Genotoxicity testing of combined treatment with cisplatin, bleomycin, and 5-fluorouracil in somatic cells of Drosophila melanogaster

Abstract

The simultaneous treatment with the cross-linking agent cisplatin, the radiomimetic antitumoral drug bleomycin, and the anti-metabolite drug 5-fluorouracil has been used as a regimen to treat patients with squamous cell carcinoma of the head and neck. Considering that these drugs interact directly with DNA, one of the important late-occurring complications from treatment of primary malignancies is the therapy-related secondary cancers as a result of the genotoxic activity of the drugs on normal cells. In this sense, the genotoxicity of this combination was evaluated using the wing somatic mutation and recombination test in Drosophila melanogaster. The mutant spots observed in marker-heterozygous and balancer-heterozygous flies were compared in order to quantitatively and qualitatively estimate the genotoxic effect of these drugs. Cisplatin (0.003 and 0.006mM), bleomycin (0.005 and 0.01mM), and both combinations preferentially induced recombinational events, while mutation is the major event regarding the genetic toxicity of 5-fluorouracil (0.025 and 0.05mM). The combination of these drugs produced synergistic and antagonistic genotoxic effects, depending on the concentrations used, which could impose a higher risk of secondary effects associated with their genotoxic effects, emphasizing the importance of long-term monitoring in patients being treated with these drugs.