Biological Dosimetry of Hexavalent Chromium

点击翻译按钮获取中文摘要

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.