L’objectif de ce travail est l’étude de la plante face aux molécules issues de la phototransformation de la sulcotrione. La recherche d’anomalies a été menée sur des extrémités racinaires d’Allium cepa L. var. aggregatum par un dénombrement au microscope des anomalies chromosomiques causées par l’ajout des différents xénobiotiques. L’étude a été réalisée en deux temps. Tout d’abord l’impact génotoxique d’un mélange constitué de la sulcotrione et de ses photoproduits a été évalué. Puis les caractéristiques de chaque produit de dégradation ont été analysées indépendamment. Il s’est avéré que la sulcotrione et ses produits de transformation CMBA et XDD ont des caractéristiques de toxicité qui sont spécifiques de chacun d’entre eux, avec une toxicité plus importante pour XDD. Il a été observé que XDD peut s’hydrolyser. Les études sur les produits de seconde génération ont permis d’identifier HMBA qui présente de nombreuses similitudes avec l’acide salicylique et provoque notamment une croissance racinaire accrue chez les espèces monocotylédones testées. / Cytotoxicity and genotoxicity of non irradiated and irradiated sulcotrione were investigated in Allium cepa test. Then, the cytotoxic effects of 2-chloro-4-mesylbenzoic acid (CMBA) and xanthene-1,9-dione-3,4-dihydro-6-methylsulfonyl (XDD), the two main photoproducts of sulcotrione were investigated at different concentrations. We analyze plant response treated with sulcotrione phototransformation by-products. Chromosomal aberrations were observed in Allium cepa root meristems. First, we investigated the genotoxic impact of a sulcotrione mixture and its photoproducts. Then each by-product was independently tested. Sulcotrione CMBA and XDD have specific toxicity, and XDD has a greater toxicity. In our latest analysis we observed that XDD can be hydrolyzed. HMBA was identified as a salicylic acid derivative and can increase root growth in monocotyledonous species.

Carcinogen-induced DNA base modification and subsequent DNA lesions are the critical events for the expression of premalignant phenotype of the cell. We have therefore investigated the chemopreventive efficacy of a vanadium salt against diethylnitrosamine (DEN)-induced early DNA and chromosomal damages in rat liver. Hepatocarcinogenesis was induced in male Sprague-Dawley rats with a single, necrogenic, intraperitoneal injection of DEN (200 mg/kg body weight). 8-Hydroxy-2′-deoxyguanosines (8-OHdGs), strand-breaks and DNA-protein crosslinks (DPCs) were measured by HPLC, comet assay and spectrofluorimetry, respectively. There was a significant and steady elevation of modified bases 8-OHdGs along with substantial increments of the extent of single-strand-breaks (SSBs), DPCs and chromosomal aberrations (CAs) following DEN exposure. Supplementation of vanadium as ammonium metavanadate (NH4VO3, +V oxidation state) at a dose of 0.5 ppm in terms of the salt weight throughout the experiment abated the formations of 8-OHdGs (P < 0.0001; 79.54%), tailed DNA (P < 0.05; 31.55%) and length:width of DNA mass (P < 0.02; 61.25%) in preneoplastic rat liver. Vanadium treatment also inhibited DPCs (P < 0.0001; 58.47%) and CAs (P < 0.001; 45.17%) studied at various time points. The results indicate that the anticlastogenic potential of vanadium in vivo might be due to the observed reductions in liver-specific 8-OHdGs, SSBs and/or DPCs by this trace metal. We conclude that, vanadium plays a significant role in limiting DEN-induced genotoxicity and clastogenicity during the early stages of hepatocarcinogenesis in rats.

Made available in DSpace on 2016-08-19T17:47:09Z (GMT). No. of bitstreams: 1 Antonio Alberto Carvalho.pdf: 630872 bytes, checksum: 13ecf29f7245808d06388075ae78be17 (MD5) Previous issue date: 2006-06-16 / In this study the results of the evaluation cytogenetics of 694 patients with suspected of being carriers of chromosomal abnormality, seen in Sarah Network of Hospitals for Rehabilitation - San Luis Unit, in the period from December 1996 to January 2005. / Neste estudo são apresentados os resultados da avaliação citogenética de 694 pacientes, com suspeita de serem portadores de anomalia cromossômica, atendidos na Rede Sarah de Hospitais de Reabilitação - Unidade São Luís, no período de dezembro de 1996 a janeiro de 2005.

Gene activity is regulated at two separate layers. Through structural and chemical properties of DNA – the primary layer of encoding – local signatures may enable, or disable, the binding of proteins or complexes of them with regulatory potential to the DNA. At a higher level – the structural layer of encoding – gene activity is regulated through the properties of higher order DNA structure, chromatin, and chromosome organization. Cells with abnormal chromosome compaction or organization, e.g. cancer cells, may thus have perturbed regulatory activities resulting in abnormal gene activity. Hence, there is a great need to decode the transcriptional regulation encoded in both layers to further our understanding of the factors that control activity and life of a cell and, ultimately, an organism. Modern genome-wide studies with those aims rely on data-intense experiments requiring sophisticated computational and statistical methods for data handling and analyses. This thesis describes recent advances of analyzing experimental data from quantitative biological studies to decipher the structural layer of encoding in human cells. Adopting an integrative approach when possible, combining multiple sources of data, allowed us to study the influences of chromatin (Papers I and II) and chromosomal aberrations (Paper IV) on transcription. Combining chromatin data with chromosomal aberration data allowed us to identify putative driver oncogenes and tumor-suppressor genes in cancer (Paper IV). Bayesian approaches enabling the incorporation of background information in the models and the adaptability of such models to data have been very useful. Their usages yielded accurate and narrow detection of chromosomal breakpoints in cancer (Papers III and IV) and reliable positioning of nucleosomes and their dynamics during transcriptional regulation at functionally relevant regulatory elements (Paper II). Using massively parallel sequencing data, we explored the chromatin landscapes of human cells (Papers I and II) and concluded that there is a preferential and evolutionary conserved positioning at internal exons nearly unaffected by the transcriptional level. We also observed a strong association between certain histone modifications and the inclusion or exclusion of an exon in the mature gene transcript, suggesting a functional role in splicing.

Made available in DSpace on 2014-10-09T12:44:18Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T13:56:53Z (GMT). No. of bitstreams: 1 06865.pdf: 2088769 bytes, checksum: 011acb7fa0ff799f54b79805918ddfb3 (MD5) / Dissertacao (Mestrado) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP

Made available in DSpace on 2014-10-09T12:44:18Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T13:56:53Z (GMT). No. of bitstreams: 1 06865.pdf: 2088769 bytes, checksum: 011acb7fa0ff799f54b79805918ddfb3 (MD5) / Dissertacao (Mestrado) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP

Thesis (PhD (Psychiatry))--Stellenbosch University, 2008. / BACKGROUND: Schizophrenia is a heterogeneous illness resulting from complex gene-environment interplay. The majority of molecular genetic work done has involved Caucasian populations, with studies in these and Asian populations showing 2-32% of sufferers to have chromosomal aberrations. So far the discovery of a specific susceptibility mechanism or gene still eludes us, but the use of endophenotypes is advocated as a useful tool in this search. No cytogenetic studies of this nature have been reported in any African schizophrenia population. AIM: The aim of the study was to combine genotypic and phenotypic data, collected in a homogenous population in a structured manner, with the hope of characterising an endophenotype that could be used for more accurate identification of individuals with possible chromosomal abnormalities. METHODOLOGY: A structured clinical interview was conducted on 112 Xhosa schizophrenia patients. (Diagnostic Interview for Genetic Studies, including Schedules for the Assessment of Negative and Positive Symptoms.) Blood samples (karyotyping and/or FISH analysis) as well as urine samples (drug screening) were obtained and nine head and facial measurements were performed. Descriptive statistics were compiled with reference to demographic, clinical and morphological variables. Comparisons between mean differences for these variables were made.

Submitted by admin tede (tede@pucgoias.edu.br) on 2018-06-20T19:01:11Z No. of bitstreams: 1 ANDREYA GONÇALVES COSTA MOTTA.pdf: 1269655 bytes, checksum: d3b8bb83fce2a80358844cba4c05d288 (MD5) / Made available in DSpace on 2018-06-20T19:01:11Z (GMT). No. of bitstreams: 1 ANDREYA GONÇALVES COSTA MOTTA.pdf: 1269655 bytes, checksum: d3b8bb83fce2a80358844cba4c05d288 (MD5) Previous issue date: 2018-03-08 / The understanding of the biological effects radioinducites in the organism can help the cytogenetic dosimetry in monitoring the health of professionals occupationally exposed to radiation, so radiology technicians must pay attention to all necessary and obligatory measures of protection because they are responsible for the procedures that refer to the diagnoses involving exposure to ionizing radiation. The objective of this research was to perform a cytogenetic analysis of 20 professional radiology technicians exposed occupationally to ionizing radiation through the collection of heparinized peripheral blood and culture of T lymphocytes to verify the frequencies of chromosomal aberrations and micronuclei. All subjects had to have more than 3 years of service time, regardless of age, sex, smoking habits or alcohol. The control group had the same age and sex as the exposed group. Micronucleus analysis occurred faster and more accurately than the analysis of chromosomal aberrations, suggesting that it is used as the first choice in radiological screening. Metaphase analysis and the cytokinesis blockade test allowed the quantification of a high frequency of unstable chromosomal aberrations and micronuclei in subjects with a workday from 6 hours to 12 hours daily. The results of the frequency of unstable chromosomal aberrations in the exposed group were 0.031 ± 0.030 and in the control group 0.002 ± 0.004. In the micronuclei frequencies of the exposed group the obtained result was 0.0035 ± 0.003 and in the control group 0,0004 ± 0.001 confirming the methodology of cytogenetic analysis as quality control in the biodosimetric investigation for the identification and prevention of possible genomic damages. Subsequent studies are needed to find out if factors such as smoking and alcoholism can influence changes in the health of these professionals. / A compreensão dos efeitos biológicos radioinduzidos no organismo pode auxiliar a dosimetria citogenética no monitoramento da saúde dos profissionais ocupacionalmente expostos a radiação, assim, os técnicos em radiologia devem se atentar a todas as medidas necessárias e obrigatórias de proteção por serem responsáveis pelos procedimentos que referentes aos diagnósticos clínicos que envolvam a exposição à radiação ionizante. O objetivo desta pesquisa foi realizar análise citogenética de 20 profissionais técnicos em radiologia expostos ocupacionalmente a radiação ionizante, através da coleta de sangue periférico heparinizado e cultura de linfócitos T para verificar as frequências de aberrações cromossômicas e de micronúcleos. Todos os indivíduos tinham que ter mais de 3 anos de tempo de serviço, independente da idade, sexo, hábitos tabagista ou etilista. O grupo controle teve a idade e sexo equiparados com o grupo exposto. A análise de micronúcleos ocorreu de forma mais rápida e precisa do que a análise de aberrações cromossômicas, sugerindo que ela seja utilizada como primeira escolha em triagem radiológica. A análise de metáfases e o teste de bloqueio de citocinese permitiu a quantificação de uma alta frequência de aberrações cromossômicas instáveis e de micronúcleos nos indivíduos com a jornada de trabalho entre 6 horas a 12 horas diárias. Os resultados encontrados da frequência de aberrações cromossômicas instáveis no grupo exposto foi 0,031±0,030 e no grupo controle 0,002±0,004. Nas frequências de micronúcleos do grupo exposto o resultado obtido foi 0,0035±0,003 e no grupo controle 0,0004±0,001 confirmando a metodologia de análise citogenética como controle de qualidade na investigação biodosimétrica para a identificação e prevenção de possíveis danos genômicos. Estudos subsequentes são necessários para averiguar se fatores como o fumo e o etilismo podem influenciar as alterações na saúde destes profissionais.

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Resumo: Devido às crescentes expansões demográficas e industriais observadas nas últimas décadas, o meio ambiente tem recebido uma carga significativamente crescente de efluentes domésticos, industriais e agrícolas, causando impactos severos nos ecossistemas e um potencial comprometimento à saúde humana. Dentre os efluentes domésticos, podemos citar uma gama de poluentes, tais como químicos de diversas categorias, além de contaminações por agentes biológicos diversos. Já os efluentes industriais contêm poluentes orgânicos e/ou inorgânicos, dependendo da atividade industrial. Baseando-se nestes dados, este trabalho teve como objetivo investigar, por meio de ensaios biológicos com dois organismos-teste, a possível presença de contaminantes com potencial citotóxico, genotóxico e mutagênico, que são despejados ao longo do rio Preto, inclusive na Represa Municipal de São José do Rio Preto. O material biológico utilizado neste estudo constituiu-se de sementes de Allium cepa (cebola) e peixes da espécie Oreochromis niloticus (Tilápia). Coletas de águas foram realizadas, sazonalmente, nos meses de agosto de 2006 e 2007 (estação seca) e março de 2007 e 2008 (estação chuvosa), em seis pontos distintos: Ponto 1 (P1), 8 km antes do represamento; Ponto 2 (P2), 1 km antes do represamento; Ponto 3 (P3), local de despejo do esgoto; Ponto 4 (P4), margem oposta do despejo do esgoto; Ponto 5 (P5), saída do represamento; Ponto 6 (P6), 1 km após o represamento. Análises químicas foram realizadas para todas as coletas realizadas. Para a realização do estudo, 100 sementes de Allium cepa foram submetidas à germinação, em placa de Petri, em amostras de águas coletadas nos seis diferentes pontos do rio Preto, em água ultra pura (controle negativo) e em uma substância reconhecidamente aneugênica (Trifluralina - controle positivo), sempre à temperatura ambiente... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Due to increasing population and industrial expansion observed in recent decades, the environment has received a significant increased burden of domestic industrial and agricultural sewerage, which can cause severe impacts on ecosystems, and a potential damage to human health as well. A wide range of harmful pollutants can be found in domestic effluent, such as chemicals from various categories, in addition to contamination by various biological agents. On the other hand, industrial effluents contain organic and / or inorganic pollutants, depending on industrial activity. Based on these data, this study aimed to investigate, by means of biological tests with two test-organism, the possible presence of contaminants with cytotoxic, genotoxic and mutagenic potential, which are dumped along the Preto river, an important river that flows in the region of Sao Jose do Rio Preto/SP. The biological material used in this study consisted of seeds of Allium cepa (onion) and one specie of fish (Tilapia: Oreochromis niloticus). Water samples were taken seasonally in August 2006 and 2007 (dry season) and March 2007, and 2008 (rainy season), in six distinct sites: Site 1 (S1), 8 km before the damming, Site 2 (S2), 1 km before the damming, Site 3 (S3), place of sewerage discharge; Site 4 (S4), opposite margin of sewage discharge, Site 5 (S5), end of the damming; Site 6 (S6) 1 km after damming. Chemical analyses were performed for all collected samples. For the study, 100 seeds of A. cepa were submitted to germination in Petri dishes with samples water from six different sites of the Preto river, Ultra pure water (negative control), and with an aneugenic substance (Trifluralin - positive control). For most of collection points and periods studied, root meristems cells of A. cepa, exposed to water samples collected along the Preto river, showed no significant differences... (Complete abstract click electronic access below) / Orientador: Maria Aparecida Marin-Morales / Coorientador: Maria Tecília Vilela de Azeredo-Oliveira / Banca: Regina Teresa Rosim Monteiro / Banca: Carmem Silvia Fontanetti Christofoletti / Banca: Eduardo Alves de Almeida / Banca: Mary Massumi Itoyama / Doutor