Figure 7.

Proposed role of ROS in dopamine-mediated oxidatively generated DNA damage and subsequent neuronal cell death. The auto-oxidation of catecholamine neurotransmitters, such as dopamine, and related catecholamines, is substantially enhanced by the presence of transitions metals, especially copper, in their oxidized form. In the presence of O₂, these catechols can redox cycle producing quinone metabolites, which can bind directly to DNA forming covalent DNA adducts, via semi-quinone intermediates while simultaneously reducing the metal. Superoxide is then generated by the reduction of molecular oxygen followed by the re-generation of the metal to its oxidized state. Superoxide can also react with Cu(I) to produce H₂O₂ which then can complex with either Cu(I) or Cu(II) bound to DNA to form DNA-Cu(I)OOH. Following the formation of this DNA-Cu(I)OOH a variety of oxidative DNA lesions, including the unidentified oxidation DNA products studied here, result due to the production of hydroxyl radicals at site-specific regions of the DNA. Singlet oxygen may also be produced from this complex yielding 8-oxodG.