Chapter 5. Oxidation of the C5′ Position in DNA and the Role of Purine 5′,8-Cyclo-2′-deoxynucleoside Lesions

Purine 5′,8-cyclo-2′-deoxynucleosides are tandem-type lesions observed among DNA modifications. These lesions are generated by the reaction of HO˙ radicals with genetic material via C5′-radical chemistry and can be present in two diasteroisomeric forms 5′R and 5′S for both 5′,8-cyclo-2′-deoxyadenosine and 5′,8-cyclo-2′-deoxyguanosine. This chapter describes the analytical protocols for their quantitative determination, the detection limits of the levels of lesions in various types of cells and animal model systems, and the relationships between the levels of lesions and human health, disease, and aging. The purine 5′,8-cyclo-2′-deoxynucleosides identified in mammalian cellular DNA in vivo, can be repaired only by nucleotide excision repair with low efficiencies and their accumulation in the genome results in severe adverse effects on cellular functions. The use of these lesions as candidate biomarkers of DNA damage is increasingly appreciated because the purine 5′,8-cyclo-2′-deoxynucleosides do not suffer from stability issues and artifacts of other oxidatively-generated DNA lesions.