DNA single strand breaks in peripheral blood lymphocytes induced by three nitroimidazole derivatives.
Tinidazole (TNZ), ornidazole (ONZ) and metronidazole (MTZ) are antiparasitic drugs (nitroimidazole derivatives) that have proven to be effective against Trichomonas vaginalis, Entoamoeba histolytica, Giardia lamblia and Helicobacter pylori. The reduction of the nitro group and the generation of short-lived reactive intermediates are the basis of its parasiticidal activity. This reduction is associated with its mutagenic activity in bacteria, although in mammalian cells DNA damage seems to be related to the production of reactive oxygen species (ROS). Using alkaline single cell electrophoresis, a significant increase in single strand breaks and alkali labile sites in human peripheral blood lymphocytes (PBL) exposed to MTZ, ONZ and TNZ at 10, 100 and 500 microg/ml is observed. MTZ causes less damage, especially at higher concentrations, when compared with TNZ, the most harmful of the drugs tested. These findings suggest that primary damage is induced under aerobic conditions and confirms that these nitroimidazoles are DNA damaging agents.
Rodriguez Ferreiro
Gisell
G
Grupo de Genética Toxicología y Salud Ambiental, Centro de Investigaciones Biomédicas, Instituto Superior de Ciencias Medicas de la Habana, Havana, Cuba.
Cancino Badías
Lourdes
L
Lopez-Nigro
Marcela
M
Palermo
Ana
A
Mudry
Marta
M
González Elio
Prieto
P
Carballo
Marta Ana
MA
D000328:Adult; D000994:Antitrichomonal Agents / Q000633:toxicity*; D002478:Cells, Cultured; D020552:Comet Assay; D004249:DNA Damage / Q000235:genetics*; D004277:DNA, Single-Stranded / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008214:Lymphocytes / Q000097:blood / Q000187:drug effects*; D008297:Male; D008795:Metronidazole / Q000633:toxicity; D009593:Nitroimidazoles / Q000633:toxicity*; D009950:Ornidazole / Q000633:toxicity; D014011:Tinidazole / Q000633:toxicity
D000994:Antitrichomonal Agents; D004277:DNA, Single-Stranded; D009593:Nitroimidazoles; D014011:Tinidazole; D008795:Metronidazole; D009950:Ornidazole