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New York University School of Medicine

Superfund Research Program

Detection of Cr-DNA Adducts in Human Cells

Project Leader: Max Costa
Grant Number: P42ES010344
Funding Period: 2000 - 2006

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Project Summary (2000-2006)

The goal of this project is to develop new methodologies for assessing the impact of environmental exposure of hexavalent chromium to the human population and identify factors of susceptibility that enhance Cr toxicity. Hexavalent chromium is a well-established human carcinogen and is a contaminant at numerous Superfund toxic waste sites. Carcinogenesis by hexavalent chromium is thought to involve the formation of Cr-DNA adducts. About 50% of the chromium is bound to DNA as ternary complexes of Cr(III) with either amino acids or glutathione. Additionally, hexavalent chromium has been shown to interact with DNA in a non-random fashion targeting itself to promoters and coding regions of highly inducible genes. Researchers are developing a bacterial repair enzyme (UvrABC) ligation-mediated PCR technique to detect Cr-DNA adducts in human lymphocytes following exposure to hexavalent chromium. This approach is being used to test for hot spots of Cr-DNA adduction in promoter and coding regions of genes. Ultimately, these studies will help develop biomarkers of exposure and effect of carcinogenic hexavalent chromium.

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