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|Title:||Microprobe XRF mapping and XAS investigations of the intracellular metabolism of arsenic for understanding arsenic-induced toxicity|
|Citation:||Chemical Research in Toxicology, 2008; 21(9):1760-1769|
|Publisher:||Amer Chemical Soc|
|Kristie L. Munro, Anna Mariana, Andrejs I. Klavins, Amalanie J. Foster, Barry Lai, Stefan Vogt, ZhongHou Cai, Hugh H. Harris and Carolyn T. Dillon|
|Abstract:||Arsenic (As) is responsible for mass-poisonings worldwide following the ingestion of As-contaminated drinking water. Importantly, however, As toxicity is exploited in the antileukemia drug, Trisenox (As2O3), which successfully cures 65-80% of patients suffering relapsed acute promyelocytic leukemia. In an effort to determine the intracellular organelle and biomolecular targets of As, microprobe X-ray fluorescence (XRF) and X-ray absorption spectroscopy (XAS) analyses were performed on HepG2 cells following their exposure to high doses of arsenite (1 mM) or arsenate (20 mM). Microprobe XRF elemental mapping of thin-sectioned cells showed As accumulation in the euchromatin region of the cell nucleus (following arsenite exposure) synonymous with As targeting of DNA or proteins involved in DNA transcription. X-ray absorption near edge spectroscopy (XANES) and extended X-ray absorption fine structure (EXAFS) analysis of arsenite-treated cells, however, showed the predominance of an As tris-sulfur species, providing increased credence to As interactions with nuclear proteins as a key factor in As-induced toxicity.|
|Keywords:||Cell Line, Tumor; Cell Nucleus; Humans; Arsenates; Arsenites; Electron Probe Microanalysis; Spectrometry, X-Ray Emission; Drug Screening Assays, Antitumor; Inhibitory Concentration 50; Cell Survival; Molecular Structure; Dose-Response Relationship, Drug; Time Factors|
|Description:||Copyright © 2008 American Chemical Society|
|Appears in Collections:||Chemistry and Physics publications|
Environment Institute publications
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