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

Grujičić, Darko; Djordjevic, Olivera Milosevic; Arsenijevic, Slobodan; Marinković, Darko

doi:10.1007/s10238-007-0120-4

Cited by 11 publications

(8 citation statements)

References 25 publications

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“…The median MNBN level in mothers was 2.36 per 1,000 cells, which was slightly lower than previously reported levels in literature (Grujicic et al 2007; Milošević-Djordjević et al 2003), as expected from our semiautomated system because of the strict scoring criteria applied for automated image analysis (Decordier et al 2011). MN frequencies increased with age and were higher in maternal samples compared with cord blood, in agreement with the literature (Decordier et al 2007; Levario-Carrillo et al 2005; Lope et al 2010; Pedersen et al 2009, 2010; Stankovic et al 2004).…”

Section: Discussionsupporting

confidence: 53%

Maternal and Gestational Factors and Micronucleus Frequencies in Umbilical Blood: The NewGeneris Rhea Cohort in Crete

Loock

Fthenou

Decordier

et al. 2011

Environ Health Perspect

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Background: The use of cancer-related biomarkers in newborns has been very limited.Objective: We investigated the formation of micronuclei (MN) in full-term and preterm newborns and their mothers from the Rhea cohort (Crete), applying for the first time in cord blood a validated semiautomated analysis system, in both mono- and binucleated T lymphocytes.Methods: We assessed MN frequencies in peripheral blood samples from the mothers and in umbilical cord blood samples. We calculated MN in mononucleated (MNMONO) and binucleated (MNBN) T lymphocytes and the cytokinesis block proliferation index (CBPI) in 251 newborns (224 full term) and 223 mothers, including 182 mother–child pairs. Demographic and lifestyle characteristics were collected.Results: We observed significantly higher MNBN and CBPI levels in mothers than in newborns. In newborns, MNMONO and MNBN were correlated (r = 0.35, p < 0.001), and we found a moderate correlation between MNMONO in mothers and newborns (r = 0.26, p < 0.001). MNMONO frequencies in newborns were positively associated with the mother’s body mass index and inversely associated with gestational age and mother’s age, but we found no significant predictors of MNBN or CBPI in newborns.Conclusions: Although confirmation is needed by a larger study population, the results indicate the importance of taking into account both mono- and binucleated T lymphocytes for biomonitoring of newborns, because the first reflects damage expressed during in vivo cell division and accumulated in utero, and the latter includes additional damage expressed as MN during the in vitro culture step.

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Section: Discussionsupporting

confidence: 53%

Maternal and Gestational Factors and Micronucleus Frequencies in Umbilical Blood: The NewGeneris Rhea Cohort in Crete

Loock

Fthenou

Decordier

et al. 2011

Environ Health Perspect

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“…Thus, our previously published results on the mothers who received partly the same therapy (Grujičić et al 2007), showed the increase of both number of BN cells containing MN and number of MNs in BN cells. The increase was explained by accumulation of DNA damage as a consequence of the applied therapy.…”

Section: Discussionmentioning

confidence: 64%

“…Not very long ago, in the in vivo study of genotoxicity of anesthetic substances and combined therapy in post-surgical treatment of cervical cerclage based on ritodrine hydrochloride, erythromycin and verapamil, we concluded that the combined pharmacotherapy treatment significantly increased the MN frequency in peripheral blood lymphocytes of pregnant women who received therapy during six days (Grujičić et al 2007).…”

Section: Discussionmentioning

confidence: 93%

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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“…15 Thus, the same authors 20 reported that the investigated betamimetics (ritodrine, fenoterol and hexoprenaline) combined with verapamil and administered to pregnant women during 7 days to 5 months significantly increased the MN frequency in umbilical blood lymphocytes of neonates, regardless of therapeutic does.…”

Section: Discussionmentioning

confidence: 94%

“…[11][12][13][14] Our previous report showed that combined therapy with ritodrine, verapamil and erythromycin in post-operative treatment of cervical cerclage of pregnant women resulted in statistically significant increase of the MN frequency in the peripheral blood lymphocytes. 15 Therefore, it would be of interest to evaluate in vitro separate and combined genotoxic effect of two medicaments that are widely used in gynecological practice. Here, we are presenting our data from the study on genotoxic potential of ritodrine and verapamil, that were tested for their ability to induce MN in cultured human peripheral lymphocytes of healthy donors.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2010

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

Cited by 11 publications

References 25 publications

Maternal and Gestational Factors and Micronucleus Frequencies in Umbilical Blood: The NewGeneris Rhea Cohort in Crete

Maternal and Gestational Factors and Micronucleus Frequencies in Umbilical Blood: The NewGeneris Rhea Cohort in Crete

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

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

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