Superfund Research Program
DNA Adducts as Biomarkers of Exposure and Effect
Project Leader: James A. Swenberg
Grant Number: P42ES005948
Funding Period: 1995-2018
Project Summary (1995-2000)
The objective of this project is to develop improved methods for measuring exposure and effect of environmental carcinogens so that more accurate biologically-based risk assessments of low exposures to humans can be made. Marked improvements in GC/high resolution mass spectrometry capabilities are being used to investigate the effect of several major chemicals on the National Priority List (NPL) on the direct formation or modulation of endogenous formation of N2,3- ethenoguanine (EG). [13C2]-Trichloroethylene, tetrachloroethylene, and trichloroethane is being administered to rodents and the amount of endogenous EG and EG formed by direct alkylation is being determined by monitoring the exact masses of the EG adducts. Additional studies focus on the DNA repair pathways of these adducts. Finally, scientists are determining the molecular dose of DNA adducts and the effect of exposure on cell proliferation of another NPL chemical, dinitrotoluene.