Pawel Jaruga
National Institute of Standards and Technology, USA
Title: Measurement of oxidatively modified DNA bases and nucleosides by isotope-dilution mass spectrometry
Biography
Biography: Pawel Jaruga
Abstract
Among cellular structures, the genome is particularly prone to damage, which can result from spontaneous reactions, replication linked failures, or oxidative processes due to metabolic derivatives or to external agents. Damage to DNA causes more severe consequences than damage to replaceable cellular macromolecules because the genome must be preserved for the life of the cell, and because it can be copied and proliferated into next generations of the cells. Reactions of free radicals and other redox capable agents with DNA generate an abundance of products in nuclear and mitochondrial DNA of living organisms. Growing evidence points to the involvement of this type of damage in the etiology of numerous diseases including carcinogenesis. Comprehensive understanding of the mechanisms, cellular repair, and biological consequences of DNA damage requires accurate measurement of resulting products. There are various analytical techniques, with their own advantages and drawbacks, which can be used for this purpose. Mass spectrometric techniques with isotope dilution provide structural interpretation of products and accurate quantification, which ascertain reliable measurement. Gas chromatography-mass spectrometry or liquid chromatography-mass spectrometry, in single or tandem versions, have been used for the measurement of numerous DNA products such as sugar and base lesions, 8,5′-cyclopurine-2′-deoxynucleosides, base-base tandem lesions, and DNA-protein crosslinks, in vitro and in vivo. Basic concepts and results will be presented and discussed.