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 [Cr₃O(OCOEt)⁶(OH₂)₃]⁺ (A), a prospective antidiabetic drug that undergoes similar H₂O₂ induced oxidation reactions in the blood as other Cr supplements, was also oxidized to carcinogenic CrVI and CrV in living cells. Single adipocytes treated with A had approximately 1 μm large Cr hotspots containing CrIII, CrV, and CrVI (primarily CrVI thiolates) species. These results strongly support the hypothesis that the antidiabetic activity of CrIII and the carcinogenicity of CrVI compounds arise from similar mechanisms involving highly reactive CrVI and CrV intermediates, and highlight concerns over the safety of CrIII nutritional supplements.