DNA Adducts as Biomarkers in Toxicology

The measurement of biopolymer modifications due to exposure to environmental chemicals or endogenous physiological processes can provide valuable information on toxicological exposure and disease risk. The covalent modification of DNA represents an especially important case since unrepaired DNA adducts can have wide-ranging genetic and epigenetic consequences with significant impact on human health. In this chapter, we examine how quantification of DNA adducts can inform on exposure to a variety of DNA damaging agents present in the environment and those produced endogenously due to physiological processes. This information can be used to set limits on exposure and for predicting susceptibility to genetic diseases such as cancer, diabetes, and immunological dysfunction. With the development of increasingly sensitive analytical methods that also provide detailed structural information, we are on the verge of a new era of DNA adductomics – the complete characterization of the entire spectrum of DNA damage in humans. In this review, we will provide a brief overview of the various methods that have been used to measure DNA adducts as well as a critical appraisal of their strengths and weaknesses. We will then highlight some of the more important DNA adducts that have been linked to human disease and conclude with some examples of how measurement of chemotherapy induced adducts may be used to predict treatment response.