A systematic study of a 15-member group of purine molecular systems is proposed.
The aims are to characterize the direct-ionization products of purines. Rationale for the project comes from the probability that the behavior of purines, as consitituents of DNA, is central to the response of DNA to ionizing radiation. The overall objective, therefore, is to identify and characterize the direct-ionization products of purines, and their reactions, which may provide insight into the radiation response of DNA. For that reason, four of the molecular systems contain adenine, while seven of them contain guanine. Of particular interest will be the molecular cations and their subsequent products. One reason is that the guanine cation or G+, is thought to be a primary radiation product of DNA. Full characterization of this product, to the extent possible by the crystallographic method, has not yet been achieved, although progress toward this aim has recently been reported. Also, the subsequent products, or fate, of G+ are unknown. As a result, the true importance of G+ is also unknown. Therefore it is possible that a full understanding of purine radiochemistry may be necessary in order to understand the significance of G+ DNA. Also proposed is a set of preliminary studies aimed at developing methods to use dinucleoside phosphates (DNP's) in similar studies. The rational for doing so is that DNP's which crystallize as helical fragments, will more faithfully model DNA.
The aims of the preliminary studies are to prepare suitable samples of DNP's. The proposed experimental approach is to use the methods of magnetic resonance crystallography (ESR and ENDOR). In addition, low temperature methods will be used to stabilize normally unstable products. Finally, controlled warming studies will be performed in order to identify product transformations whenever possible.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA036810-01A2
Application #
3174385
Study Section
Radiation Study Section (RAD)
Project Start
1986-04-01
Project End
1989-03-31
Budget Start
1986-04-01
Budget End
1987-03-31
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Georgia State University
Department
Type
Schools of Arts and Sciences
DUNS #
837322494
City
Atlanta
State
GA
Country
United States
Zip Code
30302
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
Nelson, William H (2005) Dose-response relationships for radicals trapped in irradiated solids. Radiat Res 163:673-80
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
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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