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Adelaide Research and Scholarship
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Schools and Disciplines
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School of Chemistry and Physics
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Chemistry and Physics Publications
Permanent link to this item:
http://hdl.handle.net/2440/47040
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| Type: | Article |
| Title: | Time-dependent uptake, distribution and biotransformation of chromium(VI) in individual and bulk human lung cells: application of synchrotron radiation techniques |
| Author: | Harris, Hugh Hamlyn
Levina, A.
Dillon, Carolyn T.
Mulyani, I.
Lai, B.
Cai, Z.
Lay, P. A. |
| Citation: | Journal of Biological Inorganic Chemistry, 2005; 10 (2):105-118 |
| Publisher: | Springer-Verlag |
| Issue Date: | 2005 |
| ISSN: | 0949-8257 |
| School/Discipline: | School of Chemistry and Physics : Chemistry |
Statement of
Responsibility: | Hugh H. Harris, Aviva Levina, Carolyn T. Dillon, Irma Mulyani, Barry Lai, Zhonghou Cai and Peter A. Lay |
| Abstract: | Chromium(VI) is a human carcinogen, primarily affecting the respiratory tract probably via active transport into cells, followed by the reduction to Cr(III) with the formation of DNA-damaging intermediates. Distribution of Cr and endogenous elements within A549 human lung adenocarcinoma epithelial cells, following treatment with Cr(VI) (100 μM, 20 min or 4 h) were studied by synchrotron-radiation-induced X-ray emission (SRIXE) of single freeze-dried cells. After the 20-min treatment, Cr was confined to a small area of the cytoplasm and strongly co-localized with S, Cl, K, and Ca. After the 4-h treatment, Cr was distributed throughout the cell, with higher concentrations in the nucleus and the cytoplasmic membrane. This time-dependence corresponded to ~100% or 0% clonogenic survival of the cells following the 20-min or 4-h treatments, respectively, and could potentially be explained by a new cellular protective mechanism. Such processes may also be important in reducing the potential hazards of Cr(III) dietary supplements, for which there is emerging evidence that they exert their anti-diabetic effects via biological oxidation to Cr(VI). The predominance of Cr(III) was confirmed by micro-XANES spectroscopy of intracellular Cr hotspots. X-ray absorption spectroscopy (XANES and EXAFS, using freeze-dried cells after the 0–4-h treatments) was used to gain insight into the chemical structures of Cr(III) complexes formed during the intracellular reduction of Cr(VI). The polynuclear nature of such complexes (probably with a combination of carboxylato and hydroxo bridging groups and O-donor atoms of small peptides or proteins) was established by XAFS data analyses. |
| Keywords: | Chromium; Cancer; Human cells; Synchrotron-radiation-induced X-ray emission; X-ray absorption spectroscopy |
| Description: | The original publication can be found at www.springerlink.com |
| RMID: | 0020081440 |
| DOI: | 10.1007/s00775-004-0617-1 |
| Published version: | http://www.springerlink.com/content/95270tu0nntbwx52/ |
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| Appears in Collections: | Chemistry and Physics Publications
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