Superoxide dismutases enhance H2O2-induced DNA damage and alter its site specificity

Superoxide dismutases (SODs) are involved in the protection of cells from o xygen toxicity. However, several papers have reported that the overexpressi on of CuZn-SOD causes oxidative damage to cells. We investigated a mechanis m by which an excess of SODs accelerates oxidative stress. The presence of CuZn-SOD, Mn-SOD or Mn(II) enhanced the frequency of DNA damage induced by hydrogen peroxide (H2O2) and Cu(II), and altered the site specificity of th e latter: H2O2 induced Cu(II)-dependent DNA damage with high frequency at t he 5'-guanine of poly G sequences; when SODs were added, the frequency of c leavages at thymine and cytosine residues increased. SODs also enhanced the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine by H2O2 and Cu(II). We co nclude that SODs may increase carcinogenic risks, e.g. of tumors in Down sy ndrome. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.