Chromosomal damage to cells from the action of ionizing radiation may lead to inactivation or mutation. The damage may arise in two general ways. In one, the damage is from energy deposited within DNA itself and its hydration sheath (leading to """"""""direct"""""""" or """"""""unscavengeable"""""""" effects); in the other the damage is from energy deposited elsewhere (leading to """"""""indirect"""""""" or """"""""scavengeable"""""""" effects). While there is widespread agreement that scavengeable damage is the result of OH radicals from water radiolysis, there remain several questions about the initiation and progression of unscavengeable damage. These are important health-related issues since it is estimated that about half the cellular effects arise from unscavengeable sources. The long-range objectives of this project are identification of the physical and chemical mechanisms responsible for the radical products causing unscavengeable damage to DNA. Several investigations are needed to meet these objectives. Thus, the specific aims of this project are: (1) to continue study of monomeric DNA subunits for the purpose of identifying possible radiation-induced radical products and obtaining their spectral characteristics as an aid in interpreting results from more complicated systems; (2) to investigate electron, proton, and hole transfer in DNA-like systems with a systematic progression in complexity and realism as follows: (2a) cocrystallized base pairs in a water-free environment; (2b) both duplexed and non-duplexed oligomers (dimers) in a hydrated environment; (2c) hydrated oligomers containing all bases; 93) to investigate secondary reactions with the principal objective of learning how unscavengeable damage may lead to strand breaks. To meet these aims, a variety of studies will be performed using high- resolution magnetic resonance spectroscopy (ENDOR) to study crystals of the chosen molecular systems. This provides well-characterized systems for study, and the use of ENDOR provides a high probability for unambiguous interpretation of the results.
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