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University of North Carolina-Chapel Hill

Superfund Research Program

Biomarkers of Human Susceptibility to Vinyl Chloride

Project Leaders: David G. Kaufman, Howard L. Liber (Massachusetts General Hospital)
Grant Number: P42ES005948
Funding Period: 1995 - 2000

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Project Summary (1995-2000)

The major goal of this project is to utilize biomarkers of exposure and effect to test for possible genetic differences in susceptibility to vinyl chloride (VC) induced mutations. VC is a widespread environmental contaminant, and a known carcinogen in humans. Preliminary data suggests that some workers exposed to VC have persistent elevated mutant frequencies in their peripheral blood lymphocytes, and that others do not. It is postulated that either xenobiotic metabolism or DNA repair are responsible for such differential susceptibility. These issues are being addressed by studies of 735 exposed individuals and controls, determination of mutation frequencies at the X-linked hypoxanthine guanine phosphoribosyl transferase (hprt) locus in 50 subjects per year, analysis of the hprt mutants, studies of differential susceptibility that could be due to variable capacity for vinyl chloride metabolism, and a search for the presence of one particular mutated p21ras protein - with aspartic acid at codon 13 instead of glycine (Asp13p21ras) - in the serum of individuals exposed to VC.

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