In vitro evaluation of the genotoxicity of ritodrine and verapamil in human lymphocytes

The aim of this study was to investigate the genotoxic effects of ritodrine and verapamil on human peripheral lymphocytes in vitro using micronucleus (MN) test. Also, fluorescence in situ hybridization (FISH) with a centromeric probe was performed to determine the origin of the induced MN. Cells wer...

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Bibliographic Details
Published in:Human & experimental toxicology 2011-05, Vol.30 (5), p.398-405
Main Authors: MILOSEVIC-DJORDJEVIC, O, GRUJICIC, D, JOKSIC, G, MARINKOVIC, D
Format: Article
Language:English
Subjects:
Adult
Biological and medical sciences
Cells, Cultured
Cellular biology
Chromosomes
Cytotoxicity
Dose-Response Relationship, Drug
Drug Synergism
Drug toxicity and drugs side effects treatment
Female
Humans
In Situ Hybridization, Fluorescence
Lymphocytes
Lymphocytes - drug effects
Lymphocytes - ultrastructure
Medical sciences
Micronuclei, Chromosome-Defective - chemically induced
Micronucleus Tests
Miscellaneous (drug allergy, mutagens, teratogens...)
Molecular Structure
Mutagens - chemistry
Mutagens - toxicity
Pharmacology. Drug treatments
Prescription drugs
Ritodrine - chemistry
Ritodrine - toxicity
Toxicity
Verapamil - chemistry
Verapamil - toxicity
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Summary:The aim of this study was to investigate the genotoxic effects of ritodrine and verapamil on human peripheral lymphocytes in vitro using micronucleus (MN) test. Also, fluorescence in situ hybridization (FISH) with a centromeric probe was performed to determine the origin of the induced MN. Cells were treated with 8.4 × 10 —6 M — 25.2 × 10— 4 M concentrations for ritodrine and 0.56—11 × 10— 5 M concentrations for verapamil, separately and combined. The MN frequencies showed increase after all treatments, but the difference between treated cells and untreated controls were found to be statistically significant only in the concentration range from 8.4 × 10— 5 M — 4.5 × 10—4 M for ritodrine, 1.1 — 3.3 × 10—5 M for verapamil, and in combined treatment with concentrations 8.4 × 10 —5 M + 1.1 × 10—5 M for ritodrine and verapamil. The highest tested concentrations of both medicaments showed cytotoxic effect. Both medicaments decreased the nuclear division index (NDI) in tested concentrations. The results of FISH analysis suggest that verapamil, separately or combined with ritodrine, shows to a larger extent aneugenic than clastogenic effect.
ISSN:0960-3271
1477-0903
DOI:10.1177/0960327110372404