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Comparative Study
. 2015 Jul 17;29(11):1319-24.
doi: 10.1097/QAD.0000000000000564.

Comparing genotoxic signatures in cord blood cells from neonates exposed in utero to zidovudine or tenofovir

Alexandre Vivanti  1 , Tayebeh S Soheili, Wendy Cuccuini, Sonia Luce, Laurent Mandelbrot, Jerome Lechenadec, Anne-Gael Cordier, Elie Azria, Jean Soulier, Marina Cavazzana, Stéphane Blanche, Isabelle André-Schmutz
Affiliations
Comparative Study

Comparing genotoxic signatures in cord blood cells from neonates exposed in utero to zidovudine or tenofovir

Alexandre Vivanti et al. AIDS. .

Abstract

Objectives: 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.

Design: 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.

Conclusion: 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.

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Figures

Fig. 1
Fig. 1
The frequency of aneuploidy in CD3+ cells stimulated with phytohemagglutinin for 72 h.
Fig. 2
Fig. 2
Gene-expression profiles in cord blood cells.
See this image and copyright information in PMC

References

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