Genotoxic signature in cord blood cells of newborns exposed in utero to a Zidovudine-based antiretroviral combination

J Infect Dis. 2013 Jul 15;208(2):235-43. doi: 10.1093/infdis/jit149. Epub 2013 Apr 4.


Background: The genotoxicity of zidovudine has been established in experimental models. The objective of the study was to identify genotoxicity markers in cord blood cells from newborns exposed in utero to antiretroviral (ARV) combinations containing zidovudine.

Methods: Cells were investigated by karyotyping and gene expression analysis of the CD34(+) hematopoietic stem/progenitor cell (HPC) compartment.

Results: Karyotyping of the cord blood cells from 15 ARV-exposed newborns and 12 controls revealed a higher proportion of aneuploid cells in the exposed group (median, 18.8% [interquartile range, 10.0%-26.7%] vs 6.6% [interquartile range, 3.1%-11.7%]; P < .001). All chromosomes were involved, with a random distribution of these alterations. Gene expression profiling of CD34(+) HPCs from 7 ARV-exposed and 6 control newborns revealed that >300 genes were significantly upregulated or downregulated by at least 1.5-fold in the exposed group (P < .05 for all comparisons). Significant alterations of genes involved in cell cycle control, mitotic checkpoints, and DNA repair were identified. Although this study does not allow discrimination between the roles of each of the 3 drugs, both cytogenetic and transcriptional findings are similar to those in cellular experiments that used zidovudine alone.

Conclusions: The cord blood cells, including hematopoietic stem cells, from newborns exposed in utero to a zidovudine-based ARV combination present cytogenetic and transcriptional abnormalities compatible with DNA damage.

Keywords: aneuploidy; genotoxicity; pregnancy; transcriptome; zidovudine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / adverse effects*
  • Antigens, CD34 / genetics
  • Antigens, CD34 / metabolism
  • Cell Cycle / genetics
  • DNA Repair / genetics
  • Drug Combinations
  • Female
  • Fetal Blood / cytology
  • Fetal Blood / drug effects*
  • Fetal Blood / physiology
  • Gene Expression Profiling / methods
  • HIV Infections / drug therapy
  • HIV Infections / genetics
  • HIV Infections / metabolism
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / drug effects*
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Infant, Newborn
  • Infectious Disease Transmission, Vertical
  • Karyotyping / methods
  • Maternal-Fetal Exchange / physiology
  • Pregnancy
  • Pregnancy Complications, Infectious / drug therapy
  • Pregnancy Complications, Infectious / metabolism
  • Pregnancy Complications, Infectious / virology
  • Prenatal Exposure Delayed Effects
  • Stem Cells / metabolism
  • Transcriptome / genetics
  • Young Adult
  • Zidovudine / adverse effects*
  • Zidovudine / pharmacokinetics


  • Anti-HIV Agents
  • Antigens, CD34
  • Drug Combinations
  • Zidovudine