Induction of Strand Breaks in Polyribonucleotides and DNA by the Sulphate Radical Anion: Role of Electron Loss Centres as Precursors of Strand Breakage

Abstract

The interaction of the sulphate radical anion, SO^·−₄, with the polyribonucleotides, poly U and poly C, in deaerated, aqueous solutions at pH 7·5 results in strand breakage (sb) with efficiencies of 57 and 23%, respectively, determined by time resolved laser light scattering (TRLS). Most sb are produced within 70 µs, the risetime of the detection system. Oxygen inhibits the induction of sb in poly U and poly C by SO^·−₄ through its interaction with a radical precursor to sb. In contrast, the interaction of SO^·−₄ with poly A and single stranded DNA does not lead to significant strand breakage (≤ 5% efficiency). From optical studies, the interaction of poly A and poly G with SO^·−₄ radicals yields predominantly the corresponding one electron oxidized base radicals. With poly C and poly U, it is proposed that the SO^·−₄ radical interacts predominantly by addition to the base moiety to produce the C(5)-yl and C(6)-yl sulphate radical adducts which react with oxygen. These base adducts subsequently interact with the sugar-phosphate moiety by H-atom abstraction to yield C(2)′ sugar radicals with rate constants in the range 1·3–1·7 × 10⁵ s⁻¹. It is proposed that the C(2)′ sugar radical leads to strand breakage within 70 µs, in competition with its transformation into the C(1)′-sugar radical involving base release. From optical studies on the interaction of SO^·−₄ with double stranded DNA, it is suggested that the predominant radical species produced in DNA is the one-electron oxidized radical of guanine, consistent with positive charge migration in DNA. Since the efficiency of SO^·−₄ to induce sb in single stranded DNA is low, it is concluded that the one-electron oxidized guanine radical does not effectively induce strand breakage in DNA.