4.7 Article

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

期刊

JOURNAL OF INFECTIOUS DISEASES
卷 208, 期 2, 页码 244-248

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OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jit146

关键词

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

资金

  1. Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health

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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.

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