Saturnino Rosiane Soares, Machado Nayane Moreira, Lopes Jeyson Cesary, Nepomuceno Júlio César
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.
Drug Chem Toxicol. 2018 Jan;41(1):9-15. doi: 10.1080/01480545.2016.1188302. Epub 2017 Mar 9.
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, flr were 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, flr developed tumors at the highest concentration tested.
两性霉素B(AmB)是一种从结节链霉菌中提取的抗真菌抗生素。其杀菌活性主要取决于它与真菌细胞膜中存在的固醇基团的结合。鉴于该药物的毒性,本研究的目的是基于应用于黑腹果蝇的翅体细胞突变和重组试验(SMART)以及上皮肿瘤检测试验(wts),评估其诱变、致癌和重组活性。用不同浓度的AmB(0.01、0.02和0.04mg/mL)对幼虫进行长期处理。结果显示,AmB是一种前诱变剂,在与高水平细胞色素P450的高生物活化(HB)杂交个体中斑点数量增加。结果还表明,AmB诱导的主要遗传毒性事件是重组性。同源重组可在致癌作用的不同阶段起决定作用。为验证该化合物的致癌潜力,用SMART试验中使用的相同三种AmB浓度处理wts/mwh和wts/ORR、flr的幼虫。结果未提供证据表明AmB对wts/mwh个体具有致癌潜力。然而,wts/ORR、flr的个体在测试的最高浓度下出现了肿瘤。