Screening the mutagenic activities of commonly used antiparasite drugs by the simultest, a simplified Salmonella/microsome plate incorporation assay

As atividades mutagenicas de 16 drogas com acao anti-parasitaria foram avaliadas pelo Simultest em ensaios qualitativos (spot testes) e quantitativos (incorporacao em placa) com uma mistura das linhagens indicadoras de Salmonella typhimurium TA97, TA98, TA100 e TA102. Quatro drogas anti-doenca de Chagas (nifurtimox, benzonidazol, CL 64,855 e MK 436) e duas drogas anti-amebiase (metronidazol e tinidazol) deram resultados positivos em testes qualitativos e a incorporacao de fracao microssomal de figado de rato nao alterou os resultados. Curvas comparadas de efeito da dose da atividade mutagenica do metronidazol, benzonidazol e CL 64,855 detectadas oelo Simultest e linhagens indicadoras individuais demonstraram que as duas abordagens possuem sensibilidades semelhantes. Os resultados corroboram a validade do Simultest como uma versao simplificada, rapida e economica do teste de Ames no rastreamento preliminar de drogas potencialmente mutagenicas

Evaluation of genotoxic activity in the blood and urine of guinea pigs treated with nifurtimox and benznidazole

1. The mutagenicity of serum and urine from fuinea pigs treated with a single oral dose (500 mg/Kg) of benznidazole and nifurtimox was assayed using the Salmonella/plate incorporation test with strain TA100 and a nitroreductase-deficient derivative, TA100NR. 2. The urine and blood of animals treated with nifurtimox were not mutagenic for either tester strain. 3. The urine and blood of animals receiving benznidazole were mutagenic to the TA100 but not to the TA100NR strain. Similar results were obtained with nitrofurantoin-treated animals. Maximum mutagenicity values were obtained in serum and urine of treated animals 90 min and 24 h after administration, respectively. 4. Mutagenicity induced by benznidazole in the serum and urine of treated animals was not altered when assayed in anaerobic environments. 5. These results indicate that benznidazole and nifurtimox are not metabolized by the mammalian host into stable mutagenic derivatives detectable by the Ames test. Based on these data, we suggest that the potential cancer risk to patients treated with these drugs is small but should be further evaluated