Search

Tinidazole is an antiparasitic drug belonging to the 5-nitroimidazole family. It is prescribed against protozoal infestations and is widely used in Mexico as well as other underdeveloped countries where infectious diseases are the first cause of children mortality. The drug is a direct mutagen in Salmonella typhimurium TA100 strain and the presence of S9 mixture did not modify its mutagenic effect. At low doses no mutagenicity was detected with strains TA100NR, TA98 or UTH8414 (Uvr+ derivative of TA100). Urine from four patients under tinidazole treatment exhibited a mutagenic activity on strain TA100, greater than the expected from the tinidazole concentrations determined by high-performance liquid chromatography (HPLC). Components from the urine samples were separated on thin-layer chromatography (TLC) plates, and their mutagenic effects tested by direct application of the Salmonella assay onto sections of the developed chromatoplate. The Rf of one component (0.62) corresponded to the one obtained for a tinidazole standard and showed the expected mutagenicity, while a second component with an Rf=0.39, exhibited a mutagenic potency slightly greater than the observed for tinidazole; however, as in the case of the drug itself, reduction of the nitro group was necessary for a mutagenic activity.

Mebendazole is an anthelmintic drug widely used in Cuba and in Mexico. Its interaction with tubulin interferes with the assemblage of the mitotic apparatus in the parasite cells, thus suggesting a possible genotoxic activity leading to chromosomal malsegregation. The heterozygous diploid strain D30 of Aspergillus nidulans was used to establish the ability of mebendazole to induce mitotic recombination and/or chromosomal non-disjunction, and the haploid strain FGSC #219 of A. nidulans was used to study the ability of mebendazole to induce point mutations in the methG suppressor system. Our results show that mebendazole can induce chromosomal non-disjunction but it fails to promote point mutations.

A 2-5-month treatment with niclosamide, a widely used drug in developing countries, has been reported to induce lymphosarcomas in toad liver and kidney. The genotoxic effects of this drug have also been evaluated in Salmonella typhimurium, in somatic and germinal cells of mice and in human lymphocytes exposed in vitro and in vivo. The present study shows that niclosamide is also capable of inducing mitotic crossing-over and non-disjunction in Aspergillus nidulans, which points to the wide potential of this drug as a genotoxic agent.