Tetrahydrobiopterin (BH
4) prevented an increase in the formation of 8-hydroxydeoxyguanosine (8-OHdG) in calf thymus DNA by the peroxynitrite (ONOO
-) or Fe
2+ + hydrogen peroxide (H
2O
2) system. But, the addition of BH
4 to the Cu
2+ + ascorbic acid (AsA) system caused a very large increase in base damage. Without the addition of AsA (in the presence of Cu
2+ alone), BH
4 could also induce 8-OHdG formation. Experiments utilizing the Cu
+ chelator bathocuproine, catalase and superoxide dismutase revealed that Cu
+ and H
2O
2 intermediates relate to Cu
2+ + BH
4-induced 8-OHdG formation. Electron spin resonance experiments also showed that the hydroxyl radical is not a major intermediate. These results suggest that although BH
4 is known to prevent oxidative damage in proteins and lipids, it has the potential to cause oxidative DNA damage depending on the existence of copper ions.
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