Bacterial mutagens in the urine of patients under tinidazole treatment

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 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 R f 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 R f = 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.