8‐Oxo‐7,8‐Dihydro‐2′‐Deoxyguanosine: A Major DNA Oxidation Product

Singlet O2 Reactions with Radical Cations of 8-Bromoguanine and 8-Bromoguanosine: Guided-Ion Beam Mass Spectrometric Measurements and Theoretical Treatments

“…Human leukocyte enzymes myeloperoxidase and eosinophil peroxidase, which are released in association with helminthic infections and various inflammatory disease processes, can selectively catalyze the reaction of bromide (at a physiological plasma [Br – ] = 20–100 μM) with hydrogen peroxide to form hypobromous acid (HOBr) and a hypobromite ion (OBr – ) in vivo. − Besides oxidizing the cellular materials of invading pathogens, excess HOBr and OBr – may brominate host DNA, proteins, and lipids. , Guanine is the preferred purine target for bromination as a free nucleobase, while adenine is the major target for bromination in double-stranded DNA . Stable brominated DNA adducts include 8-bromo-2′-deoxyguanosine, 8-bromo-2′-deoxyadenosine, and 5-bromo-2′-deoxycytidine. , Notably, 8-bromo-2′-deoxyguanosine was observed prior to 8-oxo-2′-deoxyguanosine (abbreviated as OG, the most commonly used biomarker for oxidatively generated DNA damage) with respect to the order of guanine modifications, suggesting that 8-bromo-2′-deoxyguanosine is a biomarker for early inflammation . Moreover, only 8-bromo-2′-deoxyguanosine, not 8-bromo-2′-deoxyadenosine nor 5-bromo-2′-deoxycytidine, is a mutagenic lesion .…”

“…4 Stable brominated DNA adducts include 8-bromo-2′-deoxyguanosine, 8-bromo-2′-deoxyadenosine, and 5-bromo-2′-deoxycytidine. 4,6 Notably, 8-bromo-2′-deoxyguanosine was observed prior to 8-oxo-2′-deoxyguanosine (abbreviated as OG, the most commonly used biomarker for oxidatively generated DNA damage) 7 with respect to the order of guanine modifications, suggesting that 8-bromo-2′-deoxyguanosine is a biomarker for early inflammation. 8 Moreover, only 8-bromo-2′-deoxyguanosine, not 8-bromo-2′-deoxyadenosine nor 5-bromo-2′-deoxycytidine, is a mutagenic lesion.…”