title: Side-by-side comparison of DNA damage induced by low-energy electrons and high-energy photons with solid TpTpT trinucleotide.
abstract: The genotoxic effects of high-energy ionizing radiation have been largely attributed to the ionization of H2O leading to hydroxyl radicals and the ionization of DNA leading mostly to damage through base radical cations. However, the contribution of low-energy electrons (LEEs; ≤ 10 eV), which involves subionization events, has been considered to be less important than that of hydroxyl radicals and base radical cations. Here, we compare the ability of LEEs and high-energy X-ray photons to induce DNA damage using dried thin films of TpTpT trinucleotide as a simple and representative model for DNA damage. The main radiation-induced damage of TpTpT as measured by high-performance liquid chromatography (HPLC) with UV detection and HPLC coupled to tandem mass spectrometry analyses included thymine release (-Thy), strand breaks (pT, Tp, pTpT, TpTp, and TpT), and the formation of base modifications [5,6-dihydrothymine (5,6-dhT), 5-hydroxymethyluracil (5-hmU), and 5-formyluracil (5-fU)]. The global profile of products was very similar for both types of radiation indicating converging pathways of formation. The percent damage of thymine release, fragmentation, and base modification was 20, 19, and 61 for high-energy X-rays, respectively, compared to 35, 13, and 51 for LEEs (10 eV). Base release was significantly lower for X-rays. In both cases, phosphodiester bond cleavage gave mononucleotides (pT and Tp) and dinucleotides (pTpT and TpTp) containing a terminal phosphate as the major fragments. For base modifications, the ratio of reductive (5,6-dhT) to oxidative products (5-hmU plus 5-fU) was 0.9 for high-energy X-rays compared to 1.7 for LEEs. These results indicate that LEEs give a similar profile of products compared to ionizing radiation.
authors.affiliation: Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Heath Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada J1H 5N4.
authors.forename: Yeunsoo
authors.initials: Y
authors.lastname: Park
authors.forename: Anita R
authors.initials: AR
authors.lastname: Peoples
authors.forename: Guru S
authors.initials: GS
authors.lastname: Madugundu
authors.forename: Léon
authors.initials: L
authors.lastname: Sanche
authors.forename: J Richard
authors.initials: JR
authors.lastname: Wagner
mesh_terms: D002851:Chromatography, High Pressure Liquid; D004249:DNA Damage; D004583:Electrons; D009841:Oligonucleotides / Q000737:chemistry*; D010432:Pentoxyl / Q000031:analogs & derivatives / Q000737:chemistry; D017785:Photons; D011839:Radiation, Ionizing; D053719:Tandem Mass Spectrometry; D013941:Thymine / Q000031:analogs & derivatives / Q000737:chemistry; D014498:Uracil / Q000031:analogs & derivatives / Q000737:chemistry
chemical_list: D009841:Oligonucleotides; C007777:5-formyluracil; C008055:5-hydroxymethyluracil; D014498:Uracil; C042836:5,6-dihydrothymine; D010432:Pentoxyl; D013941:Thymine
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