Microprobe XRF mapping and XAS investigations of the intracellular metabolism of arsenic for understanding arsenic-induced toxicity.
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.
Munro
Kristie L
KL
School of Chemistry, University of Wollongong, NSW 2522, Australia.
Mariana
Anna
A
Klavins
Andrejs I
AI
Foster
Amalanie J
AJ
Lai
Barry
B
Vogt
Stefan
S
Cai
ZhongHou
Z
Harris
Hugh H
HH
Dillon
Carolyn T
CT
D001149:Arsenates / Q000378:metabolism* / Q000633:toxicity*; D018053:Arsenites / Q000378:metabolism* / Q000633:toxicity*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004577:Electron Probe Microanalysis; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D013052:Spectrometry, X-Ray Emission; D013997:Time Factors
D001149:Arsenates; D018053:Arsenites; C015001:arsenite; C025657:arsenic acid