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Title: Carcinogenic Chromium(VI) Compounds Formed by Intracellular Oxidation of Chromium(III) Dietary Supplements by Adipocytes

Abstract

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 [Cr 3 O(OCOEt) 6 (OH 2 ) 3 ] + ( A ), a prospective antidiabetic drug that undergoes similar H 2 O 2 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:
ORCiD logo [1];  [2]; ORCiD logo [3];  [4];  [4]; ORCiD logo [4];  [5]; ORCiD logo [2]
  1. 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
  2. School of Chemistry The University of Sydney NSW 2006 Australia
  3. School of Chemistry The University of Sydney NSW 2006 Australia, School of Chemistry and Physics The University of Adelaide SA 5005 Australia
  4. Advanced Photon Source X-ray Science Division Argonne National Laboratory Argonne IL 60439 USA
  5. Garvan Institute of Medical Research 384 Victoria St Darlinghurst NSW 2010 Australia, Charles Perkins Centre The University of Sydney NSW 2006 Australia
Publication Date:
Sponsoring Org.:
USDOE
OSTI Identifier:
1401851
Grant/Contract Number:  
AC02-06CH11357
Resource Type:
Publisher's Accepted Manuscript
Journal Name:
Angewandte Chemie (International Edition)
Additional Journal Information:
Journal Name: Angewandte Chemie (International Edition) Journal Volume: 55 Journal Issue: 5; Journal ID: ISSN 1433-7851
Publisher:
Wiley Blackwell (John Wiley & Sons)
Country of Publication:
Germany
Language:
English

Citation Formats

Wu, Lindsay E., Levina, Aviva, Harris, Hugh H., Cai, Zhonghou, Lai, Barry, Vogt, Stefan, James, David E., and Lay, Peter A. Carcinogenic Chromium(VI) Compounds Formed by Intracellular Oxidation of Chromium(III) Dietary Supplements by Adipocytes. Germany: N. p., 2015. Web. doi:10.1002/anie.201509065.
Wu, Lindsay E., Levina, Aviva, Harris, Hugh H., Cai, Zhonghou, Lai, Barry, Vogt, Stefan, James, David E., & Lay, Peter A. Carcinogenic Chromium(VI) Compounds Formed by Intracellular Oxidation of Chromium(III) Dietary Supplements by Adipocytes. Germany. https://doi.org/10.1002/anie.201509065
Wu, Lindsay E., Levina, Aviva, Harris, Hugh H., Cai, Zhonghou, Lai, Barry, Vogt, Stefan, James, David E., and Lay, Peter A. Tue . "Carcinogenic Chromium(VI) Compounds Formed by Intracellular Oxidation of Chromium(III) Dietary Supplements by Adipocytes". Germany. https://doi.org/10.1002/anie.201509065.
@article{osti_1401851,
title = {Carcinogenic Chromium(VI) Compounds Formed by Intracellular Oxidation of Chromium(III) Dietary Supplements by Adipocytes},
author = {Wu, Lindsay E. and Levina, Aviva and Harris, Hugh H. and Cai, Zhonghou and Lai, Barry and Vogt, Stefan and James, David E. and Lay, Peter A.},
abstractNote = {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 [Cr 3 O(OCOEt) 6 (OH 2 ) 3 ] + ( A ), a prospective antidiabetic drug that undergoes similar H 2 O 2 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.},
doi = {10.1002/anie.201509065},
journal = {Angewandte Chemie (International Edition)},
number = 5,
volume = 55,
place = {Germany},
year = {Tue Dec 22 00:00:00 EST 2015},
month = {Tue Dec 22 00:00:00 EST 2015}
}

Journal Article:
Free Publicly Available Full Text
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https://doi.org/10.1002/anie.201509065

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Cited by: 52 works
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