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J Appl Toxicol ; 29(3): 248-54, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19086015

ABSTRACT

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.


Subject(s)
Leukocytes, Mononuclear/drug effects , Mutagens/toxicity , Nitroimidazoles/toxicity , Sister Chromatid Exchange/drug effects , Biomarkers/blood , Cell Division/drug effects , Cells, Cultured , Chromosome Banding/methods , Dose-Response Relationship, Drug , Female , Humans , Male , Metronidazole/toxicity , Mitotic Index/methods , Mutagenicity Tests , Ornidazole/toxicity , Young Adult
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