Cytogenetic evaluation of two nitroimidazole derivatives.
5-Nitroimidazoles are a well-established group of antiprotozoal and antibacterial agents. Thanks to their antimicrobial activity these chemotherapeutic agents inhibit the growth of both anaerobic bacteria and certain anaerobic protozoa such as Trichomonas vaginalis, Entamoeba histolytica and Giardia lamblia. The aim of the present study is to achieve a precise characterization of the genotoxic activity of these compounds and to establish the value of cytogenetic assays in order to determine the effect of these drugs, at therapeutic doses, to settle an improved risk assessment. Two nitroimidazole were studied, metronidazole and ornidazole, at four different concentrations (0.1, 1, 10 and 50 microg/ml of peripheral blood lymphocyte culture). Endpoints analyzed included: mitotic index (MI), replication index (RI), sister chromatid exchange (SCE) and chromosomal aberrations (CA). An analysis of variance test (ANOVA) was performed to evaluate the results. A significant decrease (P<0.0001) in MI as well as an increase in SCE (P<0.0001) and CA (0.0001) frequencies for both drugs was observed. No modifications in RI were found. The results suggest a genotoxic and cytotoxic effect of MTZ and ONZ in human peripheral blood cultures in vitro.
López Nigro
M M
MM
CIGETOX-Citogenética y Genética Toxicológica, Dpto de Bioquímica Clínica, Facultad de Farmacia y Bioquímica (FFyB), UBA, Buenos Aires, Argentina.
Palermo
A M
AM
Mudry
M D
MD
Carballo
M A
MA
D000328:Adult; D000994:Antitrichomonal Agents / Q000633:toxicity*; D018929:Cell Culture Techniques; D002455:Cell Division / Q000187:drug effects; D002869:Chromosome Aberrations / Q000139:chemically induced*; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008214:Lymphocytes; D008297:Male; D008795:Metronidazole / Q000633:toxicity*; D008938:Mitosis / Q000187:drug effects; D009152:Mutagenicity Tests; D009950:Ornidazole / Q000633:toxicity*; D018570:Risk Assessment; D012854:Sister Chromatid Exchange
D000994:Antitrichomonal Agents; D008795:Metronidazole; D009950:Ornidazole