Avaliação da atividade mutagênica e carcinogênica da anfotericina B em células somáticas de Drosophila melanogaster

Abstract

CHAPTER II: Amphotericin B (AmB) is an antifungal extracted from Streptomyces nodosus. Its fungicidal activity depends primarily on its binding to the sterol group, present in the membrane of fungi. Due to the toxicity of this drug this study aimed to evaluate their mutagenic, carcinogenic and recombinogenic activity. To do so, we used Somatic Mutation and Recombination Test (SMART) and the test for the detection of Epithelial Tumors (wts), both in Drosophila melanogaster. In the assessment using SMART, larvae from 72 h, descendants from the standard (ST) cross and the high bioactivation (HB) cross were treated with different concentrations of Amphotericin B (0.01; 0.02 e 0.04 mg/mL). The results revealed that the AmB is a promutagen exhibiting increase in the number of spots on individuals from high bioactivation (HB) cross with a high level of the cytochrome P450. The results also indicate that recombinogenicity is the main genotoxic event induced by AmB. Homologous recombination can function as a determinant at different stages of carcinogenesis. For verification, larvae from the wts test, descendants from the wts/TM3 virgin female and mwh/mwh male cross, were treated with the same three AmB concentrations separately and in association with mitomicin C (0.1 mM). The results did not, however, provide evidence that AmB has carcinogenic potential.