Oxidation State Determination in Chromium Carcinogenesis

描述(申请人提供)：一些铬(VI)化合物是有文献记载的，人类建议测量铬致癌物质的细胞内氧化状态，但铬诱发癌症的确切机制尚不清楚。细胞内铬的氧化态测定将为铬的暴露和风险评估以及了解铬的致癌机制提供重要信息。我们建议使用X射线吸收近边结构(XANES)光谱来测量细胞内铬的氧化状态。到目前为止，XANES技术依靠昂贵的同步加速器并不是很实用。这项有价值的技术可以使用更低功率、更具成本效益的系统来实现，该系统结合了革命性的环形晶体光学元件。XOS已经成功地进行了第一阶段的研究，并证明了利用桌面XANES系统在空气中操作样品进行铬氧化测定的可行性。在这个二期工程中，将设计一个完全优化的系统。人体细胞将在培养液中制备，并经铬暴露处理。将使用XANES系统监测铬(V1)还原为铬(111)的过程。将评估这种XANES技术在临床研究中的实际应用及其商业化。这将首次提供广泛的化学状态测量能力，覆盖用于医疗、研究和工业应用的紧凑、低功率桌面系统中的大部分元素周期表。

DESCRIPTION (provided by applicant): Some chromium (VI) compounds are documented human propose measuring the intracellular oxidation state of Cr carcinogens, but the exact mechanism of Cr induced cancer is unknown. Oxidation state determination of intracellular Cr will provide important information relevant to exposure and risk assessment, and for understanding the mechanism of Cr carcinogenesis. We propose measuring the intracellular oxidation state of Cr using x-ray absorption near edge structure (XANES) spectroscopy. Until now, the XANES technique was not very practical, relying on costly synchrotrons. This valuable technique could be implemented using a lower power cost-effective system incorporating a revolutionary toroidal crystal optic. XOS has successfully carried out the Phase I research and demonstrated the feasibility of Cr oxidation determination using a table-top XANES system operated with samples in air. In this Phase II project, a fully optimized system will be designed. Human cells will be prepared in culture mediums and treated with Cr exposure. The reduction of Cr(Vl) to Cr(lll) will be monitored using the XANES system. The practical application of this XANES technique for clinical research and its commercialization will be evaluated. This would make available, for the first time, a broad chemical-state measurement capability covering most of the periodic table in a compact, low-power table-top system for medical, research, and industrial applications.