title: Assessment of the mutagenic, recombinogenic, and carcinogenic potential of amphotericin B in somatic cells of Drosophila melanogaster.
abstract: Amphotericin B (AmB) is an antifungal antibiotic extracted from Streptomyces nodosus. Its fungicidal activity depends primarily on its binding to the sterol group that is present in fungal membranes. In view of the toxicity of this drug, the purpose of this study was to evaluate its mutagenic, carcinogenic, and recombinogenic activity, based on the wing somatic mutation and recombination test (SMART) and the epithelial tumor detection test (wts) applied to Drosophila melanogaster. Larvae were chronically treated with different concentrations of AmB (0.01, 0.02, and 0.04 mg/mL). The results revealed that AmB is a promutagen exhibiting increase in the number of spots on individuals from high bioactivation (HB) cross with a high level of cytochrome P450. The results also indicate that the main genotoxic event induced by AmB is recombinogenicity. Homologous recombination can act as a determinant at different stages of carcinogenesis. For verification of carcinogenic potential of this compound, larvae from the wts/mwh and wts/ORR, flr3were treated with the same three AmB concentrations used in the SMART assay. The results did not provide evidence that AmB has carcinogenic potential in wts/mwh individuals. However, individuals from wts/ORR, flr3developed tumors at the highest concentration tested.
authors.affiliation: a Institute of Genetics and Biochemistry, Federal University of Uberlândia , Uberlândia , Brazil and.|b Laboratory of Cytogenetics and Mutagenesis , University Center of Patos de Minas , Patos de Minas , Brazil.
authors.forename: Rosiane Soares
authors.initials: RS
authors.lastname: Saturnino
authors.affiliation: a Institute of Genetics and Biochemistry, Federal University of Uberlândia , Uberlândia , Brazil and.|b Laboratory of Cytogenetics and Mutagenesis , University Center of Patos de Minas , Patos de Minas , Brazil.
authors.forename: Nayane Moreira
authors.initials: NM
authors.lastname: Machado
authors.affiliation: a Institute of Genetics and Biochemistry, Federal University of Uberlândia , Uberlândia , Brazil and.|b Laboratory of Cytogenetics and Mutagenesis , University Center of Patos de Minas , Patos de Minas , Brazil.
authors.forename: Jeyson Cesary
authors.initials: JC
authors.lastname: Lopes
authors.affiliation: a Institute of Genetics and Biochemistry, Federal University of Uberlândia , Uberlândia , Brazil and.|b Laboratory of Cytogenetics and Mutagenesis , University Center of Patos de Minas , Patos de Minas , Brazil.
authors.forename: Júlio César
authors.initials: JC
authors.lastname: Nepomuceno
mesh_terms: D000666:Amphotericin B / Q000633:toxicity*; D000818:Animals; D030801:Animals, Genetically Modified; D000935:Antifungal Agents / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000187:drug effects* / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D059765:Homologous Recombination / Q000187:drug effects*; D007814:Larva / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009369:Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D018570:Risk Assessment; D014921:Wings, Animal / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D029721:Drosophila Proteins; C532921:mwh protein, Drosophila; D000666:Amphotericin B; D003577:Cytochrome P-450 Enzyme System
keywords: Amphotericin B; Drosophila melanogaster; SMART; recombination; wts