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https://hdl.handle.net/2440/53501
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Type: | Journal article |
Title: | Microprobe XRF mapping and XAS investigations of the intracellular metabolism of arsenic for understanding arsenic-induced toxicity |
Author: | Munro, K. Mariana, A. Klavins, A. Foster, A. Lai, B. Vogt, S. Cai, Z. Harris, H. Dillon, C. |
Citation: | Chemical Research in Toxicology, 2008; 21(9):1760-1769 |
Publisher: | Amer Chemical Soc |
Issue Date: | 2008 |
ISSN: | 0893-228X 1520-5010 |
Statement of Responsibility: | 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 |
DOI: | 10.1021/tx800128d |
Published version: | http://dx.doi.org/10.1021/tx800128d |
Appears in Collections: | Aurora harvest 5 Chemistry and Physics publications Environment Institute publications |
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