide (4-NQO), 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), 1,8-dinitropyrene (1,8-DNP) and 1-nitropyrene (1-NP) were also investigated. The results showed that the genotoxicity of 1-NP and MX changed in the presence of 10 mg·L−1 HAs. The genotoxicity of tested chemicals with a high hydrophobicity such as 1,8-DNP

  8. 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.

  9. 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.

  10. Genotoxicity assessment in patients with thalassemia minor.

    PubMed

    Al-Sweedan, Suleimman A; Khabour, Omar; Isam, Ruba

    2012-05-15

    Thalassemia is an inherited blood disorder that affects both genders and results in reduced synthesis of hemoglobin, and thus causing anemia. Previous studies have shown that the severe form of this disease, thalassemia major, is associated with genotoxicity. This includes increases in the level of sister chromatid exchange (SCEs), chromosomal aberrations (CAs) and micronuclei. In this study, we assessed genotoxicity in the lymphocytes of thalassemia minor subjects using sister chromatid exchange (SCE) and chromosomal aberration (CA) assays. In addition, we investigated the level of oxidative DNA damage by measuring 8-hydroxy-2'-deoxyguanosine (8OHdG) biomarker in urine samples. Eighteen thalassemia minor subjects and eighteen matched normal healthy controls were volunteered in the study. In addition, seven thalassemia major patients were recruited as positive controls. The results showed increases in the frequency of SCEs (P<0.05) in thalassemia minor compared to healthy controls. However, no difference in CAs frequency was detected between thalassemia minor and controls (P>0.05). Both SECs and CAs in thalassemia major patients were significantly higher compared to other groups (P<0.05). Regarding urine 8OHdG levels, the result showed a slight increase in thalassemia minor compared to healthy controls but the difference was not significant (P>0.05). In conclusion, our results showed that thalassemia minor is associated with genotoxicity to blood lymphocytes as indicated by SCEs assay. PMID:22414564

  11. Metabolism, genotoxicity, and carcinogenicity of comfrey.

    PubMed

    Mei, Nan; Guo, Lei; Fu, Peter P; Fuscoe, James C; Luan, Yang; Chen, Tao

    2010-10-01

    Comfrey has been consumed by humans as a vegetable and a tea and used as an herbal medicine for more than 2000 years. Comfrey, however, produces hepatotoxicity in livestock and humans and carcinogenicity in experimental animals. Comfrey contains as many as 14 pyrrolizidine alkaloids (PA), including 7-acetylintermedine, 7-acetyllycopsamine, echimidine, intermedine, lasiocarpine, lycopsamine, myoscorpine, symlandine, symphytine, and symviridine. The mechanisms underlying comfrey-induced genotoxicity and carcinogenicity are still not fully understood. The available evidence suggests that the active metabolites of PA in comfrey interact with DNA in liver endothelial cells and hepatocytes, resulting in DNA damage, mutation induction, and cancer development. Genotoxicities attributed to comfrey and riddelliine (a representative genotoxic PA and a proven rodent mutagen and carcinogen) are discussed in this review. Both of these compounds induced similar profiles of 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived DNA adducts and similar mutation spectra. Further, the two agents share common mechanisms of drug metabolism and carcinogenesis. Overall, comfrey is mutagenic in liver, and PA contained in comfrey appear to be responsible for comfrey-induced toxicity and tumor induction. PMID:21170807

  12. 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.

  13. Anti-genotoxic hydrazide from Crinum defixum.

    PubMed

    Bordoloi, Manobjyoti; Kotoky, Rumi; Mahanta, Jiban J; Sarma, Tarun C; Kanjilal, Purnendu B

    2009-06-01

    Crinum defixum Ker-Gawl popularly known as Bon-naharu (meaning wild garlic) in Assam. It is found abundantly growing wild on riverbanks of Dhansiri River in Golaghat District of Assam. It is used as ethnomedicine in this part of India for a number of ailments. Bioassay guided chemical investigation of the bulbs of Crinum defixum Ker-Gawl afforded to isolate a new hydrazide derivative and its structure was determined as (E)-N'-[(E)-2-butenoyl]-2-butenoylhydrazide by spectroscopic methods. The compound was assayed for anti-genotoxic activity by onion root tip assay (by observing different types of chromosomal aberrations such as chromosomal bridges, stickiness, delayed anaphase, polyploidy and vagrant chromosome). The phyto-compound was found to have anti-genotoxic activity and imparted a clear dose dependent protective effect against the genotoxic effect of H(2)O(2). Further, the compound seems to be more effective against clastogenic aberrations than physiological aberration at the highest concentration used (250 ppm). PMID:18995928

  14. 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. PMID:9707093

  15. A predictive toxicogenomics signature to classify genotoxic versus non-genotoxic chemicals in human TK6 cells

    PubMed Central

    Williams, Andrew; Buick, Julie K.; Moffat, Ivy; Swartz, Carol D.; Recio, Leslie; Hyduke, Daniel R.; Li, Heng-Hong; Fornace, Albert J.; Aubrecht, Jiri; Yauk, Carole L.

    2015-01-01

    Genotoxicity testing is a critical component of chemical assessment. The use of integrated approaches in genetic toxicology, including the incorporation of gene expression data to determine the DNA damage response pathways involved in response, is becoming more common. In companion papers previously published in Environmental and Molecular Mutagenesis, Li et al. (2015) [6] developed a dose optimization protocol that was based on evaluating expression changes in several well-characterized stress-response genes using quantitative real-time PCR in human lymphoblastoid TK6 cells in culture. This optimization approach was applied to the analysis of TK6 cells exposed to one of 14 genotoxic or 14 non-genotoxic agents, with sampling 4 h post-exposure. Microarray-based transcriptomic analyses were then used to develop a classifier for genotoxicity using the nearest shrunken centroids method. A panel of 65 genes was identified that could accurately classify toxicants as genotoxic or non-genotoxic. In Buick et al. (2015) [1], the utility of the biomarker for chemicals that require metabolic activation was evaluated. In this study, TK6 cells were exposed to increasing doses of four chemicals (two genotoxic that require metabolic activation and two non-genotoxic chemicals) in the presence of rat liver S9 to demonstrate that S9 does not impair the ability to classify genotoxicity using this genomic biomarker in TK6cells. PMID:26425668

  16. Development of an automated dual-mode supercritical fluid chromatography and reversed-phase liquid chromatography mass-directed purification system for small-molecule drug discovery.

    PubMed

    Hettiarachchi, Kanaka; Kong, May; Yun, Andersen; Jacobsen, John R; Xue, Qifeng

    2014-04-01

    We report the development of a dual-mode mass-directed supercritical fluid chromatography and reversed-phase liquid chromatography purification system. The addition of a third pump allows for flexible mobile phase control between the two techniques, and enables operation of either chromatography mode within minutes by activation of a set of switching valves on a single system. Software control, fluidic pathways, interface to the mass spectrometer, and fraction collection have been modified for compatibility between both separation methods. The conditioning solvent and tuning parameters for the mass spectrometer were adjusted to achieve an ideal signal trace in either mode with good linearity (r(2) > 0.970) over a range of concentrations and minimal noise for accurate peak detection and isolation. The registration success rate is 90% and overall sample recovery for either technique is 80-90%. Combining two orthogonal separation and purification modes in one single system has improved the purification throughput of complex mixtures and has been a valuable, cost-saving tool in our laboratory. PMID:24470330

  17. 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. PMID:20806283

  18. 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. PMID:27464173

  19. 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. PMID:27343868

  20. 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

  1. Compact diode-directly-pumped passively mode-locked TEM00 Nd:GdVO4 laser at 1341 nm using a semiconductor saturable absorber mirror

    NASA Astrophysics Data System (ADS)

    Liu, K.; Li, F. Q.; Liu, Y.; Cao, D.; Bo, Y.; Peng, Q. J.; Cui, D. F.; Zhang, J. Y.; Xu, Z. Y.

    2011-11-01

    We report on a compact 880-nm diode-directly-pumped passively mode-locked TEM00 Nd:GdVO4 laser at 1341 nm with a semiconductor saturable absorber mirror (SESAM) for the first time. Under the absorbed pump power of 14.6 W, the maximum output power of 1.27 W was obtained at the repetition rate of 85.3 MHz with the pulse width of 45.3 ps, corresponding to an optical-optical efficiency of 8.8% and the slope efficiency of 33.3%, respectively. The beam quality factor was measured to be M 2 = 1.18, indicating a TEM00 mode.

  2. High-power diode-directly-pumped tenth-order harmonic mode-locked TEM00 Nd:YVO4 laser with 1 GHz repetition rate

    NASA Astrophysics Data System (ADS)

    Li, F.-Q.; Zong, N.; Han, L.; Tian, C.-Y.; Bo, Y.; Peng, Q.-J.; Cui, D.-F.; Xu, Z.-Y.

    2011-02-01

    A high-efficiency high-power diode-directly-pumped tenth-order harmonic mode-locked TEM00 Nd:YVO4 laser with 1 GHz repetition rate was first demonstrated. The maximum output power was 10.4 W with optical-optical efficiency of 41.8% and slope efficiency of 78.1%, respectively, the pulse width was about 30 ps at the output power of 9.6 W. Based on the large third-order nonlinearity of Nd:YVO4, the tenth-order harmonic mode-locked pulses were induced by the intensity-dependent Kerr effect and the cooperative action of counter-propagating pulses colliding in the laser crystal for a colliding-pulse-modelocking-like cavity. The pulses were further modulated by a semiconductor saturable absorber mirror.

  3. Promising anticancer activity of a lichen, Parmelia sulcata Taylor, against breast cancer cell lines and genotoxic effect on human lymphocytes.

    PubMed

    Ari, Ferda; Ulukaya, Engin; Oran, Seyhan; Celikler, Serap; Ozturk, Sule; Ozel, Mustafa Zafer

    2015-05-01

    Plants are still to be explored for new anti-cancer compounds because overall success in cancer treatment is still not satisfactory. As a new possible source for such compounds, the lichens are recently taking a great attention. We, therefore, explored both the genotoxic and anti-growth properties of lichen species Parmelia sulcata Taylor. The chemical composition of P. sulcata was analyzed with comprehensive gas chromatography-time of flight mass spectrometry. Anti-growth effect was tested in human breast cancer cell lines (MCF-7 and MDA-MB-231) by the MTT and ATP viability assays, while the genotoxic activity was studied by assays for micronucleus, chromosomal aberration and DNA fragmentation in human lymphocytes culture. Cell death modes (apoptosis/necrosis) were morphologically assessed. P. sulcata inhibited the growth in a dose-dependent manner up to a dose of 100 μg/ml and induced caspase-independent apoptosis. It also showed genotoxic activity at doses (>125 μg/ml) higher than that required for apoptosis. These results suggest that P. sulcata may induce caspase-independent apoptotic cell death at lower doses, while it may be genotoxic at relatively higher doses. PMID:24676908

  4. Evaluation of toxicity and genotoxicity of 2-chlorophenol on bacteria, fish and human cells.

    PubMed

    Vlastos, Dimitris; Antonopoulou, Maria; Konstantinou, Ioannis

    2016-05-01

    Due to the extensive use of chlorophenols (CPs) in anthropogenic activities, 2-Chlorophenol (2-CP), among other CPs, can enter aquatic ecosystems and can be harmful to a variety of organisms, including bacteria, fish and humans, that are exposed directly and/or indirectly to such contaminated environments. Based on the existing knowledge and in order to move a step forward, the purpose of this study is to investigate the toxic and mainly the genotoxic effects of 2-CP using a combination of bioassays. The tests include the marine bacterium Vibrio fischeri and micronuclei induction in the erythrocytes of Carassius auratus as well as in cultured human lymphocytes. The results obtained reveal that 2-CP is able to induce dose-dependent toxic and genotoxic effects on the selected tested concentrations under the specific experimental conditions. PMID:26897408

  5. 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

  6. 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. PMID:26729043

  7. 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

  8. 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

    2016-06-01

    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.

  9. 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

  10. Identification of the set of genes, including nonannotated morA, under the direct control of ModE in Escherichia coli.

    PubMed

    Kurata, Tatsuaki; Katayama, Akira; Hiramatsu, Masakazu; Kiguchi, Yuya; Takeuchi, Masamitsu; Watanabe, Tomoyuki; Ogasawara, Hiroshi; Ishihama, Akira; Yamamoto, Kaneyoshi

    2013-10-01

    ModE is the molybdate-sensing transcription regulator that controls the expression of genes related to molybdate homeostasis in Escherichia coli. ModE is activated by binding molybdate and acts as both an activator and a repressor. By genomic systematic evolution of ligands by exponential enrichment (SELEX) screening and promoter reporter assays, we have identified a total of nine operons, including the hitherto identified modA, moaA, dmsA, and napF operons, of which six were activated by ModE and three were repressed. In addition, two promoters were newly identified and direct transcription of novel genes, referred to as morA and morB, located on antisense strands of yghW and torY, respectively. The morA gene encodes a short peptide, MorA, with an unusual initiation codon. Surprisingly, overexpression of the morA 5' untranslated region exhibited an inhibitory influence on colony formation of E. coli K-12. PMID:23913318

  11. Non-linear infrared spectroscopy of the water bending mode: Direct experimental evidence of hydration shell reorganization?

    PubMed Central

    Chuntonov, Lev; Kumar, Revati

    2014-01-01

    The structure and dynamics of liquid water are further studied by investigating the bend vibrational mode of HDO/D2O and pure H2O via two-dimensional infrared spectroscopy (2D-IR) and linear absorption. The experimental findings and theoretical calculations support a picture in which the HDO bend is localized and the H2O bend is delocalized. The HDO and H2O bends present a loss of the frequency-frequency correlation in subpicosecond time scale. While the loss of correlation for the H2O bend is likely to be associated with the vibrational dynamics of a delocalized transition, the loss of the correlation in the localized HDO bend appears to arise from the fluctuations/rearrangements of the local environment. Interestingly, analysis of the HDO 2D-IR spectra shows the presence of multiple overlapping inhomogeneous distributions of frequencies that interchange in a few picoseconds. Theoretical calculations allow us to propose an atomistic model of the observed vibrational dynamics in which the different in homogeneous distributions and their interchange are assigned to water molecules with different hydrogen-bond states undergoing chemical exchange. The frequency shifts as well as the concentration of the water molecules with single and double hydrogen-bonds as donors derived from the theory are in good agreement with our experimental findings. PMID:24871901

  12. 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.

  13. 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.

  14. 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. PMID:27374557

  15. 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

  16. Genotoxicity of dried Hoodia parviflora aerial parts.

    PubMed

    Lynch, Barry; Lau, Annette; Baldwin, Nigel; Hofman-Hüther, Hana; Bauter, Mark R; Marone, Palma Ann

    2013-05-01

    Hoodia parviflora is being developed commercially for use in weight loss food and dietary supplement products. Its effects are ascribed to a number of glycosides that have been shown to be present in plant extracts from several Hoodia species, the best known of which is H. gordonii. H. parviflora has been identified as an alternative to H. gordonii, and, as part of the process to develop H. parviflora, in vitro genotoxicity tests, as recommended by recent European Food Safety Authority guidance, were conducted on a dried powder preparation of H. parviflora aerial parts. The preparation was tested for reverse mutation at doses up to 5,000μg/plate in Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537, and in Escherichia coli WP2 uvrA TA, both in the presence and in the absence of an exogenous source of metabolic activation (rat liver S9). In addition, the dried powder was evaluated in an in vitro cytotoxicity chromosome aberration assay using human lymphocytes. Test conditions included both a 4 (up to 2500μg/mg) and 44-h exposure period (up to 1000μg/mg) and the incorporation of an exogenous source of metabolic activation (4-h exposure only). H. parviflora dried powder was non-genotoxic in both in vitro assays. PMID:23348409

  17. 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.

  18. 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.

  19. Development of an integrated sampler based on direct 222Rn/ 220Rn progeny sensors in flow-mode for estimating unattached/attached progeny concentration

    NASA Astrophysics Data System (ADS)

    Mishra, Rosaline; Sapra, B. K.; Mayya, Y. S.

    2009-11-01

    A flow-mode integrated sampler consisting of a wire-mesh and filter-paper array along with passive solid state nuclear track detectors has been developed for estimating unattached and attached fraction of 222Rn/ 220Rn progeny concentration. The essential element of this sampler is the direct 222Rn/ 220Rn progeny sensor (DRPS/DTPS), which is an absorber-mounted-LR115 type nuclear track detector that selectively registers the alpha particles emitted from the progeny deposited on its surface. During sampling at a specified flow-rate, the unattached progeny is captured on the wire-mesh; while the attached progeny gets transmitted and is captured on the filter-paper. The alpha particles emitted by the deposited progeny atoms are registered on the sensors placed at a specified distance facing the wire-mesh and the filter-paper, respectively. The various steps involved in the development of this flow-mode direct progeny sampler such as the optimization of the sampling rate and the distance between the sensor and the deposition substrate are discussed. The sensitivity factor of the DTPS-loaded sampler for 220Rn progeny deposited on the wire-mesh and filter-paper is found to be 23.77 ± 0.64 (track cm -2 h -1) (Bq m -3) -1 and 22.30 ± 0.18 (track cm -2 h -1) (Bq m -3) -1, respectively; while that of DRPS-loaded sampler for 222Rn progeny deposition, is 3.03 ± 0.14 (track cm -2 h -1) (Bq m -3) -1 and 2.08 ± 0.07 (track cm -2 h -1) (Bq m -3) -1, respectively. The highlight of this flow-mode sampler is its high sensitivity and that it utilizes the passive technique for estimating the unattached and attached progeny concentration, thus doing away with the alpha counting procedures.

  20. 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. PMID:14627292

  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

    2016-01-01

    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

  3. 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

  4. High speed direct imaging of thin metal film ablation by movie-mode dynamic transmission electron microscopy

    DOE PAGESBeta

    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 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

  5. 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. PMID:15474415

  6. In vitro evaluation of cytotoxicity and genotoxicity of a commercial titanium alloy for dental implantology.

    PubMed

    Velasco-Ortega, Eugenio; Jos, Angeles; Cameán, Ana M; Pato-Mourelo, Jesús; Segura-Egea, Juan J

    2010-09-30

    Titanium and its alloys have many applications in dentistry, being used in orthodontics, endodontics, prosthetics and implantology. But the use in the biomedical field depends on its biocompatibility, as the Council Directive 93/42/EEC of 14 June 1993 concerning medical devices has established. The aim of this study was to investigate the cytotoxicity and genotoxicity of a commercial titanium/aluminium/vanadium alloy (Ti-6Al-4V) developed by an innovative sand-blast process with aluminium oxide, and nitric-acid passivation. This procedure created a material with an average surface roughness of 1.73±0.16μm with applications in dental implants. International Organization for Standardization (ISO) procedures 7405:2008 and 10993-5:2009 were used to perform the cytotoxicity tests, and bacterial and cell-mutation assays to evaluate genotoxicity. The results show that this titanium alloy (Ti-6Al-4V) was neither cytotoxic nor genotoxic in any of the tests performed. It can be concluded that this new Ti-6Al-4V material with the roughness characteristics specified shows good biocompatibility and can be considered of choice in dental implantology. PMID:20615479

  7. 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. PMID:7713029

  8. 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.

  9. 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.

  10. Evaluation of genotoxic and antigenotoxic effects of hydroalcoholic extracts of Zuccagnia punctata Cav.

    PubMed

    Zampini, Iris Catiana; Villarini, Milena; Moretti, Massimo; Dominici, Luca; Isla, María Inés

    2008-01-17

    Zuccagnia punctata Cav. (Fabaceae), a widely used plant species in Argentine folk medicine, has been shown to have a broad spectrum of antibacterial, antifungal, antioxidant and cytoprotective activities. In this study, the hydroalcoholic extract of Zuccagnia punctata and 2',4'-dihydroxychalcone isolated from it were investigated for genotoxicity/antigenotoxicity in the in vitro comet assay test on human hepatoma HepG2 cells. No acute toxicity of the extract could be determined. HepG2 cells were treated with three different concentrations (2.5, 5.0 and 10.0 microg/mL) or 2',4'-dihydroxychalcone (0.01, 0.10 and 1.00 microg/mL). To explore the potential mechanisms of action, two approaches were followed: co-treatment with 4-nitroquinoline-N-oxyde (4-NQO), a direct genotoxic compound, and a pre-treatment protocol with benzo[a]pyrene (B[a]P), an indirect genotoxic compound. The natural products neither affected cell viability nor induced DNA damage in the concentration range tested. Zuccagnia punctata tinctures were able to diminish the DNA damage induced in HepG2 cells by 4-NQO and B[a]P in 31% and 10%, respectively at 10 microg/mL. Pre-treatment of HepG2 cells with 2',4'-dihydroxychalcone was highly effective in decreasing B[a]P-induced DNA damage at a statistically significant level, with an almost clear dose-response relationship. The inhibition values were 28.2-43.9% for the tested concentrations of 0.01-1 microg/mL, respectively. The results clearly indicate that the phytoextract from Zuccagnia punctata, under the experimental conditions tested, is not genotoxic and that 2',4'-dihydroxychalcone contributes to a high degree to the antigenotoxic effects of Zuccagnia punctata tincture. PMID:18023546

  11. 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. PMID:25976910

  12. High-throughput in vivo genotoxicity testing: an automated readout system for the somatic mutation and recombination test (SMART).

    PubMed

    Lombardot, Benoit; Oh, Chun-Taek; Kwak, Jihoon; Genovesio, Auguste; Kang, Myungjoo; Hansen, Michael Adsett Edberg; Han, Sung-Jun

    2015-01-01

    Genotoxicity testing is an important component of toxicity assessment. As illustrated by the European registration, evaluation, authorization, and restriction of chemicals (REACH) directive, it concerns all the chemicals used in industry. The commonly used in vivo mammalian tests appear to be ill adapted to tackle the large compound sets involved, due to throughput, cost, and ethical issues. The somatic mutation and recombination test (SMART) represents a more scalable alternative, since it uses Drosophila, which develops faster and requires less infrastructure. Despite these advantages, the manual scoring of the hairs on Drosophila wings required for the SMART limits its usage. To overcome this limitation, we have developed an automated SMART readout. It consists of automated imaging, followed by an image analysis pipeline that measures individual wing genotoxicity scores. Finally, we have developed a wing score-based dose-dependency approach that can provide genotoxicity profiles. We have validated our method using 6 compounds, obtaining profiles almost identical to those obtained from manual measures, even for low-genotoxicity compounds such as urethane. The automated SMART, with its faster and more reliable readout, fulfills the need for a high-throughput in vivo test. The flexible imaging strategy we describe and the analysis tools we provide should facilitate the optimization and dissemination of our methods. PMID:25830368

  13. High-Throughput In Vivo Genotoxicity Testing: An Automated Readout System for the Somatic Mutation and Recombination Test (SMART)

    PubMed Central

    Kwak, Jihoon; Genovesio, Auguste; Kang, Myungjoo; Hansen, Michael Adsett Edberg; Han, Sung-Jun

    2015-01-01

    Genotoxicity testing is an important component of toxicity assessment. As illustrated by the European registration, evaluation, authorization, and restriction of chemicals (REACH) directive, it concerns all the chemicals used in industry. The commonly used in vivo mammalian tests appear to be ill adapted to tackle the large compound sets involved, due to throughput, cost, and ethical issues. The somatic mutation and recombination test (SMART) represents a more scalable alternative, since it uses Drosophila, which develops faster and requires less infrastructure. Despite these advantages, the manual scoring of the hairs on Drosophila wings required for the SMART limits its usage. To overcome this limitation, we have developed an automated SMART readout. It consists of automated imaging, followed by an image analysis pipeline that measures individual wing genotoxicity scores. Finally, we have developed a wing score-based dose-dependency approach that can provide genotoxicity profiles. We have validated our method using 6 compounds, obtaining profiles almost identical to those obtained from manual measures, even for low-genotoxicity compounds such as urethane. The automated SMART, with its faster and more reliable readout, fulfills the need for a high-throughput in vivo test. The flexible imaging strategy we describe and the analysis tools we provide should facilitate the optimization and dissemination of our methods. PMID:25830368

  14. Genotoxicity testing of Maillard reaction products.

    PubMed

    Shibamoto, T

    1989-01-01

    Since the development of short-term genotoxicity tests such as the Ames assay, the mutagenicity of Maillard reaction products has been tested extensively. Some products have exhibited strong activity. For example, one of the earliest studies demonstrated some mutagenic activity in a dichloromethane extract of a D-glucose/ammonia Maillard model system. Many researchers have attempted to pinpoint the principal chemical(s) of mutagenicity of the Maillard products using various sugar-amino acid browning model systems over last two decades. However, no mutagenic individual Maillard product has been isolated and identified. Nitrite has been also used as a reactant in browning reaction model systems, primarily to investigate the formation of potentially mutagenic or carcinogenic N-nitroso compounds. Recently some potent mutagens isolated from pyrolyzed amino acids or proteins have begun to receive attention as Maillard reaction products. PMID:2675034

  15. 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. PMID:25287225

  16. 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 ...

  17. 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...

  18. Genotoxic and mutagenic potential of nitramines.

    PubMed

    Fjellsbø, Lise Marie; Verstraelen, Sandra; Kazimirova, Alena; Van Rompay, An R; Magdolenova, Zuzana; Dusinska, Maria

    2014-10-01

    Climate change is one of the major challenges in the world today. To reduce the amount of CO2 released into the atmosphere, CO2 at major sources, such as power plants, can be captured. Use of aqueous amine solutions is one of the most promising methods for this purpose. However, concerns have been raised regarding its impacts on human health and the environment due to the degradation products, such as nitrosamines and nitramines that may be produced during the CO2 capture process. While several toxicity studies have been performed investigating nitrosamines, little is known about the toxic potential of nitramines. In this study a preliminary screening was performed of the genotoxic and mutagenic potential of nitramines most likely produced during amine based CO2 capture; dimethylnitramine (DMA-NO2), methylnitramine (MA-NO2), ethanolnitramine (MEA-NO2), 2-methyl-2-(nitramino)-1-propanol (AMP-NO2) and piperazine nitramine (PZ-NO2), by the Bacterial Reverse Mutation (Ames) Test, the Cytokinesis Block Micronucleus (CBMN) Assay and the in vitro Single-Cell Gel Electrophoresis (Comet) Assay. MA-NO2 and MEA-NO2 showed mutagenic potential in the Ames test and a weak genotoxic response in the CBMN Assay. AMP-NO2 and PZ-NO2 significantly increased the amount of DNA strand breaks; however, the level of breaks was below background. Most previous studies on nitramines have been performed on DMA-NO2, which in this study appeared to be the least potent nitramine. Our results indicate that it is important to investigate other nitramines that are more likely to be produced during CO2 capture, to ensure that the risk is realistically evaluated. PMID:25042035

  19. 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. PMID:25834172

  20. 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.

  1. 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

  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. 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). PMID:27283681

  4. 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.

  5. Correlations between embryotoxic and genotoxic effects of phenytoin in mice.

    PubMed

    Barcellona, P S; Barale, R; Campana, A; Zucconi, D; Rossi, V; Caranti, S

    1987-01-01

    The anticonvulsant drug phenytoin (DPH) has been suspected to produce embryotoxicity through an arene oxide intermediate. This drug was also found to be a genotoxic agent. These hypotheses were tested in pregnant mice modulating the phases I and II metabolizing enzymes. DPH was studied by assessing embryotoxicity, teratogenicity, and genotoxicity, the latter by the micronucleus test on the polychromatic erythrocytes of dams and fetuses. DPH embryotoxicity was potentiated by inhibiting both cytochrome P-450 and epoxide hydrase and decreased by inducing cytochrome P-450. Equivocal results were obtained by modulating cytochrome P-448. The main DPH metabolite, p-hydroxyphenytoin (HPPH), was ineffective both per se and after cytochrome induction or epoxide hydrase inhibition. DPH did not exert genotoxicity on the maternal organism, no matter which modulating agent was used. In the fetus, however, weak genotoxic effects were observed. These effects significantly increased with inhibition of epoxide hydrase; they disappeared with induction of both cytochromes P-448 and P-450 or with inhibition of the latter. No genotoxicity was exerted by HPPH, even when the enzymatic pattern was modulated. It is concluded that the major role in DPH embryotoxicity is played by the unchanged drug, while the presence of the arene oxide is determinant for genotoxic effects. PMID:2885938

  6. 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. PMID:26430459

  7. Quantification of umu genotoxicity level of urban river water.

    PubMed

    Kameya, T; Nagato, T; Nakagawa, K; Yamashita, D; Kobayashi, T; Fujie, K

    2011-01-01

    In recent years, the request of environmental safety management for carcinogenic substances, mutagenic substances and/or reproductive toxicity substances (CMR) has increased. This study focused on clarifying the genotoxicity level of environmental water and its release source by using the umu test provided in ISO13829. Although a genotoxicity index "induction ratio (IR)" is used in ISO13829, we normalised it to make it possible to compare various environmental water quantitatively to each other as a new index "genotoxic activity (GA=(IR-1)/Dose)". Sample water was collected and concentrated to 100 times or 1,000 times by a solid phase extraction method. As the test results, it was found that GA level in actual river water varied widely from less than the determination limit of 23 [1/L] to 1,100 [1/L] by quantitative comparison, and the value was also equivalent to more than 50 times the level of tap water. The GA level of household wastewater was not so high, but the levels of treated water from wastewater treatment plant (WTP) were from 220 [1/L] to 3,200 [1/L]. Raw sewage of some WTP shows high level genotoxicity. A part of genotoxicity substances, for example 50%, could be removed by conventional wastewater treatment, but it was not enough to reduce the water environmental load of genotoxicity. PMID:21278461

  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. PMID:27331299

  9. Genotoxic testing of titanium dioxide anatase nanoparticles using the wing-spot test and the comet assay in Drosophila.

    PubMed

    Carmona, Erico R; Escobar, Bibi; Vales, Gerard; Marcos, Ricard

    2015-01-15

    Titanium dioxide nanoparticles (TiO2 NPs) are widely used for preparations of sunscreens, cosmetics, food and personal care products. However, the possible genotoxic risk associated with this nano-scale material exposure is not clear, especially in whole organisms. In the present study, we explored the in vivo genotoxic activity of TiO2 NPs as well as their TiO2 bulk form using two well-established genotoxic assays, the wing spot test and the comet assay in Drosophila melanogaster. To determine the extent of tissue damage induced by TiO2 NPs in Drosophila larvae, the trypan blue dye exclusion test was also applied. Both compounds were supplied to third instar larvae by ingestion at concentration ranging from 0.08 to 1.60 mg/mL. The results obtained in the present study indicate that TiO2 NPs can reach and induce cytotoxic effects on midgut and imaginal disc tissues of larvae, but they do not promote genotoxicity in the wing-spot test of Drosophila. However, when both nano- and large-size forms of TiO2 were evaluated with the comet assay in Drosophila hemocytes, a significant increase in DNA damage, with a direct dose-response pattern, was observed for TiO2 NPs. The results obtained with the comet assay suggest that the primary DNA damage associated with TiO2 NPs exposure in Drosophila could be associated with specific physico-chemical properties of nano-TiO2, since no effects were observed with the bulk form. This study remarks the usefulness of using more than one genetic end-point in the evaluation of the genotoxic potential of nanomaterials. PMID:25726144

  10. A comparison of GPS solutions for strain and SKS fast directions: Implications for modes of shear in the mantle of a plate boundary zone

    NASA Astrophysics Data System (ADS)

    houlie, nicolas; Stern, Tim

    2014-05-01

    We study the strain rate field computed using the GPS GEONET dataset collected during the last decade. We show that we can infer the amount of simple shear accumulated in the mantle by comparing the compression strain orientation with the SKS fast directions. We suggest the mantle beneath the southern part of the south island is under pure shear while to the north the amount of distributed shear is larger. At last, we confirm that, in that context, the strike of New Zealand fault systems make a 60 degree angle with the compression strain rate axis. We compute the strain rate field and the vectors for the principal axis of strain in within New Zealand based on 10 years of data from the Geonet network. A comparison of the principal axis of extension with the fast directions from SKS splitting shows a consistent 20 degree divergence in the northern south Island with the two sets of vectors becoming parallel in central South Island. We firstly interpret these data as confirmation of mantle flow driving crustal kinematics. In addition we suggest the data are consistent with a mode of predominately simple and pure shear in northern and central South Island respectively.

  11. 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

  12. Methylation of lysine 9 in histone H3 directs alternative modes of highly dynamic interaction of heterochromatin protein hHP1β with the nucleosome.

    PubMed

    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

    2012-09-28

    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

  13. 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…

  14. 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. PMID:25964273

  15. 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

  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. Calcium channel blockers protect against aluminium-induced DNA damage and block adaptive response to genotoxic stress in plant cells.

    PubMed

    Achary, V Mohan M; Parinandi, Narasimham L; Panda, Brahma B

    2013-03-18

    Calcium is an important second messenger in signal transduction pathways. The role of Ca(2+) signalling in Al-induced DNA damage, cell death, and adaptive response to genotoxic stress caused by ethyl methanesulfonate (EMS) or methylmercuric chloride (MMCl) in the root cells of Allium cepa was investigated in the current study. Root cells in planta were treated with Al(3+) (800μM of AlCl(3)) for 3h without or with 2h pre-treatment with the Ca(2+) chelator (EGTA) or Ca(2+) channel blockers (lanthanum chloride, verapamil) or CaM/CDPK antagonist (W7). In addition, root cells in planta were conditioned by treatment with Al(3+) (5 or 10μM of AlCl(3)) for 2h followed by the genotoxic challenge with MMCl (1.25μM) or EMS (2.5 or 5mM) for 3h without or with the pre-treatment of the chosen Ca(2+) chelator/channel blockers/antagonist. Following the treatments, cell death and DNA damage were investigated in the root cells by comet assay. Furthermore, genotoxicity in the root meristems was determined after 18-30h of recovery. These results revealed that Al(3+) (800μM) significantly induced DNA damage and cell death in the root cells of A. cepa. On the other hand, conditioning of the root cells with Al(3+) at low concentrations (5 or 10μM) offered adaptive response leading to the protection against genotoxic stress induced by MMCl and EMS. Pre-treatment of root cells with the Ca(2+) chelator/channel blockers/antagonist not only alleviated Al(3+)-induced DNA damage and cell death induced but also blocked the Al(3+)-mediated adaptive response to genotoxic stress induced by MMCl and EMS. For the first time, the results of the present study highlighted the role of Ca(2+) signalling underlying the biphasic mode of action of Al(3+) that induced DNA damage and cell death at high doses and offered adaptation to genotoxic response in plants at low doses. PMID:23313746

  18. 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...

  19. 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...

  20. Genotoxic risk and oxidative DNA damage in workers exposed to antimony trioxide.

    PubMed

    Cavallo, Delia; Iavicoli, Ivo; Setini, Andrea; Marinaccio, Alessandro; Perniconi, Barbara; Carelli, Giovanni; Iavicoli, Sergio

    2002-01-01

    The growing use of antimony (Sb) compounds in industry and the consequent increase in the number of exposed workers make it important to carry out a health risk assessment. The main goal of this study was to assess the genotoxicity of Sb(2)O(3) in occupationally exposed workers. Genotoxicity was evaluated by the sister chromatid exchange (SCE) and micronucleus tests, and the enzyme (Fpg)-modified comet assay. In addition, antimony exposure levels were established by environmental monitoring with personal air samplers. We studied 23 male workers assigned to different fire retardant treatment tasks in the car upholstery industry and a control group of 23 healthy nonexposed males. The exposed workers were divided into two groups on the basis of their tasks and the work cycle: Group A comprised finishing and intermediate inspection operators who directly handled a mixture containing Sb(2)O(3); Group B were jet operators, not directly exposed to the compound. Environmental monitoring detected low Sb exposure levels but significant differences between the two groups, with Group A having the higher exposure level. Cytogenetic analyses showed no difference between exposed workers and controls for micronuclei and SCE. The enzyme-modified comet assay showed a probable relation between moderate levels of oxidative DNA damage and exposure to antimony, with a significantly higher proportion of workers in Group A having oxidative DNA damage compared to controls. The results support the theory that oxidative DNA damage is involved in the genotoxicity of antimony and indicate the need for further research in this field. PMID:12355552

  1. Ecotoxicity and genotoxicity assessment of exhaust particulates from diesel-powered buses.

    PubMed

    Kováts, Nora; Acs, András; Ferincz, Arpád; Kovács, Anikó; Horváth, Eszter; Kakasi, Balázs; Jancsek-Turóczi, Beatrix; Gelencsér, András

    2013-10-01

    Diesel exhaust is one of the major sources of fine and ultra-fine particulate matter in urban air. Toxicity of diesel-powered engine emissions has been quite widely assessed; however, much less information is available on their ecotoxicity. In our study, the kinetic version of the Vibrio fischeri bioluminescence inhibition bioassay based on the ISO 21338:2010 standard was used to characterise the ecotoxicity of diesel-powered buses. It is a direct contact test in which solid samples are tested in suspension and test organisms are in direct contact with toxic particles. The age of the selected buses fell into a wide range; the oldest one was produced in 1987. Diesel engines of different emission standards (Euro0-Euro4) were included. Measured EC50 values of Euro0-Euro1 engine emissions fell into the same range, 1.24-0.96 μg ml(-1), respectively. On the contrary, emission of Euro4 vehicle proved to be non-toxic. Genotoxic potential of the samples was also estimated, using the colorimetric SOS-chromotest™. Genotoxicity was detected also for Euro0 and Euro1 buses, showing correlation with the ecotoxic potential. The fact that the particulates from Euro4 vehicles did not show ecotoxic/genotoxic effect implies that replacing old Euro1 and Euro2 buses can be a highly effective solution for reducing environmental hazard of automotive emissions. The whole-aerosol testing method is a cheap alternative that can be used in engine developments and emission control. PMID:23609923

  2. 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. PMID:25829077

  3. 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. PMID:23640391

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. Glycidamide genotoxicity modulated by Caspases genes polymorphisms.

    PubMed

    de Lima, João Pereira; Silva, Susana N; Rueff, José; Pingarilho, Marta

    2016-08-01

    Acrylamide (AA) is amongst acknowledged carcinogenic dietary factors. Its DNA-reactive metabolite is glycidamide (GA). The present study intended to correlate the role of key polymorphic genes of apoptosis (CASP7, CASP8, CASP9, CASP10, LTA and TNFRSF1B) with biomarkers of effect of DNA damage, namely the sister chromatid exchange assay (SCE) and the comet assay in whole blood cells exposed to GA. The aim was to assess as a proof of concept the role that pro-apoptotic effector proteins might have in the yields of genotoxic effects when those effector proteins are coded by polymorphic genes. Whole blood from a small group of volunteers was exposed to GA to assess DNA damage and the volunteers were genotyped for polymorphic genes related to apoptosis pathways. A relation between the induction of SCE and several variants of the polymorphism CASP8 rs1035142 G>T was observed. Also, a relation between the % tail DNA and the CASP10 I522L polymorphism was found. Furthermore, associations between % tail DNA and several SNP-SNP interactions of CASP8 and CASP10 were found. A possible correlation between DNA damage and the genetic susceptibility, bestowed by polymorphic genes in the apoptosis inducing pathways was verified. PMID:27062911

  10. 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

  11. Systematic Protein Level Regulation via Degradation Machinery Induced by Genotoxic Drugs.

    PubMed

    Kume, Kohei; Ishida, Kazushige; Ikeda, Miyuki; Takemoto, Kazuhiro; Shimura, Tsutomu; Young, Lynn; Nishizuka, Satoshi S

    2016-01-01

    In this study we monitored protein dynamics in response to cisplatin, 5-fluorouracil, and irinotecan with different concentrations and administration modes using "reverse-phase" protein arrays (RPPAs) in order to gain comprehensive insight into the protein dynamics induced by genotoxic drugs. Among 666 protein time-courses, 38% exhibited an increasing trend, 32% exhibited a steady decrease, and 30% fluctuated within 24 h after drug exposure. We analyzed almost 12,000 time-course pairs of protein levels based on the geometrical similarity by correlation distance (dCor). Twenty-two percent of the pairs showed dCor > 0.8, which indicates that each protein of the pair had similar dynamics. These trends were disrupted by a proteasome inhibitor, MG132, suggesting that the protein degradation system was activated in response to the drugs. Among the pairs with high dCor, the average dCor of pairs with apoptosis-related protein was significantly higher than those without, indicating that regulation of protein levels was induced by the drugs. These results suggest that the levels of numerous functionally distinct proteins may be regulated by common degradation machinery induced by genotoxic drugs. PMID:26625007

  12. Assessment of genotoxicity of catecholics using impedimetric DNA-biosensor.

    PubMed

    Ensafi, Ali A; Amini, Maryam; Rezaei, B

    2014-03-15

    The potential toxicity of catecholics is a big concern, because the catechol-derived semiquinone radical after the oxidation of catechol (CA) can donate an H-atom to generate quinone, and during this process a superoxide anion radical may be produced. Considering the fact that catecholics are highly consumed in our daily life and some drugs also contain one or more CA moieties, we speculate that CA's toxicity might not be insurmountable. Therefore, finding approaches to investigate catecholics potential toxicity is of great significance. Here in, an electrochemical protocol for direct monitoring of genotoxicity of catecholics is described. CA encapsulated on MWCNTs (CA@MWCNT) through continuous cyclic voltammetric on the surface of pencil graphite electrode (PGE). Subsequently, a DNA functionalized biosensor (DNA/CA@MWCNT/PGE) was prepared and characterized for the detection and the investigation of DNA damage induced by radicals generated from catecholics. The change in the charge transfer resistance (Rct) after the incubation of the DNA biosensor in the damaging solution for a certain time was used as an indicator for DNA damage. Incubation of DNA-modified electrode with CA solution containing Cu(II), Cr(VI) and Fe(III) has been shown to result in oxidative damage to the DNA and change in the electrochemical properties. It was found that the presence of Cu(II), Cr(VI) and Fe(III) in solution caused damage to DNA. The inhibitory effect of glutathione and plumbagin on the CA-mediated DNA damage has also been investigated using the biosensor. The minimum concentration of the metal ions for CA induced DNA damage was investigated. Recognition of suitable matrixes for CA-mediated DNA damage can be assessed using proposed DNA biosensor. Such direct monitoring of the DNA damage holds great promise for designing new biosensors with modification of the biosensor with different damaging agents. PMID:24121207

  13. High-altitude medicines: a short-term genotoxicity study.

    PubMed

    Ghosh, Manosij; Biswas, Dhrubojyoti; Mukherjee, Anita

    2010-08-01

    People live in the mountains distributed across the world and are exposed to reduced inspired oxygen and lower barometric pressure along with other factors that lead to high-altitude diseases. The present study was conducted to examine what extent of marketed medicines used in the management of high-altitude sickness has been tested for their genotoxic activity. Comet assay or the single-cell gel electrophoresis was utilized to evaluate genotoxicity of the six medicines on human peripheral whole blood cells and isolated lymphocytes at the concentrations 250 microg/mL, 500 microg/mL and 1 mg/mL. The comet assay endpoints included percentage Tail DNA (% Tail DNA) and olive tail moment (OTM) as they were considered to be sensitive and reliable scores across different laboratories. The results show that dexamethasone, deriphylline and furosemide can induce significant DNA damage in human whole blood and lymphocytes alike. Acetazolamide, ibuprofen and nifedipine show no genotoxic effect, neither on human whole blood nor on human lymphocytes. Taking into account the results of genotoxicity, it will be a prudent choice to restrict the use of these compounds for longer periods, until more information on the in vitro mutagenicity and in vivo genotoxicity studies are available. PMID:20504830

  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. Laser induced fluorescence measurements of ion velocity in a DC magnetron microdischarge with self-organized drift wave modes propagating in the direction opposite the E x B electron drift velocity

    NASA Astrophysics Data System (ADS)

    Young, Chris; Gascon, Nicolas; Lucca Fabris, Andrea; Cappelli, Mark; Ito, Tsuyohito; Stanford Plasma Physics Laboratory Collaboration; Osaka University CenterAtomic; Molecular Technologies Collaboration

    2015-09-01

    Evidence is presented of rotating azimuthal wave structures in a planar DC magnetron microdischarge operating in argon and xenon. Plasma emission captured using a high frame rate camera reveals waves of varying azimuthal modes propagating in the negative E x B direction. The dominant stable mode structure depends on discharge voltage. The negative drift direction is attributed to a local field reversal arising from strong density gradients that drive excess ions towards the anode. The transition between modes is shown to be consistent with models of gradient drift-wave dispersion in the presence of such a field reversal when the fluid representation includes ambipolar diffusion along the direction parallel to the magnetic field. Time-average and time-synchronized laser induced fluorescence measurements are carried out to elucidate the anode-bound ion dynamics driven by the field reversal. This research is supported by the Air Force Office of Scientific Research.

  16. Aluminium-induced DNA damage and adaptive response to genotoxic stress in plant cells are mediated through reactive oxygen intermediates.

    PubMed

    Murali Achary, V Mohan; Panda, Brahma B

    2010-03-01

    Experiments employing growing root cells of Allium cepa were conducted with a view to elucidate the role of reactive oxygen intermediates (ROI) in aluminium (Al)-induced DNA damage, cell death and adaptive response to genotoxic challenge imposed by ethyl methanesulphonate (EMS) or methyl mercuric chloride (MMCl). In a first set of experiments, root cells in planta were treated with Al at high concentrations (200-800 microM) for 3 h without or with pre-treatments of dihydroxybenzene disulphonic acid (Tiron) and dimethylthiourea (DMTU) for 2 h that trap O(2)(.-)and hydrogen peroxide (H(2)O(2)), respectively. At the end of treatments, generation of O(2)(.-) and H(2)O(2), cell death and DNA damage were determined. In a second set of experiments, root cells in planta were conditioned by Al at low concentrations (5 or 10 microM) for 2 h and after a 2 h intertreatment interval challenged by MMCl or EMS for 3 h without or with a pre-treatment of Tiron or DMTU. Conditioning treatments, in addition, included two oxidative agents viz rose bengal and H(2)O(2) for comparison. Following treatments, root cells in planta were allowed to recover in tap water. Genotoxicity and DNA damage were evaluated by micronucleus (MN), chromosome aberration (CA) or spindle aberration (SA) and comet assays at different hours (0-30 h) of recovery. The results demonstrated that whereas Al at high concentrations induced DNA damage and cell death, in low concentrations induced adaptive response conferring genomic protection from genotoxic challenge imposed by MMCl, EMS and Al. Pre-treatments of Tiron and DMTU prevented Al-induced DNA damage, cell death, as well as genotoxic adaptation to MMCl and EMS, significantly. The findings underscored the biphasic (hormetic) mode of action of Al that at high doses induced DNA damage and at low non-toxic doses conferred genomic protection, both of which were mediated through ROI but perhaps involving different networks. PMID:19955331

  17. Measurements of the ablation-front trajectory and low-mode nonuniformity in direct-drive implosions using x-ray self-emission shadowgraphy

    DOE PAGESBeta

    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.; et al

    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

  18. 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.

  19. Direct Extraction of Tumor Response Based on Ensemble Empirical Mode Decomposition for Image Reconstruction of Early Breast Cancer Detection by UWB.

    PubMed

    Li, Qinwei; Xiao, Xia; Wang, Liang; Song, Hang; Kono, Hayato; Liu, Peifang; Lu, Hong; Kikkawa, Takamaro

    2015-10-01

    A direct extraction method of tumor response based on ensemble empirical mode decomposition (EEMD) is proposed for early breast cancer detection by ultra-wide band (UWB) microwave imaging. With this approach, the image reconstruction for the tumor detection can be realized with only extracted signals from as-detected waveforms. The calibration process executed in the previous research for obtaining reference waveforms which stand for signals detected from the tumor-free model is not required. The correctness of the method is testified by successfully detecting a 4 mm tumor located inside the glandular region in one breast model and by the model located at the interface between the gland and the fat, respectively. The reliability of the method is checked by distinguishing a tumor buried in the glandular tissue whose dielectric constant is 35. The feasibility of the method is confirmed by showing the correct tumor information in both simulation results and experimental results for the realistic 3-D printed breast phantom. PMID:26552095

  20. 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

  1. 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

  2. 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.

  3. Evaluation of subchronic genotoxic potential of Swarna Makshika Bhasma

    PubMed Central

    Savalgi, Pavan B.; Patgiri, Biswajyoti; Thakkar, Jalaram H.; Ravishankar, B.; Gupta, Varun B.

    2012-01-01

    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. PMID:23723652

  4. 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

  5. Monitoring hospital wastewaters for their probable genotoxicity and mutagenicity.

    PubMed

    Sharma, Pratibha; Mathur, N; Singh, A; Sogani, M; Bhatnagar, P; Atri, R; Pareek, S

    2015-01-01

    Cancer is a leading cause of death worldwide. Excluding the genetic factors, environmental factors, mainly the pollutants, have been implicated in the causation of the majority of cancers. Wastewater originated from health-care sectors such as hospitals may carry vast amounts of carcinogenic and genotoxic chemicals to surface waters or any other source of drinking water, if discharged untreated. Humans get exposed to such contaminants through a variety of ways including drinking water. The aim of the present study was, thus, to monitor the genotoxic and mutagenic potential of wastewaters from three big hospitals located in Jaipur (Rajasthan), India. One of them was operating an effluent treatment plant (ETP) for treatment of its wastewater and therefore both the untreated and treated effluents from this hospital were studied for their genotoxicity. Two short-term bacterial bioassays namely the Salmonella fluctuation assay and the SOS chromotest were used for the purpose. Results of fluctuation assay revealed the highly genotoxic nature of all untreated effluent samples with mutagenicity ratios (MR) up to 23.13 ± 0.18 and 42.25 ± 0.35 as measured with Salmonella typhimurium strains TA98 and TA100, respectively. As determined with the chromotest, all untreated effluents produced significant induction factors (IF) ranging from 3.29 ± 1.11 to 13.35 ± 3.58 at higher concentrations. In contrast, treated effluent samples were found to be slightly genotoxic in fluctuation test only with an MR = 3.75 ± 0.35 for TA100 at 10 % concentration. Overall, the results indicated that proper treatment of hospital wastewaters may render the effluents safe for disposal contrary to the untreated ones, possessing high genotoxic potential. PMID:25487460

  6. Impact of isomalathion on malathion cytotoxicity and genotoxicity in human HepaRG cells.

    PubMed

    Josse, Rozenn; Sharanek, Ahmad; Savary, Camille C; Guillouzo, Andre

    2014-02-25

    Isomalathion is a major impurity of technical grade malathion, one of the most abundantly applied insecticides; however little is known about its hepatotoxicity. In the present study, cytotoxicity and genotoxicity of malathion and isomalathion either individually or in combination, were assessed using the metabolically competent human liver HepaRG cell line. Isomalathion reduced cell viability starting at a 100 μM concentration after a 24h exposure. It also significantly induced caspase-3 activity in a dose-dependent manner starting at 5 μM. On the contrary, even at concentrations as high as 500 μM malathion affected neither cell viability nor caspase-3 activity. Moreover, co-exposure of both compounds resulted in decreased toxicity of isomalathion. By contrast, malathion and isomalathion either separately or in combination, slightly induced micronuclei formation at low concentrations and had additive genotoxic effects when combined at 25 μM. Individually or combined isomalathion directly inhibited activity of carboxyesterases which are involved in detoxication of malathion. In addition, transcripts of CYP2B6 and CYP3A4, two CYPs responsible for malathion phase I metabolism, were strongly induced by the mixture while isomalathion alone only moderately decreased CYP1A2 and increased CYP2B6 transcripts. However, these CYPs were not altered at the protein or activity levels. Taken altogether, our results showed that isomalathion was much more cytotoxic than malathion while both compounds had comparable genotoxic effects in HepaRG hepatocytes at low concentrations and brought further support to the importance of considering impurities and interactions during evaluation of health risks of pesticides. PMID:24333466

  7. 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.

  8. The use of dose-response data in a margin of exposure approach to carcinogenic risk assessment for genotoxic chemicals in food.

    PubMed

    Benford, Diane J

    2016-05-01

    Genotoxic substances are generally not permitted for deliberate use in food production. However, an appreciable number of known or suspected genotoxic substances occur unavoidably in food, e.g. from natural occurrence, environmental contamination and generation during cooking and processing. Over the past decade a margin of exposure (MOE) approach has increasingly been used in assessing the exposure to substances in food that are genotoxic and carcinogenic. The MOE is defined as a reference point on the dose-response curve (e.g. a benchmark dose lower confidences limit derived from a rodent carcinogenicity study) divided by the estimated human intake. A small MOE indicates a higher concern than a very large MOE. Whilst the MOE cannot be directly equated to risk, it supports prioritisation of substances for further research or for possible regulatory action, and provides a basis for communicating to the public. So far, the MOE approach has been confined to substances for which carcinogenicity data are available. In the absence of carcinogenicity data, evidence of genotoxicity is used only in hazard identification. The challenge to the genetic toxicology community is to develop approaches for characterising risk to human health based on data from genotoxicity studies. In order to achieve wide acceptance, it would be important to further address the issues that have been discussed in the context of dose-response modelling of carcinogenicity data in order to assign levels of concern to particular MOE values, and also whether it is possible to make generic conclusions on how potency in genotoxicity assays relates to carcinogenic potency. PMID:26297741

  9. 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

  10. 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. PMID:21752384

  11. 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.

  12. 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.

  13. 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.

  14. 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…

  15. Genotoxic potential of selected cytostatic drugs in human and zebrafish cells.

    PubMed

    Gajski, Goran; Gerić, Marko; Žegura, Bojana; Novak, Matjaž; Nunić, Jana; Bajrektarević, Džejla; Garaj-Vrhovac, Vera; Filipič, Metka

    2016-08-01

    Due to their increasing use, the residues of anti-neoplastic drugs have become emerging pollutants in aquatic environments. Most of them directly or indirectly interfere with the cell's genome, which classifies them into a group of particularly dangerous compounds. The aim of the present study was to conduct a comparative in vitro toxicological characterisation of three commonly used cytostatics with different mechanisms of action (5-fluorouracil [5-FU], cisplatin [CDDP] and etoposide [ET]) towards zebrafish liver (ZFL) cell line, human hepatoma (HepG2) cells and human peripheral blood lymphocytes (HPBLs). Cytotoxicity was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and acridine orange/ethidium bromide staining. All three drugs induced time- and dose-dependent decreases in cell viability. The sensitivity of ZFL and HepG2 cells towards the cytotoxicity of 5-FU was comparable (half maximal inhibitory concentration (IC50) 5.3 to 10.4 μg/mL). ZFL cells were more sensitive towards ET- (IC50 0.4 μg/mL) and HepG2 towards CDDP- (IC50 1.4 μg/mL) induced cytotoxicity. Genotoxicity was determined by comet assay and cytokinesis block micronucleus (CBMN) assay. ZFL cells were the most sensitive, and HPBLs were the least sensitive. In ZFL cells, induction of DNA strand breaks was a more sensitive genotoxicity endpoint than micronuclei (MNi) induction; the lowest effective concentration (LOEC) for DNA strand break induction was 0.001 μg/mL for ET, 0.01 μg/mL for 5-FU and 0.1 μg/mL for CDDP. In HepG2 cells, MNi induction was a more sensitive genotoxicity endpoint. The LOEC values were 0.01 μg/mL for ET, 0.1 μg/mL for 5-FU and 1 μg/mL for CDDP. The higher sensitivity of ZFL cells to cytostatic drugs raises the question of the impact of such compounds in aquatic ecosystem. Since little is known on the effect of such drugs on aquatic organisms, our results demonstrate that ZFL cells provide a relevant and sensitive tool to

  16. 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

    2012-07-01

    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

  17. 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

  18. 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

  19. Genotoxic effects of acrylamide and glycidamide in mouse lymphoma cells.

    PubMed

    Mei, Nan; Hu, Jiaxiang; Churchwell, Mona I; Guo, Lei; Moore, Martha M; Doerge, Daniel R; Chen, Tao

    2008-02-01

    In addition to occupational exposures to acrylamide (AA), concerns about AA health risks for the general population have been recently raised due to the finding of AA in food. In this study, we evaluated the genotoxicity of AA and its metabolite glycidamide (GA) in L5178Y/Tk(+/-) mouse lymphoma cells. The cells were treated with 2-18 mM of AA or 0.125-4 mM of GA for 4 h without metabolic activation. The DNA adducts, mutant frequencies and the types of mutations for the treated cells were examined. Within the dose range tested, GA induced DNA adducts of adenine and guanine [N3-(2-carbamoyl-2-hydroxyethyl)-adenine and N7-(2-carbamoyl-2-hydroxyethyl)-guanine] in a linear dose-dependent manner. The levels of guanine adducts were consistently about 60-fold higher across the dose range than those of adenine. In contrast, no GA-derived DNA adducts were found in the cells treated with any concentrations of AA, consistent with a lack of metabolic conversion of AA to GA. However, the mutant frequency was significantly increased by AA at concentrations of 12 mM and higher. GA was mutagenic starting with the 2mM dose, suggesting that GA is much more mutagenic than AA. The mutant frequencies were increased with increasing concentrations of AA and GA, mainly due to an increase of proportion of small colony mutants. To elucidate the underlying mutagenic mechanism, we examined the loss of heterozygosity (LOH) at four microsatellite loci spanning the entire chromosome 11 for mutants induced by AA or GA. Compared to GA induced mutations, AA induced more mutants whose LOH extended to D11Mit22 and D11Mit74, an alteration of DNA larger than half of the chromosome. Statistical analysis of the mutational spectra revealed a significant difference between the types of mutations induced by AA and GA treatments (P=0.018). These results suggest that although both AA and GA generate mutations through a clastogenic mode of action in mouse lymphoma cells, GA induces mutations via a DNA adduct

  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. 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. PMID:1644382

  2. Genotoxic activity of particulate material in petroleum refinery effluents

    SciTech Connect

    Metcalfe, C.D.; Sonstegard, R.A.; Quilliam, M.A.

    1985-08-01

    The purpose of this study was to evaluate the genotoxic hazard associated with the discharge of suspended particulates in oil refinery effluents. Particulate extracts were tested by in vitro assays for mutagenic (Ames test) and clastogenic (sister chromatid exchange assay) activity, both with and without mammalian microsomal activation.

  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. 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 ...

  6. 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. PMID:24836934

  7. 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.

  8. 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.

  9. 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. PMID:17688899

  10. 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...

  11. 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 inhibitor Camptothecin and accumulate γH2A at heterochromatin. Together, these data suggest that PRC2 modulates the response to genotoxic stress. PMID:26578794

  12. In-Vitro Carbofuran Induced Genotoxicity in Human Lymphocytes and Its Mitigation by Vitamins C and E

    PubMed Central

    Sharma, Ratnesh Kumar; Sharma, Bechan

    2012-01-01

    Various efforts have been made in past in order to predict the underlying mechanism of pesticide-induced toxicity using in vitro and animal models, however, these predictions may or may not be directly correlated with humans. The present study was designed to investigate the carbofuran induced genotoxicity and its amelioration by vitamins C and E by treating human peripheral blood lymphocytes (PBLs) with different concentrations (0, 0.5, 1.25, 2.5, 3.75 and 5.0 μM) of this compound. The treatment of PBLs with carbofuran displayed significant DNA damage in concentration dependent manner. The carbofuran induced genotoxicity could be ameliorated to considerable extent by pretreatment of PBLs with equimolar (10 μM) concentration of each of the vitamins C and E; the magnitude of protection by vitamin E being higher than by vitamin C. Also, it was found that the level of protection by these vitamins was higher when PBLs were treated with lower concentrations of pesticide. The significant DNA damage as observed by H2O2, a positive control in the present study, and its amelioration by natural antioxidants (vitamins C and E) lend an evidence to suggest that carbofuran would have caused genotoxicity via pesticide induced oxidative stress. PMID:22377731

  13. Genome-wide redistribution of H3K27me3 is linked to genotoxic stress and defective growth.

    PubMed

    Basenko, Evelina Y; Sasaki, Takahiko; Ji, Lexiang; Prybol, Cameron J; Burckhardt, Rachel M; Schmitz, Robert J; Lewis, Zachary A

    2015-11-17

    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 inhibitor Camptothecin and accumulate γH2A at heterochromatin. Together, these data suggest that PRC2 modulates the response to genotoxic stress. PMID:26578794

  14. Identification of early target genes of aflatoxin B1 in human hepatocytes, inter-individual variability and comparison with other genotoxic compounds

    SciTech Connect

    Josse, Rozenn; Dumont, Julie; Fautrel, Alain; Robin, Marie-Anne; Guillouzo, André

    2012-01-15

    Gene expression profiling has recently emerged as a promising approach to identify early target genes and discriminate genotoxic carcinogens from non-genotoxic carcinogens and non-carcinogens. However, early gene changes induced by genotoxic compounds in human liver remain largely unknown. Primary human hepatocytes and differentiated HepaRG cells were exposed to aflatoxin B1 (AFB1) that induces DNA damage following enzyme-mediated bioactivation. Gene expression profile changes induced by a 24 h exposure of these hepatocyte models to 0.05 and 0.25 μM AFB1 were analyzed by using oligonucleotide pangenomic microarrays. The main altered signaling pathway was the p53 pathway and related functions such as cell cycle, apoptosis and DNA repair. Direct involvement of the p53 protein in response to AFB1 was verified by using siRNA directed against p53. Among the 83 well-annotated genes commonly modulated in two pools of three human hepatocyte populations and HepaRG cells, several genes were identified as altered by AFB1 for the first time. In addition, a subset of 10 AFB1-altered genes, selected upon basis of their function or tumor suppressor role, was tested in four human hepatocyte populations and in response to other chemicals. Although they exhibited large variable inter-donor fold-changes, several of these genes, particularly FHIT, BCAS3 and SMYD3, were found to be altered by various direct and other indirect genotoxic compounds and unaffected by non-genotoxic compounds. Overall, this comprehensive analysis of early gene expression changes induced by AFB1 in human hepatocytes identified a gene subset that included several genes representing potential biomarkers of genotoxic compounds. -- Highlights: ► Gene expression profile changes induced by aflatoxin B1 in human hepatocytes. ► AFB1 modulates various genes including tumor suppressor genes and proto-oncogenes. ► Important inter-individual variations in the response to AFB1. ► Some genes also altered by other

  15. Characterisation of potentially genotoxic compounds in sediments collected from United Kingdom estuaries.

    PubMed

    Thomas, Kevin V; Balaam, Jan; Barnard, Nicola; Dyer, Robert; Jones, Claire; Lavender, Jacqueline; McHugh, Mathew

    2002-10-01

    The mutagenic activity bioassay Mutatox was used to assess the mutagenic activity associated with sediments collected from five UK estuaries. Assays were performed on extracts of sediment pore water and residual particulate material isolated from sediment samples collected from the rivers Tyne, Tees, Mersey, and Thames as well as Southampton Water. No mutagenic activity was associated with the pore water extracts, however, 7 of the 28 organic solvent extracts of sediment particulate material contained potential genotoxins. By using Mutatox in association with bioassay-directed fractionation, attempts were made to identify the mutagenic compounds present in the extracts. The fractionation procedure used normal phase solid phase extraction, C18 reverse phase HPLC and cyano/amino bonded silica normal phase HPLC. GC-MS (EI and NICI) analysis was used to identify polycyclic aromatic hydrocarbons (PAH), alkyl substituted PAH, nitro-polycyclic aromatic compounds (nitro-PACs), polycyclic aromatic ketones, oxygenated-PACs, and other known mutagens contributing to the genotoxicity measured in the samples. Some potentially genotoxic compounds remain unidentified. PMID:12363302

  16. 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. PMID:25627585

  17. Application of SOS umu-test for the detection of genotoxic volatile chemicals and air pollutants

    SciTech Connect

    Ong, T.M.; Stewart, J.; Wen, Y.F.; Whong, W.Z.

    1987-01-01

    The SOS umu-test has been used for the detection of DNA-damaging agents. In this system the plasmid pSK1002 carrying a fused gene umuC-lacZ was introduced into Salmonella typhimurium TA1535. The SOS function induced by genotoxic agents is detected by a colorimetric measurement of beta-galactosidase activity encoded by the lacZ gene, which is regulated by the Umu operon. This system was used with modifications to study the SOS function inducibility of volatile chemicals (propylene oxide, methyl bromide, and ethylene dibromide) and air pollutants (diesel emission, welding fumes, and cigarette smoke). Tester cells were exposed directly to the test material. The enzyme activity of the treated cells was measured according to the established procedure. Results of the study showed that all chemicals and pollutants tested induced SOS function in a dose-related manner. These results indicate that the SOS umu-test is potentially useful for the in situ detection of genotoxic agents in occupational settings.

  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. PMID:25765378

  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. PMID:21645631

  20. 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

  1. 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. PMID:27136795

  2. Tobacco Dust Induced Genotoxicity as an Occupational Hazard in Workers of Bidi Making Cottage Industry of Central India

    PubMed Central

    Khanna, Asha; Gautam, Daya Shankar; Gokhale, Mamta; Jain, Salil Kumar

    2014-01-01

    Context: To explore genotoxicity in bidi rollers occupationally exposed to bidi tobacco dust. Aims: To assess the extent of genotoxicity of tobacco dust to bidi rollers of Jabalpur, Madhya Pradesh, India and cytotoxicity of bidi tobacco extract. Settings and Design: Blood samples from 31 bidi rollers and 30 controls taken after written informed consent were analyzed for chromosome aberrations (CA) and comet assay. Materials and Methods: Genotoxicity was studied by CA in cultured peripheral blood lymphocytes of bidi rollers and the deoxyribonucleic acid (DNA) damage studies were done by comet assay of their blood. The toxicity of bidi tobacco extract to normal human lymphocytes was studied by MMT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay as drop in viability. Statistical Analysis Used: Student's t-test and DMRT. Results: There is a general trend of increase in CA% of both in exposed and control groups with age, but in every group the bidi rollers have a significantly higher CA% than the controls. The CA % is also directly related to exposure. The comet assay findings reveal that the mean comet length and tail length increases with exposure time. The toxicity of bidi tobacco extract (TE) to normal human lymphocytes was tested in vitro by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay at 2 h of incubation. The trend of drop in viability with increasing concentrations of TE was clearly evident from the data from four donors in spite of their individual differences in viability. Conclusions: The results obtained in this investigation indicate that bidi rollers seem to be facing the occupational hazard of genotoxicity due to handling bidi tobacco and inhalation of tobacco dust. They should be advised to work under well-ventilated conditions. PMID:24748730

  3. A battery of in vivo and in vitro tests useful for genotoxic pollutant detection in surface waters.

    PubMed

    Pellacani, Claudia; Buschini, Annamaria; Furlini, Mariangela; Poli, Paola; Rossi, Carlo

    2006-04-20

    Since the 1980s, stricter water quality regulations have been promulgated in many countries throughout the world. We discuss the application of a battery of both in vivo and in vitro genotoxicity tests on lake water as a tool for a more complete assessment of surface water quality. The lake water concentrated by adsorption on C18 silica cartridges were used for the following in vitro biological assays: gene conversion, point mutation, mitochondrial DNA mutability assays on the diploid Saccharomyces cerevisiae D7 strain, with or without endogenous P450 complex induction; DNA damage on fresh human leukocytes by the comet. Toxicity testing on yeast and human cells was also performed. In vivo genotoxicity was determined by the comet assay on two well-established bio-indicator organisms of water quality (Cyprinus carpio erythrocytes and Dreissena polymorpha haemocytes) exposed in situ. The in vivo experiments and the water samplings were carried out during different campaigns to detect seasonal variations of both the water contents and physiological state of the animals. Temperature and oxygen level seasonal variations and different pollutant contents in the lake water appeared to affect the DNA migration in carp and zebra mussel cells. Seasonal variability of lake water quality was also evident in the in vitro genotoxicity and cytotoxicity tests, with regards to water pollutant quantity and quality (direct-acting compounds or indirect-acting compounds on yeast cells). However, the measured biological effects did not appear clearly related to the physical-chemical characteristics of lake waters. Therefore, together with the conventional chemical analysis, mutagenicity/genotoxicity assays should be included as additional parameters in water quality monitoring programs: their use could permit the quantification of mutagenic hazard in surface waters. PMID:16313981

  4. Somatic cell genotoxicity at the glycophorin A locus in humans

    SciTech Connect

    Jensen, R.H.; Grant, S.G.; Langlois, R.G.; Bigbee, W.L.

    1990-12-28

    We have developed an assay for detecting variant erythrocytes that occur as a result of in vivo allele loss at the glycophorin A (GPA) locus on chromosome 4 in humans. This gene codes for an erythroid- specific cell surface glycoprotein, and with our assay we are able to detect rare variant erythrocytes that have lost expression of one of the two GPA alleles. Two distinctly different variant cell types are detected with this assay. One variant cell type (called N{O}) is hemizygous. Our assay also detects homozygous variant erythrocytes that have lost expression of the GPA(M) allele and express the GPA(N) allele at twice the heterozygous level. The results of this assay are an enumeration of the frequency of N{O} and NN variant cell types for each individual analyzed. These variant cell frequencies provide a measure of the amount of somatic cell genotoxicity that has occurred at the GPA locus. Such genotoxicity could be the result of (1) reactions of toxic chemicals to which the individual has been exposed, or (2) high energy radiation effects on erythroid precursor cells, or (3) errors in DNA replication or repair in these cells of the bone marrow. Thus, the GPA-based variant cell frequency can serve as a biodosimeter that indicates the amount of genotoxic exposure each individual has received. Because two very different kinds of variant cells are enumerated, different kinds of genotoxicity should be distinguishable. Results of the GPA somatic genotoxicity assay may also provide valuable information for cancer-risk estimation on each individual. 16 refs.

  5. Genotoxicity in native fish associated with agricultural runoff events

    USGS Publications Warehouse

    Whitehead, A.; Kuivila, K.M.; Orlando, J.L.; Kotelevtsev, S.; Anderson, S.L.

    2004-01-01

    The primary objective of the present study was to test whether agricultural chemical runoff was associated with in-stream genotoxicity in native fish. Using Sacramento sucker (Catostomus occidentalis), we combined field-caging experiments in an agriculturally dominated watershed with controlled laboratory exposures to field-collected water samples, and we coupled genotoxicity biomarker measurements in fish with bacterial mutagenicity analysis of water samples. We selected DNA strand breakage as a genotoxicity biomarker and Ames Salmonella mutagenicity tests as a second, supporting indicator of genotoxicity. Data from experiments conducted during rainfall runoff events following winter application of pesticides in 2000 and 2001 indicated that DNA strand breaks were significantly elevated in fish exposed to San Joaquin River (CA, USA) water (38.8, 28.4, and 53.6% DNA strand breakage in year 2000 field, year 2000 lab, and year 2001 field exposures, respectively) compared with a nearby reference site (15.4, 8.7, and 12.6% DNA strand breakage in year 2000 field, year 2000 lab, and year 2001 field exposures, respectively). Time-course measurements in field experiments supported a linkage between induction of DNA strand breakage and the timing of agricultural runoff. San Joaquin River water also caused significant reversion mutation in two Ames Salmonella tester strains. Salmonella mutagenicity corroborated in-stream effects, further strengthening a causal relationship between runoff events and genotoxicity. Potentially responsible agents are discussed in the context of timing of runoff events in the field, concordance between laboratory and field exposures, pesticide application patterns in the drainage, and analytical chemistry data.

  6. A comparison of foamy and lentiviral vector genotoxicity in SCID-repopulating cells shows foamy vectors are less prone to clonal dominance

    PubMed Central

    Everson, Elizabeth M; Olzsko, Miles E; Leap, David J; Hocum, Jonah D; Trobridge, Grant D

    2016-01-01

    Hematopoietic stem cell (HSC) gene therapy using retroviral vectors has immense potential, but vector-mediated genotoxicity limits use in the clinic. Lentiviral vectors are less genotoxic than gammaretroviral vectors and have become the vector of choice in clinical trials. Foamy retroviral vectors have a promising integration profile and are less prone to read-through transcription than gammaretroviral or lentiviral vectors. Here, we directly compared the safety and efficacy of foamy vectors to lentiviral vectors in human CD34+ repopulating cells in immunodeficient mice. To increase their genotoxic potential, foamy and lentiviral vectors with identical transgene cassettes with a known genotoxic spleen focus forming virus promoter were used. Both vectors resulted in efficient marking in vivo and a total of 825 foamy and 460 lentiviral vector unique integration sites were recovered in repopulating cells 19 weeks after transplantation. Foamy vector proviruses were observed less often near RefSeq gene and proto-oncogene transcription start sites than lentiviral vectors. The foamy vector group were also more polyclonal with fewer dominant clones (two out of six mice) than the lentiviral vector group (eight out of eight mice), and only lentiviral vectors had integrants near known proto-oncogenes in dominant clones. Our data further support the relative safety of foamy vectors for HSC gene therapy. PMID:27579335

  7. A comparison of foamy and lentiviral vector genotoxicity in SCID-repopulating cells shows foamy vectors are less prone to clonal dominance.

    PubMed

    Everson, Elizabeth M; Olzsko, Miles E; Leap, David J; Hocum, Jonah D; Trobridge, Grant D

    2016-01-01

    Hematopoietic stem cell (HSC) gene therapy using retroviral vectors has immense potential, but vector-mediated genotoxicity limits use in the clinic. Lentiviral vectors are less genotoxic than gammaretroviral vectors and have become the vector of choice in clinical trials. Foamy retroviral vectors have a promising integration profile and are less prone to read-through transcription than gammaretroviral or lentiviral vectors. Here, we directly compared the safety and efficacy of foamy vectors to lentiviral vectors in human CD34(+) repopulating cells in immunodeficient mice. To increase their genotoxic potential, foamy and lentiviral vectors with identical transgene cassettes with a known genotoxic spleen focus forming virus promoter were used. Both vectors resulted in efficient marking in vivo and a total of 825 foamy and 460 lentiviral vector unique integration sites were recovered in repopulating cells 19 weeks after transplantation. Foamy vector proviruses were observed less often near RefSeq gene and proto-oncogene transcription start sites than lentiviral vectors. The foamy vector group were also more polyclonal with fewer dominant clones (two out of six mice) than the lentiviral vector group (eight out of eight mice), and only lentiviral vectors had integrants near known proto-oncogenes in dominant clones. Our data further support the relative safety of foamy vectors for HSC gene therapy. PMID:27579335

  8. Evaluation of the genotoxicity/mutagenicity and antigenotoxicity/antimutagenicity induced by propolis and Baccharis dracunculifolia, by in vitro study with HTC cells.

    PubMed

    Roberto, Matheus Mantuanelli; Matsumoto, Sílvia Tamie; Jamal, Cláudia Masrouah; Malaspina, Osmar; Marin-Morales, Maria Aparecida

    2016-06-01

    The ethanolic extract of propolis, especially the Brazilian green type, is widely and mainly used for therapeutic purposes despite the lack of knowledge about its effects and its cellular mode of action. This type of propolis, derived from Baccharis dracunculifolia (alecrim-do-campo), has been extensively commercialized and the consumers use it to enhance health. This work aimed to assess the genotoxic/mutagenic and antigenotoxic/antimutagenic potentials of the ethanolic extracts of Brazilian green propolis and of B. dracunculifolia, on mammalian cells. It was not observed genotoxic and mutagenic effects by both extracts. After evaluate the exposure of the cells to each extract with a recognized mutagen, simultaneously, the results showed a significant reduction on DNA damage. The experiment carried out with a pre-incubation period was more effective than without incubation test, showing that the tested extracts were able to inactivate the mutagen before it could react with the DNA. PMID:26891814

  9. Reduced effect of bromide on the genotoxicity in secondary effluent of a municipal wastewater treatment plant during chlorination.

    PubMed

    Wu, Qian-Yuan; Li, Yi; Hu, Hong-Ying; Sun, Ying-Xue; Zhao, Feng-Yun

    2010-07-01

    Chlorination of wastewater can form genotoxic, mutagenic, and/or carcinogenic disinfection byproduct (DBPs). In this study, the effect of bromide on genotoxicity in secondary effluent of a municipal wastewater treatment plant during chlorination was evaluated by the SOS/umu test. The presence of bromide notably decreased the genotoxicity in secondary effluent during chlorination, especially under conditions of high ammonia concentration. Bromide significantly decreased the concentration of ofloxacin, a genotoxic chemical in secondary effluent, during chlorination with high concentration of ammonia, while genotoxic DBPs formation of humic acid and aromatic amino acids associated with bromide limitedly contributed to the changes of genotoxicity in secondary effluent under the conditions of this study. By fractionating dissolved organic matter (DOM) in the secondary effluent into different fractions, the fractions containing hydrophilic substances (HIS) and hydrophobic acids (HOA) contributed to the decrease in genotoxicity induced by bromide. Chlorination of HOA without bromide increased genotoxicity, while the addition of bromide decreased genotoxicity. PMID:20521844

  10. Genotoxicity of 2-bromo-3′-chloropropiophenone

    SciTech Connect

    Meng, Fanxue; Yan, Jian; Li, Yan; Fu, Peter P.; Fossom, Linda H.; Sood, Ramesh K.; Mans, Daniel J.; Chu, Pei-I; Moore, Martha M.; Chen, Tao

    2013-07-15

    Impurities are present in any drug substance or drug product. They can be process-related impurities that are not completely removed during purification or are formed due to the degradation of the drug substance over the product shelf-life. Unlike the drug substance, impurities generally do not have beneficial effects and may present a risk without associated benefit. Therefore, their amount should be minimized. 2-Bromo-3′-chloropropiophenone (BCP) is an impurity of bupropion, a second-generation antidepressant and a smoking cessation aid. The United States Pharmacopeia recommends an acceptable level for BCP that is not more than 0.1% of the bupropion. Because exposure to genotoxic impurities even at low levels is of significant concern, it is important to determine whether or not BCP is genotoxic. Therefore, in this study the Ames test and the in vitro micronucleus assay were conducted to evaluate the genotoxicity of BCP. BCP was mutagenic with S9 metabolic activation, increasing the mutant frequencies in a concentration-dependent manner, up to 22- and 145-fold induction over the controls in Salmonella strains TA100 and TA1535, respectively. BCP was also positive in the in vitro micronucleus assay, resulting in up to 3.3- and 5.1-fold increase of micronucleus frequency for treatments in the absence and presence of S9, respectively; and 9.9- and 7.4-fold increase of aneuploidies without and with S9, respectively. The addition of N-acetyl-L-cysteine, an antioxidant, reduced the genotoxicity of BCP in both assays. Further studies showed that BCP treatment resulted in induction of reactive oxygen species (ROS) in the TK6 cells. The results suggest that BCP is mutagenic, clastogenic, and aneugenic, and that these activities are mediated via generation of reactive metabolites. - Highlights: • 2-Bromo-3′-chloropropiophenone is an impurity of bupropion. • BCP was positive in both the Ames test and the in vitro micronucleus assay. • It induced high frequencies of

  11. Prediction and Direct Measurement of Scattered Plate-Wave Fields Using S0 to A0 Mode Conversion at Non-Symmetric Circular Inhomogeneities

    NASA Astrophysics Data System (ADS)

    Cegla, F. B.; Veidt, M.

    2007-03-01

    The scattering of A0 waves from blind holes and added masses when plane S0 waves are incident was investigated. Predictions from an approximate theoretical model and experimental results were found to be in good agreement at low frequency thickness products. The presented technique has the advantage of being most sensitive to the mode converted scattered A0 field while it hardly picks up any of the incident wave mode. This method has potential applications in plate wave diffraction tomography where the wave field of the scattered flexural wave has to be accurately determined in order to reconstruct an image of damage such as corrosion thinning or laminar disbonds.

  12. High efficiency passively mode-locked Nd:YVO4 laser with direct in-band pumping at 914 nm.

    PubMed

    Waritanant, Tanant; Major, Arkady

    2016-06-13

    We report on the performance of a semiconductor saturable absorber mirror passively mode-locked Nd:YVO4 laser with in-band pumping at 914 nm and with the highest slope efficiency to date among the mode-locked Nd-lasers. The laser produced 6.7 W of output power with repetition rate of 87 MHz and pulse duration of 16 ps. The slope efficiency of 77.1% and the optical-to-optical efficiency of 60.7% were achieved. PMID:27410304

  13. Genotoxic and developmental effects in sea urchins are sensitive indicators of effects of genotoxic chemicals

    SciTech Connect

    Anderson, S.L. . Energy and Environment Division); Hose, J.E. . Dept. of Biology); Knezovich, J.P. . Health and Ecological Assessment Division)

    1994-07-01

    Purple sea urchin (Strongylocentrotus purpuratus) gametes and embryos were exposed to three known mutagenic chemicals (phenol, benzidine,and pentachlorophenol) over concentration ranges bracketing the effect levels for fertilization success. Normal development and cytogenetic effects (anaphase aberrations) were assessed after the cultures were allowed to develop for 48 h. Using radiolabeled chemicals, the authors also characterized concentrations in the test water as well as doses in the embryos following 2- and 48-h exposures. The authors observed dose responses for all chemicals and all responses, except for phenol, which showed no significant effect on development. Fertilization success was never the most sensitive end point. anaphase aberrations were the most sensitive response for phenol, with an LOEC of 2.5 mg/L exposure concentration. Anaphase aberrations and development were equivalent in sensitivity for benzidine within the tested dose range, and an LOEC of <0.1 mg/L was observed. Development was the most sensitive reasons for pentachlorophenol (LOEC 1 mg/L). the LOEC values for this study were generally lower than comparable data for aquatic life or human health protection. The authors conclude that genotoxicity and development evaluations should be included in environmental management applications and that tests developed primarily for human health protection do not reliably predict the effects of toxic substances on aquatic life.

  14. A review of biomonitoring studies measuring genotoxicity in humans exposed to hair dyes.

    PubMed

    Preston, R Julian; Skare, Julie A; Aardema, Marilyn J

    2010-01-01

    Hair dye ingredients frequently produce positive results in short-term in vitro genotoxicity tests, although results from in vivo assays are typically negative, especially for ingredients in use today. The use of hair dyes is quite widespread resulting in the exposure both for persons working in hairdressing salons and for individuals who have their hair dyed. This provides the opportunity to add to the data from standard in vitro and in vivo genotoxicity tests by investigating whether or not genotoxic responses are detected in such exposed individuals. A number of biomonitoring studies of humans exposed to hair dyes have been conducted using either cytogenetic alterations or DNA damage as measures of genotoxicity, or urine mutagenicity as a measure of exposure to genotoxic compounds. In this paper, each study is critically reviewed and interpreted. Overall, there is no consistent evidence of genotoxicity in humans exposed to hair dyes occupationally or through individual use. PMID:19892773

  15. Genotoxicity of Air Borne Particulates Assessed by Comet and the Salmonella Mutagenicity Test in Jeddah, Saudi Arabia

    PubMed Central

    ElAssouli, Sufian M.; AlQahtani, Mohamed H.; Milaat, Waleed

    2007-01-01

    Fine airborne respirable particulates less than 10 micrometer (PM10) are considered one of the top environmental public health concerns, since they contain polycyclic aromatic hydrocarbons (PAHs) which are among the major carcinogenic compounds found in urban air. The objective of this study is to assess the genotoxicity of the ambient PM10 collected at 11 urban sites in Jeddah, Saudi Arabia. The PM10 extractable organic matter (EOM) was examined for its genotoxicity by the single cell gel electrophoresis (SCGE) comet assay and the Salmonella mutagenicity (Ames) test. Gas chromatography-mass spectrometry was used to quantify 16 PAH compounds in four sites. Samples from oil refinery and heavy diesel vehicles traffic sites showed significant DNA damage causing comet in 20–44% of the cells with tail moments ranging from 0.5–2.0 compared to samples from petrol driven cars and residential area, with comet in less than 2% of the cells and tail moments of < 0.02.In the Ames test, polluted sites showed indirect mutagenic response and caused 20–56 rev/ m3, mean while residential and reference sites caused 2–15 rev /m3. The genotoxicity of the EOM in both tests directly correlated with the amount of organic particulate and the PAHs concentrations in the air samples. The PAHs concentrations ranged between 0.83 ng/m3 in industrial and heavy diesel vehicles traffic sites to 0.18 ng /m3 in the residential area. Benzo(ghi)pyrene was the major PAH components and at one site it represented 65.4 % of the total PAHs. Samples of the oil refinery site were more genotoxic in the SCGE assay than samples from the heavy diesel vehicles traffic site, despite the fact that both sites contain almost similar amount of PAHs. The opposite was true for the mutagenicity in the Ames test. This could be due to the nature of the EOM in both sites. These findings confirm the genotoxic potency of the PM10 organic extracts to which urban populations are exposed. PMID:17911660

  16. Hexavalent chromium is cytotoxic and genotoxic to American alligator cells.

    PubMed

    Wise, Sandra S; Wise, Catherine; Xie, Hong; Guillette, Louis J; Zhu, Cairong; Wise, John Pierce; Wise, John Pierce

    2016-02-01

    Metals are a common pollutant in the aquatic ecosystem. With global climate change, these levels are anticipated to rise as lower pH levels allow sediment bound metals to be released. The American alligator (Alligator mississippiensis) is an apex predator in the aquatic ecosystem and is considered a keystone species; as such it serves as a suitable monitor for localized pollution. One metal of increasing concern is hexavalent chromium (Cr(VI)). It is present in the aquatic environment and is a known human carcinogen and reproductive toxicant. We measured the cytotoxicity and genotoxicity of Cr(VI) in American alligator cells derived from scute tissue. We found that particulate and soluble Cr(VI) are both cytotoxic and genotoxic to alligator cells in a concentration-dependent manner. These data suggest that alligators may be used as a model for assessing the effects of environmental Cr(VI) contamination as well as for other metals of concern. PMID:26730726

  17. Genotoxicity of Euphorbia hirta: an Allium cepa assay.

    PubMed

    Yuet Ping, Kwan; Darah, Ibrahim; Yusuf, Umi Kalsom; Yeng, Chen; Sasidharan, Sreenivasan

    2012-01-01

    The potential genotoxic effects of methanolic extracts of Euphorbia hirta which is commonly used in traditional medicine to treat a variety of diseased conditions including asthma, coughs, diarrhea and dysentery was investigated using Allium cepa assay. The extracts of 125, 250, 500 and 1,000 µg/mL were tested on root meristems of A. cepa. Ethylmethanesulfonate was used as positive control and distilled water was used as negative control. The result showed that mitotic index decreased as the concentrations of E. hirta extract increased. A dose-dependent increase of chromosome aberrations was also observed. Abnormalities scored were stickiness, c-mitosis, bridges and vagrant chromosomes. Micronucleated cells were also observed at interphase. Result of this study confirmed that the methanol extracts of E. hirta exerted significant genotoxic and mitodepressive effects at 1,000 µg/mL. PMID:22735780

  18. Toxicity and genotoxicity of wastewater from gasoline stations

    PubMed Central

    2009-01-01

    The toxicity and genotoxicity of wastewater from eight gasoline stations in Brasília, Brazil's capital city, was studied by assessing chromosomal aberrations, chromosomal malsegregation and the mitotic index in Alliumcepa root cells, and the occurrence of micronucleus and nuclear abnormalities in peripheral erythrocytes of tilapia fish (Oreochromis niloticus). The content of gasoline station effluents was also analyzed based on several physico-chemical parameters. None of the wastewater samples was genotoxic to A. cepa root cells, although cell proliferation was significantly inhibited, especially at the highest concentrations. Likewise, no micronuclei were observed in O. niloticus peripheral erythrocytes, even after exposure to high concentrations, but there was an increase in the number of nuclear abnormalities and fish mortality. These results show that although the effluent from gasoline stations is processed by an oil/water separation system before being discharged into the main sewage system, the wastewater still contains toxic compounds. PMID:21637464

  19. Toxicity and genotoxicity of wastewater from gasoline stations.

    PubMed

    Oliveira-Martins, Cynthia R; Grisolia, Cesar K

    2009-10-01

    The toxicity and genotoxicity of wastewater from eight gasoline stations in Brasília, Brazil's capital city, was studied by assessing chromosomal aberrations, chromosomal malsegregation and the mitotic index in Alliumcepa root cells, and the occurrence of micronucleus and nuclear abnormalities in peripheral erythrocytes of tilapia fish (Oreochromis niloticus). The content of gasoline station effluents was also analyzed based on several physico-chemical parameters. None of the wastewater samples was genotoxic to A. cepa root cells, although cell proliferation was significantly inhibited, especially at the highest concentrations. Likewise, no micronuclei were observed in O. niloticus peripheral erythrocytes, even after exposure to high concentrations, but there was an increase in the number of nuclear abnormalities and fish mortality. These results show that although the effluent from gasoline stations is processed by an oil/water separation system before being discharged into the main sewage system, the wastewater still contains toxic compounds. PMID:21637464

  20. Nuclear PTEN controls DNA repair and sensitivity to genotoxic stress.

    PubMed

    Bassi, C; Ho, J; Srikumar, T; Dowling, R J O; Gorrini, C; Miller, S J; Mak, T W; Neel, B G; Raught, B; Stambolic, V

    2013-07-26

    Loss of function of the phosphatase and tensin homolog deleted on chromosome 10 (PTEN) tumor suppressor gene is associated with many human cancers. In the cytoplasm, PTEN antagonizes the phosphatidylinositol 3-kinase (PI3K) signaling pathway. PTEN also accumulates in the nucleus, where its function remains poorly understood. We demonstrate that SUMOylation (SUMO, small ubiquitin-like modifier) of PTEN controls its nuclear localization. In cells exposed to genotoxic stress, SUMO-PTEN was rapidly excluded from the nucleus dependent on the protein kinase ataxia telangiectasia mutated (ATM). Cells lacking nuclear PTEN were hypersensitive to DNA damage, whereas PTEN-deficient cells were susceptible to killing by a combination of genotoxic stress and a small-molecule PI3K inhibitor both in vitro and in vivo. Our findings may have implications for individualized therapy for patients with PTEN-deficient tumors. PMID:23888040

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

    PubMed

    Siddique, Yasir Hasan; Afzal, Mohammad

    2005-07-01

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

  2. Polycyclic organic material (POM) in urban air. Fractionation, chemical analysis and genotoxicity of particulate and vapour phases in an industrial town in Finland

    NASA Astrophysics Data System (ADS)

    Pyysalo, Heikki; Tuominen, Jari; Wickström, Kim; Skyttä, Eija; Tikkanen, Leena; Salomaa, Sisko; Sorsa, Marja; Nurmela, Tuomo; Mattila, Tiina; Pohjola, Veijo

    Polycyclic organic material (POM) was collected by high-volume sampling on filter and on XAD-2 resin from the air of a small industrial town in Finland. Concurrent chemical analysis and the assays for genotoxic activity were performed on the particulate and the vapour phases of ambient air POM and their chemical fractions. Furthermore, correlations between seasonal meteorological parameters and POM concentrations were studied to reveal characteristic POM profiles for various emission sources. The range of total POM concentrations varied from 115 to 380 ng m -3 in late spring and from 17 to 83 ng m -3 in early winter. No direct correlation of ambient POM was seen with the temperature, but rather with the wind direction from various emission sources. Especially the low molecular weight compounds were associated with wind direction from industrial sources. Genotoxic activity, as detected by the Ames Salmonella/microsome test and the SCE assay in CHO cells, was found not only in the paniculate phase samples but also in the vapour phase. The polar fractions of some of the samples showed genotoxic activity, and also direct mutagenicity was observed with both the assay systems; these facts support the significance of compounds other than conventional polycyclic aromatic hydrocarbons (PAH) in the samples.

  3. Genotoxicity of organic extracts of house dust from Shanxi, China.

    PubMed

    Naufal, Ziad; Zhou, Guo-dong; McDonald, Thomas; Li, Zhiwen; Li, Zhu; Donnelly, K C

    2007-12-01

    Indoor combustion of solid fuel such as coal may generate respirable particles containing polycyclic aromatic hydrocarbons (PAH) that may adhere to settled dust. Dust might therefore present a major source of PAH exposure in humans. This study evaluated the in vitro and in vivo genotoxicity of PAH mixtures extracted from house dust samples. Four dust samples (E1-4) were collected from houses in Shanxi, China, where coal is heavily used for heating and cooking. For comparison, a coal sample was also collected from one of the houses and included in the analyses. The samples were extracted with methylene chloride:acetone (95:5 v/v), dried, and redissolved in appropriate solvents for assessment in genotoxicity assays. Samples were evaluated for their ability to induce point mutations in bacteria and DNA adducts in vivo. DNA adduct levels were analyzed by nuclease P1-enhanced 32P-postlabeling. PAH were quantified using gas chromatography/mass spectrometry. Based on chemical analysis, sample E1 had the highest concentration by sampling area of benzo[a]pyrene (BaP) (181 microg/m2) and total PAH (10100 microg/m2). However, based on the microbial genotoxicity assay, sample E3, with the highest carcinogenic PAH/total PAH ratio (26%), produced the greatest number of revertants. In mice, administration of the extract of coal induced more adducts (9.81 adducts per 10(9) nucleotides) than dust extracts. The results of this study confirm the presence of genotoxic chemicals in residential dust. Inhalation of respirable particles containing similar mixtures of PAH represents a cancer risk for humans. PMID:18049997

  4. Monosodium glutamate is not likely to be genotoxic.

    PubMed

    Rogers, Michael D

    2016-08-01

    The International Glutamate Technical Committee (IGTC) wishes to comment on a recent publication in the Journal entitled "Genotoxicity of monosodium glutamate" (authored by Ataseven N, Yüzbaşıoğlu D, Keskin AÇ and Ünal F) (Ataseven et al. 2016). In particular, we wish to highlight that, in our considered view, the results of this study were inappropriately discussed and that references were selectively used. PMID:27372553

  5. Cell cycle control, checkpoint mechanisms, and genotoxic stress.

    PubMed Central

    Shackelford, R E; Kaufmann, W K; Paules, R S

    1999-01-01

    The ability of cells to maintain genomic integrity is vital for cell survival and proliferation. Lack of fidelity in DNA replication and maintenance can result in deleterious mutations leading to cell death or, in multicellular organisms, cancer. The purpose of this review is to discuss the known signal transduction pathways that regulate cell cycle progression and the mechanisms cells employ to insure DNA stability in the face of genotoxic stress. In particular, we focus on mammalian cell cycle checkpoint functions, their role in maintaining DNA stability during the cell cycle following exposure to genotoxic agents, and the gene products that act in checkpoint function signal transduction cascades. Key transitions in the cell cycle are regulated by the activities of various protein kinase complexes composed of cyclin and cyclin-dependent kinase (Cdk) molecules. Surveillance control mechanisms that check to ensure proper completion of early events and cellular integrity before initiation of subsequent events in cell cycle progression are referred to as cell cycle checkpoints and can generate a transient delay that provides the cell more time to repair damage before progressing to the next phase of the cycle. A variety of cellular responses are elicited that function in checkpoint signaling to inhibit cyclin/Cdk activities. These responses include the p53-dependent and p53-independent induction of Cdk inhibitors and the p53-independent inhibitory phosphorylation of Cdk molecules themselves. Eliciting proper G1, S, and G2 checkpoint responses to double-strand DNA breaks requires the function of the Ataxia telangiectasia mutated gene product. Several human heritable cancer-prone syndromes known to alter DNA stability have been found to have defects in checkpoint surveillance pathways. Exposures to several common sources of genotoxic stress, including oxidative stress, ionizing radiation, UV radiation, and the genotoxic compound benzo[a]pyrene, elicit cell cycle

  6. In vivo genotoxicity of estragole in male F344 rats.

    PubMed

    Ding, Wei; Levy, Dan D; Bishop, Michelle E; Pearce, Mason G; Davis, Kelly J; Jeffrey, Alan M; Duan, Jian-Dong; Williams, Gary M; White, Gene A; Lyn-Cook, Lascelles E; Manjanatha, Mugimane G

    2015-05-01

    Estragole, a naturally occurring constituent of various herbs and spices, is a rodent liver carcinogen which requires bio-activation. To further understand the mechanisms underlying its carcinogenicity, genotoxicity was assessed in F344 rats using the comet, micronucleus (MN), and DNA adduct assays together with histopathological analysis. Oxidative damage was measured using human 8-oxoguanine-DNA-N-glycosylase (hOGG1) and EndonucleaseIII (EndoIII)-modified comet assays. Results with estragole were compared with the structurally related genotoxic carcinogen, safrole. Groups of seven-week-old male F344 rats received corn oil or corn oil containing 300, 600, or 1,000 mg/kg bw estragole and 125, 250, or 450 mg/kg bw safrole by gavage at 0, 24, and 45 hr and terminated at 48 hr. Estragole-induced dose-dependent increases in DNA damage following EndoIII or hOGG1 digestion and without enzyme treatment in liver, the cancer target organ. No DNA damage was detected in stomach, the non-target tissue for cancer. No elevation of MN was observed in reticulocytes sampled from peripheral blood. Comet assays, both without digestion or with either EndoIII or hOGG1 digestion, also detected DNA damage in the liver of safrole-dosed rats. No DNA damage was detected in stomach, nor was MN elevated in peripheral blood following dosing with safrole suggesting that, as far both safrole and estragole, oxidative damage may contribute to genotoxicity. Taken together, these results implicate multiple mechanisms of estragole genotoxicity. DNA damage arises from chemical-specific interaction and is also mediated by oxidative species. PMID:25361439

  7. PAH characteristics and genotoxicity in the ambient air of a petrochemical industry complex

    SciTech Connect

    Tsai, Jiun-Horng; Peng, Being-Hwa; Lee, Ding-Zang; Lee, Ching-Chang

    1995-05-01

    Polycyclic aromatic hydrocarbons (PAHs) samples, at four sampling sites, in the ambient air of petrochemical plants were collected by several PS-1 samplers from October 1993 to July 1994 in a petrochemical complex area located in southern Taiwan. In addition, the genotoxicity of the PAH samples were investigated by the Ames Salmonella/microsomal assay system. The winter/summer ratios of total-PAH composition were 0.60, 1.39, 2.97, and 1.28 for sites A, B, C, and D, respectively. This result implied that wind direction is the most significant parameter affecting the total-PAH composition in these four sampling sites. Sampling sites B, C, and D were located on the downwind side of the petrochemical plant and gave higher total-PAH composition than those of sampling site A. Particle phase PAHs had higher mutagenicity than those in the gas phase.

  8. Genotoxicity of the phosphoramidate agent tabun (Ga). (Reannouncement with new availability information)

    SciTech Connect

    Wilson, B.W.; Kawakami, T.G.; Cone, N.; Henderson, J.D.; Rosenblatt, L.S.

    1994-12-31

    Five mutagenicity tests were performed on Agent GA (Tabun, phosphoramidocyanidic acid, dimethyl-, ethyl ester) as part of a program to demilitarize chemical warfare agents. GA was mutagenic in Salmonella spp. assays with S-9 and it was a direct-acting mutagen to mouse lymphoma cells. GA did not promote unscheduled DNA synthesis in rat hepatocytes; it induced sister chromatid exchanges in mouse cells in vitro but not in vivo. The conclusion that GA is a weakly acting mutagen is supported by the fact that it was mutagenic in only three of the five assays, and that increases in mutagenicity were often less than 2-fold the controls and occurred near toxic levels. Tabun, Agent GA, Phosphoroamidocyanidic acid, Dimethyl-, Ethyl ester, Genotoxicity, Mutagenic assays.

  9. Rotenone isolated from Pachyrhizus erosus displays cytotoxicity and genotoxicity in K562 cells.

    PubMed

    Estrella-Parra, Edgar A; Gomez-Verjan, Juan C; González-Sánchez, Ignacio; Vázquez-Martínez, Edgar Ricardo; Vergara-Castañeda, Edgar; Cerbón, Marco A; Alavez-Solano, Dagoberto; Reyes-Chilpa, Ricardo

    2014-01-01

    Pachyrhizus erosus (Fabaceae) is a herb commonly known as 'yam bean', which has been cultivated in México since pre-Columbian times for its edible tubers. The seeds are also known for their acaricidal and insecticidal properties due to rotenone and other isoflavonoid contents. Rotenone has exhibited cytotoxic activity against several human tumour cell lines; however, its mechanism of action is still not fully understood. In this study, we determined the cytotoxicity of rotenone isolated from P. erosus seeds on K562 human leukaemia cells. Rotenone exhibited significant cytotoxic activity (IC50 = 13.05 μM), as determined by the MTT assay. Three other isolated isoflavonoids were not cytotoxic. Rotenone genotoxicity was detected using the comet assay. Rotenone induced cell death, and caspase-3 activation as indicated by TUNEL assay, and immunocytofluorescence. Plasmid nicking assay indicated that rotenone does not interact directly with DNA. PMID:25055205

  10. Chemical structure-related mechanisms underlying in vivo genotoxicity induced by nitrofurantoin and its constituent moieties in gpt delta rats.

    PubMed

    Kijima, Aki; Ishii, Yuji; Takasu, Shinji; Matsushita, Kohei; Kuroda, Ken; Hibi, Daisuke; Suzuki, Yuta; Nohmi, Takehiko; Umemura, Takashi

    2015-05-01

    Nitrofurans are antimicrobial compounds containing a nitro group at the 5-position of the furan ring and an amine or hydrazide side chain derivative. One member of the nitrofurans, nitrofurantoin (NFT), is a renal carcinogen in male rats despite its still controversial genotoxicity. We investigated chemical structure-related modes of action of NFT, and reporter gene mutation assays for NFT and its constituent moieties were performed. NFT, 5-nitro-2-furaldehyde (NFA), or 1-aminohydantoin (AHD) was administered to male F344 gpt delta rats by gavage for 4 or 13 weeks at a carcinogenic or the maximum tolerated dose. NFT caused a significant increase in gpt mutant frequency (MF) at 13 weeks with G-base substitution mutations. An increase in gpt MF was also observed in the NFA-treated group at 13 weeks, but not in the AHD-treated group. 8-Hydroxydeoxyguanosine (8-OHdG) levels in the kidney DNA of NFT-treated rats were significantly increased after 4 weeks. NFT caused accumulation of hyaline droplets indicated by positive immunostaining and western blot analysis for α2u-globulin in the proximal tubules. An additional study, in which female gpt delta rats were given NFT at the same dose used for males, was performed to mitigate the effect of α2u-globulin. NFT exerted the same effects on female rat kidneys to the same extent as males in terms of gpt MF and 8-OHdG level. Thus, it is highly probable that the structure of the nitro furan plays a key role in NFT-induced genotoxicity and genotoxic mechanisms including oxidative DNA damage are involved in NFT-induced renal carcinogenesis. α2u-globulin-mediated nephropathy may be a prerequisite for NFT-induced renal carcinogenesis in male rats, and additionally NFT could be a latent carcinogen in female rats and other animal species. PMID:25772432

  11. Borax counteracts genotoxicity of aluminum in rat liver.

    PubMed

    Turkez, Hasan; Geyikoğlu, Fatime; Tatar, Abdulgani

    2013-10-01

    This study was carried out to evaluate the protective role of borax (BX) on genotoxicity induced by aluminum (Al) in rat liver, using liver micronucleus assay as an indicator of genotoxicity. Sprague-Dawley rats were randomly separated into six groups and each group had four animals. Aluminum chloride (AlCl₃; 5 mg/kg b.w.) and BX (3.25 and 13 mg/kg b.w.) were injected intraperitoneally to rats. Besides, animals were also treated with Al for 4 consecutive days followed by BX for 10 days. Rats were anesthetized after Al and BX injections and the hepatocytes were isolated for counting the number of micronucleated hepatocytes (MNHEPs). AlCl₃ was found to significantly (p < 0.05) increase the number of MNHEPs. Rats treated with BX, however, showed no increase in MNHEPs. Moreover, simultaneous treatments with BX significantly modulated the genotoxic effects of AlCl₃ in rats. It can be concluded that BX has beneficial influences and has the ability to antagonize Al toxicity. PMID:22491726

  12. Environmental genotoxicity evaluation using cytogenetic end points in wild rodents.

    PubMed Central

    de Souza Bueno, A M; de Bragança Pereira, C A; Rabello-Gay, M N

    2000-01-01

    We analyzed cytogenetic end points in three populations of two species of wild rodents--Akodon montensis and Oryzomys nigripes--living in an industrial, an agricultural, and a preservation area at the Itajaí Valley, state of Santa Catarina, Brazil. Our purpose was to evaluate the performance of the following end points in the establishment of a genotoxic profile of each area: the polychromatic/normochromatic cell ratio; the mitotic index; the frequency of micronucleated cells both in the bone marrow and peripheral blood; and the frequency of cells with chromosome aberrations in the bone marrow. Preparations were obtained using conventional cytogenetic techniques. The results showed a) the role of the end points used as biomarkers in the early detection of genotoxic agents and in the identification of species and populations at higher risk; b) the difference in sensitivity of the species selected as bioindicators in relation to the cytogenetic end points analyzed; c) the need to use at least two sympatric species to detect the presence of genotoxins in each locality; and d) the need to use several end points when trying to establish a genotoxic profile of an area. PMID:11133397

  13. Genotoxicity assessment of a pharmaceutical effluent using four bioassays

    PubMed Central

    2009-01-01

    Pharmaceutical industries are among the major contributors to industrial waste. Their effluents when wrongly handled and disposed of endanger both human and environmental health. In this study, we investigated the potential genotoxicity of a pharmaceutical effluent, by using the Allium cepa, mouse- sperm morphology, bone marrow chromosome aberration (CA) and micronucleus (MN) assays. Some of the physico-chemical properties of the effluent were also determined. The A. cepa and the animal assays were respectively carried out at concentrations of 0.5, 1, 2.5, 5 and 10%; and 1, 5, 10, 25 and 50% of the effluent. There was a statistically different (p < 0.05), concentration-dependent inhibition of onion root growth and mitotic index, and induction of chromosomal aberrations in the onion and mouse CA test. Assessment of sperm shape showed that the fraction of the sperm that was abnormal in shape was significantly (p < 0.05) greater than the negative control value. MN analysis showed a dose-dependent induction of micronucleated polychromatic erythrocytes across the treatment groups. These observations were provoked by the toxic and genotoxic constituents present in test samples. The tested pharmaceutical effluent is a potentially genotoxic agent and germ cell mutagen, and may induce adverse health effects in exposed individuals. PMID:21637694

  14. Genotoxic Potential and Physicochemical Parameters of Sinos River, Southern Brazil

    PubMed Central

    Scalon, Madalena C. S.; Rechenmacher, Ciliana; Siebel, Anna Maria; Kayser, Michele L.; Rodrigues, Manoela T.; Maluf, Sharbel W.; Rodrigues, Marco Antonio S.

    2013-01-01

    The present study aimed to evaluate the physicochemical parameters and the genotoxic potential of water samples collected in the upper, middle, and lower courses of the Sinos River, southern Brazil. The comet assay was performed in the peripheral blood of fish Hyphessobrycon luetkenii exposed under laboratory conditions to water samples collected in summer and winter in three sampling sites of Sinos River. Water quality analysis demonstrated values above those described in Brazilian legislation in Parobé and Sapucaia do Sul sites, located in the middle and in the lower courses of the Sinos River, respectively. The Caraá site, located in the upper river reach, presented all the physicochemical parameters in accordance with the allowed limits in both sampling periods. Comet assay in fish revealed genotoxicity in water samples collected in the middle course site in summer and in the three sites in winter when compared to control group. Thus, the physicochemical parameters indicated that the water quality of the upper course complies with the limits set by the national guidelines, and the ecotoxicological assessment, however, indicated the presence of genotoxic agents. The present study highlights the importance of combining water physicochemical analysis and bioassays to river monitoring. PMID:24285934

  15. Genotoxic assessment on river water using different biological systems.

    PubMed

    Nunes, Emilene Arusievicz; de Lemos, Clarice Torres; Gavronski, Léia; Moreira, Tiago Nunes; Oliveira, Nânci C D; da Silva, Juliana

    2011-06-01

    This paper reports genotoxicity and toxicity data in water samples collected in Sinos River, an important water course in the hydrographic region of Guaíba Lake, Rio Grande do Sul State, south of Brazil. This river is exposed to intense anthropic influence by numerous shoes, leather, petrochemical, and metallurgy industries. Water samples were collected at two moments (winter 2006 and spring 2006) at five sites of Sinos River and evaluated using in vitro V79 Chinese hamster lung fibroblasts (cytotoxicity, comet assay and micronucleus test) and Allium cepa test (toxicity and micronucleus test). Comet and micronucleus tests revealed that water samples collected exerted cytotoxic, toxic, genotoxic and mutagenic effects. The results showed the toxic action of organic and inorganic agents found in the water samples in all sites of Sinos River, for both data collections. The main causes behind pollution were the domestic and industrial toxic discharges. The V79 and A. cepa tests were proved efficient to detect toxicity and genotoxicity caused by complex mixtures. This study also showed the need for constant monitoring in sites with strong environmental degradation caused by industrial discharges and urban sewages. PMID:21435689

  16. Genotoxicity of Superparamagnetic Iron Oxide Nanoparticles in Granulosa Cells.

    PubMed

    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; SEON(LA-BSA)), or with dextran (SEON(DEX)). Both micronuclei testing and the detection of γH2A.X revealed no genotoxic effects of SEON(LA-BSA), SEON(DEX) or SEON(LA). Thus, it was demonstrated that different coatings of SPIONs improve biocompatibility, especially in terms of genotoxicity towards cells of the reproductive system. PMID:26540051

  17. Molecular and cytogenetic assessment of Dipterygium glaucum genotoxicity.

    PubMed

    Altwaty, Nada H; El-Sayed, Osama E; Aly, Nariman A H; Baeshen, Mohamed N; Baeshen, Nabih A

    2016-01-01

    The aim of the present study is to assess the genotoxicity of Dipterygium glaucum grows widely in Saudi Arabia desert to produce safety herbal products. This work is considered the first and pioneer report so far due to the lack and poor evaluated reports of the plant species for their mutagensity, genotoxicity and cytogenetics effects. Cytogenetic effects of D. glaucum on mitotic in roots of Vicia faba showed reduction in mitotic activity using three extracts; water, ethanol and ethyl acetate. Chromosomal abnormalities were recorded that included stickiness of chromosomes, chromatin bridge, fragments, lagging chromosome and micronuclei. Protein bands and RAPD analyses of V. faba treated with three D. glaucum extracts revealed some newly induced proteins and DNA fragments and other disappeared. Chemical constitution of the plant species should be identified with their biological activities against human and animal cells like HeLa cancer cell line. We are recommending using additional genotoxicity tests and other toxicity tests on animal culture with different concentrations and also utilizing several drought and heat tolerant genes of the plant species in gene cloning to develop and improve other economical crop plants instead of using the species as oral herbal remedy. PMID:27142548

  18. Monitoring Genotoxicity Potential in the Mumbuca Stream, Minas Gerais, Brazil.

    PubMed

    de Campos Júnior, Edimar Olegário; Pereira, Boscolli Barbosa; Morelli, Sandra

    2015-01-01

    Rivers are sites for water catchment to supply metropolitan areas but also serve as receptors for discharge of urban sewage, wastewater, and agri-industrial effluents. Bioindicators or sentinel organisms are widely used as markers of pollution in various environments. The objective of this study was to evaluate the genotoxic potential and consequent quality of the water from the Mumbuca stream, which supplies the city of Monte Carmelo, located in the Minas Triangle region, Minas Gerais, Brazil. This was achieved using two variable response bioindicators (Rhamdia quelen and Geophagus brasiliensis), the micronucleus (MN) test, and determining the presence of metals by flame atomic absorption spectrometry. Results showed that site 3 water (region of residential flow and intense industrial pottery activity) presented a greater possibility for induction of genotoxic activity, as evidenced by the increase in the MN frequency in Rhamdia quelen and Geophagus brasiliensis in comparison with the reference-site water. The water of the Mumbuca stream was influenced by genotoxic agents, especially lead and chromium, assessed by the rise in MN rate. Data suggested that discharge of industrial effluents in a specific stretch of the stream interfered with biota functions. PMID:26503827

  19. Genotoxicity and carcinogenicity of acrylamide: a critical review.

    PubMed

    Carere, Angelo

    2006-01-01

    In 2002, public health concerns were raised by Swedish studies showing that relatively high levels of acrylamide were formed during the frying, roasting, or baking of a variety of foods, including potatoes, cereal products and coffee at temperatures above 120 degrees C. Acrylamide possesses a range of hazardous properties, the key effects being carcinogenicity, genotoxicity, neurotoxicity and reproductive toxicity. Acrylamide is clearly carcinogenic in studies in animals, in which it causes increased tumour incidence at a variety of sites. Although the mechanisms for tumour induction in experimental animals have not yet fully elucidated, the in vivo genotoxicity at gene and chromosome level in somatic and germ cells in rodents cannot be discounted from contributing to it. At this time, there is no information to indicate any significant difference between rodents and humans in sensitivity to cancer formation from acrylamide. The present available epidemiological studies of human industrial and accidental exposures have to be considered not suitable for use in the cancer risk assessment of acrylamide in food, due to several limitations. In reviewing the genotoxicity and carcinogenicity of acrylamide, the author has taken into account also the evaluations made by the IARC in 1994, the FAO/WHO in 2002 by the European Commission Scientific Committee on Food (SCF) in 2002 and by the Joint FAO/WHO Expert Committee on Food Additive (JECFA) in 2005. PMID:17033134

  20. ASSESSMENT OF GENOTOXIC ACTIVITY OF PETROLEUM HYDROCARBON-BIOREMEDIATED SOIL

    SciTech Connect

    BRIGMON, ROBIN

    2004-10-20

    The relationship between toxicity and soil contamination must be understood to develop reliable indicators of environmental restoration for bioremediation. Two bacterial rapid bioassays: SOS chromotest and umu-test with and without metabolic activation (S-9 mixture) were used to evaluate genotoxicity of petroleum hydrocarbon-contaminated soil following bioremediation treatment. The soil was taken from an engineered biopile at the Czor Polish oil refinery. The bioremediation process in the biopile lasted 4 years, and the toxicity measurements were done after this treatment. Carcinogens detected in the soil, polyaromatic hydrocarbons (PAHs), were reduced to low concentrations (2 mg/kg dry wt) by the bioremediation process. Genotoxicity was not observed for soils tested with and without metabolic activation by a liver homogenate (S-9 mixture). However, umu-test was more sensitive than SOS-chromotest in the analysis of petroleum hydrocarbon-bioremediated soil. Analytical results of soil used in the bioassays confirmed that the bioremediation process reduced 81 percent of the petroleum hydrocarbons including PAHs. We conclude that the combined test systems employed in this study are useful tools for the genotoxic examination of remediated petroleum hydrocarbon-contaminated soil.

  1. Genetic toxicity assessment: employing the best science for human safety evaluation Part VII: Why not start with a single test: a transformational alternative to genotoxicity hazard and risk assessment.

    PubMed

    Ku, Warren W; Aubrecht, Jiri; Mauthe, Robert J; Schiestl, Robert H; Fornace, Albert J

    2007-09-01

    A transformational alternative for genotoxicity hazard and risk assessment is proposed to the current standard regulatory test battery. In principle, the proposed approach consists of a single in vitro test system with high genomic sequence homology to humans that addresses the relevant principal genetic lesions assessed in the current test battery. The single test system also possesses higher throughput attributes to permit the screening of large numbers of compounds and allow for an initial differentiation of genotoxic mechanisms (i.e., direct vs. indirect mechanisms) by how the hazard end point is measured. To differentiate compounds showing positive results, toxicogenomic analysis can be conducted to evaluate genotoxic mechanisms and further support risk assessment. Lastly, the results from the single test system can be followed up with a complementary in vivo assessment to establish mechanistic relevance at potential target tissues. Here, we propose the in vitro (yeast) DNA deletion (DEL) recombination assay as a single test alternative to the current genotoxicity test battery with a mechanistic follow up toxicogenomic analysis of genotoxic stress response as one approach that requires broader evaluation and validation. In this assay, intrachromosomal recombination events between a repeated DNA sequence lead to DNA deletions, which have been shown to be inducible by a variety of carcinogens including those both negative and positive in the standard Salmonella Ames assay. It is hoped that the general framework outlined along with this specific example will provoke broader interest to propose other potential test systems. PMID:17548889

  2. Pyroelectric response mechanism of barium strontium titanate ceramics in dielectric bolometer mode: The underlying essence of the enhancing effect of direct current bias field

    SciTech Connect

    Mao, Chaoliang; Cao, Sheng; Yan, Shiguang; Yao, Chunhua; Cao, Fei; Wang, Genshui; Dong, Xianlin; Hu, Xu; Yang, Chunli

    2013-06-17

    Pyroelectric response mechanism of Ba{sub 0.70}Sr{sub 0.30}TiO{sub 3} ceramics under dielectric bolometer (DB) mode was investigated by dielectric and pyroelectric properties measurement. The variations of total, intrinsic, and induced pyroelectric coefficients (p{sub tot}, p{sub int}, p{sub ind}) with temperatures and bias fields were analyzed. p{sub int} plays the dominant role to p{sub tot} through most of the temperature range and p{sub ind} will be slightly higher than p{sub int} above T{sub 0}. The essence of the enhancing effect of DC bias field on pyroelectric coefficient can be attributed to the high value of p{sub int}. This mechanism is useful for the pyroelectric materials (DB mode) applications.

  3. Genotoxicity testing of peptides: Folate deprivation as a marker of exaggerated pharmacology

    SciTech Connect

    Guérard, Melanie Zeller, Andreas; Festag, Matthias; Schubert, Christine; Singer, Thomas; Müller, Lutz

    2014-09-15

    The incidence of micronucleated-cells is considered to be a marker of a genotoxic event and can be caused by direct- or indirect-DNA reactive mechanisms. In particular, small increases in the incidence of micronuclei, which are not associated with toxicity in the target tissue or any structurally altering properties of the compound, trigger the suspicion that an indirect mechanism could be at play. In a bone marrow micronucleus test of a synthetic peptide (a dual agonist of the GLP-1 and GIP receptors) that had been integrated into a regulatory 13-week repeat-dose toxicity study in the rat, small increases in the incidence of micronuclei had been observed, together with pronounced reductions in food intake and body weight gain. Because it is well established that folate plays a crucial role in maintaining genomic integrity and pronounced reductions in food intake and body weight gain were observed, folate levels were determined from plasma samples initially collected for toxicokinetic analytics. A dose-dependent decrease in plasma folate levels was evident after 4 weeks of treatment at the mid and high dose levels, persisted until the end of the treatment duration of 13-weeks and returned to baseline levels during the recovery period of 4 weeks. Based on these properties, and the fact that the compound tested (peptide) per se is not expected to reach the nucleus and cause DNA damage, the rationale is supported that the elevated incidence of micronucleated polychromatic erythrocytes is directly linked to the exaggerated pharmacology of the compound resulting in a decreased folate level. - Highlights: • A synthetic peptide has been evaluated for potential genotoxicity • Small increases in an integrated (13-weeks) micronucleus test were observed • Further, animals had a pronounced reductions in food intake and body weight gain • A dose-dependent decrease in plasma folate levels was evident from week 4 onwards • Elevated micronuclei-incidence due to the

  4. Recommended lists of genotoxic and non-genotoxic chemicals for assessment of the performance of new or improved genotoxicity tests: a follow-up to an ECVAM workshop.

    PubMed

    Kirkland, David; Kasper, Peter; Müller, Lutz; Corvi, Raffaella; Speit, Günter

    2008-05-31

    At a recent ECVAM workshop considering ways to reduce the frequency of irrelevant positive results in mammalian cell genotoxicity tests [D. Kirkland, S. Pfuhler, D. Tweats, M. Aardema, R. Corvi, F. Darroudi, A. Elhajouji, H.-R. Glatt, P. Hastwell, M. Hayashi, P. Kasper, S. Kirchner, A. Lynch, D. Marzin, D. Maurici, J.-R. Meunier, L. Müller, G. Nohynek, J. Parry, E. Parry, V. Thybaud, R. Tice, J. van Benthem, P. Vanparys, P. White, How to reduce false positive results when undertaking in vitro genotoxicity testing and thus avoid unnecessary followup animal tests: Report of an ECVAM Workshop, Mutat. Res. 628 (2007) 31-55], recommendations for improvements/modifications to existing tests, and suggestions for new assays were made. Following on from this, it was important to identify chemicals that could be used in the evaluation of modified or new assays. An expert panel was therefore convened and recommendations made for chemicals to fit three different sets of characteristics, namely: This paper therefore contains these three recommended lists of chemicals and describes how these should be used for any test-evaluation programme. PMID:18539078

  5. In vitro genotoxic effects of different combinations of cobalt and metallic carbide particles.

    PubMed

    De Boeck, Marlies; Lombaert, Noömi; De Backer, Sofie; Finsy, Robert; Lison, Dominique; Kirsch-Volders, Micheline

    2003-03-01

    Occupational exposure to hard metal dust, consisting of tungsten carbide (WC) and metallic cobalt particles (Co), is associated with an increased risk of lung cancer, while no increased risk was observed in workers exposed to Co alone. In vitro, in human peripheral blood mononucleated cells (PBMC), we previously demonstrated that WC-Co is more genotoxic than Co and WC alone. A possible mechanism underlying this higher genotoxicity is a specific physicochemical interaction between Co and WC particles leading to the enhanced short-term formation of active oxygen species. The aim of this study was to evaluate the in vitro genotoxicity of other combinations of Co with metal carbide particles in comparison with WC-Co. The ability of Cr(3)C(2), Mo(2)C and NbC and of their powder mixtures with Co to induce DNA strand breaks and alkali-labile sites was assessed by the alkaline Comet assay and their potential to induce chromosome(/genome) mutations by the cytokinesis-block micronucleus test on human PBMC from two donors. PBMC were treated in vitro for 15 min, 24 h after the onset of PHA stimulation. In the micronucleus test, while the metal carbides alone did not increase the micronucleus frequency, Co alone and the four tested carbide-Co mixtures induced a statistically significant concentration-dependent increase in micronucleated binucleates. In addition to WC, NbC and Cr(3)C(2) particles were able to interact with Co, producing a higher mutagenic effect than the individual metal particles. Mo(2)C particles did not display interactive mutagenicity with Co in the micronucleus test, possibly related to their small specific surface area, compactness and/or spherical shape. With the Comet assay, applied directly at the end of the treatment, less clear results, due to inter-experimental and inter-donor variation, were obtained. These data indicate that particular interaction of a metal carbide with Co leading to enhanced mutagenicity is not specific for WC. PMID:12621074

  6. Genotoxicity of polyvinylpyrrolidone-coated silver nanoparticles in BEAS 2B cells.

    PubMed

    Nymark, Penny; Catalán, Julia; Suhonen, Satu; Järventaus, Hilkka; Birkedal, Renie; Clausen, Per Axel; Jensen, Keld Alstrup; Vippola, Minnamari; Savolainen, Kai; Norppa, Hannu

    2013-11-01

    Silver nanoparticles (AgNPs) are widely utilized in various consumer products and medical devices, especially due to their antimicrobial properties. However, several studies have associated these particles with toxic effects, such as inflammation and oxidative stress in vivo and cytotoxic and genotoxic effects in vitro. Here, we assessed the genotoxic effects of AgNPs coated with polyvinylpyrrolidone (PVP) (average diameter 42.5±14.5 nm) on human bronchial epithelial BEAS 2B cells in vitro. AgNPs were dispersed in bronchial epithelial growth medium (BEGM) with 0.6 mg/ml bovine serum albumin (BSA). The AgNP were partially well-dispersed in the medium and only limited amounts (ca. 0.02 μg Ag(+) ion/l) could be dissolved after 24h. The zeta-potential of the AgNPs was found to be highly negative in pure water but was at least partially neutralized in BEGM with 0.6 mg BSA/ml. Cytotoxicity was measured by cell number count utilizing Trypan Blue exclusion and by an ATP-based luminescence cell viability assay. Genotoxicity was assessed by the alkaline single cell gel electrophoresis (comet) assay, the cytokinesis-block micronucleus (MN) assay, and the chromosomal aberration (CA) assay. The cells were exposed to various doses (0.5-48 μg/cm(2) corresponding to 2.5-240 μg/ml) of AgNPs for 4 and 24 h in the comet assay, for 48 h in the MN assay, and for 24 and 48 h in the CA assay. DNA damage measured by the percent of DNA in comet tail was induced in a dose-dependent manner after both the 4-h and the 24-h exposures to AgNPs, with a statistically significant increase starting at 16 μg/cm(2) (corresponding to 60.8 μg/ml) and doubling of the percentage of DNA in tail at 48 μg/cm(2). However, no induction of MN or CAs was observed at any of the doses or time points. The lack of induction of chromosome damage by the PVP-coated AgNPs is possibly due to the coating which may protect the cells from direct interaction with the AgNPs, either by reducing ion leaching from the

  7. Immunotoxicity and genotoxicity testing for in-flight experiments under microgravity

    NASA Astrophysics Data System (ADS)

    Hansen, Peter-Diedrich; Hansen, Peter-Diedrich; Unruh, Eckehardt

    Life Sciences as Related to Space (F) Influence of Spaceflight Environment on Biological Systems (F44) Immunotoxicity and genotoxicity testing for In-flight experiments under microgravity Sensing approaches for ecosystem and human health Author: Peter D. Hansen Technische Universit¨t Berlin, Faculty VI - Planen, Bauen, Umwelt, a Institute for Ecological Research and Technology, Department for Ecotoxicology, Berlin, Germany Peter-diedrich.hansen@tu-berlin.de Eckehardt Unruh Technische Universit¨t Berlin, Faculty VI - Planen, Bauen, Umwelt, Institute a for Ecological Research and Technology, Department for Ecotoxicology, Berlin, Germany An immune response by mussel hemocytes is the selective reaction to particles which are identified as foreign by its immune system shown by phagocytosis. Phagocytotic activity is based on the chemotaxis and adhesion, ingestion and phagosome formation. The attachment at the surface of the hemocytes and consequently the uptake of the particles or bacteria can be directly quantified in the format of a fluorescent assay. Another relevant endpoint of phagocytosis is oxidative burst measured by luminescence. Phagocytosis-related production of ROS will be stimulated with opsonised zymosan. The hemocytes will be stored frozen at -80oC and reconstituted in-flight for the experiment. The assay system of the TRIPLELUX-B Experiment has been performed with a well-defined quantification and evaluation of the immune function phagocytosis. The indicator cells are the hemocytes of blue mussels (Mytilus edulis). The signals of the immuno cellular responses are translated into luminescence as a rapid optical reporter system. The results expected will determine whether the observed responses are caused by microgravity and/or radiation (change in permeability, endpoints in genotoxicity: DNA unwinding). The samples for genotoxicity will be processed after returning to earth. The immune system of invertebrates has not been studied so far in space. The

  8. Induction of miRNA-181a by genotoxic treatments promotes chemotherapeutic resistance and metastasis in breast cancer

    PubMed Central

    Chi, Yayun; Xue, Jingyan; Wang, Wei; Zhao, Ziqin; Fan, Meiyun; Yang, Chuan He; Shao, Zhi-ming; Pfeffer, Lawrence M.; Wu, Jiong; Wu, Zhao-Hui

    2015-01-01

    Acquired therapeutic resistance is the major drawback to effective systemic therapies for cancers. Aggressive triple-negative breast cancers (TNBC) develop resistance to chemotherapies rapidly, whereas the underlying mechanisms are not completely understood. Here we show that genotoxic treatments significantly increased the expression of miR-181a in TNBC cells, which enhanced TNBC cell survival and metastasis upon Doxorubicin treatment. Consistently, high miR-181a level associated with poor disease free survival and overall survival after treatments in breast cancer patients. The up-regulation of miR-181a was orchestrated by transcription factor STAT3 whose activation depended on NF-κB-mediated IL-6 induction in TNBC cells upon genotoxic treatment. Intriguingly, activated STAT3 not only directly bound to MIR181A1 promoter to drive transcription, it also facilitated the recruitment of MSK1 to the same region where MSK1 promoted a local active chromatin state by phosphorylating histone H3. We further identified BAX as a direct functional target of miR-181a, whose suppression decreased apoptosis and increased invasion of TNBC cells upon Dox treatment. These results were further confirmed by evidence that suppression of miR-181a significantly enhanced therapeutic response and reduced lung metastasis in a TNBC orthotopic model. Collectively, our data suggested that miR-181a induction played a critical role in promoting therapeutic resistance and aggressive behavior of TNBC cells upon genotoxic treatment. Antagonizing miR-181a may serve as a promising strategy to sensitize TNBC cells to chemotherapy and mitigate metastasis. PMID:26028030

  9. Induction of miRNA-181a by genotoxic treatments promotes chemotherapeutic resistance and metastasis in breast cancer.

    PubMed

    Niu, J; Xue, A; Chi, Y; Xue, J; Wang, W; Zhao, Z; Fan, M; Yang, C H; Shao, Z-M; Pfeffer, L M; Wu, J; Wu, Z-H

    2016-03-10

    Acquired therapeutic resistance is the major drawback to effective systemic therapies for cancers. Aggressive triple-negative breast cancers (TNBC) develop resistance to chemotherapies rapidly, whereas the underlying mechanisms are not completely understood. Here we show that genotoxic treatments significantly increased the expression of miR-181a in TNBC cells, which enhanced TNBC cell survival and metastasis upon Doxorubicin treatment. Consistently, high miR-181a level associated with poor disease free survival and overall survival after treatments in breast cancer patients. The upregulation of miR-181a was orchestrated by transcription factor STAT3 whose activation depended on NF-κB-mediated IL-6 induction in TNBC cells upon genotoxic treatment. Intriguingly, activated STAT3 not only directly bound to MIR181A1 promoter to drive transcription but also facilitated the recruitment of MSK1 to the same region where MSK1 promoted a local active chromatin state by phosphorylating histone H3. We further identified BAX as a direct functional target of miR-181a, whose suppression decreased apoptosis and increased invasion of TNBC cells upon Dox treatment. These results were further confirmed by evidence that suppression of miR-181a significantly enhanced therapeutic response and reduced lung metastasis in a TNBC orthotopic model. Collectively, our data suggested that miR-181a induction had a critical role in promoting therapeutic resistance and aggressive behavior of TNBC cells upon genotoxic treatment. Antagonizing miR-181a may serve as a promising strategy to sensitize TNBC cells to chemotherapy and mitigate metastasis. PMID:26028030

  10. Excitation of ion Bernstein waves as the dominant parametric decay channel in direct X-B mode conversion for typical spherical torus

    NASA Astrophysics Data System (ADS)

    Abbasi, Mustafa; Sadeghi, Yahya; Sobhanian, Samad; Asgarian, Mohammad Ali

    2016-03-01

    The electron Bernstein wave (EBW) is typically the only wave in the electron cyclotron (EC) range that can be applied in spherical tokamaks for heating and current drive (H&CD). Spherical tokamaks (STs) operate generally in high- β regimes, in which the usual EC ordinary (O) and extraordinary (X) modes are cut off. As it was recently investigated the existence of EBWs at nonlinear regime thus the next step would be the probable nonlinear phenomena study which are predicted to be occurred within the high levels of injected power. In this regard, parametric instabilities are considered as the major channels for losses at the X-B conversion. Hence, we have to consider their effects at the UHR region which can reduce the X-B conversion efficiency. In the case of EBW heating (EBH) at high power density, the nonlinear effects can arise. Particularly at the UHR position, the group velocity is strongly reduced, which creates a high energy density and subsequently a high amplitude electric field. Therefore, a part of the input wave can decay into daughter waves via parametric instability (PI). Thus, via the present research, the excitations of ion Bernstein waves as the dominant decay channels are investigated and also an estimate for the threshold power in terms of experimental parameters related to the fundamental mode of instability is proposed.

  11. Zero-mode waveguides

    DOEpatents

    Levene, Michael J.; Korlach, Jonas; Turner, Stephen W.; Craighead, Harold G.; Webb, Watt W.

    2007-02-20

    The present invention is directed to a method and an apparatus for analysis of an analyte. The method involves providing a zero-mode waveguide which includes a cladding surrounding a core where the cladding is configured to preclude propagation of electromagnetic energy of a frequency less than a cutoff frequency longitudinally through the core of the zero-mode waveguide. The analyte is positioned in the core of the zero-mode waveguide and is then subjected, in the core of the zero-mode waveguide, to activating electromagnetic radiation of a frequency less than the cut-off frequency under conditions effective to permit analysis of the analyte in an effective observation volume which is more compact than if the analysis were carried out in the absence of the zero-mode waveguide.

  12. GENOTOXICITY OF TEN CIGARETTE SMOKE CONDENSATES IN FOUR TEST SYSTEMS: COMPARISONS AMONG ASSAYS AND CONDENSATES

    EPA Science Inventory

    The particulate fraction of cigarette smoke, cigarette smoke condensate (CSC), is genotoxic in many short-term in vitro tests and carcinogenic in rodents. However, no study has evaluatedd a set of CSCs prepared from a diverse set of cigarettes in a variety of short-term genotoxic...

  13. INTRODUCTION AND SUMMARY. GENOTOXICITY AND CARCINOGENICITY DATA BASES: AN ASSESSMENT OF THE PRESENT SITUATION

    EPA Science Inventory

    This paper is an introduction to the Proceedings of the Intl. Symp. on Data Bases of Genotoxicity and Carcinogenicity and their Usefulness for Hazard Evaluations, held in Genova, Italy, January 1991. he purpose of this meeting was to review the present status of genotoxicity and ...

  14. A new genotoxicity assay based on p53 target gene induction.

    PubMed

    Zerdoumi, Y; Kasper, E; Soubigou, F; Adriouch, S; Bougeard, G; Frebourg, T; Flaman, J-M

    2015-08-01

    The p53 tumor suppressor protein has emerged as a universal sensor of genotoxic stress that regulates the transcription of numerous genes required for appropriate cellular response to DNA damage. Therefore, transcriptional induction of p53 target genes can be considered as a global and early indicator of genotoxic stress. By performing expression microarrays and RNA-Seq analysis on wild-type and mutant TP53 human lymphocytes respectively derived from controls and Li-Fraumeni patients and exposed to different classes of genotoxic agents, we first determined a common p53-dependent transcriptional signature of DNA damage. We then derived a simple and fast assay based on the exposure of wild-type TP53 lymphocytes to physical or chemical agents and on the quantitative measurement of selected p53 target gene transcriptional induction. The specificity of the p53 genotoxicity assay can easily be demonstrated by performing the same experiment in control lymphocytes with heterozygous TP53 mutations, which compromise responses to DNA damage. This assay allowed us to show that most of the drugs commonly used in cancer treatment, except the microtubule poisons, are highly genotoxic. The p53 genotoxicity assay should facilitate the measurement of the genotoxic effects of chemical and physical agents and the identification of drugs that are not genotoxic and do not expose patients to the risk of secondary malignancies, especially those with a constitutional defect in response to DNA damage, such as patients with Li-Fraumeni syndrome. PMID:26232255

  15. Effects of phenytoin and carbamazepine on human natural killer cell activity and genotoxicity in vitro.

    PubMed

    Margaretten, N C; Hincks, J R; Warren, R P; Coulombe, R A

    1987-01-01

    Human peripheral blood mononuclear cells (PBMC) were isolated from healthy volunteers and exposed in vitro to phenytoin or carbamazepine, two widely used antiepileptic drugs (AED). This study investigated the effects of these drugs on natural killer (NK) cell activity and antibody-dependent cell-mediated cytotoxicity (ADCC), which are both thought to protect against developing neoplasms. Also, the genotoxicity of phenytoin on human PBMC was investigated by gravity-flow alkaline elution. Concentrations of phenytoin considered therapeutic (10 and 20 micrograms/ml) and a dose considered acutely toxic (40 micrograms/ml) were used while carbamazepine levels of 8 micrograms/ml (therapeutic) and 10 and 16 micrograms/ml (acutely toxic) were tested. Phenytoin at all three concentrations significantly suppressed NK cell activity in a dose-dependent manner. Carbamazepine had no significant effect on NK cell activity at the dose levels studied. Incubation in propylene glycol, the diluent for carbamazepine, significantly decreased NK cell activity compared to saline. Phenytoin also significantly depressed interferon augmentation of NK cell cytotoxicity in a dose dependent manner. ADCC activity was significantly depressed with 20 and 40 micrograms/ml phenytoin. Alkaline elution showed a slight but significant increase in DNA single-strand breaks of PBMC exposed to 40 micrograms/ml phenytoin for 18 or 72 hr. These results show phenytoin may induce pronounced immunosuppression of NK cell and ADCC activity in patients receiving antiepileptic therapy and that this agent has a potential for genotoxic side effects. Phenytoin may also increase the potential for neoplasm development by a direct interaction with cellular DNA and/or an indirect mechanism by immunosuppression. PMID:3798446

  16. Sunlight decreased genotoxicity of azadirachtin on root tip cells of Allium cepa and Eucrosia bicolor.

    PubMed

    Kwankua, W; Sengsai, S; Kuleung, C; Euawong, N

    2010-07-01

    Utilization of neem plant (Azadirachta indica A. Juss) extract for pest control in agriculture has raised concerns over contamination by the residues to the environment. Such residues, particularly azadirachtin (Aza), may cause deleterious effect to non-target organisms. This investigation was conducted to find out if Aza could be inactivated through exposures to sunlight. Activity of Aza was assessed as its ability to cause cytotoxic and genotoxic effects in the forms of nuclei abnormality and chromosome aberration as measured by mitotic index (MI) and mitotic aberration (MA). Varying concentrations of Aza were tested on Allium cepa and Eucrosia bicolor. It was found that the MI of all root tip meristematic cells of A. cepa and E. bicolor treated with 0.00005%, 0.00010%, 0.00015%, and 0.00020% (w/v) Aza-containing neem extract for 24h, were significantly lower than the controls. Complementary to the lower levels of MI, the Aza-treated groups showed higher MA levels in all cases investigated. Furthermore, the decreasing levels of MI and the increasing levels of MA related well with the increasing concentration of Aza. Microscopic examination of root tip meristematic cells revealed that the anomaly found most often were mitotic disturbances and chromosomal bridges. Exposures of 0.00020% (w/v) Aza to sunlight for 3 days and 7 days decreased Aza ability to induce cytotoxicity and genotoxicity, both in terms of MI and MA, to root tip meristematic cells in A. cepa and E. bicolor. Photodegradation of Aza upon exposure to direct sunlight was confirmed by HPLC. The study implicates that Aza would unlikely cause long term deleterious effects to the environment since it would be inactivated by sunlight. PMID:20452021

  17. Genomic Phenotyping by Barcode Sequencing Broadly Distinguishes between Alkylating Agents, Oxidizing Agents, and Non-Genotoxic Agents, and Reveals a Role for Aromatic Amino Acids in Cellular Recovery after Quinone Exposure

    PubMed Central

    Svensson, J. Peter; Quirós Pesudo, Laia; McRee, Siobhan K.; Adeleye, Yeyejide; Carmichael, Paul; Samson, Leona D.

    2013-01-01

    Toxicity screening of compounds provides a means to identify compounds harmful for human health and the environment. Here, we further develop the technique of genomic phenotyping to improve throughput while maintaining specificity. We exposed cells to eight different compounds that rely on different modes of action: four genotoxic alkylating (methyl methanesulfonate (MMS), N-Methyl-N-nitrosourea (MNU), N,N′-bis(2-chloroethyl)-N-nitroso-urea (BCNU), N-ethylnitrosourea (ENU)), two oxidizing (2-methylnaphthalene-1,4-dione (menadione, MEN), benzene-1,4-diol (hydroquinone, HYQ)), and two non-genotoxic (methyl carbamate (MC) and dimethyl sulfoxide (DMSO)) compounds. A library of S. cerevisiae 4,852 deletion strains, each identifiable by a unique genetic ‘barcode’, were grown in competition; at different time points the ratio between the strains was assessed by quantitative high throughput ‘barcode’ sequencing. The method was validated by comparison to previous genomic phenotyping studies and 90% of the strains identified as MMS-sensitive here were also identified as MMS-sensitive in a much lower throughput solid agar screen. The data provide profiles of proteins and pathways needed for recovery after both genotoxic and non-genotoxic compounds. In addition, a novel role for aromatic amino acids in the recovery after treatment with oxidizing agents was suggested. The role of aromatic acids was further validated; the quinone subgroup of oxidizing agents were extremely toxic in cells where tryptophan biosynthesis was compromised. PMID:24040048

  18. Evaluation of the in vivo genotoxicity of Allura Red AC (Food Red No. 40).

    PubMed

    Honma, Masamitsu

    2015-10-01

    Allura Red AC (Food Red No. 40) is a red azo dye that is used for food coloring in beverage and confectionary products. However, its genotoxic properties remain controversial. To clarify the in vivo genotoxicity, we treated mice with Allura Red AC and investigated the induction of DNA damage (liver, glandular stomach), clastogenicity/anuegenicity (bone marrow), and mutagenicity (liver, glandular stomach) using Comet assays, micronucleus tests, and transgenic gene mutation assays, respectively. All studies were conducted in accordance with the Organization for Economic Co-operation and Development (OECD) guideline. Although Allura Red AC was administered up to the maximum doses recommended by the OECD guideline, no genotoxic effect was observed in any of the genotoxic endpoints. These data clearly show no evidence of in vivo genotoxic potential of Allura Red AC administered up to the maximum doses in mice. PMID:26364875

  19. The Comet Assay for the Evaluation of Genotoxic Potential of Landfill Leachate

    PubMed Central

    Widziewicz, Kamila; Kalka, Joanna; Skonieczna, Magdalena; Madej, Paweł

    2012-01-01

    Genotoxic assessment of landfill leachate before and after biological treatment was conducted with two human cell lines (Me45 and NHDF) and Daphnia magna somatic cells. The alkali version of comet assay was used to examine genotoxicity of leachate by DNA strand breaks analysis and its repair dynamics. The leachate samples were collected from Zabrze landfill, situated in the Upper Silesian Industrial District, Poland. Statistically significant differences (Kruskal-Wallice ANOVA rank model) were observed between DNA strand breaks in cells incubated with leachate before and after treatment (P < 0.001). Nonparametric Friedman ANOVA confirmed time-reliable and concentration-reliable cells response to leachate concentration. Examinations of chemical properties showed a marked decrease in leachate parameters after treatment which correlate to reduced genotoxicity towards tested cells. Obtained results demonstrate that biological cotreatment of leachate together with municipal wastewater is an efficient method for its genotoxic potential reduction; however, treated leachate still possessed genotoxic character. PMID:22666120

  20. Antigenotoxic effect of allicin against estradiol-17beta-induced genotoxic damage in cultured mammalian cells.

    PubMed

    Siddique, Yasir Hasan; Beg, Tanveer; Ara, Gulshan; Gupta, Jyoti; Afzal, Mohammad

    2010-07-01

    Antigenotoxic activity of allicin, one of the sulphur compounds of garlic (Allium sativum) which possesses antioxidant and thiol disulphide exchange activity, was studied against estradiol-17beta-induced genotoxic damage using chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) as parameters. Approximately 10, 20 and 40 microM of estradiol-17beta was tested for its genotoxic effect in the presence of metabolic activation and was found to be genotoxic at 20 and 40 microM. Approximately 20 microM of estradiol-17beta was treated along with 5, 10 and 15 microM of allicin, separately, in the presence of metabolic activation. Similar treatments were given with 40 microM of estradiol-17beta. Treatments along with allicin result in the reduction of CAs and SCEs, suggesting its anti-genotoxic activity in human lymphocytes in vitro against estradiol-17beta-induced genotoxic damage. PMID:20582805

  1. Genotoxicity of leachates from a landfill using three bioassays.

    PubMed

    Cabrera, G L; Rodriguez, D M

    1999-05-19

    In the city of Queretaro, around 500 tons of solid wastes are produced everyday and are deposited in a landfill. This is the result of social and economic activities of human beings or from their normal physiological functions. As a result of rain, leachates are produced, which, if not handled and treated correctly, may pollute the underground water. Among the bioassays developed for the detection of mutagenicity in environmental pollutants, plant systems have been proven to be sensitive, cheap, and effective. The purpose of this study was to determine the presence of genotoxic agents in the leachates of the landfill of the city using three bioassays: Tradescantia-micronucleus (Trad-MCN), Tradescantia stamen hair mutations (Trad-SHM) and Allium root anaphase aberrations (AL-RAA) and make a comparison of the results in the three assays. Leachates were sampled during both the dry and rainy seasons. Plant cuttings of Tradescantia or the roots of Allium were treated by submerging them in the leachates. Three replicates of each sample were analyzed in each of the three bioassays. As expected the samples of leachates collected during the dry season showed a higher genotoxicity than those collected during the rainy season. In conclusion, there are substances present in the leachates capable of inducing genotoxicity in the plant assays. On the other hand, the plant assays showed different degrees of sensitivity: the more sensitive was the Trad-MCN bioassay and the less sensitive the Trad-SHM assay. Therefore, when analyzing environmental pollutants it is recommended to use a battery of bioassays. PMID:10350599

  2. Ecotoxicity and genotoxicity of cadmium in different marine trophic levels.

    PubMed

    Pavlaki, Maria D; Araújo, Mário J; Cardoso, Diogo N; Silva, Ana Rita R; Cruz, Andreia; Mendo, Sónia; Soares, Amadeu M V M; Calado, Ricardo; Loureiro, Susana

    2016-08-01

    Cadmium ecotoxicity and genotoxicity was assessed in three representative species of different trophic levels of marine ecosystems - the calanoid copepod Acartia tonsa, the decapod shrimp, Palaemon varians and the pleuronectiform fish Solea senegalensis. Ecotoxicity endpoints assessed in this study were adult survival, hatching success and larval development ratio (LDR) for A. tonsa, survival of the first larval stage (zoea I) and post-larvae of P. varians, egg and larvae survival, as well as the presence of malformations in the larval stage of S. senegalensis. In vivo genotoxicity was assessed on adult A. tonsa, the larval and postlarval stage of P. varians and newly hatched larvae of S. senegalensis using the comet assay. Results showed that the highest sensitivity to cadmium is displayed by A. tonsa, with the most sensitive endpoint being the LDR of nauplii to copepodites. Sole eggs displayed the highest tolerance to cadmium compared to the other endpoints evaluated for all tested species. Recorded cadmium toxicity was (by increasing order): S. senegalensis eggs < P. varians post-larvae < P. varians zoea I < S. senegalensis larvae < A. tonsa eggs < A. tonsa LDR. DNA damage to all species exposed to cadmium increased with increasing concentrations. Overall, understanding cadmium chemical speciation is paramount to reliably evaluate the effects of this metal in marine ecosystems. Cadmium is genotoxic to all three species tested and therefore may differentially impact individuals and populations of marine taxa. As A. tonsa was the most sensitive species and occupies a lower trophic level, it is likely that cadmium contamination may trigger bottom-up cascading effects in marine trophic interactions. PMID:27203468

  3. Direct versus Indirect and Individual versus Group Modes of Language Therapy for Children with Primary Language Impairment: Principal Outcomes from a Randomized Controlled Trial and Economic Evaluation

    ERIC Educational Resources Information Center

    Boyle, James M.; McCartney, Elspeth; O'Hare, Anne; Forbes, John

    2009-01-01

    Background: Many school-age children with language impairments are enrolled in mainstream schools and receive indirect language therapy, but there have been, to the authors' knowledge, no previous controlled studies comparing the outcomes and costs of direct and indirect intervention delivered by qualified therapists and therapy assistants, and…

  4. Testing systems for biologic markers of genotoxic exposure and effect

    SciTech Connect

    Mendelsohn, M.L.

    1986-11-19

    Societal interest in genotoxicity stems from two concerns: the fear of carcinogenesis secondary to somatic mutation; and the fear of birth defects and decreasing genetic fitness secondary to heritable mutation. There is a pressing need to identify agents that can cause these effects, to understand the underlying dose-response relationships, to identify exposed populations, and to estimate both the magnitude of exposure and the risk of adverse health effects in such populations. Biologic markers refer either to evidence in surrogate organisms, or to the expressions of exposure and effect in human populations. 21 refs.

  5. Genotoxicity and oxidative stress in gasoline station attendants.

    PubMed

    Moro, Angela M; Charão, Mariele F; Brucker, Natália; Durgante, Juliano; Baierle, Marília; Bubols, Guilherme; Goethel, Gabriela; Fracasso, Rafael; Nascimento, Sabrina; Bulcão, Rachel; Gauer, Bruna; Barth, Anelise; Bochi, Guilherme; Moresco, Rafael; Gioda, Adriana; Salvador, Mirian; Farsky, Sandra; Garcia, Solange C

    2013-06-14

    We evaluated genotoxic effects of exposure to low levels of benzene, a class I human carcinogen, among gasoline station attendants (GSA). Oxidative stress and the protective effects of antioxidants on DNA damage were also analyzed. Although exposures were below ACGIH (American Conference of Governmental Industrial Hygienists) limits, the GSA group presented higher DNA damage indices and micronucleus frequencies, increased oxidative protein damage, and decreased antioxidant capacity relative to the control group. Duration of benzene exposure was correlated with DNA and protein damage. The biomarkers evaluated in this work may provide early signals of damage in subjects occupationally exposed to benzene. PMID:23628435

  6. Genotoxicity studies of the food additive ester gum.

    PubMed

    Mukherjee, A; Agarwal, K; Chakrabarti, J

    1992-07-01

    Ester gum (EG) is used in citrus oil-based beverage flavourings as a weighting or colouring agent. In the present study, concentrations of 50, 100 and 150 mg/kg body weight were administered orally to male Swiss albino mice, and sister chromatid exchange and chromosomal aberration were used as the cytogenetic endpoints to determine the genotoxic and clastogenic potential of the food additive. Although EG was weakly clastogenic and could induce a marginal increase in sister chromatid exchange frequencies, it was not a potential health hazard at the doses tested. PMID:1521837

  7. Cadmium flux and genotoxicity in an experimental marine food chain

    NASA Astrophysics Data System (ADS)

    Lin, Guangheng; Qin, Song; Tseng, C. K.

    1991-12-01

    Cadmium flux through a lab food chain ( Phaeodactylum tricornutum Bohlin- Penaeus orientalis Kishinouye- Hexagrammos otakii Jordan et Starks) and its genotoxicity were investigated. The results are as follows: 1. High doses of cadmium (>0.003 mol/L) induced flocculation and quick precipitation of Phaeodactylum tricornutum; lower doses of cadmium could be adsorbed on and absorbed by P. tricornutum without delaying its growth. Cadmium concentrations in algae increased with dosage, and cadmium ions removed from the medium were in proportion to dosage. In vivo chelation and organizable combination of absorbed cadmium ions by metabolites of P. tricornutum can be considered as bio-detoxification.

  8. Evaluation of Genotoxicity in Patients Subjected to Panoramic Radiography by Micronucleus Assay on Epithelial Cells of the Oral Mucosa

    PubMed Central

    Arora, Pallak; Devi, Parvathi; Wazir, Sartaj Singh

    2014-01-01

    Objective: Radiography is one of the most valuable diagnostic tools used in comprehensive dental care. Although there is no safe level of radiation exposure, the possible risk associated with exposure to radiation, must be elucidated. To date, a variety of assays have been proposed to assess the mutagenic potential of genotoxicants; however, these methods are typically laborious and time consuming. The aim of the present study was to evaluate the possible genotoxic effect of routinely used panoramic radiation exposure in exfoliated epithelial cells as measured by the formation of micronuclei and to compare the genotoxicity of X-rays on keratinized epithelial gingival cells and the nonkeratinized buccal epithelial cells. Materials and Methods: The study included 53 healthy individuals with a mean age of 25.21 ±12.67 years. Specimens of exfoliated epithelial cells were collected from patients subjected to panoramic radiography before and 10 days after radiation exposure. The cells were stained with Giemsa and evaluated for micronuclei by scoring 1000 cells per slide. Results: In our study, the genotoxic effect of radiation exposure from panoramic radiography showed a statistically significant increase in the MN frequency in buccal epithelial cells. A significant correlation was observed between the age of the subjects and micronuclei, although no such correlation was found between gender and micronuclei count. Conclusion: MN test serves as a simple biomarker indicating the direct exposure to DNA damaging agents such as ionizing radiation, emphasizing great sensitivity even for exposure to low doses during radiation screening. Thus, panoramic dental radiography should be cautiously used only when necessary. PMID:24910676

  9. IS GENOTOXICITY A POTENTIAL MODE OF ACTION FOR THE CARCINOGENICITY OF BROMATE

    EPA Science Inventory

    The EPA Office of Drinking Water is currently performing a risk assessment analysis of bromate, an ozonation disinfection by-product. Possible exposure to chlorination disinfection by-products in finished drinking water has heightened concern for public health safety. As a conseq...

  10. An Evaluation of the Mode of Action Framework for MutagenicCarcinogens Case Study II: Chromium (VI).

    EPA Science Inventory

    In response to the 2005 revised U.S Environmental Protection Agency’s (EPA) Cancer Guidelines, a strategy is being developed to include all mutagenicity and other genotoxicity data with any additional information to determine whether a carcinogen operates through a mutagenic mode...

  11. Genotoxicity studies in semiconductor industry. 1. In vitro mutagenicity and genotoxicity studies of waste samples resulting from plasma etching

    SciTech Connect

    Braun, R.; Huettner, E.M.; Merten, H.; Raabe, F. )

    1993-07-01

    Solid waste samples taken from the etching reactor, the turbo pump, and the waste air system of a plasma etching technology line in semiconductor production were studied as to their genotoxic properties in a bacterial repair test, in the Ames/Salmonella microsome assay, in the SOS chromotest, in primary mouse hepatocytes, and in Chinese hamster V79 cell cultures. All three waste samples were found to be active by inducing of unscheduled DNA-synthesis in mouse hepatocytes in vitro. In the bacterial rec-type repair test with Proteus mirabilis, waste samples taken from the turbo pump and the vacuum pipe system were not genotoxic. The waste sample taken from the chlorine-mediated plasma reactor was clearly positive in the bacterial repair assay and in the SOS chromotest with Escherichia coli. Mutagenic activity was demonstrated for all samples in the presence and absence of S9 mix made from mouse liver homogenate. Again, highest mutagenic activity was recorded for the waste sample taken from the plasma reactor, while samples collected from the turbo pump and from the waste air system before dilution and liberation of the air were less mutagenic. For all samples chromosomal damage in V79 cells was not detected, indicating absence of clastogenic activity in vitro. Altogether, these results indicate generation of genotoxic and mutagenic products as a consequence of chlorine-mediated plasma etching in the microelectronics industry and the presence of genotoxins even in places distant from the plasma reactor. Occupational exposure can be expected both from the precipitated wastes and from chemicals reaching the environment with the air stream.

  12. Comparison of BES measurements of ion-scale turbulence with direct gyro-kinetic simulations of MAST L-mode plasmas

    NASA Astrophysics Data System (ADS)

    Field, A. R.; Dunai, D.; Ghim, Y.-c.; Hill, P.; McMillan, B.; Roach, C. M.; Saarelma, S.; Schekochihin, A. A.; Zoletnik, S.; the MAST Team

    2014-02-01

    Observations of ion-scale (kyρi ⩽ 1) density turbulence of relative amplitude ≳0.2% are available on the Mega Amp Spherical Tokamak (MAST) using a 2D (8 radial × 4 poloidal channel) imaging beam emission spectroscopy diagnostic. Spatial and temporal characteristics of this turbulence, i.e., amplitudes, correlation times, radial and perpendicular correlation lengths and apparent phase velocities of the density contours, are determined by means of correlation analysis. For a low-density, L-mode discharge with strong equilibrium flow shear exhibiting an internal transport barrier in the ion channel, the observed turbulence characteristics are compared with synthetic density turbulence data generated from global, non-linear, gyro-kinetic simulations using the particle-in-cell code NEMORB. This validation exercise highlights the need to include increasingly sophisticated physics, e.g., kinetic treatment of trapped electrons, equilibrium flow shear and collisions, to reproduce most of the characteristics of the observed turbulence. Even so, significant discrepancies remain: an underprediction by the simulations of the turbulence amplitude and heat flux at plasma periphery and the finding that the correlation times of the numerically simulated turbulence are typically two orders of magnitude longer than those measured in MAST. Comparison of these correlation times with various linear timescales suggests that, while the measured turbulence is strong and may be ‘critically balanced’, the simulated turbulence is weak.

  13. Direct analysis of un-derivatized asymmetric dimethylarginine (ADMA) and L-arginine from plasma using mixed-mode ion-exchange liquid chromatography-tandem mass spectrometry.

    PubMed

    Bishop, Michael J; Crow, Brian; Norton, Dean; Paliakov, Ekaterina; George, Joe; Bralley, J A

    2007-11-15

    A high-throughput analytical method was developed for the measurement of asymmetric dimethylarginine (ADMA) and L-arginine (ARG) from plasma using LC/MS/MS. The sample preparation was simple and only required microfiltration prior to analysis. ADMA and ARG were assayed using mixed-mode ion-exchange chromatography which allowed for the retention of the un-derivatized compounds. The need for chromatographic separation of ADMA from symmetric dimethylarginine (SDMA) was avoided by using an ADMA specific product ion. As a result, the analytical method only required a total run time of 2 min. The method was validated by linearity, with r2>or=0.995 for both compounds, and accuracy, with no more than 7% deviation from the theoretical value. The estimated limit of detection and limit of quantification were suitable for clinical evaluations. The mean values of plasma ADMA and ARG taken from healthy volunteers (n=15) were 0.66+/-0.12 and 87+/-35 microM, respectively; the mean molar ratio of ARG to ADMA was 142+/-81. PMID:17931984

  14. Direct comparison of full-wave and ray-tracing methods for a simple model of multi-dimensional mode conversion

    NASA Astrophysics Data System (ADS)

    Xiao, Y.; Richardson, A.; Tracy, E.

    2007-11-01

    Mode conversion can occur in a nonuniform plasma when two waves of different character are locally resonant. Jaun et al. have recently developed a numerical ray-tracing algorithm for realistic tokamak models that accounts for the ray splitting that occurs at conversions [1,2]. Here we present a comparison of ray-based and full-wave methods by considering a simple model consisting of a pair of coupled wave equations in two spatial dimensions. The two spatially-dependent wave speeds, c1(x,y) and c2(x,y) are distinct for almost all (x,y), and are equal only along a line where conversion occurs. We launch a WKB-type wave packet in channel 1. There is initially no excitation in channel 2. Absorbing boundary conditions are used to avoid reflections which would complicate the results. From the full-wave output, we compute the initial energy density as a function of position and consider its evolution along a family of rays which undergo conversion. These full-wave results are then compared to the ray-based predictions. [1] A.Jaun, E.Tracy and A.Kaufman, Plasma Phys. Control. Fusion 49, 43-67 (2007). [2] E.Tracy, A.Kaufman and A.Jaun, to appear in Phys. Plasmas.

  15. Genotoxicity testing with the somatic white-ivory system in the eye of Drosophila melanogaster.

    PubMed

    Würgler, F E; Kägi, A

    1991-05-01

    The white-ivory test in Drosophila melanogaster is designed to detect chemically induced reversions of the sex-linked, recessive unstable eye-color mutation white-ivory to the wild-type form. After exposure of larvae reversions are detectable as clones of red facets in the eye of newly enclosed adult flies. Tester strains containing a quadruplication of the white-ivory gene on the X-chromosome(s) were used. In a strain with males carrying 4 copies of the gene and females carrying 8 copies of the gene, spontaneous reversions occurred proportional to the gene copy number. In contrast to this, chemically induced reversions occurred only 1.36 times more frequently in females (carrying 8 copies of the gene) than in males (carrying 4 copies). Since chemicals inducing different lesions in DNA (bleomycin, cyclophosphamide, daunomycin, diethyl sulfate and 7,12-dimethylbenz[a]anthracene) did induce statistically significant frequencies of reversions the test appears to be capable of detecting a wide variety of genotoxic chemicals with different modes of action. The recombinogen strychnine did not induce reversions. PMID:1903508

  16. Mechanisms of Hg species induced toxicity in cultured human astrocytes: genotoxicity and DNA-damage response.

    PubMed

    Pieper, Imke; Wehe, Christoph A; Bornhorst, Julia; Ebert, Franziska; Leffers, Larissa; Holtkamp, Michael; Höseler, Pia; Weber, Till; Mangerich, Aswin; Bürkle, Alexander; Karst, Uwe; Schwerdtle, Tanja

    2014-03-01

    The toxicologically most relevant mercury (Hg) species for human exposure is methylmercury (MeHg). Thiomersal is a common preservative used in some vaccine formulations. The aim of this study is to get further mechanistic insight into the yet not fully understood neurotoxic modes of action of organic Hg species. Mercury species investigated include MeHgCl and thiomersal. Additionally HgCl2 was studied, since in the brain mercuric Hg can be formed by dealkylation of the organic species. As a cellular system astrocytes were used. In vivo astrocytes provide the environment necessary for neuronal function. In the present study, cytotoxic effects of the respective mercuricals increased with rising alkylation level and correlated with their cellular bioavailability. Further experiments revealed for all species at subcytotoxic concentrations no induction of DNA strand breaks, whereas all species massively increased H2O2-induced DNA strand breaks. This co-genotoxic effect is likely due to a disturbance of the cellular DNA damage response. Thus, at nanomolar, sub-cytotoxic concentrations, all three mercury species strongly disturbed poly(ADP-ribosyl)ation, a signalling reaction induced by DNA strand breaks. Interestingly, the molecular mechanism behind this inhibition seems to be different for the species. Since chronic PARP-1 inhibition is also discussed to sacrifice neurogenesis and learning abilities, further experiments on neurons and in vivo studies could be helpful to clarify whether the inhibition of poly(ADP-ribosyl)ation contributes to organic Hg induced neurotoxicity. PMID:24549367

  17. Antiproliferative and genotoxic effects of Mikania glomerata (Asteraceae).

    PubMed

    Dalla Nora, Gracieli; Pastori, Tamara; Laughinghouse, Haywood Dail; Do Canto-Dorow, Thais Scotti; Tedesco, Solange Bosio

    2010-12-01

    Mikania glomerata is a plant used in Brazilian traditional medicine, known as 'guaco'. It possesses anti-inflammatory properties and the aqueous extracts of its leaves are indicated for the treatment of diseases of the respiratory tract. This study aimed at evaluating the antiproliferative and genotoxic effect of Mikania glomerata leaf infusions on the cell cycle of onion. The material used was collected in the native environment from Rio Grande do Sul State, Brazil. Aqueous extracts through infusions were prepared in two concentrations: 4g/L (usual concentration) and 16g/L (4x more concentrated) of each of the populations. Two groups of four onion bulbs for each plant population were used plus a control group. The rootlets were fixed in ethanol-acetic acid (3:1), conserved in ethanol 70% and slides were prepared using the squashing technique colored with orcein 2%. The cells were observed and analyzed during cell cycle. Per group of bulbs, 2000 cells were analyzed, and the mean values of the cell number of each of the phases of the cell cycle were calculated, determining the mitotic index (MI). Statistic analyses of the data were carried out by the x2 ( p= 0.05) test. We conclude that M. glomerata presents both antiproliferative and genotoxic activity. PMID:21443139

  18. Genotoxicity and subchronic oral toxicity of L-ornithine monohydrochloride.

    PubMed

    Ishida, Shigeru; Sarada, Miko; Seki, Hiroshi; McGirr, Larry; Lau, Annette; Morishita, Koji

    2013-12-01

    L-Ornithine monohydrochloride was evaluated in two in vitro genotoxicity assays and a rat 90-day oral toxicity study. No evidence of genotoxicity was observed in the reverse bacterial mutation assay or the chromosome aberration test at doses of up to 5000 μg/plate or 1686 μg/mL, respectively, both in the presence and absence of metabolic activation. Rats were administered L-ornithine monohydrochloride at dietary concentrations of 0 (basal diet), 1.25%, 2.5%, or 5.0% for 90 days. No changes in body weight, food consumption, ophthalmoscopy, or hematology were observed. Transient increases in water intake and urinary volume, and a decrease in specific gravity were observed in males receiving 5.0% L-ornithine monohydrochloride; however, these were likely attributable to the central role of ornithine in the urea cycle and the consequent increase in urea production. A decrease in serum chloride concentration and an increase in urinary chloride excretion were observed; however, these were likely attributable to administration of the hydrochloride salt of ornithine and were not considered to be of any toxicological significance. No remarkable findings were noted at necropsy. Based on the results of the study, a no-observed-adverse effect level (NOAEL) of 3445 and 3986 mg/kg body weight/day was established for male and female rats. PMID:23994624

  19. Genotoxicity studies on the root extract of Polygala tenuifolia Willdenow.

    PubMed

    Shin, Ki Young; Won, Beom Young; Ha, Hyun Jee; Yun, Yeo Sang; Lee, Hyung Gun

    2015-04-01

    The root of Polygala tenuifolia Willdenow has been used for the treatment against insomnia, amnesia, depression, palpitations with anxiety, and memory improvement. However, there is no sufficient background information on toxicological evaluation of the root to given an assurance of safety for developing dietary supplements and functional foods. As part of a safety evaluation, the potential genotoxicity of the root extract of P. tenuifolia was evaluated using a standard battery of tests (bacterial reverse mutation assay, chromosomal aberrations assay, and mouse micronucleus assay). In a reverse mutation assay using four Salmonella typhimurium strains and Escherichia coli, the extract did not increase the number of revertant colonies in any tester strain with or without metabolic activation by S9 mix, and did not cause chromosomal aberration in short-period test with the S9 mix or in the continuous (24h) test. A bone marrow micronucleus test in ICR mice dosed by oral gavage at doses up to 2000 mg/kg/day showed no significant or dose dependent increase in the frequency of micronucleated polychromatic erythrocytes (PCE). These results indicate that ingesting the rot extract P. tenuifolia is not genotoxic at the proper dose. PMID:25666111

  20. A possible role for chromium(III) in genotoxicity.

    PubMed Central

    Snow, E T

    1991-01-01

    Chromium is found in the environment in two major forms: reduced CrIII and CrVI, or chromate. Chromate, the most biologically active species, is readily taken up by living cells and reduced intracellularly, via reactive intermediates, to stable CrIII species. CrIII, the most abundant form of chromium in the environment, does not readily cross cell membranes and is relatively inactive in vivo. However, intracellular CrIII can react slowly with both nucleic acids and proteins and can be genotoxic. We have investigated the genotoxicity of CrIII in vitro using a DNA replication assay and in vivo by CaCl2-mediated transfection of chromium-treated DNA into Escherichia coli. When DNA replication was measured on a CrIII-treated template using purified DNA polymerases (either bacterial or mammalian), both the rate of DNA replication and the amount of incorporation per polymerase binding event (processivity) were greatly increased relative to controls. When transfected into E. coli, CrIII-treated M13mp2 bacteriophage DNA showed a dose-dependent increase in mutation frequency. These results suggest that CrIII alters the interaction between the DNA template and the polymerase such that the binding strength of the DNA polymerase is increased and the fidelity of DNA replication is decreased. These interactions may contribute to the mutagenicity of chromium ions in vivo and suggest that CrIII can contribute to chromium-mediated carcinogenesis. Images FIGURE 3. PMID:1935855

  1. Genotoxic and cytotoxic study of Tecoma stans Bignoniaceae.

    PubMed

    Al-Azzawi, Amad M

    2012-01-15

    Tecoma stans (Bignoniaceae) is a central and south American tree used for the control of diabetes. This plant is cultivated in Iraq. The dried leaves were soaked in ethanol and water separately for 3 days then filtered and dried. The genotoxic potential of Tecoma stans was studied by in vivo and in vitro system. This study examined the genotoxic activity of aqueous and ethanolic extracts on bone marrow cells from BALB/c mice through evaluation of mitotic index and chromosomal aberrations and cytotoxic effect of the two extracts on Mouse Embryo Fibroblast (MEF) cell line. No alteration in the total number of chromosomal aberrations or the number of cells with chromosomal aberrations observed and percentage of mitotic index at the concentrations tested remained unchanged. The higher concentrations used of the plant extracts had a cytotoxic effect on the MEF cell line. Both extracts had no significant clastogenic effect in vivo but showed cytotoxic effects on mouse embryo in vitro, caution should be exercised in the use of this substance as a medicine. PMID:22545362

  2. Silver nanospheres are cytotoxic and genotoxic to fish cells

    PubMed Central

    Wise, John Pierce; Goodale, Britton C.; Wise, Sandra S.; Craig, Gary A.; Pongan, Adam F.; Walter, Ronald B.; Thompson, W. Douglas; Ng, Ah-Kau; Aboueissa, AbouEl-Makarim; Mitani, Hiroshi; Spalding, Mark J.; Mason, Michael D.

    2015-01-01

    Nanoparticles are being widely investigated for a range of applications due to their unique physical properties. For example, silver nanoparticles are used in commercial products for their antibacterial and antifungal properties. Some of these products are likely to result in silver nanoparticles reaching the aquatic environment. As such, nanoparticles pose a health concern for humans and aquatic species. We used a medaka (Oryzias latipes) cell line to investigate the cytotoxicity and genotoxicity of 30 nm diameter silver nanospheres. Treatments of 0.05, 0.3, 0.5, 3 and 5 μg/cm2 induced 80, 45.7, 24.3, 1 and 0.1% survival, respectively, in a colony forming assay. Silver nanoparticles also induced chromosomal aberrations and aneuploidy. Treatments of 0, 0.05, 0.1 and 0.3 μg/cm2 induced damage in 8, 10.8, 16 and 15.8% of metaphases and 10.8, 15.6, 24 and 24 total aberrations in 100 metaphases, respectively. These data show that silver nanoparticles are cytotoxic and genotoxic to fish cells. PMID:20060603

  3. Genotoxicity Assessment of Erythritol by Using Short-term Assay

    PubMed Central

    Chung, Young-Shin

    2013-01-01

    Erythritol is a sugar alcohol that is widely used as a natural sugar substitute. Thus, the safety of its usage is very important. In the present study, short-term genotoxicity assays were conducted to evaluate the potential genotoxic effects of erythritol. According to the OECD test guidelines, the maximum test dose was 5,000 μg/plate in bacterial reverse mutation tests, 5,000 μg/ml in cell-based assays, and 5,000 mg/kg for in vivo testing. An Ames test did not reveal any positive results. No clastogenicity was observed in a chromosomal aberration test with CHL cells or an in vitro micronucleus test with L5178Y tk+/− cells. Erythritol induced a marginal increase of DNA damage at two high doses by 24 hr of exposure in a comet assay using L5178Y tk+/− cells. Additionally, in vivo micronucleus tests clearly demonstrated that oral administration of erythritol did not induce micronuclei formation of the bone marrow cells of male ICR mice. Taken together, our results indicate that erythritol is not mutagenic to bacterial cells and does not cause chromosomal damage in mammalian cells either in vitro or in vivo. PMID:24578795

  4. Genotoxicity Study of Polysaccharide Fraction from Astragalus membranaceus's Aerial Parts

    PubMed Central

    Park, Yeong-Chul; Kim, Min Hee; Kim, Jung Woo; Kim, Jong-Bong; Lee, Jae Geun; Yu, Chang Yeon; Kim, Seung-Hyun; Chung, Ill Min; Kim, Jae Kwang; Choi, Ri Na

    2014-01-01

    Radix Astragali, the root of Astragalus (A.) membranaceus, has been applied in a variety of diseases for a long time in Asian countries such as Korea and China. In addition, the aerial parts such as leaves and stems of A. membranaceus have received a great deal of attention. Recently, the polysaccharide fraction showing a potent immunomoduating activity was isolated from the aerial parts of A. membranaceus. Thus, the aerial parts of A. membranaceus would be worthy enough for a food material and a dietary supplement. However, they should be safe even though valuable. In our previous study, it was estimated that NOAEL for female rats are 5000 mg/kg/day of the crude polysaccharide fraction from A. membranaceus-aboveground parts. As a series of safety evaluation, genotoxicity test for the crude polysaccharide fraction was carried out in this study. In conclusion, the three genotoxicity assays provided strong overall support that the crude polysaccharide fraction lacks mutagenic and/or clastogenic potential under the GLP-based test conditions. This indicates the aerial parts of A. membranaceus would be safe enough for a food material and a dietary supplement. PMID:25071923

  5. Genotoxicity of copper oxide nanoparticles in Drosophila melanogaster.

    PubMed

    Carmona, Erico R; Inostroza-Blancheteau, Claudio; Obando, Veroska; Rubio, Laura; Marcos, Ricard

    2015-09-01

    Copper oxide nanoparticles (CuONPs) are used as semiconductors, catalysts, gas sensors, and antimicrobial agents. We have used the comet and wing-spot assays in Drosophila melanogaster to assess the genotoxicity of CuONPs and ionic copper (CuSO4). Lipid peroxidation analysis was also performed (Thiobarbituric Acid Assay, TBARS). In larval hemocytes, both CuONPs and CuSO4 caused significant dose-dependent increases in DNA damage (comet assay). In the wing-spot assay, an increase in the frequency of mutant spots was observed in the wings of the adults; CuONPs were more effective than was CuSO4. Both agents induced TBARS; again, CuONPs were more active than was CuSO4. The results indicate that CuONPs are genotoxic in Drosophila, and these effects may be mediated by oxidative stress. Most of the effects appear to be related to the presence of copper ions. PMID:26338537

  6. The genotoxic and teratogenic effects of maltitol in rats.

    PubMed

    Canimoglu, Semir; Rencuzogullari, Eyyup

    2013-11-01

    In the present study, the genotoxic and cytotoxic effects of the low-caloric artificial sweetener maltitol, which is a sugar alcohol (polyol), were investigated in the bone marrow cells of rats using the chromosome aberration (CA) test. In addition, the teratogenicity and embryotoxicity of maltitol was also investigated in rats. To reveal the genotoxicity and cytotoxicity of maltitol, rats were intraperitoneally administered 2.5, 5 and 10 g/kg body weight (bw) concentrations of maltitol for 6, 12 and 24 h treatment period. The pregnant females were intraperitoneally treated with 1, 2 and 4 g/kg bw/day concentrations of maltitol during the first 7 days of gestation (first trimester) to investigate the teratogenicity of maltitol. The embryos were collected after killing the dams by cervical dislocation under ether anaesthesia on gestation day 19. Maltitol did not induce the CA and did not decrease the mitotic index in bone marrow cells of rats at all concentrations and treatment periods. In addition, maltitol was not teratogenic; however, it decreased the foetuses weight and at the highest dose (4 g/kg bw) caused growth retardation. PMID:22585934

  7. Genotoxicity of Nicotiana tabacum leaves on Helix aspersa

    PubMed Central

    da Silva, Fernanda R.; Erdtmann, Bernardo; Dalpiaz, Tiago; Nunes, Emilene; Ferraz, Alexandre; Martins, Tales L.C.; Dias, Johny F.; da Rosa, Darlan P.; Porawskie, Marilene; Bona, Silvia; da Silva, Juliana

    2013-01-01

    Tobacco farmers are routinely exposed to complex mixtures of inorganic and organic chemicals present in tobacco leaves. In this study, we examined the genotoxicity of tobacco leaves in the snail Helix aspersa as a measure of the risk to human health. DNA damage was evaluated using the micronucleus test and the Comet assay and the concentration of cytochrome P450 enzymes was estimated. Two groups of snails were studied: one fed on tobacco leaves and one fed on lettuce (Lactuca sativa L) leaves (control group). All of the snails received leaves (tobacco and lettuce leaves were the only food provided) and water ad libitum. Hemolymph cells were collected after 0, 24, 48 and 72 h. The Comet assay and micronucleus test showed that exposure to tobacco leaves for different periods of time caused significant DNA damage. Inhibition of cytochrome P450 enzymes occurred only in the tobacco group. Chemical analysis indicated the presence of the alkaloid nicotine, coumarins, saponins, flavonoids and various metals. These results show that tobacco leaves are genotoxic in H. aspersa and inhibit cytochrome P450 activity, probably through the action of the complex chemical mixture present in the plant. PMID:23885210

  8. Genotoxicity evaluation of the flavonoid, myricitrin, and its aglycone, myricetin.

    PubMed

    Hobbs, Cheryl A; Swartz, Carol; Maronpot, Robert; Davis, Jeffrey; Recio, Leslie; Koyanagi, Mihoko; Hayashi, Shim-mo

    2015-09-01

    Myricitrin, a flavonoid extracted from the fruit, leaves, and bark of Chinese bayberry (Myrica rubra SIEBOLD), is currently used as a flavor modifier in snack foods, dairy products, and beverages in Japan. Myricitrin is converted to myricetin by intestinal microflora; myricetin also occurs ubiquitously in plants and is consumed in fruits, vegetables, and beverages. The genotoxic potential of myricitrin and myricetin was evaluated in anticipation of worldwide marketing of food products containing myricitrin. In a bacterial reverse mutation assay, myricetin tested positive for frameshift mutations under metabolic activation conditions whereas myricitrin tested negative for mutagenic potential. Both myricitrin and myricetin induced micronuclei formation in human TK6 lymphoblastoid cells under conditions lacking metabolic activation; however, the negative response observed in the presence of metabolic activation suggests that rat liver S9 homogenate may detoxify reactive metabolites of these chemicals in mammalian cells. In 3-day combined micronucleus/Comet assays using male and female B6C3F1 mice, no induction of micronuclei was observed in peripheral blood, or conclusive evidence of damage detected in the liver, glandular stomach, or duodenum following exposure to myricitrin or myricetin. Our studies did not reveal evidence of genotoxic potential of myricitrin in vivo, supporting its safe use in food and beverages. PMID:26142838

  9. Evaluation of environmental genotoxicity by comet assay in Columba livia.

    PubMed

    González-Acevedo, Anahi; García-Salas, Juan A; Gosálvez, Jaime; Fernández, José Luis; Dávila-Rodríguez, Martha I; Cerda-Flores, Ricardo M; Méndez-López, Luis F; Cortés-Gutiérrez, Elva I

    2016-01-01

    The concentrations of recognized or suspected genotoxic and carcinogenic agents found in the air of large cities and, in particular, developing countries, have raised concerns about the potential for chronic health effects in the populations exposed to them. The biomonitoring of environmental genotoxicity requires the selection of representative organisms as "sentinels," as well as the development of suitable and sensitive assays, such as those aimed at assessing DNA damage. The aim of this study was to evaluate DNA damage levels in erythrocytes from Columba livia living in the metropolitan area of Monterrey, Mexico, compared with control animals via comet assay, and to confirm the results via Micronuclei test (MN) and DNA breakage detection-fluorescence in situ hybridization (DBD-FISH). Our results showed a significant increase in DNA migration in animals from the area assayed compared with that observed in control animals sampled in non-contaminated areas. These results were confirmed by MN test and DBD-FISH. In conclusion, these observations confirm that the examination of erythrocytes from Columba livia via alkaline comet assay provides a sensitive and reliable end point for the detection of environmental genotoxicants. PMID:26608565

  10. Argentine folk medicine: genotoxic effects of Chenopodiaceae family.

    PubMed

    Gadano, A B; Gurni, A A; Carballo, M A

    2006-01-16

    Chenopodium ambrosioides L. and Chenopodium multifidum L. (Chenopodiaceae), common name: Paico, are medicinal plants. They are aromatic shrubs growing in South America. For centuries, they have been used due to its medicinal properties. However, there are few reports in literature about the genotoxic effects of these plants. There for, the aim of these work is the evaluation of genetic damage induced by decoction and infusion of this plants which were assayed in different concentrations (1, 10, 100, 1,000 microL extract/mL culture), by addition of the extract to human lymphocyte cell cultures, negative controls were included. The endpoints evaluated were chromosomal aberrations (CA), sister chromatid exchanges (SCE), cell proliferation kinetics (CPK) and mitotic index (MI). The repeated measure analysis of variance was used for statistic evaluation of the results. The results showed: (a) statistical increase in the percentage of cells with CA and in the frequency of SCE when cultures were exposed to both aromatic plants, (b) a decrease in MI of both Paicos assayed, although no modification in the CPK values was observed, (c) no effect was noticed in the analysis of Chenopodium album L., which was used as negative control of the essential oil. These results suggest a cyto and genotoxic effect of Chenopodium ambrosioides and Chenopodium multifidum aqueous extracts related to the essential oil of the plant (as Chenopodium album did not perform). PMID:16219440

  11. Genotoxicity monitoring of freshwater environments using caged carp (Cyprinus carpio).

    PubMed

    Klobucar, Göran I V; Stambuk, Anamaria; Pavlica, Mirjana; Sertić Perić, Mirela; Kutuzović Hackenberger, Branimir; Hylland, Ketil

    2010-01-01

    The present study deals with genotoxicity assessment of freshwaters using caged carp (Cyprinus carpio). Carps were transplanted from a fish-farm to three differently polluted sites in eastern Croatia. Two polluted sites were situated in the river Drava, downstream from the cities of Belisće and Osijek, while the reference site was in the Nature Park Kopacki rit, a preserved wetland area with limited anthropogenic influence. Exposure lasted for 3 weeks and was repeated for 3 years (2002-2004). DNA damage was assessed in erythrocytes of the exposed animals by the Comet assay and micronucleus test (MNT). In order to evaluate possible differences in stress responses to polluted water in situ and in aquaria a laboratory exposure was performed with water from the studied location in the second year of the study. Carp from the sites with high anthropogenic influence (Belisće and Osijek) had higher average DNA damage as expressed in both the MNT and Comet assay. Of the two, the Comet assay appeared to be more sensitive following both caging and aquaria exposures. The results from this study suggest that 3 weeks caging exposure of C. carpio may be a useful strategy to monitor for genotoxic agents in freshwater ecosystems. PMID:19626438

  12. Genotoxicity evaluation of environmental pollutants using analysis of nucleolar alterations.

    PubMed

    Mazzeo, Dânia Elisa Christofoletti; Marin-Morales, Maria Aparecida

    2015-07-01

    Nucleolar alterations resulting from the action of either chemical or physical agents can serve as important genotoxicity biomarkers. In this study, the efficiency of AgNOR banding technique to identify the presence of nucleoli in micronucleus and assess nucleolar alterations in aberrant cells of Allium cepa was evaluated. Seeds of this plant were exposed to both water samples from a river that receives untreated urban effluent and to the trifluralin herbicide (0.84 mg/L concentration), both analyzed in two different seasons (summer and winter seasons). Samples induced significant frequencies of chromosomal and nuclear aberrations and micronuclei, as observed in cells submitted to conventional chromosomal staining. The herbicide caused a significant increase in the number of nucleoli and micronuclei, interpreted as due to the elimination of excessive nucleolar material resulting from polyploidization. The use of the AgNOR technique enabled the identification of both the presence of the nucleolus in some micronuclei and the nucleolar organizer region (NOR) behavior of aberrant cells. The NOR-banding technique showed to be an efficient tool for studying the genotoxic effects caused by a xenobiotics and a complex environmental sample. PMID:25639248

  13. Genotoxic evaluation of pirfenidone using erythrocyte rodent micronucleus assay.

    PubMed

    Alcántar-Díaz, Blanca E; Gómez-Meda, Belinda C; Zúñiga-González, Guillermo M; Zamora-Perez, Ana L; González-Cuevas, Jaime; Alvarez-Rodríguez, Bertha A; Sánchez-Parada, María Guadalupe; García-Bañuelos, Jesús J; Armendáriz-Borunda, Juan

    2012-08-01

    Pirfenidone is a non-steroidal antifibrotic compound that has been proposed in clinical protocols and experimental studies as a pharmacological treatment for fibroproliferative diseases. The objective of this study was to determine the genotoxicity or cytotoxicity of three doses of pirfenidone using the micronuclei test in peripheral blood erythrocytes of rodent models. Pirfenidone was administered orally to Balb-C mice for 3 days, and also was administered topically to hairless Sprague Dawley rats during the final stage of gestation. Mice were sampled every 24 h over the course of 6 days; pregnant rats were sampled every 24 h during the last 6 days of gestation, and pups were sampled at birth. Blood smears were analyzed and the frequencies of micronucleated erythrocytes (MNEs), micronucleated polychromatic erythrocytes (MNPCEs), and the proportion of polychromatic erythrocytes (PCEs), were recorded in samples from mice, pregnant rats and rat neonates. Increases in MN frequencies (p<0.03) were noted only in the positive control groups. No genotoxic effects or decreased PCE values were observed neither in newborn rats transplacentally exposed to pirfenidone, or in two adult rodent models when pirfenidone was administered orally or topically. PMID:22683486

  14. Histopathological and genotoxic effects of chlorpyrifos in rats.

    PubMed

    Ezzi, Lobna; Belhadj Salah, Imen; Haouas, Zohra; Sakly, Amina; Grissa, Intissar; Chakroun, Sana; Kerkeni, Emna; Hassine, Mohsen; Mehdi, Meriem; Ben Cheikh, Hassen

    2016-03-01

    This study aims to investigate the effects of chlorpyrifos's sub-acute exposure on male rats. Two groups with six animals each were orally treated, respectively, with 3.1 mg/kg b w and 6.2 mg/kg b w of chlorpyrifos during 4 weeks. The genotoxic effect of chlopyrifos was investigated using the comet assay and the micronucleus test. Some hematological and liver's histopathological changes were also evaluated. Results revealed that chlorpyrifos induced histopathological alterations in liver parenchyma. The lymphoid infiltration observed in liver sections and the increase in white blood cells parameter are signs of inflammation. A significant increase in the platelet' count and in polychromatic erythrocytes/normochromatic erythrocytes (PCE/NCE) ratio was observed in chlorpyrifos-treated groups which could be due to the stimulatory effect of chlorpyrifos on cell formation in the bone marrow at lower doses. In addition, the increase of bone marrow micronucleus percentage and the comet tail length revealed a genotoxic potential of chlorpyrifos in vivo. PMID:26545888

  15. Antioxidant, genotoxic and antigenotoxic activities of daphne gnidium leaf extracts

    PubMed Central

    2012-01-01

    Background Plants play a significant role in maintaining human health and improving the quality of human life. They serve humans well as valuable components of food, as well as in cosmetics, dyes, and medicines. In fact, many plant extracts prepared from plants have been shown to exert biological activity in vitro and in vivo. The present study explored antioxidant and antigenotoxic effects of Daphne gnidium leaf extracts. Methods The genotoxic potential of petroleum ether, chloroform, ethyl acetate, methanol and total oligomer flavonoid (TOF) enriched extracts from leaves of Daphne gnidium, was assessed using Escherichia coli PQ37. Likewise, the antigenotoxicity of the same extracts was tested using the “SOS chromotest test”. Antioxidant activities were studied using non enzymatic and enzymatic method: NBT/Riboflavine and xantine oxidase. Results None of the different extracts produced a genotoxic effect, except TOF extract at the lowest tested dose. Our results showed that D. gnidium leaf extracts possess an antigenotoxic effect against the nitrofurantoin a mutagen of reference. Ethyl acetate and TOF extracts were the most effective in inhibiting xanthine oxidase activity. While, methanol extract was the most potent superoxide scavenger when tested with the NBT/Riboflavine assay. Conclusions The present study has demonstrated that D. gnidium leaf extract possess antioxidant and antigenotoxic effects. These activities could be ascribed to compounds like polyphenols and flavonoid. Further studies are required to isolate the active molecules. PMID:22974481

  16. Review of genotoxicity and rat carcinogenicity investigations with astaxanthin.

    PubMed

    Edwards, James A; Bellion, Phillip; Beilstein, Paul; Rümbeli, Robert; Schierle, Joseph

    2016-03-01

    Synthetic astaxanthin has been extensively tested for safety. Genotoxicity studies including Ames and in vitro Micronucleus Tests show absence of genotoxic potential. Although a long-term mouse study showed no carcinogenicity potential, the rat carcinogenicity study with dietary dosages of 0 (control), 0 (placebo beadlet), 40, 200 and 1000 mg astaxanthin/kg bw/day showed an increased incidence of benign, hepatocellular adenoma in females only, at 200 mg/kg bw/day and above. There was no clear evidence of toxicity during the in-life phase. Discoloration of feces was observed and a reduction in body weight gain in all groups receiving beadlets, probably reflecting a nutritional influence. Blood sampling confirmed systemic exposure and some minor clinical chemistry differences in females at 200 and 1000 mg/kg bw/day. There was no effect on adjusted liver weight. Histopathological examination showed hepatic changes indicative of slight hepatotoxicity and hepatocyte regeneration in females at 200 and 1000 mg/kg bw/day, in addition to the adenoma. Taking into account this pathological background in the female rat, and a wide variety of other supporting information, it is concluded that the hepatocellular adenoma in female rats was secondary to hepatotoxicity and regeneration, and is most probably a species-specific phenomenon of doubtful human relevance. PMID:26713891

  17. Broccoli seed extract: Genotoxicity and subchronic toxicity studies.

    PubMed

    Zhou, Yu; Yang, Hui; Li, Yongning; Lynch, B; Jia, Xudong

    2015-10-01

    Potential health benefits have been attributed to broccoli consumption. Hence, there is potential for use of broccoli seed extract (BSE) in food or for use as a dietary supplement. To assess the potential safety of a BSE product, three genotoxicity experiments, including an Ames, in vivo mouse micronucleus, and in vivo mouse sperm abnormality assay, were carried out. BSE was subject to an acute oral toxicity test and was evaluated in a 30-day feeding study in rats. BSE showed no mutagenic activity in the Ames assay and no evidence of genotoxic potential in the in vivo assays at doses up to 10 g/kg body weight (bw). The LD50 of BSE in rats was >10 g/kg bw/d. In the 30-day feeding study, in which BSE was administered in the diet to provide doses of 0, 0.3, 1.0, or 3.0 g/kg bw/d, no toxicological significant effects were noted on body weight, body weight gain, organ weights, or on the results of hematological, clinical chemistry and histopathological evaluations. The no-observed-adverse-effect level was considered to be 3.0 g/kg bw/d, the highest dose tested. Collectively, these results support the safe use of BSE as a food ingredient or product. PMID:26271574

  18. Measurement of the Branching Fraction And Search for Direct CP-Violation in the B+- --> J/Psi Pi+- Decay Mode at BaBar

    SciTech Connect

    Fobozzi, Francesco; /Naples U.

    2006-08-22

    } level. Besides the primary goal of CP-violation studies, the high luminosity of PEP-II, coupled with the high acceptance of the BABAR detector, allows competitive studies of the properties of a wide set of B decay modes. In particular, measurements of non-leptonic decays are extremely useful to understand the dynamics of the non-perturbative strong interactions involved in these processes. In this thesis a study of the non-leptonic decay mode B{sup {+-}} {yields} J/{psi}{pi}{sup {+-}} is presented.

  19. Studies of genotoxicity and mutagenicity of nitroimidazoles: demystifying this critical relationship with the nitro group.

    PubMed

    Boechat, Núbia; Carvalho, Alcione S; Salomão, Kelly; Castro, Solange L de; Araujo-Lima, Carlos F; Mello, Francisco V C; Felzenszwalb, Israel; Aiub, Claudia A F; Conde, Taline Ramos; Zamith, Helena P S; Skupin, Rolf; Haufe, Günter

    2015-06-01

    Nitroimidazoles exhibit high microbicidal activity, but mutagenic, genotoxic and cytotoxic properties have been attributed to the presence of the nitro group. However, we synthesised nitroimidazoles with activity against the trypomastigotes of Trypanosoma cruzi, but that were not genotoxic. Herein, nitroimidazoles (11-19) bearing different substituent groups were investigated for their potential induction of genotoxicity (comet assay) and mutagenicity (Salmonella/Microsome assay) and the correlations of these effects with their trypanocidal effect and with megazol were investigated. The compounds were designed to analyse the role played by the position of the nitro group in the imidazole nucleus (C-4 or C-5) and the presence of oxidisable groups at N-1 as an anion receptor group and the role of a methyl group at C-2. Nitroimidazoles bearing NO2 at C-4 and CH3 at C-2 were not genotoxic compared to those bearing NO 2 at C-5. However, when there was a CH3 at C-2, the position of the NO2 group had no influence on the genotoxic activity. Fluorinated compounds exhibited higher genotoxicity regardless of the presence of CH3 at C-2 or NO2 at C-4 or C-5. However, in compounds 11 (2-CH3; 4-NO2; N-CH2OHCH2Cl) and 12 (2-CH3; 4-NO2; N-CH2OHCH2F), the fluorine atom had no influence on genotoxicity. This study contributes to the future search for new and safer prototypes and provide. PMID:26018452

  20. Long-term exposure of rabbits to imidaclorpid as quantified in blood induces genotoxic effect.

    PubMed

    Stivaktakis, Polychronis D; Kavvalakis, Matthaios P; Tzatzarakis, Manolis N; Alegakis, Athanasios K; Panagiotakis, Michael N; Fragkiadaki, Persefoni; Vakonaki, Elena; Ozcagli, Eren; Hayes, Wallace A; Rakitskii, Valerii N; Tsatsakis, Aristidis M

    2016-04-01

    The present in-vivo study focuses on the genotoxic effect of the neonicotinoid pesticide imidacloprid (IMI) in rabbits. The purpose of the study was to establish a possible relationship between exposure to the pesticide (dose and duration) and genotoxicity. Furthermore, an analytical method for the simultaneous determination of IMI and its major metabolite 6-chloronicotinic acid (6-ClNA) in blood was developed and validated. The isolation of the two analytes from blood was performed by liquid-liquid extraction with dichloromethane. Analysis was performed by Liquid Chromatography - Atmospheric Pressure Chemical Ionization - Mass Spectrometry (LC-APCI-MS). The method was applied on the determination of IMI and 6-ClNA in serum samples obtained from rabbits fed with the insecticide at two low doses. Furthermore, parameters of genotoxicity and cytotoxicity were evaluated by measuring binucleated cells with micronuclei (BNMN), micronuclei (MN) and the Cytokinesis Block Proliferation Index (CBPI), in lymphocytes of exposed rabbits. The results revealed a genotoxic effect of IMI for both exposed groups. There were statistically significant differences in the frequencies of BNMN and MN between control and exposed groups but there was no dose-dependence, neither time-dependence of the genotoxic effect for the administered doses. This is the first time that long term exposure to IMI in rabbits was studied for the determination of its genotoxic effect. The genotoxic effect of IMI as it is depicted by the current study is in accordance with previous studies. PMID:26855213

  1. Studies of genotoxicity and mutagenicity of nitroimidazoles: demystifying this critical relationship with the nitro group

    PubMed Central

    Boechat, Núbia; Carvalho, Alcione S; Salomão, Kelly; de Castro, Solange L; Araujo-Lima, Carlos F; Mello, Francisco VC; Felzenszwalb, Israel; Aiub, Claudia AF; Conde, Taline Ramos; Zamith, Helena PS; Skupin, Rolf; Haufe, Günter

    2015-01-01

    Nitroimidazoles exhibit high microbicidal activity, but mutagenic, genotoxic and cytotoxic properties have been attributed to the presence of the nitro group. However, we synthesised nitroimidazoles with activity against the trypomastigotes of Trypanosoma cruzi, but that were not genotoxic. Herein, nitroimidazoles (11-19) bearing different substituent groups were investigated for their potential induction of genotoxicity (comet assay) and mutagenicity (Salmonella/Microsome assay) and the correlations of these effects with their trypanocidal effect and with megazol were investigated. The compounds were designed to analyse the role played by the position of the nitro group in the imidazole nucleus (C-4 or C-5) and the presence of oxidisable groups at N-1 as an anion receptor group and the role of a methyl group at C-2. Nitroimidazoles bearing NO2 at C-4 and CH3 at C-2 were not genotoxic compared to those bearing NO2 at C-5. However, when there was a CH3 at C-2, the position of the NO2 group had no influence on the genotoxic activity. Fluorinated compounds exhibited higher genotoxicity regardless of the presence of CH3 at C-2 or NO2 at C-4 or C-5. However, in compounds 11 (2-CH3; 4-NO2; N-CH2OHCH2Cl) and 12 (2-CH3; 4-NO2; N-CH2OHCH2F), the fluorine atom had no influence on genotoxicity. This study contributes to the future search for new and safer prototypes and provide. PMID:26018452

  2. The genotoxicity study of garlic and pasipy herbal drops by peripheral blood micronucleus test.

    PubMed

    Kalantari, H; Larki, A; Latifi, S M

    2007-09-01

    The in vivo rodent micronucleus test is widely used as a genotoxic assay to detect the clastogenic activity of chemicals. In this research the genotoxic effects of herbal drops of garlic and pasipy were evaluated using the micronucleus test. Maximum Tolerated Dose (MTD) was determined by a dose-response test. For each medicine three treatment groups were considered with doses of MTD, 1/2 MTD and 1/4 MTD according to the CSGMT protocol (1995 Japan). Drugs were administered orally to mice (test groups). Mitomicin C was used as a known genotoxic agent in positive control group. The peripheral blood samples before treatment (zero time samples) were considered as negative control. The appearance of a micronucleus is used as an index for genotoxic potential. The results obtained indicated that the herbal drops showed genotoxicity effect and it was dose-dependent compared to the negative control group. This genotoxicity was significant (p < 0.05) but the genotoxic effects of garlic and pasipy were "not significant" compared to the historical negative control group (p > 0.05). Therefore our results if compared to the negative control group is significant and it is worthy of consideration. PMID:17853777

  3. Mode of inhibition of HIV-1 reverse transcriptase by polyacetylenetriol, a novel inhibitor of RNA- and DNA-directed DNA polymerases.

    PubMed Central

    Loya, Shoshana; Rudi, Amira; Kashman, Yoel; Hizi, Amnon

    2002-01-01

    Polyacetylenetriol (PAT), a natural marine product from the Mediterranean sea sponge Petrosia sp., was found to be a novel general potent inhibitor of DNA polymerases. It inhibits equally well the RNA- and DNA-dependent DNA polymerase activities of retroviral reverse transcriptases (RTs) (i.e. of HIV, murine leukaemia virus and mouse mammary tumour virus) as well as cellular DNA polymerases (i.e. DNA polymerases alpha and beta and Escherichia coli polymerase I). A study of the mode and mechanism of the polymerase inhibition by PAT has been conducted with HIV-1 RT. PAT was shown to be a reversible non-competitive inhibitor. PAT binds RT independently and at a site different from that of the primer-template and dNTP substrates with high affinity (K(i)=0.51 microM and K(i)=0.53 microM with dTTP and with dGTP as the variable substrates respectively). Blocking the polar hydroxy groups of PAT has only a marginal effect on the inhibitory capacity, thus hydrophobic interactions are likely to play a major role in inhibiting RT. Preincubation of RT with the primer-template substrate prior to the interaction with PAT reduces substantially the inhibition capacity, probably by preventing these contacts. PAT does not interfere with the first step of polymerization, the binding of RT to DNA, nor does the inhibitor interfere with the binding of dNTP to RT/DNA complex, as evident from the steady-state kinetic study, whereby K(m) remains unchanged. We assume, therefore, that PAT interferes with subsequent catalytic steps of DNA polymerization. The inhibitor may alter the optimal stereochemistry of the polymerase active site relative to the primer terminus, bound dNTP and the metal ions that are crucial for efficient catalysis or, alternatively, may interfere with the thumb sub-domain movement and, thus, with the translocation of the primer-template following nucleotide incorporation. PMID:11879196

  4. Cytotoxicity, genotoxicity, and mutagenicity of 1-chloro-2-hydroxy-3-butene and 1-chloro-3-buten-2-one, two alternative metabolites of 1,3-butadiene

    SciTech Connect

    Liu, Xin-Jie; Zeng, Fang-Mao; An, Jing; Yu, Ying-Xin; Zhang, Xin-Yu; Elfarra, Adnan A.

    2013-08-15

    The cytotoxicity, genotoxicity, and mutagenicity of 1-chloro-2-hydroxy-3-butene (CHB), a known in vitro metabolite of the human carcinogen 1,3-butadiene, have not previously been investigated. Because CHB can be bioactivated by alcohol dehydrogenases to yield 1-chloro-3-buten-2-one (CBO), a bifunctional alkylating agent that caused globin-chain cross-links in erythrocytes, in the present study we investigated the cytotoxic and genotoxic potential of CHB and CBO in human normal hepatocyte L02 cells using the MTT assay, the relative cloning efficiency assay and the comet assay. We also investigated the mutagenic potential of these compounds with the Ames test using Salmonella strains TA1535 and TA1537. The results provide clear evidence for CHB and CBO being both cytotoxic and genotoxic with CBO being approximately 100-fold more potent than CHB. Interestingly, CHB generated both single-strand breaks and alkali-labile sites on DNA, whereas CBO produced only alkali-labile sites. CHB did not directly result in DNA breaks, whereas CBO was capable of directly generating breaks on DNA. Interestingly, both compounds did not induce DNA cross-links as examined by the comet assay. The Ames test results showed that CHB induced point mutation but not frameshift mutation, whereas the toxic effects of CBO made it difficult to reliably assess the mutagenic potential of CBO in the two strains. Collectively, the results suggest that CHB and CBO may play a role in the mutagenicity and carcinogenicity of 1,3-butadiene. - Highlights: • 1-Chloro-2-hydroxy-3-butene (CHB) is cytotoxic and genotoxic in human liver cells. • The CHB metabolite, 1-chloro-3-buten-2-one (CBO) is ∼ 100-fold more toxic than CHB. • CHB and CBO cause DNA alkali-labile sites, but only CBO directly causes DNA breaks. • CHB is mutagenic in the Ames test, but CBO is too toxic in the assay. • The results suggest a role for CHB in 1,3-butadiene genotoxicity and mutagenicity.

  5. US Department of Energy - Office of FreedomCar and Vehicle Technologies and US Centers for Disease Control and Prevention - National Institute for Occupational Safety and Health Inter-Agency Agreement Research on "The Analysis of Genotoxic Activities of Exhaust Emissions from Mobile Natural Gas, Diesel, and Spark-Ignition Engines"

    SciTech Connect

    William E. Wallace

    2006-09-30

    The US Department of Energy-Office of Heavy Vehicle Technologies (now the DOE-Office of FreedomCar and Vehicle Technologies) signed an Interagency Agreement (IAA) with National Institute for Occupational Safety and Health (NIOSH), No.01-15 DOE, 9/4/01, for 'The analysis of genotoxic activities of exhaust emissions from mobile natural gas, diesel, and spark-ignition engines'; subsequently modified on 3/27/02 (DOE IAG No.01-15-02M1); subsequently modified 9/02/03 (IAA Mod No. 01-15-03M1), as 'The analysis of genotoxic activities of exhaust emissions from mobile internal combustion engines: identification of engine design and operational parameters controlling exhaust genotoxicity'. The DOE Award/Contract number was DE-AI26-01CH11089. The IAA ended 9/30/06. This is the final summary technical report of National Institute for Occupational Safety and Health research performed with the US Department of Energy-Office of FreedomCar and Vehicle Technologies under that IAA: (A) NIOSH participation was requested by the DOE to provide in vitro genotoxicity assays of the organic solvent extracts of exhaust emissions from a suite of in-use diesel or spark-ignition vehicles; (B) research also was directed to develop and apply genotoxicity assays to the particulate phase of diesel exhaust, exploiting the NIOSH finding of genotoxicity expression by diesel exhaust particulate matter dispersed into the primary components of the surfactant coating the surface of the deep lung; (C) from the surfactant-dispersed DPM genotoxicity findings, the need for direct collection of DPM aerosols into surfactant for bioassay was recognized, and design and developmental testing of such samplers was initiated.

  6. New investigations into the genotoxicity of cobalt compounds and their impact on overall assessment of genotoxic risk.

    PubMed

    Kirkland, David; Brock, Tom; Haddouk, Hasnaà; Hargeaves, Victoria; Lloyd, Melvyn; Mc Garry, Sarah; Proudlock, Raymond; Sarlang, Séverine; Sewald, Katherina; Sire, Guillaume; Sokolowski, Andrea; Ziemann, Christina

    2015-10-01

    The genotoxicity of cobalt metal and cobalt compounds has been widely studied. Several publications show induction of chromosomal aberrations, micronuclei or DNA damage in mammalian cells in vitro in the absence of S9. Mixed results were seen in gene mutation studies in bacteria and mammalian cells in vitro, and in chromosomal aberration or micronucleus assays in vivo. To resolve these inconsistencies, new studies were performed with soluble and poorly soluble cobalt compounds according to OECD-recommended protocols. Induction of chromosomal damage was confirmed in vitro, but data suggest this may be due to oxidative stress. No biologically significant mutagenic responses were obtained in bacteria, Tk(+/-) or Hprt mutation tests. Negative results were also obtained for chromosomal aberrations (in bone marrow and spermatogonia) and micronuclei at maximum tolerated doses in vivo. Poorly soluble cobalt compounds do not appear to be genotoxic. Soluble compounds do induce some DNA and chromosomal damage in vitro, probably due to reactive oxygen. The absence of chromosome damage in robust GLP studies in vivo suggests that effective protective processes are sufficient to prevent oxidative DNA damage in whole mammals. Overall, there is no evidence of genetic toxicity with relevance for humans of cobalt substances and cobalt metal. PMID:26210821

  7. Medaka (Oryzias latipes) as a sentinel species for aquatic animals: Medaka cells exhibit a similar genotoxic response as North Atlantic right whale cells★

    PubMed Central

    Wise, John Pierce; Wise, Sandra S.; Goodale, Britton C.; Shaffiey, Fariba; Kraus, Scott; Walter, Ronald B.

    2015-01-01

    Hexavalent chromium (Cr(VI)) is emerging as a major concern for aquatic environments, particularly marine environments. Medaka (Oryzias latipes) has been used as a model species for human and aquatic health, including the marine environment, though few studies have directly compared toxicological responses in medaka to humans or other aquatic species. We used a medaka fin cell line to compare the genotoxic response of medaka to Cr(VI) to the response observed in North Atlantic right whale cells to see if responses in medaka were similar to those of other aquatic species, particularly aquatic mammals. We used the production of chromosomal aberrations as a measure of genotoxicity. We found that in medaka cells, concentrations of 1, 5 and 10 μM sodium chromate damaged 17, 32 and 43% of metaphases, respectively and these same concentrations 1, 2.5, 5 and 10 μM sodium chromate damaged 14, 24 and 49% of metaphases, respectively, in North Atlantic right whale lung cells and 11, 32 and 41% of metaphases, respectively, in North Atlantic right whale testes cells. These data show that genotoxic responses in medaka are comparable to those seen in North Atlantic right whale cells, consistent with the hypothesis that medaka are a useful model for other aquatic species. PMID:18930840

  8. Medaka (Oryzias latipes) as a sentinel species for aquatic animals: Medaka cells exhibit a similar genotoxic response as North Atlantic right whale cells.

    PubMed

    Wise, John Pierce; Wise, Sandra S; Goodale, Britton C; Shaffiey, Fariba; Kraus, Scott; Walter, Ronald B

    2009-03-01

    Hexavalent chromium (Cr(VI)) is emerging as a major concern for aquatic environments, particularly marine environments. Medaka (Oryzias latipes) has been used as a model species for human and aquatic health, including the marine environment, though few studies have directly compared toxicological responses in medaka to humans or other aquatic species. We used a medaka fin cell line to compare the genotoxic response of medaka to Cr(VI) to the response observed in North Atlantic right whale cells to see if responses in medaka were similar to those of other aquatic species, particularly aquatic mammals. We used the production of chromosomal aberrations as a measure of genotoxicity. We found that in medaka cells, concentrations of 1, 5 and 10 microM sodium chromate damaged 17, 32 and 43% of metaphases, respectively and these same concentrations 1, 2.5, 5 and 10 microM sodium chromate damaged 14, 24 and 49% of metaphases, respectively, in North Atlantic right whale lung cells and 11, 32 and 41% of metaphases, respectively, in North Atlantic right whale testes cells. These data show that genotoxic responses in medaka are comparable to those seen in North Atlantic right whale cells, consistent with the hypothesis that medaka are a useful model for other aquatic species. PMID:18930840

  9. Buthionine sulfoximine prevents the reduction of the genotoxic activity of maleic hydrazide by soil humic substances in Vicia faba seedlings.

    PubMed

    De Marco, A; De Simone, C; D'Ambrosio, C; Owczarek, M

    1999-01-13

    A significant reduction of the genotoxic effects caused by herbicide maleic hydrazide (MH) in Vicia faba seedlings was observed to be induced by a growth step in an organic soil as well as by a pretreatment with highly purified humic substances. In addition, such protective activity was resulted quite similar to that observed when the conditioning pretreatment was carried out with metal salts, so suggesting the involvement of the GSH biosynthesis in determining the protective activity observed. In agreement with this hypothesis, a previous exposure to buthionine sulfoximine (BSO), an inhibitor of the phytochelatins production, through the inhibition of GSH synthesis, prevented the reduction of the genotoxic activity of MH. The findings provide evidence for the involvement of the GSH biosynthesis pathway in determining the antigenotoxic activity revealed and suggest a possible involvement of the phytochelatins in this process. However, yet to be clarified is whether the stimulation of GSH production results as a consequence of a nonspecific influence on the protein synthesis by humic substances or of its direct activation due to the presence, as contaminants, of some heavy metals in both organic soil and humic acids extracts. PMID:10036330

  10. Genotoxicity investigation of araticum(Annona crassiflora Mart., 1841, Annonaceae) using SOS-Inductest and Ames test.

    PubMed

    Vilar, J B; Ferri, P H; Chen-Chen, L

    2011-02-01

    Although the use of medicinal plants or natural products has increased in recent decades all over the world, little information is available on their potential risk to health. Annona crassiflora Mart., a plant commonly known as araticum in Brazil, has been widely used in folk medicine for a long time since its seeds and leaves are often utilised in the treatment of cancer, snake bites, and venereal diseases, its fruits are consumed as tonic and astringent, and its bark powder has anti-fungal and anti-rheumatic properties. To evaluate the genotoxic and mutagenic properties induced by the ethanolic extract of araticum leaves, we performed the prophage λ induction (Inductest) and bacterial mutagenicity assays. We used Escherichia coli WP2s(λ) and RJF013 strains in the lysogenic induction test, whereas the mutagenic studies were carried out using Salmonella typhimurium histidine auxotroph strains TA97a, TA98, TA100, and TA102. Each experiment was performed three times in duplicate and included positive and negative controls. No statistically significant (p > 0.05) positive results were obtained for any of the strains tested, which suggests that the ethanolic extract of araticum leaves did not exhibit direct mechanisms of genotoxicity or mutagenicity that could be detected by the tests used in the present work. PMID:21437418

  11. Matrix deactivation: A general approach to improve stability of unstable and reactive pharmaceutical genotoxic impurities for trace analysis.

    PubMed

    Sun, Mingjiang; Bai, Lin; Terfloth, Gerald J; Liu, David Q; Kord, Alireza S

    2010-05-01

    Trace analysis of unstable and reactive pharmaceutical genotoxic impurities (GTIs) is a challenging task in pharmaceutical analysis. Many method issues such as insufficient sensitivity, poor precision, and unusual (too high/low) spiking recovery are often directly related to analytes' instability. We report herein a matrix deactivation approach that chemically stabilizes these analytes for analytical method development. In contrast to the conventional chemical derivatization approach where the analytes are transformed into stable detectable species, the matrix deactivation approach chemically deactivates the hypothetical reactive species in the sample matrix. The matrix deactivation approach was developed on the premise that the instability of certain analytes at trace level is caused by reactions between the analytes and low level reactive species in the sample matrix. Thus, quenching the reactivity of the reactive species would be a key to stabilizing the unstable and reactive analytes. For example, electrophilic alkylators could be destabilized by nucleophiles or bases through either nucleophilic substitution or elimination reactions. One way to mask those reactive species is via protonation by adding acids to the diluent. Alternatively, one can use nucleophile scavengers to deplete reactive unknown species in the sample matrix completely, in analogy to the use of antioxidants and metal chelators to prevent oxidation in the analysis of compounds liable to oxidation. This paper reports the application of the matrix deactivation to the analyses of unstable and reactive pharmaceutical genotoxic impurities. Some of the methods have been used to support development of manufacturing processes for drug substances and a recent regulatory filing. PMID:20036478

  12. Assessment of the genotoxic potential of Caramel Colour I in four short-term tests.

    PubMed

    Adams, K; Allen, J A; Brooker, P C; Jones, E; Proudlock, R J

    1992-05-01

    A battery of three short-term tests in vitro and one in vivo was used to determine the genotoxicity of Caramel Colour I. The results of the bacterial mutation assay, using five strains of Salmonella typhimurium, and the mouse micronucleus assay in vivo showed no evidence of genotoxic activity. Results from both the cytogenetics assay in vitro, using CHO cells, and the mouse lymphoma assay indicated that there was some genotoxic activity associated with Caramel Colour I but only in the absence of S-9 and at very high dose levels. PMID:1644381

  13. Acute toxicity and genotoxic activity of avocado seed extract (Persea americana Mill., c.v. Hass).

    PubMed

    Padilla-Camberos, Eduardo; Martínez-Velázquez, Moisés; Flores-Fernández, José Miguel; Villanueva-Rodríguez, Socorro

    2013-01-01

    The use of vegetal extracts requires toxicological and genotoxic evaluations to establish and verify safety before being added to human cosmetic, pharmaceutical medicine, or alimentary products. Persea americana seeds have been used in traditional medicine as treatment for several diseases. In this work, the ethanolic seed extract of Persea americana was evaluated with respect to its genotoxic potential through micronucleus assay in rodents. The frequency of micronuclei in groups of animals treated with avocado seed extract showed no differences compared to the negative control (vehicle); therefore, it is considered that the avocado seed extract showed no genotoxic activity in the micronucleus test. PMID:24298206

  14. 4-Aminoantipyrine reduces toxic and genotoxic effects of doxorubicin, cisplatin, and cyclophosphamide in male mice.

    PubMed

    Berno, Claudia Rodrigues; Rós, Barbara de Toledo; da Silveira, Ingridhy Ostaciana Maia Freitas; Coelho, Henrique Rodrigues; Antoniolli, Andréia Conceição Milan Brochado; Beatriz, Adilson; de Lima, Dênis Pires; Monreal, Antônio Carlos Duenhas; Sousa, Fabricio Garmus; da Silva Gomes, Roberto; Oliveira, Rodrigo Juliano

    2016-07-01

    The analgesic drug dipyrone is used to treat side effects (including pain and fever) of cancer chemotherapeutic agents. Dipyrone is metabolized to 4-aminoantipyrine (4-AA), a PGE2-dependent blocker and inhibitor of cyclooxygenase (COX). We evaluated the genotoxic, mutagenic, apoptotic, and immunomodulatory activities of 4-AA in vivo and the effects of its combination with the antineoplastic drugs doxorubicin, cisplatin, and cyclophosphamide. 4-AA did not cause genotoxic/mutagenic damage, splenic phagocytosis, or leukocyte alterations. However, when combined with the antineoplastic agents, 4-AA decreased their genotoxic, mutagenic, apoptotic, and phagocytic effects. These results suggest that 4-AA might interfere with DNA damage-mediated chemotherapy. PMID:27402479

  15. Acute Toxicity and Genotoxic Activity of Avocado Seed Extract (Persea americana Mill., c.v. Hass)

    PubMed Central

    Padilla-Camberos, Eduardo; Martínez-Velázquez, Moisés; Flores-Fernández, José Miguel; Villanueva-Rodríguez, Socorro

    2013-01-01

    The use of vegetal extracts requires toxicological and genotoxic evaluations to establish and verify safety before being added to human cosmetic, pharmaceutical medicine, or alimentary products. Persea americana seeds have been used in traditional medicine as treatment for several diseases. In this work, the ethanolic seed extract of Persea americana was evaluated with respect to its genotoxic potential through micronucleus assay in rodents. The frequency of micronuclei in groups of animals treated with avocado seed extract showed no differences compared to the negative control (vehicle); therefore, it is considered that the avocado seed extract showed no genotoxic activity in the micronucleus test. PMID:24298206

  16. Dietary modulation of the biotransformation and genotoxicity of aflatoxin B(1).

    PubMed

    Gross-Steinmeyer, Kerstin; Eaton, David L

    2012-09-28

    Diet and its various components are consistently identified as among the most important 'risk factors' for cancer worldwide, yet great uncertainty remains regarding the relative contribution of nutritive (e.g., vitamins, calories) vs. non-nutritive (e.g., phytochemicals, fiber, contaminants) factors in both cancer induction and cancer prevention. Among the most potent known human dietary carcinogens is the mycotoxin, aflatoxin B(1) (AFB). AFB and related aflatoxins are produced as secondary metabolites by the molds Aspergillus flavus and Aspergillus parasiticus that commonly infect poorly stored foods including peanuts, pistachios, corn, and rice. AFB is a potent hepatocarcinogenic agent in numerous animal species, and has been implicated in the etiology of human hepatocellular carcinoma. Recent research has shown that many diet-derived factors have great potential to influence AFB biotransformation, and some efficiently protect from AFB-induced genotoxicity. One key mode of action for reducing AFB-induced carcinogenesis in experimental animals was shown to be the induction of detoxification enzymes such as certain glutathione-S-transferases that are regulated through the Keap1-Nrf2-ARE signaling pathway. Although initial studies utilized the dithiolthione drug, oltipraz, as a prototypical inducer of antioxidant response, dietary components such as suforaphane (SFN) are also effective inducers of this pathway in rodent models. However, human GSTs in general do not appear to be extensively induced by SFN, and GSTM1 - the only human GST with measurable catalytic activity toward aflatoxin B(1)-8,9-epoxide (AFBO; the genotoxic metabolite of AFB), does not appear to be induced by SFN, at least in human hepatocytes, even though its expression in human liver cells does appear to offer considerable protection against AFB-DNA damage. Although induction of detoxification pathways has served as the primary mechanistic focus of chemoprevention studies, protective effects of

  17. Tunable asymmetric mode conversion using the dark-mode of three-mode waveguide system.

    PubMed

    Kim, Joonsoo; Lee, Seung-Yeol; Lee, Yohan; Kim, Hwi; Lee, Byoungho

    2014-11-17

    A design scheme for low-reflection asymmetric mode conversion structure in three-mode waveguide system is proposed. By using a dark-mode of three-mode system, which can be interpreted in terms of destructive interference of transition amplitudes, the transmission characteristics for forward and backward directions can be designed separately. After explanation of the proposed design scheme, we demonstrate an example of asymmetric mode converter that consists of two gratings. The proposed scheme may be useful for the design of tunable asymmetric transmission devices due to its design flexibility and efficient design process. PMID:25402109

  18. Direct analysis of highly oxidised organic aerosol constituents by on-line ion trap mass spectrometry in the negative-ion mode.

    PubMed

    Warscheid, Bettina; Hoffmann, Thorsten

    2002-01-01

    On-line ion trap mass spectrometry (ITMS) enables the characterisation of constituents of biogenic secondary organic aerosols in complex organic reaction mixtures. This real-time analysis is achieved by directly introducing the airborne particles into the ion source of the mass spectrometer. Negative-ion chemical ionisation at atmospheric pressure (APCI(-)) was used as the ionisation method of choice. The aerosols were generated from the gas-phase ozonolysis of two C10H16-terpenes (alpha-pinene and limonene), and investigated by performing on-line APCI(-)-ITMS(n). Highly oxidised compounds were tentatively identified as important particle-phase products. Based on recent investigations of low-energy collision-induced dissociation pathways of a wide range of deprotonated multifunctional carboxylic acid species derived from monoterpene precursors (Warscheid B, Hoffmann T. Rapid Commun. Mass Spectrom. 2001; 15: 2259), the formation of structurally different C10H16O5 and C10H16O6 species, such as acidic esters from alpha-pinene and aldo-hydroxycarboxylic acids from limonene, is proposed. PMID:11870886

  19. Sludge reduction by direct addition of chlorine dioxide into a sequencing batch reactor under operational mode of repeatedly alternating aeration/non-aeration.

    PubMed

    Peng, Hong; Liu, Weiyi; Li, Yuanmei; Xiao, Hong

    2015-01-01

    The effect of direct addition of chlorine dioxide (ClO2) into a repeatedly alternating aeration/non-aeration sequencing batch reactor (SBR) on its sludge reduction and process performance was investigated. The experimental results showed that the sludge reduction efficiency was 32.9% and the observed growth yield (Yobs) of SBR was 0.11 kg VSS (volatile suspended solids) /kg COD (chemical oxygen demand) for 80 days' operation at the optimum ClO2 dosage of 2.0 mg/g TSS (total suspended solids). It was speculated that cell lysis and cryptic growth, uncoupled metabolism and endogenous metabolism were jointly responsible for the sludge reduction in this study. COD, NH3-N, total nitrogen (TN) and total phosphorus (TP) in the effluent increased on average 29.47, 4.44, 1.97 and 0.05 mg/L, respectively. However, the effluent quality still satisfied the first-class B discharge standards for municipal wastewater treatment plants in China. In that case, the sludge maintained fine viability with the specific oxygen uptake rate (SOUR) being 14.47 mg O2/(g VSS·h) and demonstrated good settleability with the sludge volume index (SVI) being 116 mL/g. The extra cost of sludge reduction at the optimum ClO2 dosage was estimated to be 2.24 CNY (or 0.36 dollar)/kg dry sludge. PMID:26524444

  20. Down syndrome fibroblasts and mouse Prep1-overexpressing cells display increased sensitivity to genotoxic stress.

    PubMed

    Micali, Nicola; Longobardi, Elena; Iotti, Giorgio; Ferrai, Carmelo; Castagnaro, Laura; Ricciardi, Mario; Blasi, Francesco; Crippa, Massimo P

    2010-06-01

    PREP1 (PKNOX1) maps in the Down syndrome (DS) critical region of chromosome 21, is overexpressed in some DS tissues and might be involved in the DS phenotype. By using fibroblasts from DS patients and by overexpressing Prep1 in F9 teratocarcinoma and Prep1(i/i) MEF to single out the role of the protein, we report that excess Prep1 increases the sensitivity of cells to genotoxic stress and the extent of the apoptosis directly correlates with the level of Prep1. The apoptotic response of Prep1-overexpressing cells is mediated by the pro-apoptotic p53 protein that we show is a direct target of Prep1, as its depletion reverts the apoptotic phenotype. The induction of p53 overcomes the anti-apoptotic role of Bcl-X(L), previously shown to be also a Prep1 target, the levels of which are increased in Prep1-overexpressing cells as well. Our results provide a rationale for the involvement of PREP1 in the apoptotic phenotype of DS tissues and indicate that differences in Prep1 level can have drastic effects. PMID:20110257

  1. Down syndrome fibroblasts and mouse Prep1-overexpressing cells display increased sensitivity to genotoxic stress

    PubMed Central

    Micali, Nicola; Longobardi, Elena; Iotti, Giorgio; Ferrai, Carmelo; Castagnaro, Laura; Ricciardi, Mario; Blasi, Francesco; Crippa, Massimo P.

    2010-01-01

    PREP1 (PKNOX1) maps in the Down syndrome (DS) critical region of chromosome 21, is overexpressed in some DS tissues and might be involved in the DS phenotype. By using fibroblasts from DS patients and by overexpressing Prep1 in F9 teratocarcinoma and Prep1i/i MEF to single out the role of the protein, we report that excess Prep1 increases the sensitivity of cells to genotoxic stress and the extent of the apoptosis directly correlates with the level of Prep1. The apoptotic response of Prep1-overexpressing cells is mediated by the pro-apoptotic p53 protein that we show is a direct target of Prep1, as its depletion reverts the apoptotic phenotype. The induction of p53 overcomes the anti-apoptotic role of Bcl-XL, previously shown to be also a Prep1 target, the levels of which are increased in Prep1-overexpressing cells as well. Our results provide a rationale for the involvement of PREP1 in the apoptotic phenotype of DS tissues and indicate that differences in Prep1 level can have drastic effects. PMID:20110257

  2. Interplay between Smoking-induced Genotoxicity and Altered Signaling in Pancreatic Carcinogenesis

    PubMed Central

    Batra, Surinder K.

    2012-01-01

    Despite continuous research efforts directed at early diagnosis and treatment of pancreatic cancer (PC), the status of patients affected by this deadly malignancy remains dismal. Its notoriety with regard to lack of early diagnosis and resistance to the current chemotherapeutics is due to accumulating signaling abnormalities. Hoarding experimental and epidemiological evidences have established a direct correlation between cigarette smoking and PC risk. The cancer initiating/promoting nature of cigarette smoke can be attributed to its various constituents including nicotine, which is the major psychoactive component, and several other toxic constituents, such as nitrosamines, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, and polycyclic aromatic hydrocarbons. These predominant smoke-constituents initiate a series of oncogenic events facilitating epigenetic alterations, self-sufficiency in growth signals, evasion of apoptosis, sustained angiogenesis, and metastasis. A better understanding of the molecular mechanisms underpinning these events is crucial for the prevention and therapeutic intervention against PC. This review presents various interconnected signal transduction cascades, the smoking-mediated genotoxicity, and genetic polymorphisms influencing the susceptibility for smoking-mediated PC development by modulating pivotal biological aspects such as cell defense/tumor suppression, inflammation, DNA repair, as well as tobacco-carcinogen metabolization. Additionally, it provides a large perspective toward tumor biology and the therapeutic approaches against PC by targeting one or several steps of smoking-mediated signaling cascades. PMID:22623649

  3. Cytotoxicity and genotoxicity of nano - and microparticulate copper oxide: role of solubility and intracellular bioavailability

    PubMed Central

    2014-01-01

    Background Nano- or microscale copper oxide particles (CuO NP, CuO MP) are increasingly applied as catalysts or antimicrobial additives. This increases the risk of adverse health effects, since copper ions are cytotoxic under overload conditions. Methods The extra- and intracellular bioavailability of CuO NP and CuO MP were explored. In addition, different endpoints related to cytotoxicity as well as direct and indirect genotoxicity of the copper oxides and copper chloride (CuCl2) were compared. Results Comprehensively characterized CuO NP and CuO MP were analysed regarding their copper ion release in model fluids. In all media investigated, CuO NP released far more copper ions than CuO MP, with most pronounced dissolution in artificial lysosomal fluid. CuO NP and CuCl2 caused a pronounced and dose dependent decrease of colony forming ability (CFA) in A549 and HeLa S3 cells, whereas CuO MP exerted no cytotoxicity at concentrations up to 50 μg/mL. Cell death induced by CuO NP was at least in part due to apoptosis, as determined by subdiploid DNA as well as via translocation of the apoptosis inducing factor (AIF) into the cell nucleus. Similarly, only CuO NP induced significant amounts of DNA strand breaks in HeLa S3 cells, whereas all three compounds elevated the level of H2O2-induced DNA strand breaks. Finally, all copper compounds diminished the H2O2-induced poly(ADP-ribosyl)ation, catalysed predominantly by poly(ADP-ribose)polymerase-1 (PARP-1); here, again, CuO NP exerted the strongest effect. Copper derived from CuO NP, CuO MP and CuCl2 accumulated in the soluble cytoplasmic and nuclear fractions of A549 cells, yielding similar concentrations in the cytoplasm but highest concentrations in the nucleus in case of CuO NP. Conclusions The results support the high cytotoxicity of CuO NP and CuCl2 and the missing cytotoxicity of CuO MP under the conditions applied. For these differences in cytotoxicity, extracellular copper ion levels due to dissolution of

  4. Occupational exposure in airport personnel: characterization and evaluation of genotoxic and oxidative effects.

    PubMed

    Cavallo, Delia; Ursini, Cinzia Lucia; Carelli, Giovanni; Iavicoli, Ivo; Ciervo, Aureliano; Perniconi, Barbara; Rondinone, Bruna; Gismondi, Massimo; Iavicoli, Sergio

    2006-06-01

    Airport personnel can be exposed to several polycyclic aromatic hydrocarbons (PAHs) from jet fuel vapours, jet fuel combustion products and diesel exhaust. The aim of this study was to characterize the exposure and to evaluate genotoxic and oxidative effects in airport personnel (n=41) in comparison with a selected control group (n=31). Environmental monitoring of exposure was carried out analysing 23 PAHs on air samples collected from airport apron, airport building and terminal/office area during 5 working days. The urinary 1-hydroxy-pyrene (1-OHP) following 5 working days, was used as biomarker of exposure. Genotoxic effects and early direct-oxidative DNA damage were evaluated by micronucleus (MN) and Fpg-modified comet assay on lymphocytes and exfoliated buccal cells, and by chromosomal aberrations (CA) and sister chromatid exchange (SCE) analyses. For comet assay, tail moment (the product of comet relative tail intensity and length) values from Fpg-enzyme treated cells (TMenz) and from untreated cells (TM) were used as parameters of oxidative and direct DNA damage, respectively. We found 27,703 microg/m(3) total PAHs in airport apron, 17,275 microg/m(3) in airport building and 9,494 microg/m(3) in terminal/office area. Urinary OH-pyrene did not show differences between exposed and controls. The exposed group showed a higher mean value of SCE frequency in respect to controls (4.6 versus 3.8) and an increase (1.3-fold) of total structural CA in particular breaks (up to 2.0-fold) and fragments (0.32% versus 0.00%), whereas there were no differences of MN frequency in both cellular types. Comet assay evidenced in the exposed group a higher value in respect to controls of mean TM and TMenz in both exfoliated buccal cells (TM 118.87 versus 68.20, p=0.001; TMenz 146.11 versus 78.32, p<0.001) and lymphocytes (TM 43.01 versus 36.01, p=0.136; TMenz 55.86 versus 43.98, p=0.003). An oxidative DNA damage was found, for exfoliated buccal cells in the 9.7% and for

  5. Genotoxicity of 2-alkylcyclobutanones, markers for an irradiation treatment in fat-containing food—Part I: cyto- and genotoxic potential of 2-tetradecylcyclobutanone

    NASA Astrophysics Data System (ADS)

    Delincée, Henry; Soika, Christiane; Horvatovich, Péter; Rechkemmer, Gerhard; Marchioni, Eric

    2002-03-01

    Previous experiments had indicated a slight genotoxic potential both in rat and in human colon cells of a sample of 2-dodecylcyclobutanone, a compound formed by irradiation of food containing palmitic acid in its triglycerides. Up to date, there is no evidence that 2-alkylcyclobutanones occur in non-irradiated foodstuffs, consequently it is prudent to test several members of the class of 2-alkylcyclobutanones which are produced by treatment of fat-containing food with ionising radiation. In this work, 2-tetradecylcyclobutanone (derived from stearic acid) has been tested for its cytotoxic and genotoxic potential. Human colon tumor cell lines, i.e. HT 29 and HT 29 clone 19A, were employed as models for in vitro experiments for cytotoxicity and genotoxicity tests. Cytotoxicity was measured by tetrazolium salt reduction assays (MTT and WST-1) and genotoxicity by determining DNA damage using the Comet Assay. Neither cytotoxic nor genotoxic effects were induced by 2-TCB in HT 29 or HT 29 cl 19A cells at an incubation time of 30 min at 37°C, not even at the highest concentration (400 μM) tested. After prolonged incubation times (1-2 days) at higher concentrations (>50 μM) cytotoxicity did, however, appear. Studies on other 2-alkylcyclobutanones are in progress.

  6. Assessment of phenolic content, free-radical-scavenging capacity genotoxic and anti-genotoxic effect of aqueous extract prepared from Moricandia arvensis leaves.

    PubMed

    Skandrani, I; Limem, I; Neffati, A; Boubaker, J; Ben Sghaier, M; Bhouri, W; Bouhlel, I; Kilani, S; Ghedira, K; Chekir-Ghedira, L

    2010-02-01

    The present study was undertaken to provide a set of data on the safety of an aqueous extract (AQE) from Moricandia arvensis. For this reason, Escherichia coli tested strains PQ35 and PQ37 were used to detect induction of DNA lesions by AQE. The SOS Chromotest showed that AQE induced a marginally genotoxic effect, as expressed by the induction factor (IF) value only with E. coli PQ37 tested strain (IF=1.77 at a dose of 250 microg/assay). The measurement of the anti-genotoxic activity of the AQE was also studied by inhibition of beta-galactosidase induction. A significant anti-genotoxic effect was observed with different tested doses of AQE, which suggests that M. arvensis extract has the potential to protect DNA from the action of nitrofurantoïn (NF) and free radicals generated by hydrogen peroxide (H2O2). In addition to anti-genotoxic activity, AQE showed a free-radical-scavenging capacity towards ABTS+* and DPPH*. Total phenolic content was also evaluated following Folin-Ciocalteu method and results indicated high correlation between total phenol content and anti-genotoxic and antioxidant activities for AQE, but the highest correlation was showed with its capacity to stabilize ABTS+* (R2=0.9944). PMID:19951736

  7. Analysis of genotoxic potentiality of stevioside by comet assay.

    PubMed

    Nunes, A P M; Ferreira-Machado, S C; Nunes, R M; Dantas, F J S; De Mattos, J C P; Caldeira-de-Araújo, A

    2007-04-01

    Stevioside is a natural non-caloric sweetener extracted from Stevia rebaudiana (Bertoni) leaves. It has been widely used in many countries, including Japan, Korea, China, Brazil and Paraguay, either as a substitute for sucrose in beverages and foods or as a household sweetener. The aim of this work was to study its genotoxic potentiality in eukaryotic cells. Wistar rats were treated with stevioside solution (4mg/mL) through oral administration (ad libitum) and the DNA-induced damage was evaluated using the single cell gel electrophoresis (comet assay). The results showed that treatment with stevioside generates lesions in peripheral blood, liver, brain and spleen cells in different levels, the largest effect being in liver. Therefore, these undesired effects must be better understood, once the data present here point to possible stevioside mutagenic properties. PMID:17187912

  8. Tempol protects human lymphocytes from genotoxicity induced by cisplatin.

    PubMed

    Khabour, Omar F; Alzoubi, Karem H; Mfady, Doa'a S; Alasseiri, Mohammed; Hasheesh, Taghrid F

    2014-01-01

    The use of cisplatin in treatments of human malignancies is limited by its side effects that include DNA damage and the subsequent risk of developing secondary cancer. In this study, we examined the possible protective effect of Tempol against DNA damage induced by cisplatin in human lymphocytes using chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) assays. Cisplatin induced significant elevation in the frequencies of CAs and SCEs in cultured human lymphocytes (P < 0.01). Treatment of lymphocytes with Tempol significantly lowered CAs and SCEs induced by cisplatin. Tempol alone did not affect spontaneous levels of SCEs and CAs observed in the control group (P > 0.05). In conclusion, Tempol protects human lymphocytes against genotoxicity induced by the anticancer drug cisplatin. PMID:24955171

  9. Micronuclei in genotoxicity assessment: from genetics to epigenetics and beyond

    PubMed Central

    Luzhna, Lidiya; Kathiria, Palak; Kovalchuk, Olga

    2013-01-01

    Micronuclei (MN) are extra-nuclear bodies that contain damaged chromosome fragments and/or whole chromosomes that were not incorporated into the nucleus after cell division. MN can be induced by defects in the cell repair machinery and accumulation of DNA damages and chromosomal aberrations. A variety of genotoxic agents may induce MN formation leading to cell death, genomic instability, or cancer development. In this review, the genetic and epigenetic mechanisms of MN formation after various clastogenic and aneugenic effects on cell division and cell cycle are described. The knowledge accumulated in literature on cytotoxicity of various genotoxins is precisely reflected and individual sensitivity to MN formation due to single gene polymorphisms is discussed. The importance of rapid MN scoring with respect to the cytokinesis-block micronucleus assay is also evaluated. PMID:23874352

  10. Destruction of genotoxic wastes mixed with radioactive products

    SciTech Connect

    Simonnet, F.; Orts, J.C.; Simonnet, G. )

    1989-12-01

    Before their disposal, genotoxic substances are destroyed by strong oxidizing agents. If there are molecules labelled with radionuclides in the medium which is oxidized, then this treatment may bring about the release of gaseous radioactive compounds. We have looked for evidence of such a release following the action of K permanganate and sodium hypochlorite on molecules labelled with {sup 3}H, {sup 14}C, {sup 32}P, and {sup 125}I. Among the compounds examined, only those labelled with 14C showed significant quantities of radioactive gas released, with values up to 60% of the total radioactivity. For the other products, less than 0.6% of the radioactivity appeared in a volatile form.

  11. Solid-phase genotoxicity assay for organic compounds in soil

    SciTech Connect

    Alexander, R.R.; Chung, N.; Alexander, M.

    1999-03-01

    A genotoxicity assay was developed for samples from environments in which toxic organic compounds are largely sorbed. The assay entails measurement of the rate of mutation of a strain of Pseudomonas putida to rifampicin resistance. The ratio of induced to spontaneous mutants was a function of the concentration of a test mutagen in soil. In studies of the utility of the assay in samples amended with 2-aminofluorene as a test mutagen, the ratio of induced to spontaneous mutants declined with time. The decline paralleled the disappearance of extractable 2-aminofluorene from the soil. The ratio of induced to spontaneous mutants also feel in four other soils with dissimilar properties. The authors suggest that this solid-phase assay is more appropriate for the estimation of genotoxicants sorbed in soil than assays involving extractants or suspensions of soil or sediment samples.

  12. Genotoxic effects of cisplatin in somatic tissue of Drosophila melanogaster

    SciTech Connect

    Katz, A.J.

    1987-01-01

    Third instar larvae of Drosophila melanogaster transdihybrid for mwh and flr were exposed to varying concentrations of cisplatin by feeding on dry media wetted with aqueous solutions of the test compound. Larval feeding continued until pupation, and surviving transdihybrid adults were collected seven days following commencement of feeding. Wings of adults were removed and scored under 400X magnification for the presence of twin spots and single spots comprised of clones of cells possessing malformed wing hairs. Cisplatin was found to induce both twin spots and single spots, and significant linear concentration-response relationships were obtained with respect to the induction of all endpoints. This capacity to induce mitotic exchange in the somatic tissue of Drosophila compares well with the compound's reported ability to induce chromosome breaks in Drosophila germ cells. However, not all compounds possess similar genotoxic profiles in the somatic an germ tissue of Drosophila.

  13. Formation of glutathionyl dinitrosyl iron complexes protects against iron genotoxicity.

    PubMed

    Lewandowska, Hanna; Sadło, Jarosław; Męczyńska, Sylwia; Stępkowski, Tomasz M; Wójciuk, Grzegorz; Kruszewski, Marcin

    2015-07-28

    Dinitrosyl iron(i) complexes (DNICs), intracellular NO donors, are important factors in nitric oxide-dependent regulation of cellular metabolism and signal transduction. It has been shown that NO diminishes the toxicity of iron ions and vice versa. To gain insight into the possible role of DNIC in this phenomenon, we examined the effect of GS-DNIC formation on the ability of iron ions to mediate DNA damage, by treatment of the pUC19 plasmid with physiologically relevant concentrations of GS-DNIC. It was shown that GS-DNIC formation protects against the genotoxic effect of iron ions alone and iron ions in the presence of a naturally abundant antioxidant, GSH. This sheds new light on the iron-related protective effect of NO under the circumstances of oxidative stress. PMID:26079708

  14. Direct synthesis of nitrogen-doped graphene on platinum wire as a new fiber coating method for the solid-phase microextraction of BXes in water samples: Comparison of headspace and cold-fiber headspace modes.

    PubMed

    Memarian, Elham; Hosseiny Davarani, Saied Saeed; Nojavan, Saeed; Movahed, Siyavash Kazemi

    2016-09-01

    In this work, a new solid-phase microextraction fiber was prepared based on nitrogen-doped graphene (N-doped G). Moreover, a new strategy was proposed to solve problems dealt in direct coating of N-doped G. For this purpose, first, Graphene oxide (GO) was coated on Pt wire by electrophoretic deposition method. Then, chemical reduction of coated GO to N-doped G was accomplished by hydrazine and NH3. The prepared fiber showed good mechanical and thermal stabilities. The obtained fiber was used in two different modes (conventional headspace solid-phase microextraction and cold-fiber headspace solid-phase microextraction (CF-HS-SPME)). Both modes were optimized and applied for the extraction of benzene and xylenes from different aqueous samples. All effective parameters including extraction time, salt content, stirring rate, and desorption time were optimized. The optimized CF-HS-SPME combined with GC-FID showed good limit of detections (LODs) (0.3-2.3 μg/L), limit of quantifications (LOQs) (1.0-7.0 μg/L) and linear ranges (1.0-5000 μg/L). The developed method was applied for the analysis of benzene and xylenes in rainwater and some wastewater samples. PMID:27543024

  15. A new strategy to probe the genotoxicity of silver nanoparticles combined with cetylpyridine bromide.

    PubMed

    Chi, Zhenxing; Liu, Rutao; Zhao, Lingzi; Qin, Pengfei; Pan, Xingren; Sun, Feng; Hao, Xiaopeng

    2009-04-01

    The environmental genotoxic behavior of silver nanoparticles (nanoAg) combined with the detergent cetylpyridine bromide (CPB) was examined in vitro. The experimental results showed that the genotoxicity of nanoAg itself is weak, but nanoAg shows obvious genotoxicity after combined with CPB. The combined materials have a strong coeffect on calf thymus DNA (ctDNA) at a concentration of 3.3 x 10(-6 )gmL(-1) nanoAg and 6.0 x 10(-6) molL(-1) CPB. After the addition of ctDNA to the nanoAg-CPB system, the particles are scattered and the diameter decreases, which indirectly reveal that nanoAg-CPB has genotoxicity. PMID:19070536

  16. GENOTOXIC PROPERTIES OF HALOACETONITRILES: DRINKING WATER BY-PRODUCTS OF CHLORINE DISINFECTION

    EPA Science Inventory

    Chlorinated and brominated haloacetonitriles (HAN), known drinking water contaminants which form during chlorine disinfection, were investigated for genotoxic activity. The HAN produced DNA strand breaks in cultured human lymphoblastic (CCRF-CEM) cells, bound to the nucleophilic ...

  17. Detection of genotoxic, cytotoxic, and protective activities of Eugenia dysenterica DC. (Myrtaceae) in mice.

    PubMed

    Vieira, Pabline Marinho; Veronezi, Eduardo; Silva, Carolina R; Chen-Chen, Lee

    2012-06-01

    Eugenia dysenterica DC. (Myrtaceae), popularly known in Brazil as cagaiteira, is a widespread plant species in the Brazilian Cerrado. In folk medicine, the leaves of this plant are used to treat diarrhea and dysentery. The fruits are used for fresh consumption and industrial purposes. Because of the use of this plant as a therapeutic resource and food, the present study evaluated the genotoxic, cytotoxic, antigenotoxic, and anticytotoxic effects of the lyophilized ethanolic leaf extract of E. dysenterica using the mouse bone marrow micronucleus test. The genotoxicity and antigenotoxicity of this extract were evaluated using the frequency of micronucleated polychromatic erythrocytes, and the cytotoxicity and anticytotoxicity were assessed by the polychromatic and normochromatic erythrocyte ratio. According to our results, the lyophilized ethanolic leaf extract of E. dysenterica exhibited genotoxic and cytotoxic effects at the higher doses and protection against cyclophosphamide-induced genotoxic and cytotoxic actions at all doses tested. PMID:22404573

  18. CHARACTERIZING THE GENOTOXICITY OF HAZARDOUS INDUSTRIAL WASTES AND EFFLUENTS USING SHORT-TERM BIOASSAYS

    EPA Science Inventory

    This chapter demonstrates that short-term bioassays can reliably and expeditiously measure the genotoxic potential of hazardous industrial wastes and effluents. etrochemical wastes have been studied in detail, especially discharges from chemical manufacturing plants and textile a...

  19. Evaluating enzymes that generate genotoxic benzo[a]pyrene metabolites using sensor arrays.

    PubMed

    Wang, Bingquan; Jansson, Ingela; Schenkman, John B; Rusling, James F

    2005-03-01

    Arrays with individually addressable, demountable electrodes coated with ultrathin DNA/enzyme films were evaluated to estimate relative rates of genotoxic bioactivation of benzo[a]pyrene (BP) for several different enzymes simultaneously. Specifically, cytochrome (cyt) P450cam, cyt P40 1A2, and myoglobin in the array were activated with H2O2 to metabolize BP to genotoxic metabolites. DNA damage by the metabolites was detected by increases in square wave voltammetric oxidation peaks using Ru(bpy)3(2+) as catalyst. Cyt P450cam and cyt P450 1A2 showed 3-fold higher activity for genotoxic bioactivation of BP than myoglobin. The ability of the arrays to generate and detect metabolite-based DNA damage simultaneously for several enzymes is a rapid and promising approach to identify and characterize enzymes involved in genotoxicity of drugs and pollutants. PMID:15732919

  20. Genotoxicity Biomarkers Associated with Exposure to Traffic And Near-Road Atmospheres: A Review

    EPA Science Inventory

    Genotoxicity Biomarkers Associated with Exposure to Traffic And Near-Road Atmospheres: A Review Diesel and gasoline emissions, which are the primary components of traffic exhaust, are known or possible human carcinogens, re...

  1. Characterizing the genotoxicity of hazardous industrial wastes and effluents using short-term bioassays

    SciTech Connect

    Houk, V.S.; DeMarini, D.M.

    1989-01-01

    This paper demonstrates that short-term bioassays can reliably and expeditiously measure the genotoxic potential of hazardous industrial wastes and effluents. Petrochemical wastes have been studied in detail, especially discharges from chemical manufacturing plants and textile and dye effluents. However, there is little information on effluents from pesticide manufacturers. The most extensive evaluations have been conducted on effluents from pulp and paper mills. These studies have shown which pulping plants generate the most genotoxic effluents, which process wastes are most hazardous, have isolated and identified the compounds responsible for the genotoxic activity, have described the environmental fate of these compounds, have evaluated the types of genetic damage likely to occur upon exposure to the effluents, and have identified several treatment methods that effectively reduce the genotoxicity of the effluents. The coupling of bioassays for biological analysis with chemical evaluation provides the most powerful approach to assessing the overall health effects of complex industrial wastes and effluents.

  2. MICROBIAL GENOTOXICITY AS AN ENVIRONMENTAL INDICATOR FOR NEAR-COASTAL SEDIMENT PORE WATERS

    EPA Science Inventory

    Lewis, Michael A., Carol. B. Daniels and Cynthia A. Chancy. Submitted. The genotoxic potential of environmental media collected from coastal areas impacted by anthropogenic contaminants has not been reported frequently in the scientific literature, particularly in the Gulf of Mex...

  3. METABOLISM, MICROFLORA EFFECTS, AND GENOTOXICITY IN HALOACETIC ACID-TREATED CULTURES OF RAT CECAL MICROBIOTA

    EPA Science Inventory

    Haloacetic acids are by-products of drinking water disinfection. Several compounds in this class are genotoxic and have been identified as rodent hepatocarcinogens. Enzymes produced by the normal intestinal bacteria can transform some promutagens and procarcinogens to their bio...

  4. Substituent effects on the genotoxicity of 4-nitrostilbene derivatives.

    PubMed

    Hooberman, B H; Brezzell, M D; Das, S K; You, Z; Sinsheimer, J E

    1994-11-01

    4-Nitrostilbene and twelve of its derivatives (eleven E-stilbenes and two Z-stilbenes) were examined for possible quantitative structure-activity relationships of their in vitro and in vivo genotoxicity. Relative mutagenicity was studied with and without S9 activation in Salmonella strains TA98 and TA100, as well as in the nitroreductase deficient strains TA98/NR and TA100/NR. Chromosomal aberrations in the bone-marrow cells of mice following intraperitoneal administration of the nitrostilbenes were observed as an indicator of in vivo genotoxicity. All of the compounds were active in TA98 and TA100 without S9 activation, with the exception of 4-amino-4'-nitrostilbene in TA100. Mutagenic activity was greatly reduced or eliminated in the NR strains, which is consistent with metabolic activation of the compounds by bacterial reductase. The presence of S9 lowered the activity of most of the nitrostilbenes presumedly by enzymatic detoxication. Hammet values of substituents, partition coefficients and frontier orbital energies (ELUMO and EHOMO) were studied for correlations with mutagenicity of the eleven E-stilbenes. Correlations could be established between mutagenicity in TA98 without S9 activation and the Hammet values. The same mutagenicity could also be correlated to ELUMO. Rationales for these correlations include the concept that electron-withdrawing groups which lower ELUMO should facilitate the reduction of the nitro group, leading to the proximate mutagen hydroxylamine. The correlations are also explained by the concept that electron-withdrawing groups should help stabilize the hydroxylamine intermediate and make the ultimate mutagenic species, the nitrenium ions, more reactive toward DNA. The relationship between mutagenicity and electronic effects of substituent groups found in vitro could not be extended to the in vivo results. However, except for the dinitrostilbenes, where insolubility prevented their testing, all the nitrostilbenes produced a

  5. Investigations into the genotoxic potential of olive extracts.

    PubMed

    Kirkland, David; Edwards, James; Woehrle, Tina; Beilstein, Paul

    2015-01-01

    The phenolic anti-oxidant 3-hydroxytyrosol (HT) is a major constituent of olives and olive oil. Published data showed it was negative in the Ames test at concentrations up to 5 μL per plate, but did induce chromosomal aberrations in human lymphocytes. HIDROX, an olive extract containing approximately 2.4% HT, was reported as both positive and equivocal in an Ames test in different papers from the same laboratory. Negative results for micronucleus induction in vivo in both an acute study and as part of a 90-day rat toxicity study were also reported for HIDROX. Given the widespread use and consumption of olives, olive oil and olive extracts, it was important to obtain more data. Here we confirm that pure HT, and an olive extract containing 15% HT, both induced micronuclei in cultured cells in vitro, but show that these responses were either due to high levels of cytotoxicity or to reaction of HT with culture medium components to produce hydrogen peroxide. Another extract (H40) containing 40% HT also induced micronuclei in vitro, probably via the same mechanism. However, both extracts were negative in robust Ames tests. The 15% HT formulated extract did not induce micronuclei in rat bone marrow after 4 weeks of dosing up to 561 mg HT/kg/day. H40 produced increased rat bone marrow micronucleus frequencies at 250 and 500 mg HT/kg/day in a 90-day toxicity study, but the results were questionable for various reasons. However, when two different batches of this extract were tested in acute micronucleus studies at doses up to 2000 mg HT/kg, giving plasma exposures that exceeded those in the 90-day study, negative results were obtained. Based on weight of evidence it is concluded that the olive extracts tested are not genotoxic at high doses in vivo, and any genotoxic risks for human consumers are negligible. PMID:25726171

  6. DNA melting and genotoxicity induced by silver nanoparticles and graphene.

    PubMed

    Ivask, Angela; Voelcker, Nicolas H; Seabrook, Shane A; Hor, Maryam; Kirby, Jason K; Fenech, Michael; Davis, Thomas P; Ke, Pu Chun

    2015-05-18

    We have revealed a connection between DNA-nanoparticle (NP) binding and in vitro DNA damage induced by citrate- and branched polyethylenimine-coated silver nanoparticles (c-AgNPs and b-AgNPs) as well as graphene oxide (GO) nanosheets. All three types of nanostructures triggered an early onset of DNA melting, where the extent of the melting point shift depends upon both the type and concentration of the NPs. Specifically, at a DNA/NP weight ratio of 1.1/1, the melting temperature of lambda DNA dropped from 94 °C down to 76 °C, 60 °C, and room temperature for GO, c-AgNPs and b-AgNPs, respectively. Consistently, dynamic light scattering revealed that the largest changes in DNA hydrodynamic size were also associated with the binding of b-AgNPs. Upon introduction to cells, b-AgNPs also exhibited the highest cytotoxicity, at the half-maximal inhibitory (IC50) concentrations of 3.2, 2.9, and 5.2 mg/L for B and T-lymphocyte cell lines and primary lymphocytes, compared to the values of 13.4, 12.2, and 12.5 mg/L for c-AgNPs and 331, 251, and 120 mg/L for GO nanosheets, respectively. At cytotoxic concentrations, all NPs elicited elevated genotoxicities via the increased number of micronuclei in the lymphocyte cells. However, b-AgNPs also induced micronuclei at subtoxic concentrations starting from 0.1 mg/L, likely due to their stronger cellular adhesion and internalization, as well as their subsequent interference with normal DNA synthesis or chromosome segregation during the cell cycle. This study facilitates our understanding of the effects of NP chemical composition, surface charge, and morphology on DNA stability and genotoxicity, with implications ranging from nanotoxicology to nanobiotechnology and nanomedicine. PMID:25781053

  7. Genotoxic potential of leaf extracts of Jatropha gossypiifolia L.

    PubMed

    Almeida, P M; Araújo, S S; Santos, I R M R; Marin-Morales, M A; Benko-Iseppon, A M; Santos, A V; Randau, K P; Brasileiro-Vidal, A C

    2016-01-01

    Jatropha gossypiifolia L. (Euphorbiaceae) is widely used in popular medicine. However, further toxicological studies are necessary for its reliable use. The present study aimed to evaluate the cytotoxic, genotoxic, and mutagenic effects of ethanolic and aqueous leaf extracts of J. gossypiifolia, using the test system Allium cepa. In addition, the phytochemical profile of the extracts was also obtained. Seeds of A. cepa were subjected to different concentrations of the two extracts (0.001, 0.01, 0.1, 1, and 10 mg/mL). Distilled water was used for the negative control and methyl methanesulfonate (4 x 10(-4) M) and trifluralin (0.84 ppm) for the positive controls. The values of mitotic index at all concentrations of ethanolic extract and at 0.1, 1, and 10 mg/mL aqueous extract showed a significant decrease. Alterations, such as chromosome adherence, C-metaphases, chromosome bridges, nuclear buds, and micronuclei were verified in both extracts but chromosome loss indicating genotoxic activity was observed only in the ethanolic extract. Presence of micronuclei on administration of the extracts, also indicated mutagenic action at the chromosome level. In the ethanolic extract, aneugenicity seemed to be the main activity, probably as a result of the action of terpenes and/or flavonoids, whereas in the aqueous extract, clastogenic action appeared to be the principal activity, presumably as a consequence of the effect of flavonoids and/or saponins. Thus, we suggest that the extracts of this species should be used with great caution for medicinal purpose. PMID:26909961

  8. Antimicrobial and Genotoxicity Effects of Zero-valent Iron Nanoparticles

    PubMed Central

    Barzan, Elham; Mehrabian, Sedigheh; Irian, Saeed

    2014-01-01

    Background: In a world of nanotechnology, the first concern is the potential environmental impact of nanoparticles. An efficient way to estimate nanotoxicity is to monitor the responses of bacteria exposed to these particles. Objectives: The current study explored the antimicrobial properties of nZVI (zero-valent Iron nanoparticles) on the Gram-negative bacterial systems Erwinia amylovora, Xanthomonas oryzae and the Gram-positive bacterial systems Bacillus cereus and Streptomyces spp. The genotoxicity potential of nZVI was also assayed. Materials and Methods: The toxicity of nZVI was tested by two different methods: Growing bacteria in liquid (broth dilution) and agar media (challenge test) containing different nZVI concentrations for 24-72 hours. The genotoxicity of nZVI was assessed using the preincubation version of the Ames test. Results: The lowest concentrations of nZVI that inhibited the visible growth (MIC) of E. amylovora, X. oryzae, B. cereus and Streptomyces spp. were 625, 550, 1250 and 1280 ppm, respectively. The minimum bactericidal concentration (MBC) for E. amylovora and X. oryzae were 10,000 and 5,000 ppm of nZVI, respectively. MBC was not observed for the Gram positive bacteria. No bacteriostatic and bactericidal effects were observed for oxidized nZVI. Mutant frequency did not increase according to the vehicle control at the concentrations assayed, indicating a lack of mutagenicity associated with nZVI. Conclusions: nZVI nanoparticles are not mutagenic at low concentrations, therefore they can be used without detrimental effects on soil bacteria. PMID:25147712

  9. N-acetylation of three aromatic amine hair dye precursor molecules eliminates their genotoxic potential.

    PubMed

    Zeller, Andreas; Pfuhler, Stefan

    2014-01-01

    N-acetylation has been described as a detoxification reaction for aromatic amines; however, there is only limited data available showing that this metabolic conversion step changes their genotoxicity potential. To extend this database, three aromatic amines, all widely used as precursors in oxidative hair dye formulations, were chosen for this study: p-phenylenediamine (PPD), 2,5-diaminotoluene (DAT) and 4-amino-2-hydroxytoluene (AHT). Aiming at a deeper mechanistic understanding of the interplay between activation and detoxification for this chemical class, we compared the genotoxicity profiles of the parent compounds with those of their N-acetylated metabolites. While PPD, DAT and AHT all show genotoxic potential in vitro, their N-acetylated metabolites completely lack genotoxic potential as shown in the Salmonella typhimurium reversion assay, micronucleus test with cultured human lymphocytes (AHT), chromosome aberration assay with V79 cells (DAT) and Comet assay performed with V79 cells. For the bifunctional aromatic amines studied (PPD and DAT), monoacetylation was sufficient to completely abolish their genotoxic potential. Detoxification through N-acetylation was further confirmed by comparing PPD, DAT and AHT in the Comet assay using standard V79 cells (N-acetyltransferase (NAT) deficient) and two NAT-proficient cell lines,V79NAT1*4 and HaCaT (human keratinocytes). Here we observed a clear shift of dose-response curves towards decreased genotoxicity of the parent aromatic amines in the NAT-proficient cells. These findings suggest that genotoxic effects will only be found at concentrations where the N-acetylation (detoxifying) capacity of the cells is overwhelmed, indicating that a 'first-pass' effect in skin could be taken into account for risk assessment of these topically applied aromatic amines. The findings also indicate that the use of liver S-9 preparations, which generally underestimate Phase II reactions, contributes to the generation of irrelevant

  10. Validation study of the combined repeated-dose toxicity and genotoxicity assay using gpt delta rats

    PubMed Central

    Akagi, Jun-ichi; Toyoda, Takeshi; Cho, Young-Man; Mizuta, Yasuko; Nohmi, Takehiko; Nishikawa, Akiyoshi; Ogawa, Kumiko

    2015-01-01

    Transgenic rodents carrying reporter genes to detect organ-specific in vivo genetic alterations are useful for risk assessment of genotoxicity that causes cancer. Thus, the Organization for Economic Co-operation and Development has established the guideline for genotoxicity tests using transgenic animals, which may be combined with repeated-dose toxicity studies. Here, we provide evidence to support equivalence of gpt delta and wild type (WT) rats in terms of toxicological responses to a genotoxic hepatocarcinogen, N-nitrosodiethylamine (DEN), and a non-genotoxic hepatocarcinogen, di(2-ethylhexyl)phthalate (DEHP). gpt delta rats treated with DEHP showed similar increases in liver and kidney weights, serum albumin, albumin/globulin ratios, and incidence of diffuse hepatocyte hypertrophy compared to WT F344 and Sprague–Dawley (SD) rats. DEN-treated gpt delta rats showed equivalent increases in the number and area of precancerous GST-P-positive foci in the liver compared to WT rats. The livers of DEN-treated gpt delta rats also showed increased frequencies of gpt and Spi− mutations; such changes were not observed in DEHP-treated gpt delta rats. These results indicated that gpt delta rats (both F344 and SD backgrounds) showed comparable DEHP-induced toxicity and DEN-induced genotoxicity to those observed in WT rats. With regard to the administration period, the general toxicity of 1.2% DEHP was evident throughout the experimental period, and the genotoxicity of 10 p.p.m. DEN could be detected after 2 weeks of administration and further increased at 4 weeks. These results suggested that combined assays using gpt delta rats could detect both general toxicity and genotoxicity by the canonical 4-week administration protocol. Therefore, this assay using gpt delta rats would be applicable for risk assessment including early detection of genotoxic carcinogens and ultimately serve to reduce cancer risks in humans from environmental chemicals. PMID:25683344

  11. Validation study of the combined repeated-dose toxicity and genotoxicity assay using gpt delta rats.

    PubMed

    Akagi, Jun-Ichi; Toyoda, Takeshi; Cho, Young-Man; Mizuta, Yasuko; Nohmi, Takehiko; Nishikawa, Akiyoshi; Ogawa, Kumiko

    2015-05-01

    Transgenic rodents carrying reporter genes to detect organ-specific in vivo genetic alterations are useful for risk assessment of genotoxicity that causes cancer. Thus, the Organization for Economic Co-operation and Development has established the guideline for genotoxicity tests using transgenic animals, which may be combined with repeated-dose toxicity studies. Here, we provide evidence to support equivalence of gpt delta and wild type (WT) rats in terms of toxicological responses to a genotoxic hepatocarcinogen, N-nitrosodiethylamine (DEN), and a non-genotoxic hepatocarcinogen, di(2-ethylhexyl)phthalate (DEHP). gpt delta rats treated with DEHP showed similar increases in liver and kidney weights, serum albumin, albumin/globulin ratios, and incidence of diffuse hepatocyte hypertrophy compared to WT F344 and Sprague-Dawley (SD) rats. DEN-treated gpt delta rats showed equivalent increases in the number and area of precancerous GST-P-positive foci in the liver compared to WT rats. The livers of DEN-treated gpt delta rats also showed increased frequencies of gpt and Spi(-) mutations; such changes were not observed in DEHP-treated gpt delta rats. These results indicated that gpt delta rats (both F344 and SD backgrounds) showed comparable DEHP-induced toxicity and DEN-induced genotoxicity to those observed in WT rats. With regard to the administration period, the general toxicity of 1.2% DEHP was evident throughout the experimental period, and the genotoxicity of 10 p.p.m. DEN could be detected after 2 weeks of administration and further increased at 4 weeks. These results suggested that combined assays using gpt delta rats could detect both general toxicity and genotoxicity by the canonical 4-week administration protocol. Therefore, this assay using gpt delta rats would be applicable for risk assessment including early detection of genotoxic carcinogens and ultimately serve to reduce cancer risks in humans from environmental chemicals. PMID:25683344

  12. Supersymmetric mode converters

    NASA Astrophysics Data System (ADS)

    Heinrich, Matthias; Miri, Mohammad-Ali; Stützer, Simon; Nolte, Stefan; Szameit, Alexander; Christodoulides, Demetrios N.

    2015-08-01

    In recent years, the ever-increasing demand for high-capacity transmission systems has driven remarkable advances in technologies that encode information on an optical signal. Mode-division multiplexing makes use of individual modes supported by an optical waveguide as mutually orthogonal channels. The key requirement in this approach is the capability to selectively populate and extract specific modes. Optical supersymmetry (SUSY) has recently been proposed as a particularly elegant way to resolve this design challenge in a manner that is inherently scalable, and at the same time maintains compatibility with existing multiplexing strategies. Supersymmetric partners of multimode waveguides are characterized by the fact that they share all of their effective indices with the original waveguide. The crucial exception is the fundamental mode, which is absent from the spectrum of the partner waveguide. Here, we demonstrate experimentally how this global phase-matching property can be exploited for efficient mode conversion. Multimode structures and their superpartners are experimentally realized in coupled networks of femtosecond laser-written waveguides, and the corresponding light dynamics are directly observed by means of fluorescence microscopy. We show that SUSY transformations can readily facilitate the removal of the fundamental mode from multimode optical structures. In turn, hierarchical sequences of such SUSY partners naturally implement the conversion between modes of adjacent order. Our experiments illustrate just one of the many possibilities of how SUSY may serve as a building block for integrated mode-division multiplexing arrangements. Supersymmetric notions may enrich and expand integrated photonics by versatile optical components and desirable, yet previously unattainable, functionalities.

  13. Further investigations into the genotoxicity of quinoxaline-di-N-oxides and their primary metabolites.

    PubMed

    Liu, Qianying; Zhang, Jianwu; Luo, Xun; Ihsan, Awais; Liu, Xianglian; Dai, Menghong; Cheng, Guyue; Hao, Haihong; Wang, Xu; Yuan, Zonghui

    2016-07-01

    Quinoxaline-di-N-oxides (QdNOs) are potential antibacterial agents with a wide range of biological properties. Quinocetone (QCT), carbadox (CBX), olaquindox (OLA), mequindox (MEQ) and cyadox (CYA) are classical QdNOs. Though the genotoxicity of parent drugs has been evaluated, the genotoxicity of their primary N → O reduced metabolites remains unclear. In the present study, a battery of four different short-term tests, mouse lymphoma assay (MLA), Ames test, chromosomal aberration assay in vitro and bone marrow erythrocyte micronucleus assay in vivo was carried out to investigate the genotoxicity of the six primary N → O reduced metabolites. Additionally, the genotoxicity of five parent drugs was evaluated by the MLA. Strong genotoxicity of N1-MEQ, B-MEQ and B-CBX was found in three of the assays but not in the Ames assay, and the rank order was N1-MEQ>B-MEQ>B-CBX that is consistent with prototype QdNOs. Negative results for the five QdNOs were noted in the MLA. We present for the first time a comparison of the genotoxicity of primary N → O reduced metabolites, and evaluate the ability of five QdNOs to cause mutations in the MLA. The present study demonstrates that metabolites are involved in genetic toxicity mediated by QdNOs, and improve the prudent use of QdNOs for public health. PMID:27170491

  14. Granular Activated Carbon Treatment May Result in Higher Predicted Genotoxicity in the Presence of Bromide.

    PubMed

    Krasner, Stuart W; Lee, Tiffany Chih Fen; Westerhoff, Paul; Fischer, Natalia; Hanigan, David; Karanfil, Tanju; Beita-Sandí, Wilson; Taylor-Edmonds, Liz; Andrews, Robert C

    2016-09-01

    Certain unregulated disinfection byproducts (DBPs) are more of a health concern than regulated DBPs. Brominated species are typically more cytotoxic and genotoxic than their chlorinated analogs. The impact of granular activated carbon (GAC) on controlling the formation of regulated and selected unregulated DBPs following chlorine disinfection was evaluated. The predicted cyto- and genotoxicity of DBPs was calculated using published potencies based on the comet assay for Chinese hamster ovary cells (assesses the level of DNA strand breaks). Additionally, genotoxicity was measured using the SOS-Chromotest (detects DNA-damaging agents). The class sum concentrations of trihalomethanes, haloacetic acids, and unregulated DBPs, and the SOS genotoxicity followed the breakthrough of dissolved organic carbon (DOC), however the formation of brominated species did not. The bromide/DOC ratio was higher than the influent through much of the breakthrough curve (GAC does not remove bromide), which resulted in elevated brominated DBP concentrations in the effluent. Based on the potency of the haloacetonitriles and halonitromethanes, these nitrogen-containing DBPs were the driving agents of the predicted genotoxicity. GAC treatment of drinking or reclaimed waters with appreciable levels of bromide and dissolved organic nitrogen may not control the formation of unregulated DBPs with higher genotoxicity potencies. PMID:27467860

  15. Genetic Evidence for Genotoxic Effect of Entecavir, an Anti-Hepatitis B Virus Nucleotide Analog

    PubMed Central

    Liu, Ying; Hu, Xiaoqing; Takeda, Shunichi; Qing, Yong

    2016-01-01

    Nucleoside analogues (NAs) have been the most frequently used treatment option for chronic hepatitis B patients. However, they may have genotoxic potentials due to their interference with nucleic acid metabolism. Entecavir, a deoxyguanosine analog, is one of the most widely used oral antiviral NAs against hepatitis B virus. It has reported that entecavir gave positive responses in both genotoxicity and carcinogenicity assays. However the genotoxic mechanism of entecavir remains elusive. To evaluate the genotoxic mechanisms, we analyzed the effect of entecavir on a panel of chicken DT40 B-lymphocyte isogenic mutant cell line deficient in DNA repair and damage tolerance pathways. Our results showed that Parp1-/- mutant cells defective in single-strand break (SSB) repair were the most sensitive to entecavir. Brca1-/-, Ubc13-/- and translesion-DNA-synthesis deficient cells including Rad18-/- and Rev3-/- were hypersensitive to entecavir. XPA-/- mutant deficient in nucleotide excision repair was also slightly sensitive to entecavir. γ-H2AX foci forming assay confirmed the existence of DNA damage by entecavir in Parp1-/-, Rad18-/- and Brca1-/- mutants. Karyotype assay further showed entecavir-induced chromosomal aberrations, especially the chromosome gaps in Parp1-/-, Brca1-/-, Rad18-/- and Rev3-/- cells when compared with wild-type cells. These genetic comprehensive studies clearly identified the genotoxic potentials of entecavir and suggested that SSB and postreplication repair pathways may suppress entecavir-induced genotoxicity. PMID:26800464

  16. Genetic Evidence for Genotoxic Effect of Entecavir, an Anti-Hepatitis B Virus Nucleotide Analog.

    PubMed

    Jiang, Lei; Wu, Xiaohua; He, Fang; Liu, Ying; Hu, Xiaoqing; Takeda, Shunichi; Qing, Yong

    2016-01-01

    Nucleoside analogues (NAs) have been the most frequently used treatment option for chronic hepatitis B patients. However, they may have genotoxic potentials due to their interference with nucleic acid metabolism. Entecavir, a deoxyguanosine analog, is one of the most widely used oral antiviral NAs against hepatitis B virus. It has reported that entecavir gave positive responses in both genotoxicity and carcinogenicity assays. However the genotoxic mechanism of entecavir remains elusive. To evaluate the genotoxic mechanisms, we analyzed the effect of entecavir on a panel of chicken DT40 B-lymphocyte isogenic mutant cell line deficient in DNA repair and damage tolerance pathways. Our results showed that Parp1-/- mutant cells defective in single-strand break (SSB) repair were the most sensitive to entecavir. Brca1-/-, Ubc13-/- and translesion-DNA-synthesis deficient cells including Rad18-/- and Rev3-/- were hypersensitive to entecavir. XPA-/- mutant deficient in nucleotide excision repair was also slightly sensitive to entecavir. γ-H2AX foci forming assay confirmed the existence of DNA damage by entecavir in Parp1-/-, Rad18-/- and Brca1-/- mutants. Karyotype assay further showed entecavir-induced chromosomal aberrations, especially the chromosome gaps in Parp1-/-, Brca1-/-, Rad18-/- and Rev3-/- cells when compared with wild-type cells. These genetic comprehensive studies clearly identified the genotoxic potentials of entecavir and suggested that SSB and postreplication repair pathways may suppress entecavir-induced genotoxicity. PMID:26800464

  17. In vitro genotoxicity testing of carvacrol and thymol using the micronucleus and mouse lymphoma assays.

    PubMed

    Maisanaba, Sara; Prieto, Ana I; Puerto, Maria; Gutiérrez-Praena, Daniel; Demir, Eşref; Marcos, Ricard; Cameán, Ana M

    2015-06-01

    Currently, antimicrobial additives derived from essential oils (Eos) extracted from plants or spices, such as Origanum vulgare, are used in food packaging. Thymol and carvacrol, the major EO compounds of O. vulgare, have demonstrated their potential use as active additives. These new applications use high concentrations, thereby increasing the concern regarding their toxicological profile and especially their genotoxic risk. The aim of this work was to investigate the potential in vitro genotoxicity of thymol (0-250 μM) and carvacrol (0-2500 μM) at equivalent doses to those used in food packaging. The micronucleus (MN) test and the mouse lymphoma (MLA) assay on L5178Y/Tk(±) mouse lymphoma cells were used. The negative results for thymol with the MN with and without the S9 fraction and also with the MLA assay reinforce the view that this compound is not genotoxic in mammalian cells. However, carvacrol presented slight genotoxic effects, but only in the MN test at the highest concentration assayed (700 μM) and in the absence of metabolic activation. The lack of genotoxic response in the MLA assay after 4 and 24h of exposure indicates a low genotoxic potential for carvacrol. Alternatively, the general negative findings observed in both assays suggest that the MN results of carvacrol are marginal data without biological relevance. These results can be useful to identify the appropriate concentrations of these substances to be used as additives in food packaging. PMID:26046975

  18. Quantitative assessment of cumulative carcinogenic risk for multiple genotoxic impurities in a new drug substance.

    PubMed

    Bercu, Joel P; Hoffman, Wherly P; Lee, Cindy; Ness, Daniel K

    2008-08-01

    In pharmaceutical development, significant effort is made to minimize the carcinogenic potential of new drug substances (NDS). This involves appropriate genotoxicity and carcinogenicity testing of the NDS, and understanding the genotoxic potential of its impurities. Current available guidance recommends the use of the threshold of toxicological concern (TTC) for a single impurity where mutagenicity but no carcinogenicity information exists. Despite best efforts, the presence of more than one genotoxic impurity in an NDS may occur at trace levels. This paper repeats the analysis performed by others for a single genotoxic compound, but also uses statistical simulations to assess the impact on cancer risk for a mixture of genotoxic compounds. In summary, with the addition of multiple impurities all controlled to the TTC, an increase in cancer risk was observed. This increase is relatively small when considering the conservative assumptions of the TTC. If structurally similar compounds had an assumed strong correlation (+/-10-fold from the first randomly selected impurity) in cancer potency, the resulting cancer risk was not negatively impacted. Findings based on probabilistic analysis here can be very useful in making appropriate decisions about risk management of multiple genotoxic impurities measured in the final drug substance. PMID:18550240

  19. Impact of β-glucan on the Fecal Water Genotoxicity of Polypectomized Patients.

    PubMed

    Turunen, Katja T; Pletsa, Vasiliki; Georgiadis, Panagiotis; Triantafillidis, John K; Karamanolis, Dimitrios; Kyriacou, Adamantini

    2016-01-01

    The aim of the study was to determine the effect of β-glucan on the cytotoxicity and genotoxicity of polypectomized patient's fecal water (FW). Polypectomized volunteers (n = 69) were randomly assigned to consume bread with or without β-glucan, for 3 months. FW was collected at the beginning (t = 0), the 30th and 90th day and 2 wk after the intervention. Cytotoxicity and genotoxicity were estimated on Caco-2 cells, using trypan blue exclusion test and comet assay, respectively. Gastrointestinal symptoms were recorded and subjects kept a 3-day food diary at baseline and after completion. Trypan blue exclusion test revealed cell survival of approximately 87% after incubation with FW. The FW samples showed 49% genotoxicity at the baseline. Genotoxicity in the intervention group decreased during the trial reaching statistical significance on the 90th day compared to control. An increase was noticed 2 wk after the trial, but it still remained significantly lower compared to control. Group-specific analysis for β-glucan also revealed significant decrease in the genotoxicity on the 90th day compared to baseline. β-glucan ingestion in polypectomized patients significantly decreased the genotoxicity of their FW. Our findings suggest that β-glucan consumption could possibly provide protection against colon cancer development. PMID:27043932

  20. Rapid screening of potential human bladder carcinogens: genotoxicity in meiosis repair deficient Drosophila melanogaster.

    PubMed

    Lamm, L M; Reichert, D F; Lamm, D L

    1989-11-01

    To find a quick screen of potential bladder carcinogens, a genotoxicity test in Drosophila melanogaster stocks containing DNA repair mutations was evaluated. Meiosis repair deficient male Drosophila melanogaster mei-9, mei-41, and the double mutant mei-9-41 were allowed to mate with attached -x females on media containing the test agent. Genotoxic agents produce DNA damage which accumulates and can be lethal in mei males, whereas the attached -x females are able to repair the damage and survive. Thus, the sex ratio of the progeny is a measure of genotoxicity which can be correlated with mutagenicity and carcinogenicity. In this study, tea, coffee, and saccharin were not genotoxic (p greater than 0.3). Dose dependent toxicity was observed in bracken fern (p less than 0.001). The known mutagen and bladder carcinogen, cyclophosphamide, was highly genotoxic (p less than .001). Drosophila genotoxicity not only permits rapid screening of mutagens, but may also have advantages over other systems in the screening of potential bladder carcinogens. PMID:2509735

  1. Genotoxic capacity of Cd/Se semiconductor quantum dots with differing surface chemistries

    PubMed Central

    Manshian, Bella B.; Soenen, Stefaan J.; Brown, Andy; Hondow, Nicole; Wills, John; Jenkins, Gareth J. S.; Doak, Shareen H.

    2016-01-01

    Quantum dots (QD) have unique electronic and optical properties promoting biotechnological advances. However, our understanding of the toxicological structure–activity relationships remains limited. This study aimed to determine the biological impact of varying nanomaterial surface chemistry by assessing the interaction of QD with either a negative (carboxyl), neutral (hexadecylamine; HDA) or positive (amine) polymer coating with human lymphoblastoid TK6 cells. Following QD physico-chemical characterisation, cellular uptake was quantified by optical and electron microscopy. Cytotoxicity was evaluated and genotoxicity was characterised using the micronucleus assay (gross chromosomal damage) and the HPRT forward mutation assay (point mutagenicity). Cellular damage mechanisms were also explored, focusing on oxidative stress and mitochondrial damage. Cell uptake, cytotoxicity and genotoxicity were found to be dependent on QD surface chemistry. Carboxyl-QD demonstrated the smallest agglomerate size and greatest cellular uptake, which correlated with a dose dependent increase in cytotoxicity and genotoxicity. Amine-QD induced minimal cellular damage, while HDA-QD promoted substantial induction of cell death and genotoxicity. However, HDA-QD were not internalised by the cells and the damage they caused was most likely due to free cadmium release caused by QD dissolution. Oxidative stress and induced mitochondrial reactive oxygen species were only partially associated with cytotoxicity and genotoxicity induced by the QD, hence were not the only mechanisms of importance. Colloidal stability, nanoparticle (NP) surface chemistry, cellular uptake levels and the intrinsic characteristics of the NPs are therefore critical parameters impacting genotoxicity induced by QD. PMID:26275419

  2. Evaluation of the genotoxicity of process stream extracts from a coal gasification system

    SciTech Connect

    Shimizu, R.W.; Benson, J.M.; Li, A.P.; Henderson, R.F.; Brooks, A.L.

    1984-01-01

    Extracts of three complex organic environmental mixtures, two from an experimental coal gasifier (a raw gas and a clean gas sample) and one from a coke oven main, were examined for genotoxicity. Three short-term genotoxicity assay systems were used: Ames Salmonella typhimurium reverse mutation assay, Chinese hamster ovary cell/hypoxanthine-guanine phosphoribosyl transferase (CHO/HGPRT) gene locus mutation assay, and the Chinese hamster lung primary culture/sister chromatid exchange (CHL/SCE) assay. Aroclor-1254-induced rat liver homogenate fraction (S-9) was required to observe genotoxicity in both gene locus mutation assays (CHO/HGPRT and Ames). The relative survival of CHO cells exposed to extracts was highest in cells exposed to clean gas samples, with the raw gas sample being the most cytotoxic either with or without the addition of S-9. All three complex mixtures induced sister chromatid exchanges in primary lung cell cultures without the addition of S-9. The relative genotoxicity ranking of the samples varied between the mammalian and prokaryotic assay systems. The results of all three assays indicate that the cleanup process used in the experimental gasifier was effective in decreasing the genotoxic materials in the process stream. These data also reemphasize the necessity of evaluating genotoxicity of complex mixtures in a variety of short-term systems.

  3. Heavy metal toxicity and genotoxicity in water and sewage determined by microbiological methods

    SciTech Connect

    Codina, J.C.; Cazorla, F.M.; Perez-Garcia, A.; De Vicente, A.

    2000-06-01

    Acute toxicity and genotoxicity of cadmium, copper, chromium, mercury, nickel, and zinc dissolved in deionized water and in sewage were established by comparing the EC50 and EC20 values obtained by different microbial assays. For acute toxicity determination. The Netherlands Standard NEN6509 test, the spectrophotometric assays of respiratory inhibition using Saccharmyces cerevisiae and Pseudomonas fluorescens, and the Microtox' test were employed. To determine metal genotoxicity, the Salmonella typhimurium and Escherichia coli mutagenicity tests, the SOS-{beta}-galactosidase genotoxicity test, and the Mutatox{trademark} assay were used. The toxicity of the different assayed metals varied from the most toxic, mercury, to the least toxic, nickel and zinc. Two different rankings of toxicity and genotoxicity, very similar to each other, were established. The toxicity ranking was Hg > Cr > Cd {approximately} Cu {approximately} n > Ni, and the genotoxicity ranking was Hg > Cr > Cu {approximately} Cd {approximately} Ni > Zn. The association between the toxicity and genotoxicity of copper and chromium in the dissolved and suspended fractions of sewage was also determined. Copper was mainly associated with the suspended fractions and chromium with the dissolved fractions of sewage.

  4. Use of the alkaline in vivo Comet assay for mechanistic genotoxicity investigations.

    PubMed

    Hartmann, Andreas; Schumacher, Martin; Plappert-Helbig, Ulla; Lowe, Phil; Suter, Willi; Mueller, Lutz

    2004-01-01

    The alkaline Comet assay was used to investigate the in vivo genotoxicity of 17 compounds. Altogether 21 studies were conducted with these compounds. The investigations were triggered for various reasons. The main reason for performing the studies was to evaluate the in vivo relevance of in vitro genotoxicity findings with 10 compounds. Eight of these compounds showed no effects in the in vivo Comet assay while two compounds induced altered DNA migration patterns in specific organs. The remaining seven compounds were tested to follow up on neoplastic/preneoplastic or chronic toxicity changes as detected in specific target organs identified in rodent studies, to investigate the possibility of site-of-contact genotoxicity and to test the liver as a target organ for a suspected reactive metabolite. For the studies, various organs of rodents were analyzed, depending on the suspected properties of the compounds, including liver, jejunum, leukocytes, stomach mucosa, duodenum, lung and kidney. All tissues were amenable to investigation by gel electrophoresis after simple disaggregation of organs by means of mincing or, in the case of epithelial cells from the gastrointestinal tract, scraping off cells from the epithelium. In conclusion, the Comet assay was found to be a reliable and robust test to investigate in vivo genotoxicity in a variety of rodent organs. Therefore, it is concluded that in vivo Comet assay data are useful for elucidating positive in vitro genotoxicity findings and to evaluate genotoxicity in target organs of toxicity. PMID:14681313

  5. The Aerosol Coarse Mode Initiative

    NASA Astrophysics Data System (ADS)

    Arnott, W. P.; Adhikari, N.; Air, D.; Kassianov, E.; Barnard, J.

    2014-12-01

    Many areas of the world show an aerosol volume distribution with a significant coarse mode and sometimes a dominant coarse mode. The large coarse mode is usually due to dust, but sea salt aerosol can also play an important role. However, in many field campaigns, the coarse mode tends to be ignored, because it is difficult to measure. This lack of measurements leads directly to a concomitant "lack of analysis" of this mode. Because, coarse mode aerosols can have significant effects on radiative forcing, both in the shortwave and longwave spectrum, the coarse mode -- and these forcings -- should be accounted for in atmospheric models. Forcings based only on fine mode aerosols have the potential to be misleading. In this paper we describe examples of large coarse modes that occur in areas of large aerosol loading (Mexico City, Barnard et al., 2010) as well as small loadings (Sacramento, CA; Kassianov et al., 2012; and Reno, NV). We then demonstrate that: (1) the coarse mode can contribute significantly to radiative forcing, relative to the fine mode, and (2) neglecting the coarse mode may result in poor comparisons between measurements and models. Next we describe -- in general terms -- the limitations of instrumentation to measure the coarse mode. Finally, we suggest a new initiative aimed at examining coarse mode aerosol generation mechanisms; transport and deposition; chemical composition; visible and thermal IR refractive indices; morphology; microphysical behavior when deposited on snow and ice; and specific instrumentation needs. Barnard, J. C., J. D. Fast, G. Paredes-Miranda, W. P. Arnott, and A. Laskin, 2010: Technical Note: Evaluation of the WRF-Chem "Aerosol Chemical to Aerosol Optical Properties" Module using data from the MILAGRO campaign, Atmospheric Chemistry and Physics, 10, 7325-7340. Kassianov, E. I., M. S. Pekour, and J. C. Barnard, 2012: Aerosols in Central California: Unexpectedly large contribution of coarse mode to aerosol radiative forcing

  6. Genotoxicity Studies of Titanium Dioxide Nanoparticles (TiO2NPs) in the Brain of Mice

    PubMed Central

    Mohamed, Hanan R. H.

    2016-01-01

    Titanium dioxide nanoparticles (TiO2NPs) are excessively used and represent one of the top five most commonly used nanoparticles worldwide. Recently, various studies referred to their toxic potential on various organs using different treatment route. Male Swiss Webster mice were orally administrated TiO2NPs (500 mg/kg b.w.) daily for five consecutive days and then animals were sacrificed at 24 h, 7 days, or 14 days after the last treatment. The present results report that exposure to TiO2NPs produces mild to moderate changes in the cytoarchitecture of brain tissue in a time dependent manner. Moreover, Comet assay revealed the apoptotic DNA fragmentation, while PCR-SSCP pattern and direct sequencing showed point mutation of Presenilin 1 gene at exon 5, gene linked to inherited forms of the Alzheimer's disease. Therefore, from these findings, the present study concluded that TiO2NPs is genotoxic and mutagenic to brain tissue which in turn might lead to Alzheimer's disease incidence. PMID:27034902

  7. Identification of genotoxic components of the heavy ends of energy-related materials

    SciTech Connect

    Lee, M.L. . Dept. of Chemistry); Castle, R.N. . Dept. of Chemistry)

    1990-02-01

    The objective of this work was to develop capillary supercritical fluid chromatographic methods for the analysis of the high-molecular-weight components in high boiling, heavy and materials that are responsible for genotoxic activity. Since these compounds were largely unknown, 62 standard reference compounds were synthesized for comparison with actual high boiling coal-derived products. These compounds were comprised of two- and three-ring aromatic moieties coupled together with carbon, oxygen, sulfur, and nitrogen bridging groups. Mass spectral evidence indicated that a number of these compound types could be present in various coal products at a concentration level of 0.01--0.2 percent, although none of them could be positively identified because of the complexities of the fractions. A number of capillary supercritical fluid chromatographic instrumental developments were made as a result of this work. These include a supercritical fluid fractionation system for group-type separation of complex samples and a direct coupled supercritical fluid chromatograph/double focusing mass spectrometer system. Finally, a number of supercritical fluid chromatographic mobile phase combinations were evaluated for the analysis of large polycyclic aromatic compounds. 34 refs., 23 figs., 2 tabs.

  8. Genotoxicity of neutrons in Drosophila melanogaster. Somatic mutation and recombination induced by reactor neutrons.

    PubMed

    Guzmán-Rincón, J; Delfín-Loya, A; Ureña-Núñez, F; Paredes, L C; Zambrano-Achirica, F; Graf, U

    2005-08-01

    This paper describes the observation of a direct relationship between the absorbed doses of neutrons and the frequencies of somatic mutation and recombination using the wing somatic mutation and recombination test (SMART) of Drosophila melanogaster. This test was used for evaluating the biological effects induced by neutrons from the Triga Mark III reactor of Mexico. Two different reactor power levels were used, 300 and 1000 kW, and two absorbed doses were tested for each power level: 1.6 and 3.2 Gy for 300 kW and 0.84 and 1.7 Gy for 1000 kW. A linear relationship was observed between the absorbed dose and the somatic mutation and recombination frequencies. Furthermore, these frequencies were dependent on larval age: In 96-h-old larvae, the frequencies were increased considerably but the sizes of the spots were smaller than in 72-h-old larvae. The analysis of the balancer-heterozygous progeny showed a linear absorbed dose- response relationship, although the responses were clearly lower than found in the marker-trans-heterozygous flies. Approximately 65% of the genotoxicity observed is due to recombinational events. The results of the study indicate that thermal and fast neutrons are both mutagenic and recombinagenic in the D. melanogaster wing SMART, and that the frequencies are dependent on neutron dose, reactor power, and the age of the treated larvae. PMID:16038586

  9. Inhibition of TGFbeta1 Signaling Attenutates ATM Activity inResponse to Genotoxic Stress

    SciTech Connect

    Kirshner, Julia; Jobling, Michael F.; Pajares, Maria Jose; Ravani, Shraddha A.; Glick, Adam B.; Lavin, Martin J.; Koslov, Sergei; Shiloh, Yosef; Barcellos-Hoff, Mary Helen

    2006-09-15

    Ionizing radiation causes DNA damage that elicits a cellular program of damage control coordinated by the kinase activity of ataxia telangiectasia mutated protein (ATM). Transforming growth factor {beta}1 (TGF{beta}), which is activated by radiation, is a potent and pleiotropic mediator of physiological and pathological processes. Here we show that TGF{beta} inhibition impedes the canonical cellular DNA damage stress response. Irradiated Tgf{beta}1 null murine epithelial cells or human epithelial cells treated with a small molecule inhibitor of TGF{beta} type I receptor kinase exhibit decreased phosphorylation of Chk2, Rad17 and p53, reduced {gamma}H2AX radiation-induced foci, and increased radiosensitivity compared to TGF{beta} competent cells. We determined that loss of TGF{beta} signaling in epithelial cells truncated ATM autophosphorylation and significantly reduced its kinase activity, without affecting protein abundance. Addition of TGF{beta} restored functional ATM and downstream DNA damage responses. These data reveal a heretofore undetected critical link between the microenvironment and ATM that directs epithelial cell stress responses, cell fate and tissue integrity. Thus, TGF{beta}1, in addition to its role in homoeostatic growth control, plays a complex role in regulating responses to genotoxic stress, the failure of which would contribute to the development of cancer; conversely, inhibiting TGF{beta} may be used to advantage in cancer therapy.

  10. Evolved Cellular Mechanisms to Respond to Genotoxic Insults: Implications for Radiation-Induced Hematologic Malignancies.

    PubMed

    Fleenor, Courtney J; Higa, Kelly; Weil, Michael M; DeGregori, James

    2015-10-01

    Human exposure to ionizing radiation is highly associated with adverse health effects, including reduced hematopoietic cell function and increased risk of carcinogenesis. The hematopoietic deficits manifest across blood cell types and persist for years after radiation exposure, suggesting a long-lived and multi-potent cellular reservoir for radiation-induced effects. As such, research has focused on identifying both the immediate and latent hematopoietic stem cell responses to radiation exposure. Radiation-associated effects on hematopoietic function and malignancy development have generally been attributed to the direct induction of mutations resulting from radiation-induced DNA damage. Other studies have illuminated the role of cellular programs that both limit and enhance radiation-induced tissue phenotypes and carcinogenesis. In this review, distinct but collaborative cellular responses to genotoxic insults are highlighted, with an emphasis on how these programmed responses impact hematopoietic cellular fitness and competition. These radiation-induced cellular programs include apoptosis, senescence and impaired self-renewal within the hematopoietic stem cell (HSC) pool. In the context of sporadic DNA damage to a cell, these cellular responses act in concert to restore tissue function and prevent selection for adaptive oncogenic mutations. But in the contexts of whole-tissue exposure or whole-body exposure to genotoxins, such as radiotherapy or chemotherapy, we propose that these programs can contribute to long-lasting tissue impairment and increased carcinogenesis. PMID:26414506

  11. The nonlinear tearing mode

    NASA Technical Reports Server (NTRS)

    Van Hoven, G.; Steinolfson, R. S.

    1984-01-01

    A series of nonlinear computations of tearing-mode development have been performed which achieve higher values of the magnetic Reynolds number and larger wavelengths than previously considered. A prime candidate for the realization of dynamic reconnection is the resistive magnetic tearing mode, a spontaneous instability of a stressed magnetic field. Typical simulations are described for a magnetic Lundquist number S of 10 to the 4th and wavelength parameters alpha from 0.05 to 0.5. In all cases, the nonlinear mode initially evolves at the linear growth rate, followed by a period of reduced growth. Another common feature is the formation of secondary flow vortices, near the tearing surface, which are opposite in direction to the initial linear vortices.

  12. New Edge Coherent Mode Providing Continuous Transport in Long-Pulse H-mode Plasmas

    NASA Astrophysics Data System (ADS)

    Wang, H. Q.; Xu, G. S.; Wan, B. N.; Ding, S. Y.; Guo, H. Y.; Shao, L. M.; Liu, S. C.; Xu, X. Q.; Wang, E.; Yan, N.; Naulin, V.; Nielsen, A. H.; Rasmussen, J. Juul; Candy, J.; Bravenec, R.; Sun, Y. W.; Shi, T. H.; Liang, Y. F.; Chen, R.; Zhang, W.; Wang, L.; Chen, L.; Zhao, N.; Li, Y. L.; Liu, Y. L.; Hu, G. H.; Gong, X. Z.

    2014-05-01

    An electrostatic coherent mode near the electron diamagnetic frequency (20-90 kHz) is observed in the steep-gradient pedestal region of long pulse H-mode plasmas in the Experimental Advanced Superconducting Tokamak, using a newly developed dual gas-puff-imaging system and diamond-coated reciprocating probes. The mode propagates in the electron diamagnetic direction in the plasma frame with poloidal wavelength of ˜8 cm. The mode drives a significant outflow of particles and heat as measured directly with the probes, thus greatly facilitating long pulse H-mode sustainment. This mode shows the nature of dissipative trapped electron mode, as evidenced by gyrokinetic turbulence simulations.

  13. 4-AMINOBIPHENYL & DNA REACTIVITY: CASE STUDY WITHIN THE CONTEXT OF THE 2006 IPCS HUMAN RELEVANCE FRAMEWORK FOR ANALYSIS OF A CANCER MODE OF ACTION FOR HUMANS

    EPA Science Inventory

    The IPCS Human Relevance Framework was evaluated for a DNA-reactive (genotoxic) carcinogen, 4-aminobiphenyl, based on a wealth of data in animals and humans. The mode of action involves metabolic activation by N-hydroxylation, followed by N-esterification leading to the formation...

  14. Investigations into the mechanisms of aflatoxin B sub 1 genotoxicity and carcinogenicity

    SciTech Connect

    Olsen, H.E.

    1989-01-01

    Aflatoxin B{sub 1} (AFB{sub 1}) was used as a model carcinogen for investigations into the initiation, promotion and progression phases of chemically induced carcinogenesis. In initial experiments {sup 3}H-AFB{sub 1} was evaluated for its rate of tritium exchange in vitro and in vivo. Tritium exchange form {sup 3}H-AFB{sub 1} to water in vitro (pH 7.4, 37{degree}C) and in-vivo from covalently bound AFB{sub 1} had a half-life of {approx}1 week. The physical interaction of AFB{sub 1} with DNA was examined to further characterize the steps involved in initiation. Using Nuclear Magnetic Resonance spectroscopy it was established that AFB{sub 1} binds to the outside of the DNA double helix and does not intercalate between the base pairs in spite of its relatively planar structure. In contrast to results obtained from NMR experiments, AFB{sub 1} and AFM{sub 1} were found to be direct acting mutagens in the Ames test and strain sensitivity indicated the direct mutagenicity was a result of a frameshift mutation suggesting intercalation. To determine if a free radical mechanism was converting the parent compound to a mutagenic derivative, the effect of the free radical inhibitor, butylated hydroxytoluene (BHT), on the mutagenicity of AFB{sub 1} to Salmonella typhimurium TA98 was determined. DNA sequences believed responsible for reversion of different Salmonella typhimurium strains were compared to the direct mutagenicity of AFB{sub 1} in these strains and with the rules reported in the literature for the sequence specific covalent binding of AFB{sub 1}. An alternative mechanism for the metabolic activation of AFB{sub 1} and AFM{sub 1} to genotoxic metabolites was investigated.

  15. The effective degeneracy of protein normal modes

    NASA Astrophysics Data System (ADS)

    Na, Hyuntae; Song, Guang

    2016-06-01

    Normal modes are frequently computed and used to portray protein dynamics and interpret protein conformational changes. In this work, we investigate the nature of normal modes and find that the normal modes of proteins, especially those at the low frequency range (0–600 cm‑1), are highly susceptible to degeneracy. Two or more modes are degenerate if they have the same frequency and consequently any orthogonal transformation of them also is a valid representation of the mode subspace. Thus, degenerate modes can no longer characterize unique directions of motions as regular modes do. Though the normal modes of proteins are usually of different frequencies, the difference in frequency between neighboring modes is so small that, under even slight structural uncertainty that unavoidably exists in structure determination, it can easily vanish and as a result, a mode becomes effectively degenerate with its neighboring modes. This can be easily observed in that some modes seem to disappear and their matching modes cannot be found when the structure used to compute the modes is modified only slightly. We term this degeneracy the effective degeneracy of normal modes. This work is built upon our recent discovery that the vibrational spectrum of globular proteins is universal. The high density of modes observed in the vibrational frequency spectra of proteins renders their normal modes highly susceptible to degeneracy, under even the smallest structural uncertainty. Indeed, we find the degree of degeneracy of modes is proportional to the density of modes in the vibrational spectrum. This means that for modes at the same frequency, degeneracy is more severe for larger proteins. Degeneracy exists also in the modes of coarse-grained models, but to a much lesser extent than those of all-atom models. In closing, we discuss the implications of the effective degeneracy of normal modes: how it may significantly affect the ways in which normal modes are used in various normal modes

  16. The effective degeneracy of protein normal modes.

    PubMed

    Na, Hyuntae; Song, Guang

    2016-01-01

    Normal modes are frequently computed and used to portray protein dynamics and interpret protein conformational changes. In this work, we investigate the nature of normal modes and find that the normal modes of proteins, especially those at the low frequency range (0-600 cm(-1)), are highly susceptible to degeneracy. Two or more modes are degenerate if they have the same frequency and consequently any orthogonal transformation of them also is a valid representation of the mode subspace. Thus, degenerate modes can no longer characterize unique directions of motions as regular modes do. Though the normal modes of proteins are usually of different frequencies, the difference in frequency between neighboring modes is so small that, under even slight structural uncertainty that unavoidably exists in structure determination, it can easily vanish and as a result, a mode becomes effectively degenerate with its neighboring modes. This can be easily observed in that some modes seem to disappear and their matching modes cannot be found when the structure used to compute the modes is modified only slightly. We term this degeneracy the effective degeneracy of normal modes. This work is built upon our recent discovery that the vibrational spectrum of globular proteins is universal. The high density of modes observed in the vibrational frequency spectra of proteins renders their normal modes highly susceptible to degeneracy, under even the smallest structural uncertainty. Indeed, we find the degree of degeneracy of modes is proportional to the density of modes in the vibrational spectrum. This means that for modes at the same frequency, degeneracy is more severe for larger proteins. Degeneracy exists also in the modes of coarse-grained models, but to a much lesser extent than those of all-atom models. In closing, we discuss the implications of the effective degeneracy of normal modes: how it may significantly affect the ways in which normal modes are used in various normal modes

  17. Cytotoxic, mutagenicity, and genotoxicity effects of guanylhydrazone derivatives.

    PubMed

    Pinhatti, Valéria Rodrigues; da Silva, Juliana; Martins, Tales Leandro Costa; Moura, Dinara Jaqueline; Rosa, Renato Moreira; Villela, Izabel; Stopiglia, Cheila Denise Ottonelli; da Silva Santos, Selma; Scroferneker, Maria Lúcia; Machado, Carlos Renato; Saffi, Jenifer; Henriques, João Antonio Pêgas

    2016-08-01

    Several studies have reported that guanylhydrazones display a variety of desirable biological properties, such as antihypertensive, antibacterial, and antimalarial behaviour. They furthermore promote anti-pneumocystosis and anti-trypanosomiasis, exhibit antitumor activity, and show significant cytotoxicity against cancer cell lines. In this work, we have evaluated the cytotoxicity, mutagenicity, and genotoxicity of two guanylhydrazones derivatives, (E)-2-[(2,3-dimethoxyphenyl) methylene] hydrazine carboxymidamide hydrochloride (2,3-DMeB) and (E)-2-[(3,4-dimethoxyphenyl) methylene] hydrazine carboxymidamide hydrochloride (3,4-DMeB), in different biological models. Both 2,3-DMeB and 3,4-DMeB induce weak cytotoxic and mutagenic effects in bacteria and yeast. The genotoxicity of these compounds was determined in a fibroblast cell line (V79) using alkaline comet assay, as well as a modified comet assay with bacterial enzymes formamidopyrimidine DNA-glycosylase (FPG) and endonuclease III (EndoIII). Both guanylhydrazone derivatives induced DNA damage. Treatment of V79 cells with EndoIII and FPG proteins demonstrated a significant effect of 2,3-DMeB and 3,4-DMeB with respect to oxidized bases. In addition, the derivatives induced a significant increase in the frequency of micronucleated cells at high doses. The antifungal and anti-trypanosomal properties of these guanylhydrazone derivatives were also evaluated, and the obtained results suggest that 2,3-DMeB is more effective than 3,4-DMeB. The biological activity of 2,3-DMeB and 3,4-DMeB may thus be related, at least in part, to their oxidative potential, as well as to their ability to interact with DNA. Considering the previously reported in vitro antitumor activity of guanylhydrazone derivatives in combination with the lack of acute toxicity and the fact that DNA damage is only observed at high doses should render both compounds good candidates for in vivo studies on antitumor activity. PMID:27476330

  18. The cytotoxicity and genotoxicity of soluble and particulate cobalt in human lung fibroblast cells

    SciTech Connect

    Smith, Leah J.; Holmes, Amie L.; Kandpal, Sanjeev Kumar; Mason, Michael D.; Zheng, Tongzhang; Wise, John Pierce

    2014-08-01

    Cobalt exposure is increasing as cobalt demand rises worldwide due to its use in enhancing rechargeable battery efficiency, super-alloys, and magnetic products. Cobalt is considered a possible human carcinogen with the lung being a primary target. However, few studies have considered cobalt-induced toxicity in human lung cells. Therefore, in this study, we sought to determine the cytotoxicity and genotoxicity of particulate and soluble cobalt in human lung cells. Cobalt oxide and cobalt chloride were used as representative particulate and soluble cobalt compounds, respectively. Exposure to both particulate and soluble cobalt induced a concentration-dependent increase in cytotoxicity, genotoxicity, and intracellular cobalt ion levels. Based on intracellular cobalt ion levels, we found that soluble cobalt was more cytotoxic than particulate cobalt while particulate and soluble cobalt induced similar levels of genotoxicity. However, soluble cobalt induced cell cycle arrest indicated by the lack of metaphases at much lower intracellular cobalt concentrations compared to cobalt oxide. Accordingly, we investigated the role of particle internalization in cobalt oxide-induced toxicity and found that particle-cell contact was necessary to induce cytotoxicity and genotoxicity after cobalt exposure. These data indicate that cobalt compounds are cytotoxic and genotoxic to human lung fibroblasts, and solubility plays a key role in cobalt-induced lung toxicity. - Highlights: • Particulate and soluble cobalt are cytotoxic and genotoxic to human lung cells. • Soluble cobalt induces more cytotoxicity compared to particulate cobalt. • Soluble and particulate cobalt induce similar levels of genotoxicity. • Particle-cell contact is required for particulate cobalt-induced toxicity.

  19. Evaluation of the genotoxicity of process stream extracts from a coal gasification system.

    PubMed

    Shimizu, R W; Benson, J M; Li, A P; Henderson, R F; Brooks, A L

    1984-01-01

    Extracts of three complex organic environmental mixtures, two from an experimental coal gasifier (a raw gas and a clean gas sample) and one from a coke oven main, were examined for genotoxicity. Three short-term genotoxicity assay systems were used: Ames Salmonella typhimurium reverse mutation assay, Chinese hamster ovary cell/hypoxanthine-guanine phosphoribosyl transferase (CHO/HGPRT) gene locus mutation assay, and the Chinese hamster lung primary culture/sister chromatid exchange (CHL/SCE) assay. Aroclor-1254-induced rat liver homogenate fraction (S-9) was required to observe genotoxicity in both gene locus mutation assays (CHO/HGPRT and Ames). The relative survival of CHO cells exposed to extracts was highest in cells exposed to clean gas samples, with the raw gas sample being the most cytotoxic either with or without the addition of S-9. All three complex mixtures induced sister chromatid exchanges in primary lung cell cultures without the addition of S-9. The relative genotoxicity ranking of the samples varied between the mammalian and prokaryotic assay systems. Coke oven main extract produced fewer revertants in bacteria than the raw gas sample. However, the coke oven main extract was more genotoxic in the two eukaryotic systems (CHL/SCE and CHO/HGPRT) than was the raw gas sample. The results of all three assays indicate that the cleanup process used in the experimental gasifier was effective in decreasing the genotoxic materials in the process stream. These data also reemphasize the necessity of evaluating genotoxicity of complex mixtures in a variety of short-term systems. PMID:6389110

  20. Evaluation of the genotoxicity of process stream extracts from a coal gasification system

    SciTech Connect

    Shimizu, R.W.; Benson, J.M.; Li, A.P.; Henderson, R.F.; Brooks, A.L.

    1984-01-01

    Extracts of three complex organic environmental mixtures, two from an experimental coal gasifier (a raw gas and a clean gas sample) and one from a coke oven main, were examined for genotoxicity. Three short-term genotoxicity assay systems were used: Ames Salmonella typhimurium reverse mutation assay, Chinese hamster ovary cell/hypoxanthine-guanine phosphoribosyl transferase (CHO/HGPRT) gene locus mutation assay, and the Chinese hamster lung primary culture/sister chromatid exchange (CHL/SCE) assay. Aroclor-1254-induced rat liver homogenate fraction (S-9) was required to observe genotoxicity in both gene locus mutation assays. The relative survival of CHO cells exposed to extracts was highest in cells exposed to clean gas samples, with the raw gas sample being the most cytotoxic either with or without the addition of S-9. All three complex mixtures induced sister chromatid exchanges in primary lung cell cultures without the addition of S-9. The relative genotoxicity ranking of the samples varied between the mammalian and prokaryotic assay systems. Coke oven main extract produced fewer revertants in bacteria than the raw gas sample. However, the coke oven main extract was more genotoxic in the two eukaryotic systems (CHL/SCE and CHO/HGPRT) than was the raw gas sample. The results of all three assays indicate that the cleanup process used in the experimental gasifier was effective in decreasing the genotoxic materials in the process stream. These data also reemphasize the necessity of evaluating genotoxicity of complex mixtures in a variety of short-term systems. 24 references, 3 figures, 2 tables.