Damage to DNA Bases

Russo N, Toscano M, Grand A (2000) Theoretical determination of electron affinity and ionization potential of DNAand RNA bases. J Comput Chem 21 1243-1250 Sagstuen E, Hole EO, Nelson WH, Close DM (1998) Radiation damage to DNA base pairs. II. Paramagnetic resonance studies of 1 -methyluracil. 9-ethyladenine complex crystals X-irradiated at 10 K. Radiat Res 149 120-127... 

MS-MS measurements performed recently in our laboratory have shown that the yield of radiation-induced formation of (5 R)-cydodAdo (44a) in cellular DNA is at best around 0.2 lesions/109 normal nucleotides/Gy. This is in agreement with the fact that the shielding effect exerted by cellular constituents on the extent of radiation-induced damage to DNA bases and sugar is about three orders of magnitude with respect to naked DNA [12]. 

Recent research has shown that combustion sources can generate radicals that are stabilized by associated with particulate matter. This same particulate matter becomes a component of airborne PM2.5. (fine particulate matter (smaller than 2.5 microns in diameter). PM2.5 is known to initiate lung cancer and cardiopulmonary disease however, the mechanism has not been identified. DNA and cellular assay results indicate that combustion and PM2.5 can cause radical induced damage to DNA. Based on electron paramagnetic resonance (EPR) studies, the responsible species appear to be semiquinone-type radicals. These studies reveal that radicals, heretofore thought to be too unstable to survive in the atmosphere, can be stabilized by association with particles and initiate biological damage. 

Single-cell alkaline gel electrophoresis (the Comet assay) is a sensitive assay of DNA strand breaks. The Comet assay can be adapted to measure oxidative damage to DNA bases by measuring strand breaks induced by the treatment of DNA with relevant repair enzymes, eg., endonuclease III (EndoIII) for oxidized pyrimidines and formamidopyrimidine glycosylase (Fpg) for 8-oxogua and ring-opened pyrimidines, such as those resulting from the breakdown of alkylated bases. ... 

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