Gewässer sind Lebensgrundlage, jedoch gleichzeitig Schadstoffsenken für eine Vielzahl von Kontaminanten. Biologische Wirkungstests und das Biomonitoring aquatischer Proben sind daher besonders wichtig, um Umwelt-Gefahrenpotenziale erkennen zu können. Der "Comet Assay" (Einzelzell-Gelelektrophorese) ist ein Indikator von DNA-Strangbrüchen und wurde hier als Test auf gentoxische Wirkungen erprobt und angewandt. Mit bekannten, gentoxischen Substanzen wurden Nachweisgrenzen und Dosis-Wirkungs-Beziehungen für die Zelllinien RTG-2 und RTL-W1 (aus der Regenbogenforelle, Oncorhynchus mykiss) in vitro ermittelt und methodische Parameter an die Zellen angepasst. Der Test reagierte sehr sensitiv auf 4-Nitrochinolin-1-oxid. Die Substanz war daher geeignet, um in weiteren Versuchen als Positivkontrolle zu dienen. Zur Bewertung der Messdaten wurde ein geeignetes statistisches Verfahren gefunden, das auch historische Kontrollen mit einbezog. Der zeitliche Verlauf der DNA-Schädigung des Testsystems mit RTG-2-Zellen wurde ermittelt, und durch Inhibition der DNA-Reparatur mit Aphidicolin wurden Zusammenhänge zwischen der Entstehung von DNA-Strangbrüchen, der DNA-Reparaturkapazität sowie der Metabolisierungskapazität untersucht. In einer zweiten Phase wurden unbehandelte Wasserproben aus Rhein, Elbe sowie weitere Oberflächenwasserproben mit dem Comet Assay an RTG-2-Zellen getestet. Bei 15 von 49 Proben zeigten sich gentoxische Effekte. In einer dritten Phase wurden Erythrozyten von freilebenden Döbeln, Leuciscus cephalus, aus der Mosel mit dem Comet Assay untersucht. Die Fische von drei Messstellen zeigten erhöhte Werte von DNA-Schädigungen, gegenüber einer vierten, stromabwärts gelegenen Messstation. Korrelationen mit den Ergebnissen zusätzlicher Biomarker ergaben sich nur teilweise. Chemische Analysen von Wasser- oder Gewebeproben ließen keine Rückschlüsse auf verursachende Kontaminanten zu - gerade dies unterstreicht jedoch die Wichtigkeit biologischer Tests bei komplexen Proben. / Bodies of Water are both vital resources and pollutant sinks for a multitude of contaminants. Therefore, biological effect tests and biomonitoring of aquatic samples are of particular importance to detect potential environmental hazards. The "comet assay" (single cell gel electrophoresis) is an indicator for DNA strand breaks and was explored and applied as a genotoxicity test in the present study. Known genotoxic substances were used to determine the detection limits and dose-response relationships for the cell lines RTG-2 and RTL-W1 (from rainbow trout, Oncorhynchus mykiss) in vitro, and to adapt methodological parameters to the cells. The test was very sensitive to 4-Nitroquinoline-1-oxide. This substance was therefore well-suited to serve as positive control in further experiments. In order to evaluate the measurement data, an appropriate statistical procedure was developed, which also took "historical" controls into account. The time course of DNA damage in the test system using RTG-2 cells was determined, and relationships between the origin of DNA strand breaks, DNA repair capacity and the metabolizing capacity of the cells was investigated by means of inhibition of DNA repair with Aphidicoline. In the second stage, native water samples from the rivers Rhine and Elbe and further surface waters were tested with the comet assay, using RTG-2 cells. 15 out of 49 samples showed genotoxic effects. In a third stage, erythrocytes of feral chub, Leuciscus cephalus, from the Moselle river were examined with the comet assay. The fish from three measuring stations showed elevated values of DNA damage compared to fish sampled from a downstream station. There were only partly correlations with the results from additional biomarkers. Chemical analyses of water and tissue samples did not permit conclusions on effect-causing substances.However, this emphasizes the importance of biological tests in dealing with complex environmental samples.

AIMS: The rapidly growing industrial and medical use of nanomaterials, especially zinc oxide and titanium dioxide, has led to growing concerns about their toxicity. Accordingly, the intrinsic genotoxic and cytotoxic potential of these nanoparticles have been evaluated. MATERIALS & METHODS: Using a HEp-2 cell line, cytotoxicity was tested along with mitochondrial activity and neutral red uptake assays. The genotoxic potential was determined using the Comet and the cytokinesis-blocked micronucleus assays. In addition, tyrosine phosphorylation events were investigated. RESULTS & CONCLUSION: We found concentration- and time-dependent cytotoxicity and an increase in DNA and cytogenetic damage with increasing nanoparticle concentrations. Mainly for zinc oxide, genotoxicity was clearly associated with an increase in tyrosine phosphorylation. Our results suggest that both types of nanoparticles can be genotoxic over a range of concentrations without being cytotoxic.

Here I study the “plasma interactions with icy bodies in the solar system”, that is, my quest to understand the fundamental processes that govern such interactions. By using numerical modelling combined with in situ observations, one can infer the internal structure of icy bodies and their plasma environments. After a broad overview of the laws governing space plasmas a more detailed part follows. This contains the method on how to model the interaction between space plasmas and icy bodies. Numerical modelling of space plasmas is applied to the icy bodies Callisto (a satellite of Jupiter), the dwarf planet Ceres (located in the asteroid main belt) and the comet 67P/Churyumov-Gerasimenko. The time-varying magnetic field of Jupiter induces currents inside the electrically conducting moon Callisto. These create magnetic field perturbations thought to be related to conducting subsurface oceans. The flow of plasma in the vicinity of Callisto is greatly affected by these magnetic field perturbations. By using a hybrid plasma solver, the interaction has been modelled when including magnetic induction and agrees well with magnetometer data from flybys (C3 and C9) made by the Galileo spacecraft. The magnetic field configuration allows an inflow of ions onto Callisto’s surface in the central wake. Plasma that hits the surface knocks away matter (sputtering) and creates Callisto’s tenuous atmosphere. A long term study of solar wind protons as seen by the Rosetta spacecraft was conducted as the comet 67P/Churyumov-Gerasimenko approached the Sun. Here, extreme ultraviolet radiation from the Sun ionizes the neutral water of the comet’s coma. Newly produced water ions get picked up by the solar wind flow, and forces the solar wind protons to deflect due to conservation of momentum. This effect of mass-loading increases steadily as the comet draws closer to the Sun. The solar wind is deflected, but does not lose much energy. Hybrid modelling of the solar wind interaction with the coma agrees with the observations; the force acting to deflect the bulk of the solar wind plasma is greater than the force acting to slow it down. Ceres can have high outgassing of water vapour, according to observations by the Herschel Space Observatory in 2012 and 2013. There, two regions were identified as sources of water vapour. As Ceres rotates, so will the source regions. The plasma interaction close to Ceres depends greatly on the source location of water vapour, whereas far from Ceres it does not. On a global scale, Ceres has a comet-like interaction with the solar wind, where the solar wind is perturbed far downstream of Ceres. / Här studerar jag “plasmaväxelverkan med isiga kroppar i solsystemet”, det vill säga, min strävan är att förstå de grundläggande processerna som styr sådana interaktioner. Genom att använda numerisk modellering i kombination med observationer på plats vid himlakropparna kan man förstå sig på deras interna strukturer och rymdmiljöer. Efter en bred översikt över de fysiska lagar som styr ett rymdplasma följer en mer detaljerad del. Denna innehåller metoder för hur man kan modellera växelverkan mellan rymdplasma och isiga kroppar. Numerisk modellering av rymdplasma appliceras på de isiga himlakropparna Callisto (en måne kring Jupiter), dvärgplaneten Ceres (lokaliserad i asteroidbältet mellan Mars och Jupiter) och kometen 67P/Churyumov-Gerasimenko. Det tidsvarierande magnetiska fältet kring Jupiter inducerar strömmar inuti den elektriskt ledande månen Callisto. Dessa strömmar skapar magnetfältsstörningar som tros vara relaterade till ett elektriskt ledande hav under Callistos yta. Plasmaflödet i närheten av Callisto påverkas i hög grad av dessa magnetfältsstörningar. Genom att använda en hybrid-plasma-lösare har växelverkan modellerats, där effekten av magnetisk induktion har inkluderats. Resultaten stämmer väl överens med magnetfältsdata från förbiflygningarna av Callisto (C3 och C9) som gjordes av den obemannade rymdfarkosten Galileo i dess bana kring Jupiter. Den magnetiska konfigurationen som uppstår möjliggör ett inflöde av laddade joner på Callistos baksida. Plasma som träffar ytan slår bort materia och skapar Callistos tunna atmosfär. En långtidsstudie av solvindsprotoner sett från rymdfarkosten Rosetta utfördes då kometen 67P/Churyumov-Gerasimenko närmade sig solen. Ultraviolett strålning från solen joniserar det neutrala vattnet i kometens koma (kometens atmosfär). Nyligt joniserade vattenmolekyler plockas upp av solvindsflödet och tvingar solvindsprotonernas banor att böjas av, så att rörelsemängden bevaras. Denna effekt ökar stadigt då kometen närmar sig solen. Solvinden böjs av kraftigt, men förlorar inte mycket energi. Hybridmodellering av solvindens växelverkan bekräftar att kraften som verkar på solvinden till störst del får den att böjas av, medan kraften som verkar till att sänka dess fart är mycket lägre. Ceres har enligt observationer av rymdteleskopet Herschel under 2012 och 2013 haft högt utflöde av vattenånga från dess yta. Där har två regioner identifierats som källor för vattenångan. Eftersom Ceres roterar kommer källornas regioner göra det också. Plasmaväxelverkan i närheten av Ceres beror i hög grad på vattenångskällans placeringen, medan det inte gör det långt ifrån Ceres. På global nivå har Ceres en kometliknande växelverkan med solvinden, där störningar i solvinden propagerar långt nedströms från Ceres.

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2018-05-03T13:16:12Z No. of bitstreams: 2 Tese - Wanessa Fernandes Carvalho - 2018.pdf: 4178094 bytes, checksum: 12ab926257d567aaefec72a5d4d53bf7 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2018-05-03T13:23:49Z (GMT) No. of bitstreams: 2 Tese - Wanessa Fernandes Carvalho - 2018.pdf: 4178094 bytes, checksum: 12ab926257d567aaefec72a5d4d53bf7 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2018-05-03T13:23:49Z (GMT). No. of bitstreams: 2 Tese - Wanessa Fernandes Carvalho - 2018.pdf: 4178094 bytes, checksum: 12ab926257d567aaefec72a5d4d53bf7 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2018-03-23 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The increased use of pesticides, the risks and disruptions that these compounds can cause to organisms and the environment has been much discussed in recent years. 2,4-D and glyphosate herbicides are applied post-emergence in large-scale crops and play an important role in the optimization of agricultural production worldwide. Environmental quality bioindicators are used in environmental impact assessment studies because of their interaction with the environment and their ease of absorption and accumulation of xenobiotic compounds (Younes, 2000). Therefore, the objective of this study was to evaluate the genotoxic and mutagenic effects of herbicides on environmental quality bionicators. Acute toxicity of Credit® at 48%, Herbifen Super® at 97%, Weedar Full® at 83.5%, Dedalo elite® at 30%, and Imazethapyr and their binary combinations were tested on Cnesterodon decemmaculatus, Rhinella arenarum and Dendropsophus minutus. The lethal effect was determined from experiments with mortality and the sublethal was used the single cell gel electrophoresis (SCGE) bioassay and the micronucleus test. The LC5096h value for Herbifen Super® was 2.668 mg / L, Weedar Full® was 678.04 mg / L, Dedalo elite® was 0.463 mg / L and for Credit® was 91.73 mg / L and Imazethapyr® was 0.99 mg / L. The results of this study demonstrated that the comet assay and the micronucleus test are highly sensitive methods for the detection of herbicide-induced DNA damage in aquatic organisms. The herbicides tested showed different behaviors when combined at their concentrations of 5% and 10% of LC5096h. The toxic effect of the combination of Herbifen Super® and Credit® was basically due to the action of the active principle glyphosate present in Credit®. For Weedar Full® and Dedalo elite® herbicides, synergism was observed in combinations of 5% and 10% of LC5096h values. Our study is the first report on the induction of lethal acute and sublethal effects of Credit® binary combinations; Herbifen Super®, Weedar Full®, Dedalo elite®; Imazethapyr® in aquatic organisms. / O aumento da utilização dos pesticidas, os riscos e perturbações que esses compostos podem provocar aos organismos e ao meio ambiente está sendo bastante discutido nos últimos anos. Os herbicidas 2,4-D e glifosato são aplicados em pós-emergência em culturas de larga escala e desempenham um papel importante na otimização da produção agrícola em todo o mundo. Os bioindicadores de qualidade ambiental são utilizados em estudos de avaliações de impacto ambiental devido sua interação com o meio ambiente e a sua facilidade de absorção e acumulação de compostos xenobióticos (Younes, 2000). Sendo assim, o objetivo deste estudo foi avaliar os efeitos genotóxicos e mutagênicos de herbicidas em biondicadores de qualidade ambiental. A toxicidade aguda do Credit® a 48%, Herbifen Super® a 97%, Weedar Full® a 83.5%, Dedalo elite® a 30% e Imazethapyr e suas combinações binárias foram testadas em Cnesterodon decemmaculatus, Rhinella arenarum e Dendropsophus minutus. O efeito letal foi determinado a partir de experiências com mortalidade e o subletal foi utilizado o bioensaio de eletroforese em gel de célula única (SCGE) e oteste do micronúcleo. O valor LC5096h para Herbifen Super® foi de 2.668 mg / L, Weedar Full® foi de 678,04 mg/L, Dedalo elite® foi de 0,463 mg/L e para Credit® foi de 91.73 mg /L e Imazethapyr® foi de 0.99 mg/L. Os resultados deste estudo demontraram que o ensaio cometa e o teste do micronúcleo são métodos altamente sensíveis para a detecção de danos ao DNA induzidos por herbicidas em organismos aquáticos. Os herbicidas testados revelaram diferentes comportamentos ao serem combinados em suas concentrações de 5% e 10% da CL5096h. O efeito tóxico da combinação entre Herbifen Super® e Credit® deu-se basicamente pela ação do princípio ativo glifosato presente no Credit®. Para os herbicidas Weedar Full® e Dedalo elite® foi observado um sinergismo nas combinações de 5% e 10% dos valores de CL5096h. Nosso estudo constitui o primeiro relatório sobre a indução de efeitos agudos letais e subletal de combinações binárias de Credit® ; Herbifen Super® , Weedar Full® , Dedalo elite® ; Imazethapyr® em organismos aquáticos.

Made available in DSpace on 2014-07-29T15:16:29Z (GMT). No. of bitstreams: 1 MANUELA da rocha.pdf: 1137336 bytes, checksum: 8f429c6f06f0af7ebb98f1fc1b0badbe (MD5) Previous issue date: 2010-02-24 / Chemotherapy agents are increasingly being utilized due to their promising effects in cancer treatment. The desired actions of these drugs are obtained at the cost of frequent and severe side effects. It is essential that drugs utilized for cancer treatment are tested in relation to not only their cytotoxic, but also their clastogenic and genotoxic potentials to establish their clinical risk. Thus, there is increased interest in searching for new metallic compounds presenting antitumor activity with therapeutic potential and reduced side effects, such as those containing platinum (Pt), iron (Fe), titanium (Ti), rhodium (Rh), gold (Au) and ruthenium (Ru). In this work, the cytotoxic, clastogenic and genotoxic properties of cis-tetraamine(oxalato)ruthenium(III) dithionite, cis-[Ru(C2O4)(NH3)4]2(S2O6), were evaluated in peripheral human blood lymphocytes in vitro. Mitotic index (MI), chromosomal aberrations (CA) and DNA damage were analyzed by comet assay. The MI values of human peripheral blood lymphocyte cultures treated with 0.0075, 0.075, 0.75 and 7.5 μM cis-[Ru(C2O4)(NH3)4]2(S2O6) were 6.1, 3.9, 3.2 and 0.2%, respectively. The lowest concentration 0.0075 did not show cytotoxic activity compared to negative control. The CA values obtained for the 0.0075, 0.075 and 0.75 μM concentrations presenting low frequency (1.5, 1.6 and 2.3%, respectively) not expressing clastogenic activity compared to negative control and only at the highest concentration 7.5 μM, showed clastogenic activity, predominantly chromatid breaks and gaps. The data obtained by the comet assay, using cis-[Ru(C2O4)(NH3)4]2(S2O6), suggest that this compound does not show genotoxic activity at concentrations lower than 0.0075 μM. The results of these studies show that cis-[Ru(C2O4)(NH3)4]2(S2O6) has no potential cytotoxic, clastogenic and genotoxic in vitro at concentrations less than or equal to 0.0075 μM. / Estudos de citoxicidade e genotoxicidade têm sido realizados para o desenvolvimento de novos agentes anticâncer com maior seletividade e menores efeitos colaterais de agentes antitumorais convencionais. Neste trabalho, foram avaliadas as propriedades citotóxicas, clastogênicas e genotóxicas do composto ditionato de cis-tetraamino(oxalato)rutênio(III), {cis-[Ru(C2O4)(NH3)4]2(S2O6)}, em cultura de linfócitos de sangue periférico humano in vitro. Foram analisados os parâmetros índice mitótico (IM), aberrações cromossômicas (ACs) e danos induzidos no DNA detectados pelo ensaio cometa. O IM de cultura de linfócitos de sangue periférico humano tratados com 0,0075; 0,075; 0,75 e 7,5μM de {cis-[Ru(C2O4)(NH3)4]2(S2O6)} foram 6,1; 3,9; 3,2 e 0,2%, respectivamente. A menor concentração 0,0075 não apresentou atividade citotóxica comparada ao controle negativo. As ACs derivadas das concentrações 0,0075; 0,075 e 0,75, apresentaram frequência de 1,5; 1,6 e 2,3 %, respectivamente, não manifestando atividade clastogênica comparadas ao contole negativo e somente na concentração de 7,5μM, demonstrou atividade clastogênica, predominando quebras e falhas cromatídicas. Os dados obtidos por meio do ensaio cometa, utilizando {cis-[Ru(C2O4)(NH3)4]2(S2O6)}, sugerem que este composto não apresenta atividade genotóxica em concentrações menores que 0,0075 μM. Os resultados desses estudos demonstram que {cis-[Ru(C2O4)(NH3)4]2(S2O6)} não possui potencial citotóxico, clastogênico e genotóxica in vitro em concentrações menor ou igual a 0,0075 μM.

Do metal particles (including particles of pure metals, alloys, metal oxides and compounds) pose a hazard or risk to human health? In the light of this question, this thesis summarizes results from research conducted on metal particles, and describes the elaboration and implementation of an in vitro test methodology to study metal release from particles through corrosion and dissolution processes in synthetic biological media relevant for human exposure through inhalation/ingestion and dermal contact. Bioaccessible metals are defined as the pool of released metals from particles that potentially could be made available for absorption by humans or other organisms. Studies of bioaccessible metals from different metal particles within this thesis have shown that the metal release process is influenced by material properties, particle specific properties, size distribution, surface area and morphology, as well as the chemistry of synthetic biological test media simulating various human exposure scenarios. The presence of metal particles in proximity to humans and the fact that metals can be released from particles to a varying extent is the hazard referred to in the title. The bioavailable metal fraction of the released metals (the fraction available for uptake/absorption by humans through different exposure routes) is usually significantly smaller than the bioaccessible pool of released metals, and is largely related to the chemical form and state of oxidation of the released metals. Chemical speciation measurements of released chromium for instance revealed chromium to be complexed to its non-available form in simulated lung fluids. Such measurements provide an indirect measure of the potential risk for adverse health effects, when performed at relevant experimental conditions. A more direct way to assess risks is to conduct toxicological in-vitro testing of metal particles, for instance on lung cell cultures relevant for human inhalation. Induced toxicity of metal particles on lung cells includes both the effect of the particles themselves and of the released metal fraction (including bioaccessible and bioavailable metals), the latter shown to be less predominant. The toxic response was clearly influenced by various experimental conditions such as sonication treatment of particles and the presence of serum proteins. Thorough characterization of metal particles assessing parameters including chemical surface composition, degree of agglomeration in solution, size distribution, surface area and morphology was performed and discussed in relation to generated results of bioaccessibility, bioavailability and induced toxicity. One important conclusion was that neither the surface composition nor the bulk composition can be used to assess the extent of metals released from chromium-based alloy particles. These findings emphasize that information on physical-chemical properties and surface characteristics of particles is essential for an in-depth understanding of metal release processes and for further use and interpretation of bioaccessibility data to assess hazard and reduce any risks induced by human exposure to metal particles. / QC 20100803

The essay examines how characters in the Moomin novels change through relationships based on a psychosynthetic subpersonality analysis. This is a new perspective in the field of literature and therefore a solid theoretical basis in psychosynthesis is given and a presentation of my method which includes the concept of subpersonalities. Then three main constellations of characters that focus on Moomin, Sniff, Snufkin, Moominmamma, the Groke, Fillyjonk, Hemulen and Whomper Toft are analyzed. From my discussion it appears that the characters are types who each have their own way of being, thinking and feeling, and in this way Tove Jansson writes a whole where differences may exist. With my perspective, the light is directed towards how the characters integrate sides of each other and thereby develop. The results show that the characters change through the relationships between them, and that a synthesis in each constellation arises.

No description available.