Estudo comparativo da genotoxicidade do antirretroviral abacavir isolado e em combinação com zidovudina e lamivudina in vivo
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Data
2015-03-17
Autores
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Universidade Federal de Goiás
Resumo
Abacavir (ABC), zidovudine (AZT) and lamivudine (3TC) are nucleoside reversetranscriptase
inhibitors (NRTIs) widely used as the main axis of highly active
antiretroviral therapy (HAART). Despite the effectiveness of combinations of NRTI in
viral suppression, there is evidence to show that the genotoxic potential of NRTIs can
be increased when administered in combination. In this context, this study proposed
to investigate the toxic and genotoxic potential ABC induced when administered
isolated and in combination with AZT and/or 3TC, using the wing SMART in
Drosophila melanogaster. This test simultaneously evaluates two events related to
carcinogenesis, mutation and somatic recombination, and is based on the
identification of the mutants hairs resulting from lesions that lead to loss of
heterozygosity in two marker genes involved in the formation of the wings of hair:
mwh and flr3. In toxicity tests, groups of 100 larvae of third instar from the standard
cross were treated for 48 hours with different concentrations of drugs. From the
results obtained,was established a range of concentrations presenting more than
70% of survivors flies to proceed the analysis of genotoxicity. Employing the
conditional binomial test, were compared the spots of mutants hair frequencies
present in trans-heterozygotes and heterozygous flies for chromosome TM3 of each
treated group with the respective controls. The results of investigations indicated that
ABC was toxic to larvae in concentrations greater than 2 mg/ml. The combinations
which contained ABC showed toxic effects similar to isolated ABC. All treatments
were able to induce genetic alterations related to mutation and somatic
recombination. Among all combinations, AZT/3TC was the one that showed less
toxic and genotoxic potential at the concentrations tested. The potential
recombinogenic both ABC isolated or in combination was relatively high, with indices
of over 83.7%.
Descrição
Palavras-chave
ABC , Antirretroviral , Recombinação , NRTIs , Mutação , SMART , ABC , Antiretroviral , NRTIs , Recombination , Mutation , SMART
Citação
SILVA, C. J. Estudo comparativo da genotoxicidade do antirretroviral abacavir isolado e em combinação com zidovudina e lamivudina in vivo. 2015. 44 f. Dissertação (Mestrado em Biologia) - Universidade Federal de Goiás, Goiânia, 2015.