title: Mutagenic evaluation of combined paclitaxel and cisplatin treatment in somatic cells of Drosophila melanogaster.
abstract: Recent studies have added paclitaxel (PAC) to traditional cisplatin (CIS) regimen to treat squamous cell carcinoma of the head and neck. The target of these antineoplastic agents is nuclear DNA for CIS and microtubules for PAC, although it is not restricted to malignant cells. In this study, the genotoxicity of the combined treatment of PAC and CIS was investigated using the standard version of the wing Somatic Mutation and Recombination Test (SMART) in Drosophila melanogaster. Quantitative and qualitative genotoxic effects of these compounds were estimated by comparing wing spot frequencies in marker-heterozygous to balancer-heterozygous flies. Two different concentrations of PAC (0.0025 and 0.005mM) and CIS (0.025 and 0.05mM) as well as combinations of them were employed. The results demonstrated that the spindle poison PAC alone was not genotoxic in this test system, while CIS was able to induce a high incidence of DNA damage in both genotypes, mainly related to somatic recombination. The data obtained for the combined treatments showed that its genotoxicity varied with the concentrations used. In small concentrations the number of total spots induced by combination was reduced in relation to CIS 0.025mM just for marker-heterozygous flies, showing that somatic recombination was the prevalent event involved. At higher concentrations the combined treatment showed significant reductions in the frequencies of large single spots, for both genotypes, and twin spots for marker-heterozygous flies, but did not significantly reduce the total spots frequency in either genotype. The data suggest that aneugenic activity of PAC could be responsible for the reduction in the genotoxicity of CIS.
authors.affiliation: Programa de Pós-Graduação em Genética e Toxicologia Aplicada, Universidade Luterana do Brasil, Canoas, RS, Brazil.
authors.forename: Cristiane Cademartori
authors.initials: CC
authors.lastname: Danesi
authors.forename: Bruno Corrêa
authors.initials: BC
authors.lastname: Bellagamba
authors.forename: Rafael Rodrigues
authors.initials: RR
authors.lastname: Dihl
authors.forename: Heloísa Helena Rodrigues
authors.initials: HH
authors.lastname: de Andrade
authors.forename: Kênya Silva
authors.initials: KS
authors.lastname: Cunha
authors.forename: Mário Antônio
authors.initials: MA
authors.lastname: Spanó
authors.forename: Maria Luíza
authors.initials: ML
authors.lastname: Reguly
authors.forename: Mauricio
authors.initials: M
authors.lastname: Lehmann
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000633:toxicity*; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity*; D004249:DNA Damage / Q000187:drug effects; D004331:Drosophila melanogaster / Q000187:drug effects*; D019656:Loss of Heterozygosity / Q000187:drug effects; D009152:Mutagenicity Tests; D009153:Mutagens; D017239:Paclitaxel / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D009153:Mutagens; D017239:Paclitaxel; D002945:Cisplatin