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

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

DARKO GRUJICIC,¹ OLIVERA MILOŠEVIC-DJORDJEVIC,^1,2 SLOBODAN ARSENIJEVIC² and DRAGOSLAV MARINKOVIC³

¹Faculty of Science, University of Kragujevac
²Medical Faculty, University of Kragujevac
³Serbian Academy of Sciences and Arts

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.

keywords —— umbilical cord blood lymphocytes; micronuclei; betamimetic; verapamil.

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Tohoku J. Exp. Med., 2008, 215, 363-371

Correspondence: Olivera Miloševi-Djordjevi, Department of Genetics, Institute of Biology and Ecology, Faculty of Science, University of Kragujevac Radoja Domanovia 12, P.O. Box 60, 34000 Kragujevac, Serbia.

e-mail: olivera@kg.ac.yu