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Dissertations / Theses on the topic 'Mutagens'
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1
Papaparaskeva-Petrides, Christina. "Mutagens in edible mushrooms." Thesis, University of Surrey, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.314464.
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Schuisky, Peter. "Synthesis of metal complexes and potential food mutagens /." Uppsala : Swedish Univ. of Agricultural Sciences (Sveriges lantbruksuniv.), 1998. http://epsilon.slu.se/avh/1998/91-576-5517-0.gif.
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Ayrton, Andrew David. "Food mutagens : factors that modulate their metabolic activation." Thesis, University of Surrey, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.328576.
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Kanungnit, Pupatwibul Brockman Herman E. "Effects of six dietary antimutgen[sic] on the mutagenicity of five dietary mutagens in Salmonella typhimurium strains TA98 and SV50." Normal, Ill. Illinois State University, 1992. http://wwwlib.umi.com/cr/ilstu/fullcit?p9234467.
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Thesis (Ph. D.)--Illinois State University, 1992.Title from title page screen, viewed January 30, 2006. Dissertation Committee: Herman E. Brockman (chair), Alan J. Katz, Brian J. Wilkinson, Lynne A. Lucher, Radheshaym Jayaswal. Includes bibliographical references (leaves 115-123) and abstract. Also available in print.
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Tippins, T. A. "Various factors which affect the response of yeast cells to environmental mutagens." Thesis, Swansea University, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.639246.
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This project investigates the factors which may affect the response of yeast cells to potential mutagens and thus to optimise their response. The problem was approached from four main angles as follows: i) permeability - rendering the cells more permeable either by pre-treatment with selected chemicals or by selecting clones with cell wall defects; ii) repair capacity - preventing adequate repair of damaged DNA either by post-treatment with repair inhibitors or by using strains with defective repair genes; iii) genetic background - looking at reversion in the same gene but in a different genetic background or different genes in the same background; iv) treatment conditions - treating cells in buffer or broth, with or without exogenous activation, at 28 C or 37 C. The general conclusions which may be drawn from these studies are: a) most chemical mutagens are able to enter the yeast cells in sufficient quantities to cause damage to the DNA without pre-treating the cells to increase their permeability; b) the repair capacity of a cell is a very important factor in its response to a mutagen and if this capacity is greatly impaired, then the chances of survival of the cell after treatment with a mutagen are greatly reduced; c) the genetic background of a cell and the marker under consideration can affect the response of the cell to a mutagen; d) the conditions under which yeast cells are exposed to mutagens affect both the response of the yeast cells and the effectiveness of the mutagen itself. As for optimising the response of the yeast cells to mutagens this can only be done by gathering together all the information already known about the compound under study, and any related compounds, and analysing this data to discover what treatment conditions should be used and possibly what test.
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Howes, A. J. "In vitro and in vivo studies of mutagens found in cooked food." Thesis, University of Surrey, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.378734.
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Manna, David. "Mutational analysis of the central channel in the Simian virus 40 large T antigen helicase." Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file 2.82 Mb., 110 p, 2006. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&res_dat=xri:pqdiss&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:1435876.
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Sedijani, Prapti, of Western Sydney Hawkesbury University, of Science Technology and Agriculture Faculty, and School of Horticulture. "The use of mutagenic agents to increase the protein content and improve the amino acid composition of sweet potato (Ipomea batatas Lam.)." THESIS_FSTS_HOR_Sedijani_P.xml, 1997. http://handle.uws.edu.au:8081/1959.7/647.
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The sweet potato has become a major international crop and it is also the main staple food for many people in the developing world. This crop is desirable as it is high yielding, easy to grow and has a low cost of production. However, the tubers have a low protein content and a low concentration of amino acids, particularly the aspartate amino acid. This has contributed to malnutrition in some areas. To help overcome this problem this study had the aim of producing lines of sweet potato with increased nutritional values. Two varieties, Beauregard and LO322, were selected for study as they have a good flavour and a high beta-carotene content. The conditions for the tissue culture of these varieties were determined by altering the mineral and hormonal composition of the culture medium. Increases in nutritional composition were induced by treating calli with mutagenic agents which included : colchicine, ethylmethanesulphonate, UV radiation and two levels of gamma radiation. Putative mutants with reduced feedback inhibition in the pathways which lead to the synthesis of the aspartate amino acids were selected by placing calli on media containing increasing concentrations of lysine and threonine. During the final stage of the selection process, calli were placed on a medium without the addition of selection agents. The results from the tissue culture study suggest that media, 2, 4-D and explant size affect callus growth. MSMA medium (a modified Murashige and Skoog medium) was the most suitable for growing the callus of Beauregard whilst modified White's medium (MW) was better for the growth of LO322 calli. The most prolific callus growth was exhibited by explants of the cultivar Beauregard when placed on MSMA medium. This combination was used to determine the potential of mutagenic treatments to improve the nutritional qualities of the sweet potato. Results from treatments with mutagenic agents showed that all mutagens used had the capability of increasing the soluble protein content of callus. These treatments also had the capacity to increase the concentration of aspartate and other amino acids. Of the mutagens trialed, a treatment with 500 rad gamma radiation appears to be the most suitable for increasing protein and amino acid concentrations. Therefore, once the conditions for regeneration of shoots from calli have been determined this study suggests that it should be possible to produce lines of sweet potato with increased nutritional values using this agentMaster of Science (Hons)
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Cabrera, Guillermo Lopez Brockman Herman E. "Effect of five dietary antimutagens on the genotoxicity of six mutagens using three different short-term tests." Normal, Ill. Illinois State University, 1993. http://wwwlib.umi.com/cr/ilstu/fullcit?p9416862.
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Thesis (Ph. D.)--Illinois State University, 1993.Title from title page screen, viewed March 7, 2006. Dissertation Committee: Herman E. Brockman (chair), Alan J. Katz, Brian J. Wilkinson, David F. Weber, Radheshyam K. Jayaswal. Includes bibliographical references (leaves 162-177) and abstract. Also available in print.
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Donnelly, Eilish Teresa. "An investigation of DNA repair in wild-type, amino acid auxotrophs and UV-sensitive mutants of Aspergillus nidulans." Thesis, University of Ulster, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.243733.
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Shanks, Thomas Gordon. "The epidemiology of mutagens : evidence of cumulative genetic damage in the mortality rates of former smokers /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2005. http://wwwlib.umi.com/cr/ucsd/fullcit?p3167831.
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Gallampois, Christine [Verfasser]. "Integrated biological-chemical approach for the identification of polyaromatic mutagens in surface waters / Christine Gallampois." Aachen : Hochschulbibliothek der Rheinisch-Westfälischen Technischen Hochschule Aachen, 2013. http://d-nb.info/1044491787/34.
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Cosentino, Lidia. "A comparison of transgenic and endogenous loci in vivo." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0018/NQ56223.pdf.
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Hallgren, Jenny. "The role of heparin in the activation of mast cell tryptase /." Uppsala : Dept. of Molecular Biosciences, Swedish Univ. of Agricultural Sciences, 2004. http://epsilon.slu.se/v179.pdf.
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Yu, Hongbin Yu Hongbin. "Part I, Nitrosation of amidines : structure and reactivity ; Part 2, Aldehyde mediated nitrosation of amino acids ; Part 3, Thermal decomposition of N-nitrosocarboxylic acids /." free to MU campus, to others for purchase, 2002. http://wwwlib.umi.com/cr/mo/fullcit?p3052235.
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Durant, John Laighton. "Detection and identification of human cell mutagens in sediments and surface waters of the Aberjona watershed." Thesis, Massachusetts Institute of Technology, 1993. http://hdl.handle.net/1721.1/12461.
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Keir, Jennifer Leslie Ann. "The Use of Urinary Biomarkers to Assess Exposures to Polycyclic Aromatic Hydrocarbons (PAHs) and Other Organic Mutagens." Thesis, Université d'Ottawa / University of Ottawa, 2017. http://hdl.handle.net/10393/36114.
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Exposure to combustion emissions poses a threat to human health due to the complex mixture of toxic compounds. Polycyclic aromatic hydrocarbons (PAHs) are one group of compounds found within this mixture, and have known carcinogenic and mutagenic properties. Rates of exposure to PAHs depend on a wide range of variables including, but not limited to, demographic, geographical location, dietary habits, smoking habits, and occupation. Understanding magnitude of exposure to these compounds in various groups is imperative to highlight at-risk populations and provide appropriate exposure reduction recommendations. Here, urinary biomarkers are used as a non-invasive, convenient way to assess an individual’s exposure to combustion emissions. Urinary measurements of metabolites of individual PAHs as well as compounds indicative of a physiological condition resulting from combustion emission exposure are used to infer exposure. Pairing urinary data with information from questionnaires collecting data on possible sources of combustion by-product exposure was used to determine situations of high exposures.
This thesis investigated the influence of demographic, lifestyle, and occupational factors on urinary levels of PAH metabolites and/or urinary mutagenicity. More specifically, statistical methods were used to analyze population data compiled for the Canadian Health Measures Survey (CHMS). Smoking, age, and sex were identified as the variables most predictive of urinary PAH metabolite concentrations in Canadians. Together with the other demographic and lifestyle variables examined, 24-50% of the variation in the various PAH metabolites was explained. Furthermore, the results obtained illustrated that utilizing PAH metabolites other than the traditionally used 1-hydroxypyrene may be more suitable for certain exposure scenarios (e.g., fluorene metabolites for tobacco smoke exposure). Occupational exposures to combustion emission were investigated in firefighters as they experience above average risk of cancer, thus paired with their obvious involvement with combustion, are an ideal population to apply the use of urinary biomarkers to assess PAH and combustion exposure. The effect of participating in fire suppression activities (i.e., firefighting) on urinary levels of selected PAH metabolites and organic mutagens was examined. Levels of external PAH exposures were assessed using personal air monitoring and surface wipes of skin. Significant increases in urinary PAH metabolites and mutagenicity were seen after fire suppression events. Empirical relationships between urinary PAH metabolites and duration of fire event and skin concentrations of PAHs suggested that dermal contamination during live fire events is a major route of exposure. Overall, the results from both studies identified factors that may affect an individual’s concentrations of urinary biomarkers of combustion emission exposure. This may be used to identify at-risk populations and/or determine effective exposure reduction techniques to these hazardous compounds.
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Orrhage, Kerstin. "Impact of Bifidobacterium longum and Lactobacillus acidophilus on the intestinal microflora and bioavailability of some food mutagens /." Stockholm, 1999. http://diss.kib.ki.se/1999/91-628-3687-0/.
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Maddox, Catherine Michael. "Genotoxicity of 4-monochlorobiphenyl in the lung of transgenic male 344 Fisher rats." Thesis, University of Iowa, 2007. http://ir.uiowa.edu/etd/155.
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Pritchett, Blair. "Mutagenic and genotoxic potential of nitrated polyaromatic hydrocarbons in combustion byproduct mixtures." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape7/PQDD_0021/MQ55538.pdf.
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Obinaju, Blessing. "Application of attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy to measure sub-lethal effects of potential mutagens." Thesis, Lancaster University, 2015. http://eprints.lancs.ac.uk/76562/.
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Techniques employed in vibrational spectroscopy monitor the vibrational modes of functional groups within biomolecules and enable a correlation between chemical information and histological structures. Interrogation of biological samples using infrared (IR) techniques generates spectrum with wavenumber-absorbance intensities specific to biomolecules within the sample. Methods are relatively non-destructive, and so samples can subsequently be analyzed by more conventional approaches. Analyses can be carried out ex vivo or in situ in living tissue, where a reference range of a designated normal state can be derived, and anything lying outside this range is potentially atypical. Computational approaches allow one to minimize within-category confounding factors. The application of vibrational spectroscopy in contaminant biomonitoring is a welcome development which has enabled the investigation of realtime contaminant exposure effects in the tissues of sentinels. IR techniques such as attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, was able to detect changes in various tissue samples exposed to varying levels of polycyclic aromatic hydrocarbons (PAHs). This technique discriminated between spatial and temporal variations in the interrogated tissues. Multivariate analysis was able to relate the alterations at various regions of the fingerprint, to PAH exposure and was able to detect PAH exposure in tissues from sites with no documented knowledge of contamination. ATR-FTIR detected PAH-induced changes in isolated nuclei of cultured cell populations in G0/G1 and S- phases of the cell cycle. Findings from the various projects affirm, that techniques involved in IR spectroscopy are highly sensitive to minimal changes in cell molecules. The ability to generate rapid results in real-time is valuable and the wide variety of sample types which can be interrogated using IR techniques makes it a suitable technique for environment biomonitoring.
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Henderson, Daryl Stewart. "A genetic analysis of mutagen-sensitive mutations on the second chromosome of Drosophila melanogaster." Thesis, University of British Columbia, 1987. http://hdl.handle.net/2429/26418.
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Mutagen-sensitive (mus) mutations in Drosophila melanogaster render developing flies hypersensitive to the lethal effects of DNA-damaging agents. In general, mus mutations identify DNA repair-related genes. In this study, 5 new second chromosome mus mutations (mus205B¹, mus208B¹, mus209B¹, mus210B¹ and mus211B¹), selected on the basis of sensitivity to methyl methanesulfonate (MMS), were characterized using a variety of genetic tests. One test measured the MMS-sensitivity of double mutant mus strains compared to their component single mutants. Mutant interactions were examined in 8 double mus and in 2 triple mus strains containing combinations of mus201D¹, mus205B¹, mus208B¹, mus210B¹ and mus211B¹ (or mus211B²). These analyses have revealed predominantly synergistic and epistatic responses to MMS. Taken together with the findings of previous genetic and biochemical studies of Drosophila mus strains, these results suggest that 3 major repair pathways may operate in flies to correct damage caused by MMS.
Mutagen cross-sensitivity data and the results of the interaction studies suggest that mus mutations might serve as rapid and sensitive bioassays of somatic genotoxicity caused by mutagens and carcinogens. To explore this possibility, a simple mutagen test system was devised employing triple mutant mus strains. One strain (mus208B¹ mus210B¹ mus211B²) was tested for sensitivity to 14 mutagens/carcinogens and 2 non-carcinogens. Eleven of the mutagens/carcinogens were readily detected as genotoxic. Both non-carcinogens were non-genotoxic. These preliminary results demonstrate the feasibility (and some limitations) of the proposed somatic genotoxicity assay and emphasize the need for further test validation using a larger chemical data base.
The temperature-sensitive lethal mutation mus209B¹ was subjected to extensive genetic analyses and to temperature shift experiments during development. This locus was found to encode a product(s) that (1) is essential for viability at virtually all pre-imaginal developmental stages (the latter half of pupation appears to be an exception), (2) is necessary for wildtype levels of resistance to the genotoxic effects of MMS and ionizing radiation, and (3) is required for female fertility. Confirmation of the pleiotropic nature of this mutation was obtained by meiotic and cytogenetic mapping studies and by complementation tests with a series of allelic mutations. The mus209B¹ phenotypes are similar to ones conferred by mutations in Drosophila and yeast that disrupt various aspects of chromosome metabolism. In this context, some possible roles for mus209B¹ are discussed.Science, Faculty of
Zoology, Department of
Graduate
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Ngsee, Johnny Kuan. "Cassette mutagenic analysis of the signal peptide of yeast invertase." Thesis, University of British Columbia, 1987. http://hdl.handle.net/2429/27500.
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The SUC2 locus of Saccharomyces cerevisiae encodes two forms of invertase; a constitutively expressed cytoplasmic enzyme and a glucose-repressible secreted and glycosylated enzyme which is initially produced with an amino-terminal signal peptide. The coding sequence of the SUC2 locus has been placed under the control of the constitutive ADH1 promoter and transcription terminator in a centromere based yeast plasmid vector from which invertase is expressed in a Sue" strain of yeast. Oligonucleotide-directed mutagenesis has been used to create a PstI site in the gene at the point encoding the signal peptide cleavage site. An internal methionine codon, the translation start for the cytoplasmic invertase, has been replaced by a serine codon. Mutants in the signal peptide sequence have been produced by replacing the region of the gene upstream of the PstI site with synthetic oligonucleotide cassettes with mixtures of nucleotides at several positions. The mutants could be divided into three classes based on their ability to secrete invertase. The first class of mutants produced secreted invertase, but in reduced amount. There is no obvious correlation between mutation and phenotype. The second class, represented by mutant 4-55B, also exhibited a reduced level of invertase, but a significant fraction (30%) of the enzyme is intracellular. This mutant had a delay in signal peptide cleavage which retards passage of invertase through the secretory pathway. The third class was defective in secretion. Most were defective in translocation from the cytoplasm to the lumen of the endoplasmic reticulum (ER), and produced enzymatically active, non-glycosylated pre-invertase in the cytoplasm. This class of mutant invertases, when transcribed and translated in vitro, was not processed by canine pancreas signal recognition particle (SRP) and microsomes. Comparison of the sequences of the mutant signal peptides of this non-translocating class identifies amino acids at the extreme amino-terminus as the causative defect.Medicine, Faculty of
Biochemistry and Molecular Biology, Department of
Graduate
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Pettersson-Strömbäck, Anita. "Chemical exposure in the work place : mental models of workers and experts /." Umeå : Umeå University, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1646.
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Han, Jin-Soon Brockman Herman E. "Effects of active oxygen species generated from hydrogen peroxide in Neurospora crassa and Salmonella typhimurium." Normal, Ill. Illinois State University, 1991. http://wwwlib.umi.com/cr/ilstu/fullcit?p9203030.
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Thesis (Ph. D.)--Illinois State University, 1991.Title from title page screen, viewed December 8, 2005. Dissertation Committee: Herman E. Brockman (chair), Radheshym K. Jayaswal, Alan J. Katz, David F. Weber, Brian J. Wilkinson. Includes bibliographical references (leaves 113-125) and abstract. Also available in print.
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Prapti, Sedijani. "The use of mutagenic agents to increase the protein content and improve the amino acid composition of sweet potato (Ipomea batatas Lam.) /." View thesis View thesis, 1997. http://library.uws.edu.au/adt-NUWS/public/adt-NUWS20030925.092030/index.html.
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Thesis (M. Sc.) (Hons.) -- University of Western Sydney, Hawkesbury, 1997.Thesis submitted for the degree of Master of Science (Honours), School of Horticulture, University of Western Sydney, Hawkesbury, 1997. In Chapter 1, figures 1.1 and 1.2 are not reproduced in the text. Bibliography : leaves 112-135.
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Perera, Anthonige Vidya. "Genes Affecting the Repair and Survival of Escherichia coli Following Psoralen-Induced Damage: a DNA Interstrand Crosslinking Agent." PDXScholar, 2015. https://pdxscholar.library.pdx.edu/open_access_etds/2195.
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Photoactivated psoralens and other agents that form DNA interstrand crosslinks are highly cytotoxic and are useful in treating a range of diseases, including vitiligo, psoriasis, and some forms of cancer. Unlike many lesions that damage only one strand of the duplex DNA, DNA interstrand crosslinks form covalent bonds with both strands. Thus, repairing these lesions is complicated both by the lack of an undamaged strand to serve as a template for resynthesis following excision, as well as the potential to form double strand breaks if both strands are incised. A number of models have proposed that repair is likely to couple nucleotide excision repair with other repair pathways such as recombination, and/or translesion synthesis. However, several aspects of these models remain speculative, and how these medically relevant lesions are repaired by cells still remains elusive. In this study, I use Escherichia coli as a model organism to characterize which gene products contribute to survival in the presence of psoralen-induced DNA interstrand crosslinks.
In Chapter II, I demonstrate that although nucleotide excision repair initiates repair, not all subunits contribute equally to survival. Notably, uvrC is less sensitive to psoralen-induced damage than either uvrA or uvrB. I found that Cho, an alternative endonuclease, accounts for the increased resistance of uvrC mutants and contributes to survival in the presence of UvrABC. Cho was not required following angelicin treatment, a psoralen derivative that only forms monoadducts, suggesting that Cho function is specific for interstrand crosslink repair. However, Cho, by itself, is not required for the initial incision and only modestly enhances the rate that psoralen crosslinks are incised in vivo.
Following incision, many of the intermediates in the repair process remain speculative. In Chapter III, I examine how recombination and translesion synthesis mutants contribute to survival of psoralen-induced damage. I show that both recBC and recF contribute to survival, but that neither mutant is as hypersensitive as recA, potentially suggesting that pathways involving either single strand gaps or double strand break intermediates can occur during repair. Finally, I show that Polymerase V is responsible for the translesion synthesis that contributes to survival in the case of psoralen-induced damage in E.coli.
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Kurzawa-Zegota, Malgorzata. "In vitro chemically-induced DNA damage in cancer patients and healthy individuals : the effect of genotoxic compounds in cells from polyposis coli, colon cancer patients and healthy individuals." Thesis, University of Bradford, 2011. http://hdl.handle.net/10454/5186.
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In the present study DNA damage was measured in peripheral blood lymphocytes from polyposis coli and colorectal cancer patients, treated with different dietary and environmental compounds and compared with lymphocytes from healthy individuals. In addition, confounding factors such as age, gender, alcohol intake and smoking habits were taken into consideration. The assays used in this study included the Comet assay, the Micronucleus assay, the Micronucleus-FISH assay and the sister chromatid exchange assay. The food mutagens, PhIP and IQ, as well as titanium dioxide nanoparticles (TiO2 NPs) induced a dose dependent increase in the DNA damage and chromosomal abnormalities in all tested groups regardless of confounding factors. Prior to experiments physicochemical characterisation of nanoparticles was conducted. In the presence of the flavonoids, quercetin and rutin that were acting in an antioxidant manner, the DNA damage resulting from the highest doses of food mutagens was significantly reduced. Thus, dietary supplementation with flavonoid-rich vegetables and fruits may prove very effective in protection against oxidative stress. The polyposis coli and colon cancer patients were more susceptible to food mutagens, PhIP and IQ, as well as TiO2 NPs, and in the majority of cases had a higher level of DNA damage in the Comet assay and higher cytogenetic damage in the Micronucleus assay. In the final project, twelve frequently encountered (NewGeneris) chemical compounds were evaluated to establish their damaging potential in lymphocytes and spermatozoa from healthy donors. The highest damage was produced by DNA reactive aldehydes, food mutagens and benzo[a]pyrene when assessed with the neutral and alkaline Comet assay with and without metabolic activation.
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Andrieux, Florian. "Rôle de la protéine PB1 dans la fidélité du complexe polymérase des virus influenza." Thesis, Sorbonne Paris Cité, 2017. http://www.theses.fr/2017USPCC216/document.
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Les virus influenza de type A (IAV) appartiennent à la famille des Orthomyxoviridae. Ces virus enveloppés présentent un génome composé de 8 segments d’ARN simple brin, de polarité négative. Chaque segment est encapsidé par les nucléoprotéines (NP) et associé au complexe polymérase viral, hétérotrimère composé des sous-unités PB1, PB2 et PA, pour former la ribonucléoprotéine virale (RNPv). La protéine PB1 est la sous-unité catalytique responsable de l’activité ARN polymérase ARN-dépendante du complexe viral. La RNPv représente ainsi l’unité minimale de transcription et réplication du génome viral. En raison de la faible fidélité de la polymérase virale et l’absence d’activité de relecture, les IAV présentent un taux de mutation élevé, responsable du développement rapide de populations virales d’une grande diversité génétique, appelées quasi-espèces. Des études récentes ont permis d’identifier des mutants présentant une fidélité de réplication augmentée, due à des mutations uniques dans la sous-unité PB1. Comme décrit pour d’autres virus à ARN, différentes mutations peuvent avoir un effet similaire sur l’activité de la polymérase virale. Afin d’approfondir la caractérisation de la protéine PB1 nous avons recherché d’autres positions pouvant avoir un rôle dans la fidélité de la polymérase, la sélectivité des nucléotides ou la processivité du complexe. Pour cela, des banques de séquences PB1 mutées ont été générées par mutagénèse aléatoire pour deux sous-types de virus influenza A, H3N2 et H1N1pdm09, circulant actuellement chez l’homme. A partir de ces banques, des expériences de reconstitution transitoire de RNPv fonctionnelles (minigénome) en présence de ribavirine, un analogue nucléosidique mutagène, ont permis d’évaluer l’activité de la polymérase et de sélectionner, après subdivisions successives des banques, des mutations conférant une résistance au composé mutagène supérieure à celle de la polymérase sauvage. Les mutations ainsi identifiées dans différentes régions du segment PB1 ont ensuite été réintroduites de manière spécifique, par mutagénèse dirigée, dans la séquence du gène PB1. L’impact de ces mutations sur l’activité de la polymérase a été évalué par des expériences de minigénome en présence et absence de ribavirine. Les mutations pour lesquelles la résistance à la ribavirine a été confirmée ont alors été introduites par génétique inverse dans le contexte du génome viral complet. La majorité des mutations s’est avérée viable et a permis l’obtention de virus mutants infectieux. La capacité de multiplication des virus mutants a été évaluée en cellules MDCK et comparée à celle des virus sauvages correspondants, en absence et en présence de ribavirine. Ainsi, deux mutants porteurs de deux mutations différentes, localisées dans des régions distinctes de la protéine PB1, présentent une capacité à résister à la ribavirine supérieure à celle du virus sauvage. L’analyse de la diversité des populations virales, évaluée par séquençage à haut-débit, en utilisant la technologie Illumina, permettra de confirmer si cette résistance à la ribavirine est bien liée à une augmentation de la fidélité de la polymérase virale. Cette étude a ainsi permis de préciser les éléments de la protéine PB1 impliqués dans l’activité et potentiellement la fidélité de la réplication virale pour deux sous-types de virus influenza AInfluenza type A viruses (IAVs) belong to the Orthomyxoviridae family. The genome of these enveloped viruses consists of 8 single-stranded RNA segments of negative polarity. Each segment is encapsidated by oligomers of the nucleoprotein (NP) and associated with the viral polymerase complex, a heterotrimer composed of the PB1, PB2 and PA subunits to form the viral ribonucleoproteins (vRNPs). The PB1 protein is the catalytic subunit of the polymerase complex, harboring the RNA-dependent RNA polymerase activity. The vRNP represents the minimal functional unit for transcription and replication of the viral genome. Given the low fidelity and lack of proofreading activity of their polymerase, IAVs have a high mutation rate leading to the rapid development of viral populations with high genetic diversity, called quasispecies. Recent studies identified mutants with increased replication fidelity, due to single mutations in the PB1 subunit. As described with other RNA viruses, different mutations could have similar effects on the activity of the viral polymerase. To improve the characterization of the PB1 protein, we searched for other positions that may have a role on polymerase fidelity, nucleotide selectivity or complex processivity. For this purpose, random mutagenesis was used to generate libraries of mutated PB1 from influenza A virus subtypes H3N2 and H1N1pdm09, currently circulating in humans. From these libraries, transient reconstitution of functional vRNPs (minigenome) experiments were performed with ribavirin, a mutagenic nucleoside analog, to evaluate the polymerase activity. Upon selection based on the polymerase activity of successively subdivided libraries, PB1 mutations with increased polymerase activity in the presence of ribavirin relative to wild-type were identified in several regions of PB1. These mutations were specifically re-introduced in PB1 by directed mutagenesis. Their impact on polymerase activity was evaluated by minigenome experiments with and without ribavirin. Mutations with confirmed resistance against ribavirin were then introduced in the context of infectious virus by reverse genetics. Most corresponding mutant viruses could be rescued. Their growth characteristics were analysed in MDCK cells and compared to the corresponding wild-type viruses, in the presence or absence of ribavirin. Two mutants carrying two different mutations, located in distinct regions of the PB1 protein, displayed an improved capacity to resist ribavirin relative to the wild-type virus. Viral populations genetic diversity analysis by next-generation sequencing, using Illumina technology, will confirm whether the observed resistance against ribavirin is linked to an increase of the viral polymerase fidelity. This study provides insights into the PB1 domains involved in the activity and potentially the viral replication fidelity of two influenza A virus subtypes
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Prince, Polly Rodgers. "Molecular basis for genetic instability in Werner syndrome /." Thesis, Connect to this title online; UW restricted, 1999. http://hdl.handle.net/1773/6323.
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Cox, Julie. "Evaluation of Strategies to Improve In Vitro Mutagenicity Assessment: Alternative Sources of S9 Exogenous Metabolic Activation and the Development of an In Vitro Assay Based on MutaMouse Primary Hepatocytes." Thesis, Université d'Ottawa / University of Ottawa, 2019. http://hdl.handle.net/10393/39340.
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In vitro genetic toxicity tests using cultured bacterial or mammalian cells provide a cost- and time-effective alternative to animal tests. Unfortunately, existing in vitro assays are not always reliable. This is in part due to the limited metabolic capacity of the cells used, which is often critical to accurately assess chemical genotoxicity. This limited metabolic capacity necessitates the use of exogenous sources of mammalian metabolic enzymes that can simulate in vivo mammalian metabolic activation reactions. In response to this, and other limitations, alongside the worldwide trend to reduce animal testing, there is an acute need to consider various strategies to improve in vitro mutagenicity assessment. This thesis first examined the utility of exogenous metabolic activation systems based on human hepatic S9, relative to conventional induced rat liver S9, for routine genetic toxicity assessment. This was accomplished by critically evaluating existing literature, as well as new experimental data. The results revealed the limitations of human liver S9 for assessment of chemical mutagenicity. More specifically, the analyses concluded that, due to the increased risk of false negative results, human liver S9 should not be used as a replacement for induced rat liver S9. To address the limitations of conventional mammalian cell genetic toxicity assays that require exogenous hepatic S9, the thesis next evaluated the utility of an in vitro mutagenicity assay based on metabolically-competent primary hepatocytes (PHs) derived from the transgenic MutaMouse. Cultured MutaMouse PHs were thoroughly characterized, and found to temporarily retain the phenotypic attributes of hepatocytes in vivo; they express hepatocyte-specific proteins, exhibit the karyotype of typical hepatocytes, and maintain metabolic activity for at least the first 24 hours after isolation. Preliminary validation of the in vitro MutaMouse PH gene mutation assay, using a panel of thirteen mutagenic and non-mutagenic chemicals, demonstrated excellent sensitivity and specificity. Moreover, inclusion of substances requiring a diverse array of metabolic activation pathways revealed comprehensive metabolic competence. Finally, the thesis further investigated the applicability domain of the in vitro MutaMouse PH assay by challenging the assay with selected azo compounds. Comparison of these results with those obtained using the in vivo MutaMouse TGR (transgenic rodent) assay revealed that MutaMouse PHs can carry out some forms of reductive metabolism. Overall, this thesis demonstrated that a gene mutation assay based on MutaMouse PHs holds great promise for routine assessments of chemical mutagenicity.
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BOUDSOCQ, FRANCOIS. "Mecanismes moleculaires de la mutagenese sos chez escherichia coli : interactions entre le complexe mutagene umud'c et le polymere reca." Paris 11, 1998. http://www.theses.fr/1998PA112017.
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Les lesions du genome provoquees par les cancerigenes physiques ou chimiques sont responsables des mutations induites. L'apparition des mutations est avant tout le resultat d'une replication fautive operee par l'adn-polymerase sur un adn portant des lesions. Chez la bacterie ou le mecanisme de la mutagenese est le mieux connu, la proteine reca et le complexe umud'c sont deux facteurs essentiels de la mutagenese. Le polymere reca servirait a presenter le complexe umud'c au niveau de la lesion, celui-ci pourrait alors interagir avec la polymerase et l'aider a poursuivre la synthese a travers la lesion. Nous avons montre recemment au laboratoire que le complexe umud'c etait aussi un inhibiteur de la recombinaison homologue. Dans ce travail de these nous avons tout d'abord voulu savoir si le complexe umud'c etait un inhibiteur direct de la recombinaison. Pour cela nous avons quantifie l'inhibition de la recombinaison en faisant varier les concentrations de la proteine reca ou du complexe umud'c qui ont ete clones sous le controle d'un promoteur finement regule. Dans un deuxieme temps, nous avons selectionne des mutants de la proteine reca insensibles a l'action inhibitrice du complexe umud'c. Ces substitutions, placees sur la structure cristallographique de la proteine reca semblent definir deux domaines putatifs d'interaction avec le complexe umud'c. La quantification des proteines umud' et umuc apres irradiation des cellules a montre la formation tardive du complexe umud'c et une stoechiometrie d'environ un complexe umud'c par discontinuite simple-brin. La recherche d'analogues des proteines umud' et umuc a montre que la proteine umuc avait une certaine similitude avec la sous-unite de la polymerase iii. Le complexe umud'c pourrait constituer un etau alternatif a celui forme par les deux sous-unites de la polymerase iii et favoriser l'elongation du brin neosynthetise au niveau de la lesion.
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Herrmann, Jean-Louis. "Etude de la virulence de "Yersinia pseudotuberculosis" par mutagène par transposition." Paris 5, 1989. http://www.theses.fr/1989PA05P158.
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Duarte, Jonathaline Apollo. "Avaliação imunotoxicológica da anacauíta (Schinus molle l.) em cultura celular." Universidade Federal do Pampa, 2016. http://dspace.unipampa.edu.br:8080/xmlui/handle/riu/1649.
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O emprego de produtos naturais para o tratamento, cura ou prevenção de doenças pela população é datada desde os tempos mais remotos, e apesar dos inúmeros avanços na ciência, o uso de plantas com finalidade medicinal, ainda representa na maioria das vezes o único recurso terapêutico de muitas comunidades e de diversos grupos étnicos.Atualmente é possível verificarmos que apesar de todos os avanços nas indústrias farmacêuticas para a produção de fármacos sintéticos, a população ainda recorre às plantas medicinais.Entretanto, existe uma infinidade de plantas que ainda não são conhecidos os seus possíveis efeitos farmacológicos e/ou toxicológico. Diante desse contexto, a Schinus molle L. (Anacardiaceae), popularmente conhecida como anacauíta, é uma planta rica em óleo essencial, a qual vem sendo usada como uma opção de tratamento para diversas enfermidades, e apesar de seu amplo emprego na medicina popular, a literatura carece de informações voltadas para seu perfil imutoxicologico. Assim, investigouse os efeitos do óleo essencial frente a parâmetros citotóxico, mutagênico e genotoxico em cultura de linfócitos e macrófagos humanos. Inicialmente, determinaramse as DL50 para ambas as células estudadas, através do teste de proliferação celular, para então desenvolver os demais testes. As DL50 encontradas foram de 30.07μg/mL para linfócitos humanos e de 42.07μg/mL para macrófagos humanos, assim, foram definidas as concentrações a serem testadas, sendo essas DL50, DL50/10, DL50/100, DL50/1000 e DL50/10000 para as células em questão, e foi constatado que o óleo essencial foi capaz de promover citotoxicidade em concentrações superiores a DL50/1000, para ambas as células testadas. Entretanto, o mesmo proporciona efeito genotóxico em culturas de macrófagos, somente para as duas concentrações maiores e quando avaliado os frente a parâmetros mutagênicos, constatouse que, o mesmo não promove alterações cromossômicas assim como, também não alterou o índice de divisão celular, embora tenha sido capaz de proporcionar frequência de micronúcleo concentração dependente nos macrófagos. Contudo, é importante salientar a importância de conhecimento dos constituintes do óleo essencial da Schinus molle L., para maiores esclarecimentos referente a sua toxicidade, uma vez que, essa planta é amplamente empregada na medicina popular para as diversas finalidades. Dessa forma, os resultados encontrados nesse trabalho, tem a contribuir com a literatura. Para tanto, estudos complementares são necessários para auxiliar na construção completa do perfil toxicológico do óleo essencial da planta em estudo, buscando a segurança da população que a utiliza.
The use of natural products for the treatment, cure or prevention of disease by population is dated from the earliest times, and despite the numerous advances in science, the use of plants for medicinal purposes, yet is most often the only therapeutic resource many communities and various ethnic groups. It is currently possible to see that despite all the advances in the pharmaceutical industry for the production of synthetic drugs, people still make use of medicinal plants. However, there is a multitude of plants that are not yet known its possible pharmacological effects and / or toxicology. In this context, the Schinus molle L.(Anacardiaceae), popularly known as anacauíta, is a plant rich in essential oil, which has been used as a treatment option for various diseases, and despite its widespread use in therapy, the literature lacks information geared to your immunotoxicology profile. Thus, we investigated the effects of essential oil cytotoxic front parameters, mutagenic and genotoxic in cultured human lymphocytes and macrophages. Initially, the LD50 were determined for both the cells studied by the cell proliferation assay, and then to develop other tests. The LD50 was found to 30.07μg/ml for human lymphocytes and 42.07μg/ml for human macrophages, thus the concentrations to be tested have been identified and these LD50, LD50/10, LD50/100 LD50/1000 and LD50/10000 to the cells in question, and it was found that the essential oil was able to promote cytotoxicity at concentrations above LD50/1000, for both test cells, however, it provides genotoxic effects in macrophage cultures, only the two concentrations and larger when measured against the mutagens parameters, it was found that it does not promote chromosomal abnormalities as well as, did not alter the rate of cell division, although it was able to provide frequency micronucleus concentration dependent on macrophages. However, it is important to stress the importance of knowledge of essential oil constituents of Schinus molle L., for further information regarding its toxicity, since this plant is widely used in folk medicine for a variety of purposes. Thus, the results found in this work, is to contribute to the literature. Therefore, further studies are needed to help complete construction of the toxicological profile of the essential oil of the plant under study, seeking the safety of the population makes use of this.
Schinus molle L
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Moliterno, Enrique Alfredo Parachu. "Variabilidade genética e a eficiência de seleção no caráter dormência de sementes em aveia-preta(Avena strigosa Schreb.)." Universidade Federal de Pelotas, 2008. http://repositorio.ufpel.edu.br/handle/ri/1458.
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Previous issue date: 2008-02-28Seed dormancy is a trait shown by a large variety of weedy plants, which helps the purpose of perpetuating the species through space and time by delaying germination until specific environmental cues happen. Black oat, a temperate forage grass, is widely used for pasture and as a cover crop in minimum tillage systems in Southern Brazil. However, the largest portion of the seed sown belongs to an old variety, which has no genetic identity, contributing to the appearance of undesirable agronomic traits in a crop species such as seed dormancy. This trait is hold responsible for turning black oat into a potential weedy species in areas sown to other cool season cereals, such as wheat and barley. Three methods were used to screen and select for black oat genotypes expressing low seed dormancy, i.e. screening of lines collected throughout different agricultural regions of the state of Rio Grande do Sul; subjecting a specific line of the species to the effects of two chemical and one physical mutagens and crossbreeding between selected lines and commercial cultivars of the species. All three methods were undertaken under a glasshouse environment (without temperature control), and since there are no known vegetative morphological traits associated to seed dormancy the procedure consisted on selecting seedlings from non dormant seeds. These were grown in the glasshouse environment and their progeny seeds tested for germinability, thus repeating the cycle. Genetic progress was slow for all three methods and cross breeding resulted the most difficult way for the creation of new genotypes, as only less than 8% of all pollinated flowers yielded hybrid seeds. Differences in germinability percentage among seeds of the first and second selection cycles were largest for the line- screening method, less for mutant seed phenotypes and minimum for the crossbreeding method, in which only F1 seeds were tested for germinability. On average, mutant seed treatments yielded 15% germinability after the first selection cycle, increasing to 20% germinability by the end of the second selection cycle. The screening of black oat lines yielded an initial 7% germinability, which increased to 36% germinability by the end of the second cycle. A common trend for all three methods was that seed germinability was highest during the first half of the standard germination test period for oat species, which implies that seedling selection was exercised for two traits simultaneously, i.e. absence of seed dormancy and seed vigor. The identification of several genotypes producing seeds expressing both traits increases the opportunity for genetic progress in this species.
A dormência de sementes é um caráter de muitas espécies de plantas invasoras de culturas agrícolas modernas, a qual tem por objetivo preservar a multiplicação da espécie através da germinação de suas sementes ao longo do tempo e o espaço. Aveia-preta é uma gramínea forrageira temperada muito semeada para produção de forragem e proteção do solo como cultura de cobertura, em sistemas de plantio direto. Porém, a maior parte da semente utilizada para semear a espécie pertence a uma variedade que praticamente não tem sido melhorada desde sua introdução, produzindo sementes com níveis variáveis de dormência. Esse caráter tem gerado problemas na área agrícola ocupada por essa espécie, tornado-a invasora potencial de outras culturas de estação fria. Com o objetivo de contribuir à melhora do caráter dormência de sementes quanto de outros de interesse numa espécie forrageira, foram aplicados três métodos de seleção de genótipos produtores de sementes com baixo nível de dormência: avaliação de genótipos fixos (linhagens) provenientes de diferentes regiões edafoclimáticas do estado de RS, indução a mutação de um genótipo fixo por dois agentes mutagênicos químicos e um físico e hibridações artificiais entre catorze genitores (linhagens e cultivares comerciais). Conforme a influência do ambiente num caráter quantitativo como a dormência de sementes, e o fato de não ter associação conhecida com caracteres morfológicos vegetativos, a estratégia adotada foi de multiplicar as sementes de cada tratamento sob ambiente de casa de vegetação e avaliar sua germinabilidade logo após a colheita. Os progressos na expressão do caráter de interesse foram lentos para os três métodos empregados, sendo que a hibridação artificial resultou o método mais difícil desde que o porcentual de sementes hibridas obtidas em relação ao número de polinizações efetuadas foi inferior a 8%. A diferença entre a germinabilidade das sementes oriundas do primeiro ciclo de seleção em relação às seguintes foi mais marcante para as linhagens do que para aqueles genótipos mutantes. Já, no caso dos híbridos, a avaliação só abrangeu a geração F1 por causa da baixa quantidade de sementes produzidas. Enquanto o progresso para o conjunto de tratamentos com mutagênicos foi relativamente baixo, com germinabilidade inicial média de 15% e final de 20%, as linhagens iniciaram em média com 7% de germinabilidade e logo do primeiro ciclo de seleção finalizaram a avaliação com 36% germinabilidade. Um aspecto comum aos três métodos empregados foi o fato da germinabilidade das sementes ser expressa em níveis mais importantes na primeira metade do período padrão da análise de germinação para a espécie. Isso implica em que a seleção de plântulas foi feita considerando dois caracteres, ausência de dormência e vigor de sementes em forma conjunta. A obtenção de vários genótipos no presente experimento produzindo sementes com ambos os caracteres abre boas perspectivas de progresso genético em aveia preta.
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Åberg, Alf. "Mutagena effekter av thiokarbanater." Licentiate thesis, Luleå tekniska universitet, 1985. http://urn.kb.se/resolve?urn=urn:nbn:se:ltu:diva-17753.
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CARBONNAUX, FRENOVE CLAIRE. "Facteurs de croissance des fibroblastes (fgfs) et mutagenese : partie i: conformation des fgf acide et basique. partie ii: structure d'oligodesoxynucleotides contenant un site potentiellement mutagene." Paris 11, 1991. http://www.theses.fr/1991PA112003.
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Partie i: les facteurs de croissance des fibroblastes (fgfs) sont des proteines impliquees dans la croissance et la differenciation cellulaire. Nous avons etudie leur structure par dichroisme circulaire. Les resultats montrent que ces proteines sont constituees majoritairement de feuillets antiparalleles. Nous avons tente de poursuivre l'investigation par une etude rmn du fgf acide. Apres la preparation en grande quantite du fgf acide et la purification du fragment 68-140, nous avons recherche les conditions de solubilisation du materiel proteique. La tres faible solubilite du fgf acide et la denaturation partielle du fragment ont incite a orienter ces etudes structurales sur un analogue du fgf acide dont la preparation est en cours. Partie ii: le mecanisme de reconnaissance des paires de bases non complementaires (mesappariements) et l'adn par les enzymes de reparation est encore inconnu. Les modifications structurales de l'adn induites par la presence de mesappariements ont ete etudiees par rmn dans differents oligonucleotides. Les resultats montrent que les paires de bases t. G, u. G. , t. I sont integrees dans l'helice d'adn b dans la configuration wobble. Les trois mesappariements induisent des perturbations structurales identiques. La paire de bases g. A dans la sequence 29-39 du gene k-ras est en equilibre entre deux formes. A ph acide, la paire de bases adopte la structure g(syn)?a#+(anti) dans laquelle nous observons le proton h-n1 de l'adenosine protonee. A ph neutre et basique, la paire de bases adopte la structure g(anti)?a(anti) impliquant des liaisons hydrogenes bifurquees. Cette particularite pourrait etre a l'origine du faible taux de reparation du g. A.
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Silveira, Gustavo da. "Caracterização da variabilidade gerada por hibridações artificiais e mutações em caracteres de importância agronômica em aveia preta." Universidade Federal de Pelotas, 2009. http://repositorio.ufpel.edu.br/handle/ri/1175.
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Previous issue date: 2009-02-16Black oat (Avena strigosa Schreb.) is used as a forage or cover crop, green fertilizer, weed control (through competition or allelopatic effects) and soil pathogen reduction, playing an important role in crop rotation systems. Even with all these features, the high heterogeneity found in black oat fields indicates that very little progress has been made in breeding programs. Not much is known about yield potential, chemical composition of the forage and seed dormancy levels. Thus, the development of new genotypes with high forage yield performance as well as good seed quality and low dormancy will provide alternatives for the common black (preta comum) cultivar, currently predominating in the Southern Region of Brazil. Genetic variability widening can be achieved by artificial crosses and induced mutations, followed by selection. Therefore, black oat populations originating from artificial crosses and induced mutations (gamma rays) were compared in order to assess their efficiency in increasing the genetic variability. Agronomically important characters, i.e., associated to adaptation and farmer needs were measured. The results indicate that both techniques were efficient in increasing the genetic variability of forage characters, grain yield and seed dormancy levels. A high association was observed between plant stand and dry matter yield in early developmental stages. At later stages, the number of tillers was highly associated with biomass yield. In general, for both artificial hybridizations and gamma rays, differences in grain yield and seed dormancy levels were observed. Doses as well as parental combinations influenced the magnitude of the variability observed. The comparison of such techniques may help to accelerate the genetics gains in the black oat crop.
A importância da aveia preta (Avena strigosa Schreb.) esta relacionado à suas características para a produção de forragem, cobertura do solo, adubação verde, controle da infestação de plantas invasoras (através dos efeitos de competição e alelopáticos) e redução da população de patógenos do solo, especificando como espécie de grande aptidão para inclusão no sistema de rotação de culturas. Mesmo com todas estas características, a elevada heterogeneidade encontrada em pastagens de aveia preta é indicativa de que são poucos os trabalhos de pesquisa voltados para esta espécie, especialmente quanto a caracteres como potencial de produção, composição química da forragem e baixo nível de dormência nas sementes. Devido a isto, a obtenção de novas cultivares que apresentem bom comportamento forrageiro junto com a produção de sementes de qualidade e reduzido nível de dormência proverá alternativas para substituição da Preta Comum, variedade mais cultivada na região Sul. O incremento da variabilidade genética pode ser obtido através de cruzamentos artificiais e utilização de agentes mutagênicos, permitindo posteriormente a realização de seleção de constituições genéticas superiores. Neste sentido, foram avaliados caracteres de importância agronômica em populações de aveia preta originadas de cruzamentos artificiais e mutações induzidas (raios gama), de forma a analisar as técnicas de indução a variabilidade genética e a identificação de constituições genéticas adaptadas as necessidades do produtor agrícola. Os resultados evidenciaram que as duas técnicas foram eficientes na intensificação da variabilidade genética nos caracteres forrageiros, de rendimento de grãos e nível de dormência nas sementes. O caráter estande de plantas evidenciou elevada relação com a produtividade de matéria seca em estádios de desenvolvimento precoce das plantas; em fases mais adiantas o número de afilhos teve maior contribuição na produção de biomassa. De modo geral, tanto para as hibridações artificiais como para o agente mutagênico raios gama, as respostas para rendimento de grãos e nível de dormência foram diferenciadas, variando com a dose ou genitores utilizados na obtenção das populações. Consequentemente, o conhecimento de técnicas que incrementem a variabilidade genética pode auxiliar a seleção de constituições genéticas superiores, pela escolha de técnicas de melhoramento mais adequadas.
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Schwimmer, Christine. "Contribution à l'étude des relations structure-fonction du transporteur mitochondrial de nucléotides adényliques : induction et caractérisation de mutants de S.cerevisiae résistants à l'acide bongkrékique." Bordeaux 2, 1999. http://www.theses.fr/1999BOR28648.
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Carrière, Christian. "Etude par mutagenèse du rôle de la polyprotéine Gag du virus de l'immunodéficience humaine (HIV-1) dans le processus d'assemblage des particules virales." Montpellier 1, 1995. http://www.theses.fr/1995MON1T005.
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Mennecier, Samuel. "Mutagenèse spontanée et mutagenèse induite chez la bactérie radiorésistante Deinococcus radiodurans." Paris 11, 2007. http://www.theses.fr/2007PA112120.
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Deinococcus radiodurans appartient à une famille de bactéries connue pour sa capacité exceptionnelle à surmonter l’effet létal des agents qui endommagent l’ADN tels que les radiations ionisantes, le rayonnement ultraviolet ou la dessiccation. Nous avons montré la présence chez D. Radiodurans d’un système de réparation des mésappariements (MMR) fonctionnel, impliqué tant dans la fidélité de la réplication que la fidélité de la recombinaison. L’inactivation du MMR n’est pas associée à une radio-sensibilisation, suggérant que ce système ne joue qu’un rôle mineur dans la reconstitution d’un génome intact après endommagement de l’ADN. Nous avons mis en évidence l’importance de la transposition dans la mutagenèse spontanée chez D. Radiodurans, 75 % des mutations inactivant un gène rapporteur résultant d’insertions d’ISs (Insertion Sequences). Cinq ISs appartenant à des familles différentes et un MITE de type II (Miniature Inverted repeat Transposable Element) sont actifs pour la transposition. Nous avons enfin démontré l’existence d’une mutagenèse induite chez D. Radiodurans, reposant sur une augmentation de la mutagenèse ponctuelle et sur une induction de la transposition. La transposition de l’ISDra2, appartenant à une famille nouvellement caractérisée d’ISs, est induite respectivement d’un facteur 100 ou 50 après exposition des cellules au rayonnement gamma ou ultraviolet. Bien que les stratégies de réparation fidèle soient prédominantes chez D. Radiodurans, une transposition active et une mutagenèse induite par les dommages de l’ADN engendrent une variabilité génétique qui pourrait favoriser à long terme l’adaptation de cet organisme à ses habitats très diversDeinococcus radiodurans belongs to a family of bacteria characterized by an exceptional capacity to withstand the lethal effects of DNA-damaging agents, including ionizing radiation, UV light and desiccation. We demonstrated the existence of a functional mismatch repair system (MMR) involved in the fidelity of DNA replication and recombination in D. Radiodurans. Cells devoid of a functional MMR are as resistant to gamma-rays as wild type bacteria, suggesting that the MMR plays only a minor role in the reconstitution of a functional genome after DNA damage. We showed the important role of DNA transposition in spontaneous mutagenesis in D. Radiodurans, as 75 % of the mutations inactivating a reporter gene were due to IS (Insertion Sequence) insertions into its coding region. Five ISs from different families were shown to be transpositionally active. A type II Miniature Inverted-repeat Transposable Element (MITE) was also discovered as an insertion into the reporter gene. Finally, we observed the existence of induced mutagenesis in D. Radiodurans, implying increased point mutagenesis and up-regulation of DNA transposition. Transposition of ISDra2, belonging to a newly characterized IS family, was induced 100-fold after gamma-irradiation and 50-fold after UV-irradiation. Although error-free repair strategies predominate in D. Radiodurans, an up-regulation of DNA transposition, as well as induction of point mutations in cells recovering from DNA damage, can be a source of genetic variability that may have long-term evolutionary consequences on the fitness of this organism in its natural habitat
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Villani, Patrick. "Protocole d'étude des propriétés antimutagéniques de substances naturelles : application du test des micronoyaux dans les lymphocytes humains en culture." Aix-Marseille 2, 2000. http://theses.univ-amu.fr.lama.univ-amu.fr/2000AIX20667.pdf.
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Cuyubamba, Oscar R., William Pryor, Barbara S. Shane, and Giuseppe Squadrito. "¿Nos encontramos frente a una nueva clase de mutagenos?" Revista de Química, 2013. http://repositorio.pucp.edu.pe/index/handle/123456789/100645.
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El 1 ,3-dinitronaftaleno, previamente identificado en polvo ambiental, forma aductos covalentes con nucleótidos del DNA a temperatura ambiente fácilmente. La potencia mutagénica de un hidrocarburo aromático policíclico dinitrado (HAPDN), el 1, 3-dinitrofluoranteno, es prácticamente independiente de la cepa de Salmonella Typhimurium (TA98, TA98NR y TA98/1, 8DNP6) empleada en el Test de Ames. Este comportamiento poco usual sugiere que este HAPDN no requeriría de la activación metabólica vía la "nitroreductasa clásica" y/o de la acetilasa El hecho de que el 1, 3- dinitronaftaleno forma aductos covalentes con nucleótidos del DNA rápidamente está de acuerdo con que HAPDN meta disubstituídos podrían prescindir de las rutas usuales de activación metabólica.1,3-Dinitronaphthalene, previous1y identified in particulate organic matter, easily forms covalent adducts with DNA nucleotides at room temperature. The mutagenic potency of a related dinitropolycyclic aromatic hydrocarbon (dinitroPAH) with meta disubstitution, namely 1,3-dinitrofluoranthene, is rather independent of the Salmonella Typhimurium tester strain (TA98, TA98NR and TA98/l, 8DNP6) when assayed according to the Ames Test. This unusual behavior suggests that it does not require metabolic activation via the "classical nitroreductase" and/or the acetylase. The fact that 1,3--dinitronaphthalene readily forms covalent adducts with DNA nucleotides further suggests that dinitroPAH with meta nitro-groups may not require the usual metabolic activation pathways.
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CIZEAU, JEANNICK. "Effet mutagene du cis-dichlorodiammineplatine(ii) chez drosophila melanogaster." Orléans, 1994. http://www.theses.fr/1994ORLE2014.
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Le cis-dichlorodiammineplatine(ii) ou cis-ddp est une drogue antitumorale largement utilisee dans certaines therapies anticancereuses. Il reagit avec l'adn en formant des pontages intrabrins et interbrins avec les n7 des purines. Le cis-ddp a egalement une activite mutagene qui a ete determinee chez des bacteries et des cellules d'eucaryotes en culture. Le cis-ddp induit principalement des mutations ponctuelles. Nous avons etudie cet effet sur un organisme entier: drosophila melanogaster. Deux genes, white et vermilion, situes sur le chromosome x ont ete choisis comme cible de mutagenese car leur phenotype mute est facilement selectionnable. Afin d'etudier l'influence de la sequence homologue sur le spectre de mutagenese, deux experiences ont ete realisees dans deux contextes genetiques differents: male et femelle. Dans le contexte genetique male, les mutants obtenus (28 w et 4 v) correspondent a des deletions intralocus (de 4 a 109 nucleotides). Dans le contexte genetique femelle, sur 42 mutants w, 24 sont dus a des deletions intralocus (de 1 a 353 paires de bases), 18 proviennent de deletions de grande taille pouvant etre estimee a plusieurs centaines de milliers de paires de bases. Le sequencage de deux jonctions issues de large deletions montre que des sequences caracteristiques de la recombinaison illegitime sont proches des points de cassure. L'analyse de la sequence des mutations intralocus suggerent que la plupart d'entre eux resultent d'evenements de recombinaison non homologue entre deux sequences repetees situees aux bornes de la deletion, l'une etant conservee au niveau de la nouvelle jonction. De plus, la comparaison de la nature des mutations intralocus entre les deux contextes genetiques montre que la presence de la sequence homologue n'a pas d'influence sur le spectre de mutagenese du cis-ddp. Cette etude indique que le spectre de mutagenese du cis-ddp, en majorite des deletions, dans un organisme entier est tres different de celui obtenu chez des procaryotes et des cellules d'eucaryotes en culture
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Zschenker, Oliver. "Zielgerichtete Mutagenese der lysosomalen Lipase." [S.l.] : [s.n.], 2001. http://www.sub.uni-hamburg.de/disse/429/Disse.pdf.
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Réveilleau, Valérie. "Tests de mutagénèse et de cytotoxicité applicables à l'eau." Paris 5, 1996. http://www.theses.fr/1996PA05P056.
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Goold, Richard David. "Influence of endogenous female sex-steroids on mutagen metabolism." Thesis, Rhodes University, 1985. http://hdl.handle.net/10962/d1004919.
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Cytochrome P-450, the terminal oxidase of the metabolic mono-oxygenase system, is thought to exist in multiple forms, which have differing substrate specificities, and are variably inducible by different enzyme inducers. Many mutagens, themselves unreactive, require metabolic activation by one or more of these cytochrome P-450-dependent microsomal enzymes for mutagenic activity. Such mutagens may be detected in the Salmonella mutagenicity test only by the incorporation of an hepatic microsomal (59) fraction into the assay (as a first approximation to in vivo metabolism). Induction of the microsomal enzymes by different agents enhances the metabolic activation of mutagens; in fact, many mutagens are only detected when the 59 fraction has been induced by appropriate agents. Inducers of the phenobarbital-type are known to enhance microsomal steroid hydroxylation when administered at supraphysiological levels, inducers of several mono-oxygenase activities. In turn, the steroids, have been reported to be The inductive effects of the female sex-steroids and the combined effects of steroid and phenobarbital (PB) pretreatment on the metabolic activation of four mutagens have been investigated using the Salmonella assay. Female Sprague-Dawley rats were pret reated with 17a-oestradiol (E2) or progesterone (PRG) , at a level of either 1 mg/kg or 20 mg / kg daily for 14 days. A duplicate set of similarly pretreated groups were also induced with PB. Hepatic microsomal fractions were prepared from each group and incubated with each of the te st mutagens in the presence of a tester strain known to detect each particular type of mutagen. Induction of the hepatic metabolizing system by PB increased the activation of the mutagens significantly (as reflected by an increased number of revertant prototrophic S .typhimurium colonies). The administration of PRG also caused significant, and dose-dependent, induction of the activation of af l atoxin B1, benzo(a)pyrene, and dimethylnitrosamine. In general, E2 exhibited no inductive effect, but it did produce an increase in the activation of aflatoxin B1 (a reaction which is known to be catalysed by a mono-oxygenase prefe rentially inducible by PB). When use was made of a microsomal fraction that was prepared from animals which were both steroidpretreated and induced by PB, mutagenic activation was of the same order of magnitude as that observed when induction was brought about by PB alone. The absence of additive effect, taken together with the observations already mentioned, indicate that steroids induce the same cytochrome isozymes that are induced by PB. The implications of sex-hormonal regulation of the metabolic activation of mutagens are briefly discussed.KMBT_363
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Ehrenstein, Carmen. "Kontamination von Stadtgewässern mit mutagenen Substanzen." [S.l. : s.n.], 1999. http://deposit.ddb.de/cgi-bin/dokserv?idn=962783226.
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LOBO, NAPOLITANO RITA. "Mecanisme de la mutagenese frameshift induite." Université Louis Pasteur (Strasbourg) (1971-2008), 1997. http://www.theses.fr/1997STR13086.
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L'agent mutagene n-2-acetylaminofluorene forme un adduit sur la guanine qui constitue un bloc pour la replication de l'adn. Cette lesion va induire des mutations de type frameshift au sein de sequences de type (g)n et (gpc)n, la mutation correspondant a la deletion d'une unite de repetition. Afin de comprendre le(s) mecanisme(s) d'induction de ces mutations et le mecanisme de passage en face d'une lesion bloquante, nous avons construit des vecteurs contenant un adduit unique localise dans les differentes positions d'une sequence repetitive. Les resultats ont montre une frequence de mutation beaucoup plus importante quand la lesion se trouve sur la guanine situee en 3' de la repetition et ont permis de proposer un modele d'incorporation-glissement. Dans ce modele la polymerase incorpore une cytosine en face de la lesion generant un intermediaire de replication difficile a elonguer. L'appariement de cette cytosine avec la guanine situee en 5' de l'adduit va generer un intermediaire de glissement qui donne naissance a la mutation. Le gradient de frequence de mutation observe peut s'expliquer par le nombre (et la stabilite) des intermediaires de glissement qui peuvent de former. De plus, si la base en 3' de la repetition est une purine plutot qu'une pyrimidine la frequence de mutation est augmentee environ 5 fois. Afin d'etudier le mecanisme precis de la synthese en face d'une lesion nous avons construit des plasmides simple brin contenant un adduit aaf unique localise au niveau de ces points chauds. Nos resultats ont permis de montrer que les proteines sos induites umudc sont impliquees dans l'elongation des extremites ou la base terminale se trouve localisee en face de la lesion. Ces intermediaires ne conduisent pas a une mutation dans le cas de l'aaf mais correspondent aux intermediaires impliques dans la mutagenese par substitution induite. Par ailleurs, la mutagenese frameshift est independante d'umudc mais depend d'un autre facteur sos inductible.
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Ratcliffe, Andrew J. "Synthesis of non-mutagenic anticancer drugs." Thesis, University of Bath, 1987. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.378598.
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