EFFECTS OF IONIZING RADIATION ON POLYDEOXYTHYMIDYLIC ACID AND POLYDEOXYADENYLIC ACID POLYDEOXYTHYMIDYLIC ACID (RADICAL) AS MODELS FOR DNA DAMAGE (HYDROXYL RADICALS, CROSS-LINKS, CHROMATOGRAPHY, HYDROGEN ABSTRACTION, MECHANISMS)

Free bases, oligo- and polynucleotides of thymine and adenine have been used as models for DNA in the study of indirect radiation-induced base and sugar damage. Reactions of OH radicals were investigated. Due to the presence of a small yield of H atoms, the reactions of these species were also studied. In order to generate OH radicals, samples were irradiated in N(,2)O-saturated aqueous solution. The products resulting from the reactions of solute molecules with (.)OH and H atoms were isolated by high performance liquid chromatography and their structures elucidated by capillary gas chromatography-mass spectrometry. Yields of the altered bases and sugars were determined by gas chromatography. Monomeric and novel cross-linked products of thymine and adenine were discovered and characterized. Additionally, thymine radicals were found to abstract hydrogen atoms intramolecularly from an adjacent nucleotide sugar moiety of polynucleotides. This reaction possibly contributes to the formation of strand breaks in DNA which may play a major role in the deleterious effects of ionizing radiation on cells. Mechanisms of product formation are discussed in detail.