title: Comparing genotoxic signatures in cord blood cells from neonates exposed in utero to zidovudine or tenofovir.
abstract: OBJECTIVE
  Zidovudine and tenofovir are the two main nucleos(t)ide analogs used to prevent mother-to-child transmission of HIV. In vitro, both drugs bind to and integrate into human DNA and inhibit telomerase. The objective of the present study was to assess the genotoxic effects of either zidovudine or tenofovir-based combination therapies on cord blood cells in newborns exposed in utero.
  
  
  METHODS
  We compared the aneuploid rate and the gene expression profiles in cord blood samples from newborns exposed either to zidovudine or tenofovir-based combination therapies during pregnancy and from unexposed controls (n = 8, 9, and 8, respectively).
  
  
  METHODS
  The aneuploidy rate was measured on the cord blood T-cell karyotype. Gene expression profiles of cord blood T cells and hematopoietic stem and progenitor cells were determined with microarrays, analyzed in a gene set enrichment analysis and confirmed by real-time quantitative PCRs.
  
  
  RESULTS
  Aneuploidy was more frequent in the zidovudine-exposed group (26.3%) than in the tenofovir-exposed group (14.2%) or in controls (13.3%; P < 0.05 for both). The transcription of genes involved in DNA repair, telomere maintenance, nucleotide metabolism, DNA/RNA synthesis, and the cell cycle was deregulated in samples from both the zidovudine and the tenofovir-exposed groups.
  
  
  CONCLUSIONS
  Although tenofovir has a lower clastogenic impact than zidovudine, gene expression profiling showed that both drugs alter the transcription of DNA repair and telomere maintenance genes.
authors.affiliation: aInstitut National de la Santé et de la Recherche Médicale (INSERM), U1163, Université Paris Descartes, Sorbonne Paris Cité, Institut Imagine bLaboratoire d'Hématologie Biologique, Assistance Publique-Hopitaux de Paris (AP-HP) cLaboratoire Génome et Cancer, INSERM, U944 and UMR7212, Hôpital Saint Louis dService de Gynécologie Obstétrique, Hôpital Louis Mourier, Hôpitaux Universitaire Paris Nord Val de Seine (HUPNVS), AP-HP, Colombes eINSERM U1018, Centre de recherche en Epidémiologie et Santé des Populations fUniversité Paris-Sud, Le Kremlin Bicêtre gService de Gynécologie Obstétrique, Hôpital Antoine Béclère, AP-HP, Clamart hService de Gynécologie Obstétrique, Hôpital Bichat, HUPNVS, AP-HP iUniversité Paris-Diderot jInstitut Universitaire d'Hématologie, Paris kDépartement de Biothérapie lUnité d'Immunologie Hématologie Rhumatologie Pédiatrique, Hôpital Necker Enfants Malades, AP-HP mEA 7323, Pharmacologie et évaluation des médicaments chez l'enfant et la femme enceinte, Université Paris Descartes, Sorbonne Paris Cité, Paris, France. *Stéphane Blanche and Isabelle André-Schmutz contributed equally to the writing of this article.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Vivanti
authors.forename: Tayebeh S
authors.initials: TS
authors.lastname: Soheili
authors.forename: Wendy
authors.initials: W
authors.lastname: Cuccuini
authors.forename: Sonia
authors.initials: S
authors.lastname: Luce
authors.forename: Laurent
authors.initials: L
authors.lastname: Mandelbrot
authors.forename: Jerome
authors.initials: J
authors.lastname: Lechenadec
authors.forename: Anne-Gael
authors.initials: AG
authors.lastname: Cordier
authors.forename: Elie
authors.initials: E
authors.lastname: Azria
authors.forename: Jean
authors.initials: J
authors.lastname: Soulier
authors.forename: Marina
authors.initials: M
authors.lastname: Cavazzana
authors.forename: Stéphane
authors.initials: S
authors.lastname: Blanche
authors.forename: Isabelle
authors.initials: I
authors.lastname: André-Schmutz
mesh_terms: D000782:Aneuploidy; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D005260:Female; D005312:Fetal Blood / Q000187:drug effects*; D015870:Gene Expression; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics / Q000635:transmission; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy* / Q000821:virology; D000068698:Tenofovir / Q000627:therapeutic use*; D015215:Zidovudine / Q000627:therapeutic use*
chemical_list: D019380:Anti-HIV Agents; D015215:Zidovudine; D000068698:Tenofovir