title: Carcinogenic Chromium(VI) Compounds Formed by Intracellular Oxidation of Chromium(III) Dietary Supplements by Adipocytes.
abstract: Chromium(III) nutritional supplements are widely consumed for their purported antidiabetic activities. X-ray fluorescence microscopy (XFM) and X-ray absorption near-edge structure (XANES) studies have now shown that non-toxic doses of [Cr3 O(OCOEt)6 (OH2 )3 ](+) (A), a prospective antidiabetic drug that undergoes similar H2 O2 induced oxidation reactions in the blood as other Cr supplements, was also oxidized to carcinogenic Cr(VI) and Cr(V) in living cells. Single adipocytes treated with A had approximately 1 μm large Cr hotspots containing Cr(III) , Cr(V) , and Cr(VI) (primarily Cr(VI) thiolates) species. These results strongly support the hypothesis that the antidiabetic activity of Cr(III) and the carcinogenicity of Cr(VI) compounds arise from similar mechanisms involving highly reactive Cr(VI) and Cr(V) intermediates, and highlight concerns over the safety of Cr(III) nutritional supplements.
authors.affiliation: School of Chemistry, The University of Sydney, NSW, 2006, Australia.|Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst, NSW, 2010, Australia.|School of Medical Sciences, UNSW Australia, NSW, 2052, Australia.
authors.forename: Lindsay E
authors.identifier: http://orcid.org/0000-0002-1599-7574
authors.initials: LE
authors.lastname: Wu
authors.affiliation: School of Chemistry, The University of Sydney, NSW, 2006, Australia.
authors.forename: Aviva
authors.initials: A
authors.lastname: Levina
authors.affiliation: School of Chemistry, The University of Sydney, NSW, 2006, Australia.|School of Chemistry and Physics, The University of Adelaide, SA, 5005, Australia.
authors.forename: Hugh H
authors.identifier: http://orcid.org/0000-0002-3472-8628
authors.initials: HH
authors.lastname: Harris
authors.affiliation: Advanced Photon Source, X-ray Science Division, Argonne National Laboratory, Argonne, IL, 60439, USA.
authors.forename: Zhonghou
authors.initials: Z
authors.lastname: Cai
authors.affiliation: Advanced Photon Source, X-ray Science Division, Argonne National Laboratory, Argonne, IL, 60439, USA.
authors.forename: Barry
authors.initials: B
authors.lastname: Lai
authors.affiliation: Advanced Photon Source, X-ray Science Division, Argonne National Laboratory, Argonne, IL, 60439, USA.
authors.forename: Stefan
authors.identifier: http://orcid.org/0000-0002-8034-5513
authors.initials: S
authors.lastname: Vogt
authors.affiliation: Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst, NSW, 2010, Australia.|Charles Perkins Centre, The University of Sydney, NSW, 2006, Australia.
authors.forename: David E
authors.initials: DE
authors.lastname: James
authors.affiliation: School of Chemistry, The University of Sydney, NSW, 2006, Australia. peter.lay@sydney.edu.au.
authors.forename: Peter A
authors.identifier: http://orcid.org/0000-0002-3232-2720
authors.initials: PA
authors.lastname: Lay
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D002273:Carcinogens / Q000138:chemical synthesis* / Q000737:chemistry; D002857:Chromium / Q000378:metabolism*; D019587:Dietary Supplements; D008856:Microscopy, Fluorescence; D010084:Oxidation-Reduction
chemical_list: D002273:Carcinogens; D002857:Chromium
keywords: X-ray fluorescence microscopy; adipocytes; cancer; chromium; oxidation