Urine Biomarkers for Oxidative DNA Damage

Abstract

The maintenance of macromolecular integrity and function, particularly in DNA, appears to be a major determinant of the longevity and functional capacity of biological systems.¹ DNA damage induced by active oxygen species therefore may be of primary importance in cancer and aging^2–4. This suggests the need for specific biomarkers (a) to elucidate the biochemical nature of DNA lesions and their repair and (b) to monitor noninvasively the generation and removal of DNA damage in biological systems. Several types of damage are known to result from the interactions of free radicals with chromatin, including single- and double-strand breaks, base and sugar alterations, and DNA-protein crosslinks.⁵ Each of these types of damage seems to be amenable to chemical analysis by the techniques of high performance liquid chromatography (HPLC), gas chromatography/mass spectrometry (GC/MS), alkaline and neutral elution, and other chromatographic and filter techniques. Of particular interest have been the measurements of specific products of oxidative damage to DNA and proteins, such as thymine glycol, thymidine glycol, base-amino acid crosslinks, and altered amino acids. Recently, the measurement of thymine glycol (TG), thymidine glycol (dR-TG), and 5-hydroxymethyluracil (HMU) in urine has been suggested to be a suitable approach for the in situ assessment of oxidative DNA damage caused by every day metabolic processes.References