Genotoxicity testing of antiparasitic nitrofurans in the Drosophila wing somatic mutation and recombination test.

Nifurtimox and eight structurally related 5-nitrofuran compounds active against Trypanosoma cruzi were tested for genotoxicity in the wing somatic mutation and recombination test in Drosophila melanogaster. Nifurtimox, compound ada and compound 1B were clearly mutagenic and recombinogenic whereas the remaining six compounds were negative. In contrast to the situation in bacterial mutagenicity tests, nitroreductase activity is probably not decisive for the genotoxicity of these compounds in Drosophila. The three non-genotoxic nitrofurans with high antiparasitic activity are promising candidates for the replacement of nifurtimox. However, these compounds require further genotoxicity testing in eukaryotic assay systems for a final evaluation.

[1]  P. Molina,et al.  Study on the mutagenicity of nifurtimox and eight derivatives with the L-arabinose resistance test of Salmonella typhimurium. , 1988, Mutation research.

[2]  F. Würgler,et al.  Statistical methods to decide whether mutagenicity test data from Drosophila assays indicate a positive, negative, or inconclusive result. , 1988, Mutation research.

[3]  R. C. Ferreira,et al.  Activation of anti-Trypanosoma cruzi drugs to genotoxic metabolites promoted by mammalian microsomal enzymes. , 1988, Mutation research.

[4]  P. Fu,et al.  Mutagenicity of nitrofurans in Salmonella typhimurium TA98, TA98NR and TA98/1,8-DNP6. , 1987, Mutation research.

[5]  E. Vogel,et al.  Evaluation of potential mammalian genotoxins using Drosophila: the need for a change in test strategy. , 1987, Mutagenesis.

[6]  R. Nagel.  Genotoxicity studies with two antichagasic drugs. , 1987, Mutation research.

[7]  P. Molina,et al.  Activity against Trypanosoma cruzi of New Analogues of Nifurtimox , 1987, Archiv der Pharmazie.

[8]  D J Tweats,et al.  The prospects for a simplified and internationally harmonized approach to the detection of possible human carcinogens and mutagens. , 1986, Mutagenesis.

[9]  L. C. Ferreira,et al.  Mutagenicity of nifurtimox and benznidazole in the Salmonella/microsome assay. , 1986, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[10]  R. Docampo,et al.  Mechanism of toxicity of nitro compounds used in the chemotherapy of trichomoniasis. , 1985, Environmental health perspectives.

[11]  J. Castro,et al.  Micronucleus formation in bone marrow of mice treated with nifurtimox or benznidazole. , 1985, Toxicology letters.

[12]  A. Frasch,et al.  Damage of Trypanosoma cruzi deoxyribonucleic acid by nitroheterocyclic drugs. , 1985, Biochemical pharmacology.

[13]  A. Stoppani,et al.  Effects of nitroheterocyclic drugs on macromolecule synthesis and degradation in Trypanosoma cruzi. , 1985, Biochemical pharmacology.

[14]  F E Würgler,et al.  Somatic mutation and recombination test in Drosophila melanogaster. , 1984, Environmental mutagenesis.

[15]  I. Nepomnaschy,et al.  Mutagenicity of 2 anti-chagasic drugs and their metabolic deactivation. , 1983, Mutation research.

[16]  D. R. McCalla.  Mutagenicity of nitrofuran derivatives: review. , 1983, Environmental mutagenesis.

[17]  R. Mason,et al.  Generation of free radicals induced by nifurtimox in mammalian tissues. , 1981, The Journal of biological chemistry.

[18]  J. Cairns.  The origin of human cancers , 1981, Nature.

[19]  C. Takahashi,et al.  Genetic effects of nifurtimox on drosophila melanogaster, wistar rats and allium cepa , 1981 .

[20]  T. Ohnishi,et al.  Mutagenicity of nifurtimox in Escherichia coli. , 1980, Mutation research.

[21]  R. Docampo,et al.  Generation of superoxide anion and hydrogen peroxide induced by nifurtimox in Trypanosoma cruzi. , 1979, Archives of biochemistry and biophysics.

[22]  D. Lindsley,et al.  Genetic variations of Drosophila melanogaster , 1967 .