Microprobe XRF Mapping and XAS Investigations of the Intracellular Metabolism of Arsenic for Understanding Arsenic-Induced Toxicity

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• 作者：Kristie L. Munro ; Anna Mariana ; Andrejs I. Klavins ; Amalanie J. Foster ; Barry Lai ; Stefan Vogt ; ZhongHou Cai ; Hugh H. Harris ; Carolyn T. Dillon
• 刊名：Chemical Research in Toxicology
• 出版年：2008
• 出版时间：September 15, 2008
• 年：2008
• 卷：21
• 期：9
• 页码：1760-1769
• 全文大小：375K
• 年卷期：v.21,no.9(September 15, 2008)
• ISSN：1520-5010

文摘

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.