Computer simulation studies of radiation damage to biomolecules : gamma-ray irradiation of polyuridylic acid

Abstract

The objective o f this dissertation is to investigate the physical and chemical mechanisms involved when ionizing radiation interacts with biological m olecules in aqueous solution. Polyuridylic acid has been selected as the model for this study due to its relatively well characterized radiation chemistry and its similarity to DNA, the critical radiation target of the cell. Free radicals attack the uracil and ribose sugar by forming adducts with the base or by abstracting a hydrogen atom from the sugar moiety. The adducts are called intermediate radicals which will either release a hydrogen molecule or a water molecule to become the original base or they will abstract a hydrogen from the sugar moiety o f an adjacent nucleotide. The abstraction o f a hydrogen from the sugar moiety is assumed to be followed by a strand break and a base release. Only the free radicals *OH, H* and which are produced by radiolysis o f water play important role in causing damage to biomolecules. Previously performed irradiation experiments with DNA model systems, such as poly(U), are simulated in complete detail by a Monte Carlo computer code, namely OREC and RADLYS. OREC is the code for the transport of electrons through water. RADLYS simulates the prechemistry and early chemical stage of electron track development. These codes were modified to simulate the radiolysis of poly(U) in aqueous solution. In this dissertation, detailed discussions are given o f the modifications to the OREC and RADLYS codes for the simulation and the development of poly(U) as a molecular model for radiation damage to biomolecules. The 60Co Gy(E) values for strand break and base release are determined to be 1.77 and 2.00, respectively. If the radius of the cylinder is halved and length increased four times, the corresponding 60Co Gy(E) values are 2.35 and 2.75, respectively. The latter set of data displays a close agreement with those obtained experimentally by von Sonntag (1987). Detailed discussions on the comparisons of the calculational and experimental data are presented in this report. Simulations under other irradiation conditions are also reported.