Mutagenic bioassay of certain pharmacological drugs: III. Metronidazole (MTZ).
The genotoxic activity of MTZ was evaluated in vitro with the anaphase-telophase test in a CHO cell line, chromosomal aberration and micronucleus test in lymphocyte cultures, and in vivo using the micronucleus test in mouse bone marrow cells. The In vivo test was performed using clinical trial doses (23, 70 and 160 mg/kg). A significant increase in micronucleated cells (p < 0.02) was observed in the three assayed doses with a linear dose response (r = 0.91). In vitro studies showed a significant increase in the percentage of abnormal anaphases (p < 0.05), in chromosome aberrations (p < 0.01) and in the frequency of micronuclei (p < 0.02) at all the concentrations assayed (0.1, 1 and 10 micrograms/ml). These findings demonstrate the clastogenic effect of this drug which should be taken into account considering its wide human consumption.
Mudry
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MD
Genetics Department, Instituto de Investigaciones Hematológicas Mariano R. Castex, Academia Nacional de Medicina, Buenos Aires, Argentina.
Carballo
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M
Labal de Vinuesa
M
M
Gonzalez Cid
M
M
Larripa
I
I
D000705:Anaphase; D000818:Animals; D001854:Bone Marrow Cells; D016466:CHO Cells; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D006224:Cricetinae; D003571:Cytochalasin B / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008795:Metronidazole / Q000633:toxicity*; D051379:Mice; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D012737:Sex Factors; D013692:Telophase
D009153:Mutagens; D008795:Metronidazole; D003571:Cytochalasin B