γ-Radiolysis of 2′-Deoxycytidine-5′-phosphate in Deoxygenated Aqueous Solutions. OH Radical-Induced Alterations at the Sugar Moiety

Abstract

Abstract In order to elucidate some aspects of the mechanism of radical-induced strand break formation in DNA, the γ-radiolysis of N2O-saturated aqueous solutions of 2′-deoxycytidine-5′-phosphate has been studied as a model system. At pH 4 it has been observed that upon OH attack at the sugar moiety phosphate (G ≈ 0.6) and cytosine (G = 1) are released and the following cytosine-free sugars are formed: 2,5-dideoxypentos-3,4-diulose, 1 (G = O.22), 2-deoxy-pentos-4-ulose, 2 (G = 0.18), 2-deoxy-pentos-4-ulose-5-phosphate, 3 (G=0.06), 2-deoxypentonic acid-5-phosphate and its lactone, 5 (G ≈ 0.5). Some 2-deoxyribose-5-phosphate, 4 is also formed. Upon addition of H2O2 (up to 10-2 M) prior to irradiation, G(1) is drastically reduced without giving rise to another cytosine-free product. G(3) increases at the expense of G(2). G (4 + 5) also increase upon H2O2 addition. The formation of these products and the change of their G values as a function of H2O2 concentration are discussed in the light of well-documented radical reactions of carbohydrates and related compounds. The precursor of 1 has been considered to be the radical at C-3′, that of 2 and 3 the radical at C-4′ and that of 5 the radical at C-1′. Product 4 is thought to arise from a radical-induced destruction of the cytosine moiety. These primary radicals which may undergo rearrangement, or eliminate phosphate, are readily oxidised by H2O2, a reaction which leads to the change of product distribution mentioned above.