Ortega Richard, Fayard Barbara, Salomé Murielle, Devès Guillaume, Susini Jean
Laboratoire de Chimie Nucléaire Analytique et Bioenvironnementale, Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux 1, BP 120, Chemin du Solarium, 33175 Gradignan, France.
Chem Res Toxicol. 2005 Oct;18(10):1512-9. doi: 10.1021/tx049735y.
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).
六价铬化合物是已知的人类呼吸道致癌物。尽管人们在探寻细胞内还原作用的角色，但六价铬化合物导致细胞转化的机制仍未完全明了。本研究的目的是确定体外暴露于可溶性或颗粒状铬化合物后人体细胞中铬价态的分布情况。使用基于同步加速器X射线的微探针来研究细胞内Cr(VI)的还原情况，并对细胞中的铬氧化态进行成像。结果表明，可溶性Cr(VI)化合物在细胞内完全还原为Cr(III)。Cr(III)在细胞体积内均匀分布，因此存在于细胞核中。对于低溶解度的颗粒状铬酸盐化合物，Cr(VI)可以在细胞环境中作为核周区域的颗粒与细胞内和细胞核内的Cr(III)共存。化学分布图还表明，细胞内的Cr(III)源自细胞外铬酸铅的溶解和还原，而非细胞内吞噬的颗粒。低溶解度铬酸盐相对于可溶性铬酸盐化合物可能更强的致癌性可能源于细胞核内Cr(III)的联合基因毒性作用以及对强氧化剂Cr(VI)的持续暴露。
