OXIDATION STATE DETERMINATION IN CHROMIUM CARCINOGENESIS

描述：(改编自申请人的摘要)一些铬(VI) 化合物是有记录的人类致癌物质，但其确切机制是 铬诱导的癌症是未知的。铬(VI)能穿透细胞膜，但大多数 胞外铬(VI)迅速还原为无毒的铬(111)不进入 细胞，铬(III)是一种重要的微量元素，基于铬(III)的化合物是 用作膳食补充剂。然而，细胞内的铬(VI)与 大分子及其还原中间体铬(V)、铬(IV)和铬(III) 与大分子结合，并与铬的遗传毒性有关。因此， 细胞内铬的氧化态测定将提供重要的 与暴露和风险评估相关的信息，以及了解 铬的致癌机制。申请者建议测量 用X射线吸收近边结构研究铬的胞内氧化态 (XANES)光谱。到目前为止，XANES技术并不是很实用， 依靠昂贵的同步加速器。这项吸引人的技术可以实施 使用低功耗、经济高效的系统，集成了革命性的 环形晶体光学元件。在这个项目中，一个环形晶体光学元件将被 设计和制造用于聚焦和单色化x射线光子的 靠近CrK边的能量。铬(III)和铬(VI)的K边XANES谱 标准将使用紧凑的X射线管获得。这项计划的可行性 XANES将用于人体中铬的氧化态测定 细胞。 建议的商业应用：不可用

DESCRIPTION: (Adapted from the applicant's abstract) Some chromium(VI) compounds are documented human carcinogens but the exact mechanism of Cr-induced cancer is unknown. Cr(VI) can cross cell membranes but most extracellular Cr(VI) is rapidly reduced to non-toxic Cr(lll) not entering cells, Cr(III) is an important trace element and Cr(III) based compounds are used as dietary supplements. However, intracellular Cr(VI) is unreactive with macromolecules whereas its reductive intermediates, Cr(V), Cr(IV) and Cr(III) bind to macromolecules and are implicated in chromium genotoxicity. Thus, oxidation state determination of intracellular Cr will provide important information relevant to exposure and risk assessment, and for understanding the mechanism of Cr carcinogenesis. The applicants 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 attractive technique could be implemented using a lower power cost-effective system incorporating a revolutionary toroidal crystal optic. In this project, a toroidal crystal optic will be designed and fabricated for focusing and monochromatizing x-ray photons with energy near the Cr K-edge. The K-edge XANES spectra for Cr(III) and Cr(VI) standards will be obtained using a compact x-ray tube. The feasibility of the XANES will be evaluated for oxidation state determination of chromium in human cells. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE