Cytogenetic analysis of peripheral blood lymphocytes of children treated with nitrofurantoin for recurrent urinary tract infection

• Published in: Mutagenesis Vol. 17; no. 1; pp. 31 - 35
• Main Authors: Slapšytė, G., Jankauskienė, A., Mierauskienė, J., Lazutka, J.R.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-01-2002
• Subjects: Administration, Oral; Adolescent; Anti-Infective Agents, Urinary - adverse effects; Anti-Infective Agents, Urinary - pharmacology; Anti-Infective Agents, Urinary - therapeutic use; Biological and medical sciences; Cells, Cultured - drug effects; Child; Child, Preschool; Chromosome Aberrations; Chronic Disease; Dose-Response Relationship, Drug; Drug toxicity and drugs side effects treatment; Female; Humans; Infant; Kidney Diseases - complications; Lymphocytes - drug effects; Lymphocytes - ultrastructure; Male; Medical sciences; Miscellaneous (drug allergy, mutagens, teratogens...); Mutagenicity Tests; Nitrofurantoin - adverse effects; Nitrofurantoin - pharmacology; Nitrofurantoin - therapeutic use; Pharmacology. Drug treatments; Recurrence; Safety; Sensitivity and Specificity; Sister Chromatid Exchange - drug effects; Time Factors; Urinary Tract Infections - drug therapy; Urinary Tract Infections - etiology; Chromosomal aberration; Human; Recurrence; Urinary system disease; Nitrofurantoin; Mutagenicity testing; Toxicity; Sister chromatid exchange; Urinary tract disease; Antimicrobial agent; Infection; Child; Lymphocyte
• ISSN: 0267-8357; 1464-3804; 1464-3804
• DOI: 10.1093/mutage/17.1.31

The objective of this study was to determine whether nitrofurantoin, used for long-term antimicrobial prophylaxis of urinary tract infection, may induce chromosome aberrations (CAs) and sister chromatid exchanges (SCEs) in lymphocytes of treated children. Ninety-nine blood samples were taken from 69 children aged from 0.2 to 13 years and suffering from urinary tract infection. The treatment consisted of oral administration of nitrofurantoin at doses of 5–8 mg/kg/day for the first 7 days and at doses of 1–2 mg/kg/day for the rest of the treatment period. Blood was sampled before the start of the nitrofurantoin therapy and after 1, 3, 6 and 12 months of the therapy. Analysis of variance showed no statistically significant increase in CA and SCE frequencies in lymphocytes of children treated with nitrofurantoin for 1–12 months. However, a significant increase in SCE rates was determined in lymphocytes of those patients whose blood samples were available both before and after treatment with nitrofurantoin (6.21 ± 0.28 and 7.30 ± 0.39 SCE/cell, respectively, P = 0.0315, Student's paired t-test). Moreover, there was a statistically significant correlation (r = 0.6603, P = 0.0270) between cumulative dose of nitrofurantoin and SCE frequency in lymphocytes of children after 1 month of the therapy. Also, in vitro experiments indicated that nitrofurantoin was able to induce both CAs and SCEs in human lymphocytes. Positive findings with chromosome aberrations and SCEs in vitro and suggestive results with SCEs in vivo indicate that further, much larger follow-up studies are needed to elucidate the genetic safety of the therapeutic use of nitrofurantoin.