Investigação do potencial mutagênico e recombinogênico dos combinados gemcitabina+doxorrubicina e gemcitabina+cisplatina em células somáticas de Drosophila melanogaster

• Autor(a) principal: Oliveira, Igor Gomes de
• Data de Publicação: 2011
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da UFG
• Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tede/4263
• topic: Quimioterápicos; Mutagênese; Drosophila melanogaster; Chemotherapy; Mutagensis; Drosophila melanogaster; CIENCIAS BIOLOGICAS::BIOLOGIA GERAL

Clinical 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.