Vacuum‐UV and Low‐Energy Electron‐Induced DNA Strand Breaks – Influence of the DNA Sequence and Substrate

Abstract

DNA is effectively damaged by radiation, which can on the one hand lead to cancer and is on the other hand directly exploited in the treatment of tumor tissue. DNA strand breaks are already induced by photons having an energy below the ionization energy of DNA. At high photon energies, most of the DNA strand breaks are induced by low‐energy secondary electrons. In the present study we quantified photon and electron induced DNA strand breaks in four different 12mer oligonucleotides. They are irradiated directly with 8.44 eV vacuum ultraviolet (VUV) photons and 8.8 eV low energy electrons (LEE). By using Si instead of VUV transparent CaF2 as a substrate the VUV exposure leads to an additional release of LEEs, which have a maximum energy of 3.6 eV and can significantly enhance strand break cross sections. Atomic force microscopy is used to visualize strand breaks on DNA origami platforms and to determine absolute values for the strand break cross sections. Upon irradiation with 8.44 eV photons all the investigated sequences show very similar strand break cross sections in the range of 1.7–2.3×10−16 cm2. The strand break cross sections for LEE irradiation at 8.8 eV are one to two orders of magnitude larger than the ones for VUV photons, and a slight sequence dependence is observed. The sequence dependence is even more pronounced for LEEs with energies <3.6 eV. The present results help to assess DNA damage by photons and electrons close to the ionization threshold.

Hole Migration in Telomere‐Based Oligonucleotide Anions and G‐Quadruplexes

“…experimentally observed an increased cross section for low energy electron induced single strand breaks for 5′‐(TTAGGG) 2 as compared to the intermixed sequence 5′‐(TGTGTGA) 2 . On the other hand, the absolute cross section for VUV‐induced single strand break induction was found to be only weakly dependent on oligonucleotide sequence …”

“…[23] Very recently,R ackwitz et al [24] experimentally observed an increased crosss ection for low energy electron induced single strand breaks for 5'-(TTAGGG) 2 as compared to the intermixed sequence 5'-(TGTGTGA) 2 .O n the other hand, the absolute cross section for VUV-induced single strand break induction was found to be only weakly dependentono ligonucleotide sequence. [25] In our present work we have experimentally studied VUV photoabsorption in multiply deprotonated gas-phase oligonucleotidesc ontainingt he vertebrate telomere sequence dTTAGGGa nd in model G-quadruplex structures formed by 4 dTGGGGTsingle strands.…”

Length and Energy Dependence of Low-Energy Electron-Induced Strand Breaks in Poly(A) DNA

“…. VUV induced strand breaks are initiated by dissociative photo ionization and excitation [11,23]. However, irradiation with LEEs yields DNA strand break cross sections, which are one order of magnitude higher than for VUV radiation demonstrating the high efficiency of DEA compared to dissociative photo excitation and ionization.…”

“…(v) Application to other radiation sources such as UV radiation is possible [11]. These properties give us the opportunity to study interactions of different well-defined DNA molecules with LEEs of varying energies.…”

“…This yields information about resonant formation of DNA strand breaks for specific ssDNA and a presumed additivity of SB cross sections. Recently, it was shown that low-energy electron-induced DNA strand breaks depend, to some degree, on the specific DNA sequence and length [11]. Four homo-oligonucleotides (d(A12), d(G12), d(C12), and d(T12)) have been compared and the SB cross section upon irradiation with 8.8 eV electrons was the highest for the dA12 sequence, even though the differences were small.…”