Perinatal Exposure of Patas Monkeys to Antiretroviral Nucleoside Reverse-Transcriptase Inhibitors Induces Genotoxicity Persistent for up to 3 Years of Age

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 marr...

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Bibliographic Details
Published in:The Journal of infectious diseases 2013-07, Vol.208 (2), p.244-248
Main Authors: Olivero, Ofelia A., Torres, Lorangelly Rivera, Gorjifard, Sayeh, Momot, Dariya, Marrogi, Eryney, Divi, Rao L., Liu, Yongmin, Woodward, Ruth A., Sowers, Marsha J., Poirier, Miriam C.
Format: Article
Language:English
Subjects:
Aneuploidy
Animals
Animals, Newborn
Anti-HIV Agents - adverse effects
Antiretrovirals
Biological and medical sciences
Bone marrow cells
Cell nucleus
Chromosomes
Erythrocebus patas
Erythrocebus patas - genetics
Erythrocebus patas - virology
Female
Fundamental and applied biological sciences. Psychology
Genotoxicity
HIV-1
HIV/AIDS
Human immunodeficiency virus
Humans
Infants
Infectious diseases
Major and Brief Reports
Medical sciences
Mesenchymal Stromal Cells - virology
Mesoderm - cytology
Mesoderm - drug effects
Microbiology
Monkeys
Nucleosides
Nucleosides - genetics
Pregnancy
Pregnancy Complications, Infectious - virology
Prenatal Exposure Delayed Effects
Reverse Transcriptase Inhibitors - adverse effects
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Summary: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.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jit146