Time-dependent uptake, distribution and biotransformation of chromium(VI) in individual and bulk human lung cells: application of synchrotron radiation techniques

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dc.contributor.authorHarris, H.
dc.contributor.authorLevina, A.
dc.contributor.authorDillon, C.
dc.contributor.authorMulyani, I.
dc.contributor.authorLai, B.
dc.contributor.authorCai, Z.
dc.contributor.authorLay, P.
dc.date.issued2005
dc.descriptionThe original publication can be found at www.springerlink.com
dc.description.abstractChromium(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.
dc.description.statementofresponsibilityHugh H. Harris, Aviva Levina, Carolyn T. Dillon, Irma Mulyani, Barry Lai, Zhonghou Cai and Peter A. Lay
dc.identifier.citationJournal of Biological Inorganic Chemistry, 2005; 10(2):105-118
dc.identifier.doi10.1007/s00775-004-0617-1
dc.identifier.issn0949-8257
dc.identifier.issn1432-1327
dc.identifier.orcidHarris, H. [0000-0002-3472-8628]
dc.identifier.urihttp://hdl.handle.net/2440/47040
dc.language.isoen
dc.publisherSpringer-Verlag
dc.source.urihttp://www.springerlink.com/content/95270tu0nntbwx52/
dc.subjectChromium
dc.subjectCancer
dc.subjectHuman cells
dc.subjectSynchrotron-radiation-induced X-ray emission
dc.subjectX-ray absorption spectroscopy
dc.titleTime-dependent uptake, distribution and biotransformation of chromium(VI) in individual and bulk human lung cells: application of synchrotron radiation techniques
dc.typeJournal article
pubs.publication-statusPublished

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