Document Detail

Evaluation of the genotoxicity of cisplatin, paclitaxel and 5-fluorouracil combined treatment in the Drosophila wing-spot test.
MedLine Citation:
PMID:  20727378     Owner:  NLM     Status:  MEDLINE    
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.
Cristiane Cademartori Danesi; Bruno Corrêa Bellagamba; Rafael Rodrigues Dihl; Heloísa Helena Rodrigues de Andrade; Kênya Silva Cunha; Mauricio Lehmann
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-08-18
Journal Detail:
Title:  Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association     Volume:  48     ISSN:  1873-6351     ISO Abbreviation:  Food Chem. Toxicol.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-11     Completed Date:  2011-01-25     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8207483     Medline TA:  Food Chem Toxicol     Country:  England    
Other Details:
Languages:  eng     Pagination:  3120-4     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Ltd. All rights reserved.
Laboratório da Toxicidade Genética (TOXIGEN), Programa de Pós-Graduação em Genética e Toxicologia Aplicada (PPGGTA), Universidade Luterana do Brasil (ULBRA), Canoas, RS, Brazil.
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MeSH Terms
Antineoplastic Agents / toxicity*
Cisplatin / toxicity
Crosses, Genetic
Drosophila / cytology,  drug effects,  genetics*
Drug Combinations
Fluorouracil / toxicity
Genetic Markers / drug effects
Larva / drug effects,  growth & development
Mutagenicity Tests / methods
Mutagens / toxicity*
Mutation / drug effects*,  genetics
Paclitaxel / toxicity
Recombination, Genetic / drug effects*
Wing / cytology,  drug effects*,  growth & development
Reg. No./Substance:
0/Antineoplastic Agents; 0/Drug Combinations; 0/Genetic Markers; 0/Mutagens; 15663-27-1/Cisplatin; 33069-62-4/Paclitaxel; 51-21-8/Fluorouracil

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