Doutorado em Genética e Biologia Molecular (ICB)
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Navegando Doutorado em Genética e Biologia Molecular (ICB) por Por Orientador "Silva, Daniela de Melo e"
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Item Aplicações toxicogenômicas em cultura de células expostas a nanomateriais e populações humanas expostas a pesticidas(Universidade Federal de Goiás, 2017-09-04) Franco, Fernanda Craveiro; Silva, Daniela de Melo e; http://buscacv.cnpq.br/buscacv/#/espelho?nro_id_cnpq_cp_s=9895211901348365; Parise, Michelle Rocha; Silva, Claudio Carlos da; Vieira, Thais Cidália; Costa, Emília Oliveira Alves; Silva, Daniela de Melo eThe interaction of some compounds and DNA molecule can cause genotoxic changes. The tests used to evaluate genotoxicity have evolved over the years, and they have great efficiency. Currently, several traditional methodologies are used, such as the comet assay, and some more modern, based on molecular biology. Considering the importance of detecting the effects caused by exposure to potentially genotoxic agents, this thesis presents three chapters with different approaches to this topic. The first chapter aimed at evaluating published studies on the mutagenic, genotoxic and oxidative effects caused by occupational exposure to pesticides. For this, a systematic review of articles published between the years of 2011 and 2015 was carried out, focusing on these exposure conditions. The results showed that 44% of the studies addressed only men and 44% approached men and women, and 78% used rural workers as an exposed population. The most evaluated class of pesticide was organophosphorus. The studies were separated by methodologies of analysis used and all showed some type of alteration in the populations occupationally exposed to pesticides. The second chapter, published in the journal Environmental Science and Pollution Research, considered the dengue scene in the state of Goias and techniques of mosquitoes control, and sought to understand the genotoxic effects caused by exposure of endemic agents to pesticides used against Aedes aegypti, being the first study published with this group of workers. The main pesticides used were insecticides and larvicides and an increase in DNA damage was observed in the exposed population, without influence of the lifestyle factors. In the whole transcriptome assay the differential expression of genes related to various chronic diseases was observed. Finally, the third chapter was carried out in collaboration with the Institute of Experimental Medicine of the Czech Academy of Sciences, aiming the determination of cytotoxic and genotoxic effects caused by in vitro exposure to different types of metallic nanomaterials. In nanomaterials that showed cell viability reduction (cytotoxic), an increase in genotoxicity was also identified. In addition, three of the four non-cytotoxic nanomaterials evaluated showed genotoxic effects. Studies aimed at detecting the compounds genotoxic potential are extremely important for the regulatory definition and identification of risks caused by exposure. In this study, the toxicological and genotoxic effects of different compounds and mixtures were evaluated using traditional and modern techniques, in vitro or by human biomonitoring, seeking to understand and determine the risks involved in exposure to these substances.Item Avaliação do dano ao DNA pelo ensaio cometa e análise dos pontos de variação dos genes CYP2E1, CYP1A1 e OGG1 em etilistas do município de Goiânia-GO(Universidade Federal de Goiás, 2018-05-28) Lopes, Mariana Paiva; Silva, Daniela de Melo e; http://lattes.cnpq.br/9895211901348365; Silva, Daniela de Melo e; http://lattes.cnpq.br/9895211901348365; Parise, Michelle Rocha; Nunes, Hugo Freire; Costa, Emília Oliveira Alves; Avelar, Juliana BoaventuraEthanol is considered the most consumed drug in the world, is part of several cultures. However, chronic ethanol consumption has become a social and public health problem, since it has serious health consequences and is a risk factor for several diseases and mortality. The CYP2E1 gene encodes an enzyme that is the main constituent of the microsomal oxidation system of ethanol. The CYP1A1 gene encodes an enzyme that, like CYP2E1, acts on the oxidative biotransformation of phase I substrates of the metabolism of xenobiotics such as ethanol. In addition, genes related to DNA repair such as OGG1 are also of great importance as they are involved in protecting the genome by helping to maintain the cellular functions of organisms. Problems in the repair process can interfere with aging and promote disease development. Genetic variations in these genes result in significant differences in enzyme activity. However, there is still no clear correlation between the functional significance of these variations in both ethanol metabolism and ethylene repair. In the present study, the variability of specific regions of the CYP2E1, CYP1A1 and OGG1 genes were analyzed in samples of alcoholics from a Psychosocial Care Center (CAPS) of the State of Goiás, in the city of Goiânia, and the results were compared with the data obtained by the 1000Genomas project. A study of the association between the polymorphism of these genes and the damage to the DNA in ethanol was carried out. Sequencing reactions and the comet assay were performed. There was no relation between the data of the polymorphism found with DNA damage. However, in the analysis of the DNA damage between the case and control groups, greater damage was observed in the alcoholics in relation to the control group. The genotypic frequencies adhered to that expected by the HardyWeinberg Equilibrium for all the polymorphism in the Brazilian samples. Based on the polymorphism of the CYP2E1 gene, 15 haplotypes were inferred. Of these, only 4 haplotypes were common in all populations. While based on the two polymorphism of the CYP1A1 and OGG1 genes, 3 haplotypes were inferred for each gene, all present in the Brazilian study population.Item Avaliação de polimorfismos nos genes de reparo e detoxificação e a associação com o dano no DNA em etilistas(Universidade Federal de Goiás, 2017-07-06) Melo, Caroline Oliveira de Araújo; Silva, Daniela de Melo e; http://lattes.cnpq.br/9895211901348365; Parise, Michelle Rocha; Rodrigues, Flávia Melo; Avelar, Juliana Boaventura; Costa, Emília Oliveira AlvesAlcohol abuse is related to approximately 3.3 million annual deaths worldwide and is considered the first risk factor for the global burden of disease in countries of the Americas. Long-term abuse of alcohol induces numerous molecular and biochemical changes in alcohol-related tissues. It is believed that the toxic effects of alcohol are mediated by DNA damage by several mechanisms, such as by the induction of oxidative damage, DNA adducts, crosslinks and DNA strand breaks. In this sense, the aim of this study was to verify the frequency of polymorphisms in the repair and detoxification genes and the association with the DNA damage in alcoholics. The analysis of the obtained results showed a greater genotoxic damage in the alcoholics, when carrying out the Comet Assay. A point of variation was found in the GSTP1 gene and another point of variation in the XRCC1 gene. However, no statistically significant differences were observed between GSTM1 and GSTT1 genotypes and genetic damage. In this context, it can be concluded that the Comet Assay is a very effective and inexpensive method for the analysis of genotoxic damage.Item Investigações genéticas em doenças raras: uma contribuição positiva das tecnologias genômicas(Universidade Federal de Goiás, 2017-08-09) Reis, Fabiana Gonçalves dos; Cruz, Aparecido Divino da; http://lattes.cnpq.br/7868817504129985; Silva, Daniela de Melo e; http://lattes.cnpq.br/9895211901348365; Silva, Daniela de Melo e; Minasi, Lysa Bernardes; Gigonzac, Thaís Cidália Vieira; Paccez, Juliano Domiraci; Costa, Emília Oliveira AlvesNeurological disorders are a group of conditions that manifest early in the development of the child, so that delayed neuropsychomotor development (ADNPM) and intellectual disability (ID) can impair cognitive, language, motor and social behavior. The etiology of ID is quite heterogeneous and prenatal, perinatal and postnatal factors are associated with an increased risk of this deficiency. However, 30 to 50% of the cases remain with the unknown etiology. In this context, the main objective of this study was to identify submicroscopic genomic alterations (<5Mb) by means of microarray chromosomal analysis (CMA) in patients with clinical indication of ADNPM and/or ID, sent by attending physicians of the state public health network of Goiás. We analyzed 149 cases of both sexes. Of the total number of patients, 47 had the diagnosis clarified using cytogenetics by G banding. Of 102 patients with an incomplete diagnosis, 72 agreed to participate in the present study and, therefore, performed the CMA. The elucidation of the diagnosis by CMA was possible in 22 patients. Among the results obtained, three rare cases were selected to compose this thesis. The first case is from a patient in whom a de novo microduplication of 0.45 Mb in the 5q35.2q35.3 region containing the NSD1 gene was identified. The effect of the dosing of this gene has been related to Sotos Syndrome and its inverted phenotype. The second case shows the molecular detection of an absent allele on the X chromosome and the presence of 28 CGG repeats in FMR1 gene in the present allele. The CMA showed that the patient had a de novo microdeletion of 4.176 Mb in the Xq27.3-q28 region that affected 34 genes, including five genes (TMEM185A, TMEM257, FMR1, IDS, and FMR2) that were directly correlated with ID phenotypes and neurological disorders. The third case is a de novo microdeletion of 1.59 Mb in the 1p32.3 region involving the DHCR24 gene, which causes a gene dosage effect influencing the activation of enzymes that cause desmosterolosis, which is a desmosterol conversion disorder in cholesterol. Thus, the results of this thesis showed the relevance of the use of the CMA technology to diagnose patients with clinical signs of ADNPM and/or ID that presented karyotype without alterations, evidencing the importance of this technology for public health.