Mutagenic evaluation of combined paclitaxel and cisplatin treatment in somatic cells of Drosophila melanogaster.
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.
Danesi
Cristiane Cademartori
CC
Programa de Pós-Graduação em Genética e Toxicologia Aplicada, Universidade Luterana do Brasil, Canoas, RS, Brazil.
Bellagamba
Bruno Corrêa
BC
Dihl
Rafael Rodrigues
RR
de Andrade
Heloísa Helena Rodrigues
HH
Cunha
Kênya Silva
KS
Spanó
Mário Antônio
MA
Reguly
Maria Luíza
ML
Lehmann
Mauricio
M
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*
D009153:Mutagens; D017239:Paclitaxel; D002945:Cisplatin