Nucleoside reverse transcriptase inhibitors (NRTIs) when given in combination are highly effective in reducing the vertical transmission of HIV-1 from mother to infant; however, these drugs may impose a risk for cancer and mitochondria! disease later in life in exposed children. The objective of this study is to determine the relative impact of AZT, 3TC, and AZT-3TC on mitochondrial structure and function in human lymphoblastoid cells exposed in vitro and in lymphocytes and hearts of mice exposed transplacentally. The long-term objective is to determine whether NRTI-induced mtDNA mutations play a critical role in temporal changes in mitochondrial structure and function in heart and other tissues/cell types.
Two specific aims will be accomplished: 1. to determine the relative ability of AZT-3TC to induce toxicity by defining genotoxicity, mutagenicity and altered mitochondrial structure and function 2. To compare, at birth and 3 months of age, mitochondrial toxicity in cardiac tissue and lymphocytes following transplacental exposure of female B6C3F1 mice to AZT, 3TC or AZT-3TC.
| Torres, Salina M; March, Thomas H; Carter, Meghan M et al. (2010) In utero exposure of female CD-1 Mice to AZT and/or 3TC: I. Persistence of microscopic lesions in cardiac tissue. Cardiovasc Toxicol 10:37-50 |
| Torres, Salina M; Divi, Rao L; Walker, Dale M et al. (2010) In utero exposure of female CD-1 mice to AZT and/or 3TC: II. Persistence of functional alterations in cardiac tissue. Cardiovasc Toxicol 10:87-99 |
| Walker, Dale M; Kajon, Adriana E; Torres, Salina M et al. (2009) WR1065 mitigates AZT-ddI-induced mutagenesis and inhibits viral replication. Environ Mol Mutagen 50:460-72 |
| Torres, Salina M; Walker, Dale M; McCash, Consuelo L et al. (2009) Mutational analysis of the mitochondrial tRNA genes and flanking regions in umbilical cord tissue from uninfected infants receiving AZT-based therapies for prophylaxis of HIV-1. Environ Mol Mutagen 50:10-26 |
