lt is generally agreed that the biological consequences of ionizing radiation originates with effects of the radiation on DNA. lt is also generally agreed that the indirect effect of attack by hydroxyl radicals from water radiolysis is responsible for a significant portion of the consequences. However, less agreement exists on the identities of the significant products of direct DNA ionization. Since existing evidence indicates that direct effects are roughly as important as indirect ones, the long-range objectives of this work are to identify the mechanisms, and to help clarify the importance, of direct ionization effects in DNA.
The specific aims for this project, derived from existing evidence and models reported in the literature, are: (1) to continue the effort to identify and characterize the primary products of purine derivatives, and to characterize their subsequent products: (2) to investigate the character (variability of methyl coupling, protonation state, and effect of hydration) of thymine anions in a variety of systems; (3) to investigate factors which may control the elementary protonation and deprotonation reactions of the primary ions; (4) to investigate the role of """"""""bound"""""""" water in determining the identity and chemical behavior of the primary ionic products; (5) to investigate systems in which more than one base is present in order to clarify mechanisms in which anions and cations may appear preferentially among the constituents of a system. To meet these aims, a variety of experiments will be performed using well characterized molecular systems (single crystals), and focusing on the radical (paramagnetic) products of ionization events. The main experimental procedures will be those of high resolution magnetic resonance spectroscopy (ENDOR), associated with temperature control (below 10 K to 300 K).
|Jackson, Christopher M; Kochel, Christina M; Nirschl, Christopher J et al. (2016) Systemic Tolerance Mediated by Melanoma Brain Tumors Is Reversible by Radiotherapy and Vaccination. Clin Cancer Res 22:1161-72|
|Jayatilaka, Nayana; Nelson, William H (2007) Structure of radicals from X-irradiated guanine derivatives: an experimental and computational study of sodium guanosine dihydrate single crystals. J Phys Chem B 111:800-10|
|Jayatilaka, Nayana; Nelson, William H (2007) Structure of radicals from X-irradiated guanine derivatives. 2. An experimental and computational study of 9-ethylguanine single crystals. J Phys Chem B 111:7887-96|
|Tokdemir, Sibel; Nelson, William H (2006) EPR and ENDOR study of radiation-induced radical formation in purines: sodium inosine crystals X-irradiated at 10 K. J Phys Chem A 110:6552-62|
|Sagstuen, Einar; Close, David M; Vagane, Randi et al. (2006) Electron transfer in amino acid.nucleic acid base complexes: EPR, ENDOR, and DFT study of X-irradiated N-formylglycine.cytosine complex crystals. J Phys Chem A 110:8653-62|
|Tokdemir, Sibel; Nelson, William H (2005) Radiation-induced hydroxyl addition to purine molecules: EPR and ENDOR study of hypoxanthine hydrochloride monohydrate single crystals. Radiat Res 163:663-72|
|Tokdemir, Sibel; Nelson, William H (2005) EPR and ENDOR study of radiation-induced radical formation in purines: hypoxanthine hydrochloride monohydrate crystals X-irradiated at 10 K. J Phys Chem A 109:8732-44|
|Nelson, William H (2005) Dose-response relationships for radicals trapped in irradiated solids. Radiat Res 163:673-80|
|Sagstuen, Einar; Sanderud, Audun; Hole, Eli O (2004) The solid-state radiation chemistry of simple amino acids, revisited. Radiat Res 162:112-9|
|Malinen, Eirik; Sagstuen, Einar (2003) Radical formation in pyrimidine bases after X, proton and alpha-particle irradiation. Radiat Res 160:186-97|
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