Oxidation State Determination in Chromium Carcinogenesis

铬致癌过程中氧化态的测定

• 批准号: 6605848
• 负责人: ZEWU CHEN
• 金额: $ 46.59万
• 依托单位: X-RAY OPTICAL SYSTEMS, INC.
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-15 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6605848
• 关键词: X ray spectrometry; bioimaging /biomedical imaging; chemical carcinogenesis; chromium; intracellular; optics; oxidation; stable isotope; technology /technique development; tissue /cell culture

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.

描述（由申请人提供）：一些铬（VI）化合物被记录为人类建议测量铬致癌物的细胞内氧化态，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提供重要的信息，并为了解铬的致癌机制提供依据。我们建议使用X射线吸收近边结构（XANES）光谱测量细胞内的铬氧化态。到目前为止，XANES技术还不是很实用，依赖于昂贵的同步加速器。这种有价值的技术可以使用一个低功耗的成本效益的系统，包括一个革命性的环形晶体光学实现。XOS成功地进行了第一阶段的研究，并证明了使用桌面XANES系统在空气中操作样品进行铬氧化测定的可行性。在第二阶段的项目中，将设计一个完全优化的系统。将在培养基中制备人细胞，并进行铬暴露处理。将使用XANES系统监测Cr（VI）至Cr（III）的还原。将评估这种XANES技术在临床研究及其商业化中的实际应用。这将首次提供广泛的化学状态测量能力，涵盖了医疗，研究和工业应用的紧凑，低功耗桌面系统中的大部分周期表。