Chromium oxidation state imaging in mammalian cells exposed in vitro to soluble or particulate chromate compounds

Hexavalent chromium compounds are known carcinogens for the respiratory tract in humans. The mechanism of cell transformation by hexavalent chromium compounds is not fully understood although a role for intracellular reduction is sought. The aim of this study was to determine the distribution of Cr valence states in human cells after in vitro exposure to soluble or particulate chromium compounds. A synchrotron X-ray-based microprobe was used to investigate the cellular reduction of Cr(VI) and to image chromium oxidation states in cells. It was shown that soluble Cr(VI) compounds are fully reduced to Cr(III) in cells. Cr(III) is homogeneously distributed within the cell volume and therefore present within the nucleus. In the case of low solubility particulate chromate compounds, Cr(VI) can coexist in the cell environment, as particles in the perinuclear region, together with intracellular and intranuclear Cr(III). Chemical distribution maps also suggest that intracellular Cr(III) originates from extracellular dissolution and reduction of lead chromate rather than from intracellular engulfed particles. The possible stronger carcinogenicity of low solubility chromate vs soluble chromate compounds may derive from the combinative genotoxic effects of intranuclear Cr(III) and the persistent exposure to a strong oxidant, Cr(VI).