Perinatal exposure of patas monkeys to antiretroviral nucleoside reverse-transcriptase inhibitors induces genotoxicity persistent for up to 3 years of age

J Infect Dis. 2013 Jul 15;208(2):244-8. doi: 10.1093/infdis/jit146. Epub 2013 Apr 4.

Abstract

Background: Erythrocebus patas (patas) monkeys were used to model antiretroviral (ARV) drug in human immunodeficiency virus type 1-infected pregnant women.

Methods: Pregnant patas dams were given human-equivalent doses of ARVs daily during 50% of gestation. Mesenchymal cells, cultured from bone marrow of patas offspring obtained at birth and at 1 and 3 years of age, were examined for genotoxicity, including centrosomal amplification, micronuclei, and micronuclei containing whole chromosomes.

Results: Compared with controls, statistically significant increases (P < .05) in centrosomal amplification, micronuclei, and micronuclei containing whole chromosomes were found in mesenchymal cells from most groups of offspring at the 3 time points.

Conclusions: Transplacental nucleoside reverse-transcriptase inhibitor exposures induced fetal genotoxicity that was persistent for 3 years.

Keywords: Erythrocebus patas; abacavir; aneuploidy; centrosomal amplification; lamivudine; mesenchymal fibroblasts; micronuclei; nevirapine; zidovudine.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Animals, Newborn
  • Anti-HIV Agents / adverse effects*
  • Erythrocebus patas / genetics*
  • Erythrocebus patas / virology*
  • Female
  • HIV-1*
  • Humans
  • Mesenchymal Stem Cells / virology
  • Mesoderm / cytology
  • Mesoderm / drug effects*
  • Nucleosides / genetics
  • Pregnancy
  • Pregnancy Complications, Infectious / virology
  • Prenatal Exposure Delayed Effects*
  • Reverse Transcriptase Inhibitors / adverse effects*

Substances

  • Anti-HIV Agents
  • Nucleosides
  • Reverse Transcriptase Inhibitors