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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
5P42ES013660-04
Application #
7599027
Study Section
Special Emphasis Panel (ZES1)
Project Start
Project End
Budget Start
2008-04-01
Budget End
2009-03-31
Support Year
4
Fiscal Year
2008
Total Cost
$370,388
Indirect Cost
Name
Brown University
Department
Type
DUNS #
001785542
City
Providence
State
RI
Country
United States
Zip Code
02912
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