DNA damage in Down syndrome: Contribution of reactive oxygen species

Data from various studies indicate that a delicate antioxidant enzyme balan ce exists in cells. The fine-toning of antioxidant enzymes becomes imperati ve if the cell is to function successfully in an oxygen-rich environment. T he human condition known as Down syndrome (DS) or trisomy 21 has provided s ome provocative clues regarding the balance between oxidants and antioxidan ts. DS is one situation where the antioxidant balance is affected due to ge ne dosage. The human cytosolic Cu/Zn-superoxide dismutase (SOD) gene is loc ated on chromosome 21 and cells from subjects with DS contain 50% more than the normal amount of the antioxidant enzyme. A surprising variety of probl ems are caused by over-expression of the "housekeeping" enzyme SOD. Alterat ions in oxygen handling have been observed in DS.A causative role for react ive oxygen species (ROS) in the symptoms of DS has been hypothesised and a large body of supportive circumstantial evidence has been accumulated. In t his study DNA damage was evaluated in DS using the comet assay. Our data de monstrate an increase in oxidative damage to DNA after an oxidative stress induced by superoxide anion and an increase in basal oxidised sites of DNA in DS. These data support the notion that ROS are involved in the developme nt of some features of DS.