title: Superoxide dismutases enhance H2O2-induced DNA damage and alter its site specificity.
abstract: Superoxide dismutases (SODs) are involved in the protection of cells from oxygen toxicity. However, several papers have reported that the overexpression of CuZn-SOD causes oxidative damage to cells. We investigated a mechanism 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 the latter: H2O2 induced Cu(II)-dependent DNA damage with high frequency at the 5'-guanine of poly G sequences; when SODs were added, the frequency of cleavages 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 conclude that SODs may increase carcinogenic risks, e.g. of tumors in Down syndrome.
authors.affiliation: Department of Hygiene, Mie University School of Medicine, 514-8507, Mie, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Midorikawa
authors.forename: S
authors.initials: S
authors.lastname: Kawanishi
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D002417:Cattle; D003300:Copper / Q000737:chemistry; D004249:DNA Damage / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D004357:Drug Synergism; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008345:Manganese / Q000737:chemistry; D013379:Substrate Specificity; D013482:Superoxide Dismutase / Q000494:pharmacology*; D015032:Zinc / Q000737:chemistry
chemical_list: D008345:Manganese; D003300:Copper; D000080242:8-Hydroxy-2'-Deoxyguanosine; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D003849:Deoxyguanosine; D015032:Zinc