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

• 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
• ISSN: 0960-3271; 1477-0903
• DOI: 10.1177/0960327110372404

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.