Verapamil contributes to the clastogenic effects of acrylamide, cyclophosphamide, and dioxidine on somatic cells of BALB/C and C57BL/6 mice

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.

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“…13 These results provide evidence that verapamil, being nonclastogenic per se, magnifies the clastogenic effects of acrylamide, …”

Section: Discussionmentioning

confidence: 75%

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

et al. 2010

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“…The fact that verapamil (Gembruch et al 1988) and betamimetics (Friedman et al 1994), cross the placenta and that verapamil when combined with other medicaments reveals co-mutagenic effect was pointed out in many papers (Friedman et al 1990;Scheid et al 1991, Scheid andTraut 1993;Nesterova et al 1999;Seredenin et al 1999). Our results confirm the possibility that in modified intrauterine conditions the fetus reacts at the cell level, directly increasing MN frequencies in umbilical blood lymphocytes.…”

Section: Discussionmentioning

confidence: 98%

Treatment of Pregnant Women with a Betamimetic and Verapamil Increases the Micronuclei Frequency in Umbilical Cord Blood Lymphocytes

Grujičić

Milošević-Djordjević

Arsenijevic

et al. 2008

Tohoku J. Exp. Med.

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In prevention of preterm labor, betamimetics are used in gynecological practice mostly combined with antiarrhythmic verapamil because of their therapeutic cardiovascular side effects. The aim of this study was to investigate the influence of a betamimetic (ritodrine hydrochloride, fenoterol or hexoprenaline) and verapamil (administered to mothers) on the frequency of micronuclei (MN) in umbilical cord blood lymphocytes of neonates, using cytokinesis-block micronucleus test. The analyzed sample included 23 babies whose mothers received the therapy and 30 control babies whose mothers received no therapy. The average MN frequency was significantly higher in the neonates whose mothers received the therapy (8.13 ± 2.69 MN/1000 BN cells), in comparison with the baseline frequency in untreated controls (3.30 ± 2.63 MN/1000 BN cells), with probability p < 0.05. The highest MN frequency was found in neonates whose mothers received fenoterol and verapamil (2.8-fold i.e. 9.10 ± 3.00 MN/1000 BN cells), while ritodrine hydrochloride and hexoprenaline combined with verapamil induced 2.3-fold and 2.2-fold higher MN values than in controls (7.50 ± 3.33 MN/1000 BN cells and 7.29 ± 0.95 MN/1000 BN cells). Multiple linear regression analysis showed that MN frequency was affected only by the maternal therapeutic treatment, while the neonates' sex, maternal age, cigarette smoking, and therapeutic doses did not affect the MN frequency in umbilical lymphocytes of neonates. We conclude that the treatment of pregnant women with a betamimetic and verapamil significantly increases the MN frequency in umbilical cord blood lymphocytes of neonates, regardless to therapeutic doses.umbilical cord blood lymphocytes; micronuclei; betamimetic; verapamil.Tohoku

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“…The National Toxicology Program [13] reported that treatment of cultured Chinese hamster ovary cells with erythromycin did not produce an increase in the frequency of biomarkers as sister chromatid exchanges or chromosomal aberrations in either the presence or absence of metabolic activation. Numerous studies demonstrated that verapamil significantly increased genotoxic [14][15][16] and cytotoxic effects of different agents [17], and suggested that calcium ions could be necessary for the intactness of chromosomes of human lymphocytes and other cells. In this way Friedman et al [14] reported that lymphocytes of patients treated clinically with verapamil for 1 week showed higher chromosomal aberrations in comparison with lymphocytes before the treatment of the same patients.…”

Section: Discussionmentioning

confidence: 99%

The effect of combined therapy with ritodrine, erythromycin and verapamil on the frequency of micronuclei in peripheral blood lymphocytes of pregnant women

et al. 2007

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The main aim of this study was to investigate the genotoxic effect of combined pharmacotherapy applied in post-operative treatment of cervical cerclage in pregnant women over six days. This study included 19 phenotypically healthy pregnant women in mid-trimester with a diagnosis of cervical insufficiency, mean age 28+/-5.33. The frequency of micronuclei (MN) was estimated in peripheral blood lymphocytes of patients before surgical intervention and after the end of applied pharmacotherapy by application of cytokinesis block micronucleus (CBMN) test. Mean value of baseline MN frequency was 6.84+/-2.91 MN/1000 binucleated cells, and after the end of the applied therapy, 10.32+/-4.27 MN/1000 binucleated cells (P<0.001) were found. The data of cell proliferation index showed that the combined therapy did not induce significant difference in cell kinetics (P>0.05). Our results showed that combined pharmacotherapy treatment over six days significantly increased the frequency of MN in peripheral blood lymphocytes of pregnant women.

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Verapamil contributes to the clastogenic effects of acrylamide, cyclophosphamide, and dioxidine on somatic cells of BALB/C and C57BL/6 mice

Cited by 20 publications

References 12 publications

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

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

Treatment of Pregnant Women with a Betamimetic and Verapamil Increases the Micronuclei Frequency in Umbilical Cord Blood Lymphocytes

The effect of combined therapy with ritodrine, erythromycin and verapamil on the frequency of micronuclei in peripheral blood lymphocytes of pregnant women

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