Midorikawa K, Kawanishi S
Department of Hygiene, Mie University School of Medicine, 514-8507, Mie, Japan.
FEBS Lett. 2001 Apr 27;495(3):187-90. doi: 10.1016/s0014-5793(01)02383-3.
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.
超氧化物歧化酶（SOD）参与保护细胞免受氧毒性影响。然而，有几篇论文报道，铜锌超氧化物歧化酶（CuZn-SOD）的过度表达会对细胞造成氧化损伤。我们研究了超氧化物歧化酶过量加速氧化应激的机制。铜锌超氧化物歧化酶、锰超氧化物歧化酶（Mn-SOD）或锰（II）的存在会增加过氧化氢（H2O2）和铜（II）诱导的DNA损伤频率，并改变后者的位点特异性：H2O2在聚G序列的5'-鸟嘌呤处高频诱导铜（II）依赖性DNA损伤；添加超氧化物歧化酶后，胸腺嘧啶和胞嘧啶残基处的切割频率增加。超氧化物歧化酶还会增强H2O2和铜（II）诱导的8-氧代-7,8-二氢-2'-脱氧鸟苷的形成。我们得出结论，超氧化物歧化酶可能会增加致癌风险，例如唐氏综合征患者患肿瘤的风险。
