Toxicology of DNA Adducts Formed Upon Human Exposure to Carcinogens

Abstract Carcinogens arising from many sources (e.g., industrial agents, agricultural contaminants, environmental pollutants, food products, and medications) are known to attach to DNA to form nucleobase adducts. Experimental studies have shown that the chemical composition and biological consequences of these DNA lesions are widespread. This review highlights the judicious use of a range of computer modeling approaches to study previously unexplored molecular details of the cellular effects of DNA adducts and thereby aid our understanding of their toxicology. Emphasis is placed on the role of calculations in elucidating the structural implications of DNA adduct formation, as well as interactions between adducted DNA and critical cellular machinery (including enzymes involved in DNA replication and repair).