The biological and metabolic fates of endogenous DNA damage products

Abstract

DNA and other biomolecules are subjected to damaging chemical reactions during normal physiological processes and in states of pathophysiology caused by endogenous and exogenous mechanisms. In DNA, this damage affects both the nucleobases and 2-deoxyribose, with a host of damage products that reflect the local chemical pathology such as oxidative stress and inflammation. These damaged molecules represent a potential source of biomarkers for defining mechanisms of pathology, quantifying the risk of human disease and studying interindividual variations in cellular repair pathways. Toward the goal of developing biomarkers, significant effort has been made to detect and quantify damage biomolecules in clinically accessible compartments such as blood and and urine. However, there has been little effort to define the biotransformational fate of damaged biomolecules as they move from the site of formation to excretion in clinically accessible compartments. This paper highlights examples of this important problem with DNA damage products.