Evaluation of the genotoxicity of cisplatin, paclitaxel and 5-fluorouracil combined treatment in the Drosophila wing-spot test.
The somatic mutation and recombination test in Drosophila melanogaster was applied to analyze the mutagenic and recombinagenic activity of the chemotherapeutic drugs cisplatin, paclitaxel, and 5-fluorouracil, comparing the effects observed in combinatory treatments with those observed in single administrations. The results obtained in two different genotypes allowed to quantitatively and qualitatively estimate the contribution of genotoxic effects. The results obtained with the individual drug treatments showed that cisplatin and 5-fluorouracil were genotoxic, being able to increase the frequency of total spots on both genotypes. While cisplatin preferentially induced DNA damage of recombinational origin, all the damages induced by 5-fluorouracil were caused by gene and/or chromosome mutations, and the aneuploidogenic compound paclitaxel was not genotoxic. The combination of these drugs does not exert a synergist genotoxic effect in both genotypes compared to the single-agent administration. Instead, it was observed a modification in the proportion of mutation and recombination to the final genotoxicity observed. The antiproliferative activity of PAC could be responsible for the non-synergic genotoxic effect observed. Based on our results it is possible to suggest that cisplatin/paclitaxel/5-fluorouracil treatment regimen cannot impose a higher risk of the development of genotoxicity-associated secondary tumors in comparison to their individual applications.
Danesi
Cristiane Cademartori
CC
Laboratório da Toxicidade Genética (TOXIGEN), Programa de Pós-Graduação em Genética e Toxicologia Aplicada (PPGGTA), Universidade Luterana do Brasil (ULBRA), Canoas, RS, Brazil.
Bellagamba
Bruno Corrêa
BC
Dihl
Rafael Rodrigues
RR
de Andrade
Heloísa Helena Rodrigues
HH
Cunha
Kênya Silva
KS
Lehmann
Mauricio
M
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D002945:Cisplatin / Q000633:toxicity; D003433:Crosses, Genetic; D004330:Drosophila / Q000166:cytology / Q000187:drug effects / Q000235:genetics*; D004338:Drug Combinations; D005260:Female; D005472:Fluorouracil / Q000633:toxicity; D005819:Genetic Markers / Q000187:drug effects; D007814:Larva / Q000187:drug effects / Q000254:growth & development; D008297:Male; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation / Q000187:drug effects* / Q000235:genetics; D017239:Paclitaxel / Q000633:toxicity; D011995:Recombination, Genetic / Q000187:drug effects*; D014921:Wings, Animal / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development
D000970:Antineoplastic Agents; D004338:Drug Combinations; D005819:Genetic Markers; D009153:Mutagens; D017239:Paclitaxel; D002945:Cisplatin; D005472:Fluorouracil