Decomposition of nucleoside hydroperoxide by metals and metalloproteins

5-Hydroperoxymethyl-2'-deoxyuridine (HPMdU) is formed in DNA by ionizing radiation. Although relatively stable, HPMdU eventually decomposes to two products 5-hydroxymethyl-2'-deoxyuridine (HMdU) and 5-formyl-2'-deoxyuridine (FdU). We show that a number of transition metal ions and metalloproteins accelerate this process. Of the metal ions tested, Sn(II) and Fe(II) were the most active, with the former producing exclusively HMdU, and the latter, a mixture of both. Cu(I), Cu(II), Co(II), and Ni(II) induced a predominant generation of FdU, with copper ions being more effective than Co and Ni. FdU was also preferentially formed in the presence of the iron-containing proteins transferrin and ferritin, whereas HMdU was the major product in the presence of apotransferrin as well as in the presence of ceruloplasmin, a copper-containing protein.