In this study, the effects of high-LET radiation on DNA were investigated and compared with the effects of gamma radiation. Hydrated DNA samples at 77 K were irradiated with argon-ion beams ((36)Ar or (40)Ar beam at energies between 60 and 100 MeV/nucleon). The individual free radicals formed were identified and their yields were investigated by electron spin resonance spectroscopy. Argon-ion irradiation resulted in lower yields of base ion radicals and higher yields of neutral radicals than gamma irradiation. A hitherto unknown species was assigned to the radical formed by C-O bond rupture at the deoxyribose C3', resulting in a sugar carbon-centered radical. A previously characterized phosphorus-centered radical was also found. The formation of each of these species was accompanied by an immediate strand break. G values, k values, and analyses for the individual yields of neutral radicals and ion radical composition for argon-ion-irradiated hydrated DNA are reported and compared to those found previously for gamma-irradiated DNA. The lower G values and k values for ion radicals and the higher fraction of neutral radicals found for argon-ion-irradiated DNA are attributed to differences in track structure inherent in the two radiations.

[reaction: see text] A C-3'-thymidinyl radical has been photochemically generated site-specifically in DNA oligonucleotides. A nucleoside H-phosphonate bearing a C-3' acetyl group was incorporated into DNA oligomers using a hand-coupling technique. When nucleotides containing the modified monomer were photolyzed (> or =320 nm) in the presence of a hydrogen atom donor, reduction products were detected by RP-HPLC and MALDI-ToF MS analysis.

Oxidative events that target the sugar-phosphate backbone of DNA can lead to reactive fragments that interfere with DNA repair, transcription and translation by the formation of cross-links and adducts of proteins and nucleobases. Here we report the formation of several such lesions through the aerobic degradation of an independently generated C-3'-thymidinyl radical in 2'-deoxyoligonucleotides. Individual fragments were identified by independent synthesis and comparison of retention times in high-performance liquid chromatography (HPLC) and/or matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-ToF MS) along with gel electrophoresis. The formation of this reactive intermediate in the presence of oxygen was found to produce 3'-phosphoglycolaldehyde (3'-PGA) as well as 3'-ketoenolether (3'-KEE), 3'-phosphoglycolate (3'-PG), and 5'-aldehyde terminated oligonucleotide fragments. Additionally, a significant outcome of C-3'-thymidinyl radical formation in DNA oligomers is a strand break resulting in one 3'- and two 5'-phosphate-terminated oligomers. These results suggest the involvement of several sugar derived reactive species upon C-3'-radical initiated scission of single-stranded DNA under aerobic conditions. The electrophilic nature of several of these products as well as their formation through a single oxidative event can make the presence of a C-3'-DNA radical more detrimental to the cell than products derived from more frequently occurring DNA sugar radicals.

What's the damage? Trapping the C3'-thymidinyl radical in biologically significant architectures delivers both the repaired oligomer and 1-(2'-deoxy-β-D-threo-pentofuranosyl)thymidine-containing substrates. The stereoselectivity of the reduction was found to be dependent upon the DNA structure.

No abstract