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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
Statement of
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
RMID: 0020082676
DOI: 10.1021/tx800128d
Appears in Collections:Chemistry and Physics publications
Environment Institute publications

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