Biological Dosimetry of Hexavalent Chromium

铬及其化合物是大量超级基金场地的主要污染物。铬以几种氧化态存在，其中只有六价形式与这种金属的致癌和其他毒性作用有关。超级基金场地和其他环境污染源通常含有不同氧化形式的铬，这使得难以根据生物样品中铬的总水平评估人类接触有毒铬（VI）的情况。我们先前已经确定，在铬（VI）暴露的细胞中最丰富的DMA损伤形式是含有抗坏血酸和氨基酸/肽配体的诱变三元铬- DNA复合物。在这项工作中，我们建议使用三元加合物作为生物标志物的铬（VI）在人体细胞中的遗传损伤的测量的特点。将进行实验，以确定缓慢修复形式的铬-DNA加合物，生物修复和配体交换依赖性损失的作用，共同暴露于其他金属对铬-DNA加合物的生物学特性的影响，并制定一个更敏感的分析方法，用于确定主要的致突变铬-DNA修饰。

Chromium and its compounds are major contaminants at a large number of the Superfund sites. Chromium exists in several oxidation states, among which only hexavalent form is associated with carcinogenic and other toxic effects of this metal. Superfund sites and other sources of environmental contamination usually contain chromium in different oxidation forms, which makes it difficult to assess human exposure to toxic chromium(VI) based on total levels of chromium in biological samples. We have previously determined that the most abundant form of DMA damage in chromium(VI)-exposed cells are mutagenic ternary chromium- DNA complexes containing ascorbate and amino acid/peptide ligands. In this work we propose to characterize the use of measurements of ternary adducts as a biomarker of genetic damage by chromium(VI) in human cells. Experiments will be performed to identify slowly repairable forms of chromium-DNA adducts, the role of biological repair and ligand exchange-dependent loss, the influence of co-exposure to other metals on biological characteristics of chromium-DNA adducts and to develop a more sensitive analytical methodology for the determination of major mutagenic chromium-DNA modifications.