Mestrado em Ciências Biológicas (ICB)
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Navegando Mestrado em Ciências Biológicas (ICB) por Por Orientador "Cunha, Kênya Silva"
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Item Estudo da toxicidade e genotoxicidade induzidas por diferentes nanopartículas in vivo(Universidade Federal de Goiás, 2012-02-27) Andrade, Laise Rodrigues de; Cunha, Kênya Silva; http://lattes.cnpq.br/6124135410387685; Cunha, Kênya Silva; Lee, Chen Chen; Irazusta, Silvia PierreThe rapid advancement of nanotechnology has created a vast array of nanoparticles promising for industrial, energy and environmental sectors. Furthermore, many biological applications have been proposed for the nanoparticles, such as transport of genes and drugs for disease treatments, including cancer and infections. So, it is important to clarify if nanoparticles may represent a hazard to the environment and human health. In this study, we investigated the toxic potential and ability to induce DNA damage of different nanoparticles: four species of carbon nanotubes (NTC, NT, CS e MW), silver (AgNP) and nanoceria (CeO2-NP) nanoparticles. It was employed the somatic mutation and recombination test (SMART) in Drosophila melanogaster that detects the loss of heterozygosity of two genetic markers involved in the metabolic pathways of wing hairs formation - multiple wing hairs (mwh) and flare3 (flr3). In larvae, the proliferating of wings imaginal disc cells can produce hairs with mutant phenotypes expressed on the adult wings. Using the standard cross, third-stage larvae were treated with different concentrations of the nanoparticles until pupal stage. The wings of adult flies were examined microscopically for the identification of phenotypic abnormalities. In all concentrations the survival rates were higher than 90%, indicating the absence of chronic toxicity for nanoparticles evaluated. Using the conditional binomial test, the results of different treatments were compared with the respective negative control (distilled water), demonstrating no significantly increase in the NTC, NT and CS mutation and recombination frequencies (p>0.05) in mwh/flr3 genotype. In all carbon nanotubes tested, only the two higher concentrations of nanotubes MW (0.4 and 1 mg/mL) were able to induce genetic changes, mainly by mitotic recombination. The concentration of 10 mg/mL AgNP also promoted changes in the DNA and 61% of the phenotypic abnormalities were caused by recombination. The nanoceria was able to produce genotoxic effects at all concentrations tested (0.64-10 mg/mL). Overall, the mutational events were predominant, ranging from 46 to 72% of the total genotoxic effect induced by nanoceria, showing no dose-response relationship. In conclusion, our results demonstrated that carbon, silver and cerium dioxide nanoparticles have different genotoxic potential in D. melanogaster, so, another studies should be performed before any clinical and/or industrial application of nanoparticles.Item Estudo da toxicidade genética de efavirenz (EFV) e fumarato de tenofovir desoproxila (TDF) em células somáticas de drosophila melanogaster(Universidade Federal de Goiás, 2013-02-06) Moraes Filho, Aroldo Vieira de; Cunha, Kênya Silva; http://lattes.cnpq.br/6124135410387685; Cunha, Kênya Silva; http://lattes.cnpq.br/6124135410387685; Andrade, Heloisa Helena Rodrigues de; Chen, Lee Chen; Jesuino, Rosália Santos Amorim; Bataus, Luiz Artur MendesThe antiretroviral drugs appeared to prevent the multiplying HIV virus in the body, reducing its virulence, but not eliminate it from infected cells. These drugs increase the length and the quality of life of AIDS patients. In this context, Efavirenz (EFV) is non-nucleoside reverse transcriptase inhibitors. The Tenofovir Disoproxil Fumarate (TDF), oral prodrug of tenofovir, is analogue of adenosine 5 'monophosphate, belonging to the class of nucleotide reverse transcriptase inhibitors. These drugs act on the mechanisms of HIV replication by inhibiting the action of reverse transcriptase and thus preventing viral DNA synthesis. In order to assess the toxic and toxic-genetic potential of EFV and TDF, the present study used the Test for Detection of Somatic Mutation and Recombination (SMART) in Drosophila melanogaster. 3rd stage larvae originating from standard cross (ST) between males mwh and females flr³, were treated with solution of EFV and TDF and distilled water (negative control), for approximately 48 hours (chronic treatment) until they reach the pupal stage. These strains are carriers of specific gene markers, located on the left arm of chromosome 3, which allow you to monitor events related to mutation, mitotic recombination and chromosome aberrations. The statistical diagnosis was obtained by conditional binomial test. In this work, the results demonstrated that the EFV was toxic in high concentrations, but showed no induction of toxic genetic events. Inversely, the TDF showed no toxicity at the concentrations tested, but was showed induction of toxic genetic events at all concentrations, with a prevalence of recombinogenic events. Then, it is essential to analyze constantly the effects risk/benefit of isolated drugs and identify toxic and toxic genetic activity of each drug in order to ensure the quality of life for patients who use monotherapies and offers support for investigations with therapies that use combinations of antiretroviral drugs.Item Investigação do potencial mutagênico e recombinogênico dos combinados gemcitabina+doxorrubicina e gemcitabina+cisplatina em células somáticas de Drosophila melanogaster(Universidade Federal de Goiás, 2011-03-27) Oliveira, Igor Gomes de; Cunha, Kênya Silva; http://lattes.cnpq.br/6124135410387685Clinical studies have shown that the combinations of chemotherapeutic drugs gemcitabine (GEM) plus cisplatin (CIS) and gemcitabine (GEM) plus doxorubicin (DXR) exert important cytotoxic activity against several types of cancer in advanced stages as well as metastatic cancer. CIS, DXR and GEM have different mechanisms of action. GEM is a pro-drug that must be phosphorylated by deoxycytidine kinase to evolve into its active form. Both gemcitabine diphosphate and gemcitabine triphosphate inhibit processes required for DNA synthesis. CIS induces a variety of DNA structural changes, mainly intra- and interstrand cross-links between adjacent purine bases. DXR acts as a topoisomerase II inhibitor. This study compares the genetic toxicity effects induced by GEM+CIS and GEM+DXR co-treatments with the single drug treatments. We used the Somatic Mutation And Recombination Test (SMART), which simultaneously detects and quantifies mutagenic and recombinogenic toxicological endpoints through loss of heterozygosity of two genetic markers involved in the metabolic pathways of the Drosophila melanogaster wing hairs formation. Using the standard cross, the third-stage larvae were chronically treated with different concentrations of GEM (0.008, 0.010, 0.012 and 0.014 mM) combined with CIS (0.05 mM) or DXR (0.2 mM). Comparing with GEM single treatment, GEM+CIS and GEM+DXR co-treatments induced a synergistic effect manifested as an increment in the mutant clones frequencies. Homologous recombination was the main genotoxic effect observed.