Nitroimidazole derivatives: non-randomness sister chromatid exchanges in human peripheral blood lymphocytes.
Nitroimidazole derivatives exhibited genotoxic effect in different experimental conditions. This study focuses on an evaluation of possible genomic targets, at a chromosomal level, of two 5-nitroimidazoles (ornidazole and metronidazole) using the in vitro human peripheral blood culture as experimental system. We observed that both derivatives showed a decrease in mitotic index (MI) (P < 0.001), an increase in sister chromatid exchanges (SCE) frequency (P < 0.001) and no modifications in cellular proliferation kinetics (CPK). As a null hypothesis we considered the assumption that larger chromosomes should harbor more SCE, which was viewed using a novel sequential G-band (400 band resolution)/SCE technique. The analysis showed highly significant chi square values (P < 0.001), indicating that SCE frequency per chromosome is not proportional to chromosome length. SCE could be considered an instability indicator due to the high correlation between SCEs in certain chromosomal bands and the exposure to nitroimidazole derivatives.
Ana Carballo
Marta
M
CIGETOX-Citogenética Humana y Genética Toxicológica, Departamento Bioquímica Clínica. INFIBIOC, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junin 956 (1113), Ciudad Autónoma de Buenos Aires, Argentina. macarballo2003@yahoo.com.ar
Martinez
Romari Alejandra
RA
Mudry
Marta Dolores
MD
D015415:Biomarkers / Q000097:blood; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002871:Chromosome Banding / Q000379:methods; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D008297:Male; D008795:Metronidazole / Q000633:toxicity; D008940:Mitotic Index / Q000379:methods; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009593:Nitroimidazoles / Q000633:toxicity*; D009950:Ornidazole / Q000633:toxicity; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D055815:Young Adult
D015415:Biomarkers; D009153:Mutagens; D009593:Nitroimidazoles; D008795:Metronidazole; D009950:Ornidazole