DNA Adducts as Biomarkers for Carcinogenesis Analysed by Capillary Electrophoresis and Laser-Induced-Fluorescence Detection

DNA adducts are the direct products of damage by endogenous or exogenous reactive agents to a critical macromolecular target such as DNA (Figure 17.1). Approximately 90% of the chemicals considered carcinogenic for humans form DNA adducts (Stiborovà et al. 1998). Although the majority of such DNA damage is eliminated by DNA repair processes, some persistent adducts often cause permanent mutations in important growth-controlling genes or loci, resulting in aberrant cellular growth and cancer (Hemminki et al. 2000). The amount of these reflects an integration of both the toxicokinetic properties of a genotoxic compound and the cellular DNA repair. Measurements of endogenous and exogenous DNA adducts are thus of interest in that they provide molecular, mechanism-based bridges between carcinogen exposure and disease end-points and can serve as biomarkers for carcinogenesis. In practice, investigations of such DNA damage can be viewed as a supplementary test that may, in some instances, help to facilitate the assessment of a compound with an unusual or puzzling profile of activity in statutory genotoxicity assays, animal bioassays, or both (Phillips et al. 2000).