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Oxidative DNA damages involve reduction- oxidation reactions between certain metals and com- pounds, and result in genetic abnormalities lead- ing to diseases including cancer and neurodegener- ative disorders. Here, we report that DNA dam- ages mediated by combination of a neurotransmitter dopamine and copper accompany a unique DNA con- formational change. Copper(II) (Cu(II)) was shown as bound to consecutive guanines (G-G) of DNA, by demonstrating the G-G selective inhibition of restric- tion enzymes. When dopamine was added to calf thymus DNA in the presence of Cu(II), DNA gua- nines were oxidized. UV and 1 HN MR analyses sug- gested that dopamine was oxidized to the quinone form in the presenc eo f Cu(II). The circular dichro- ism experiments showed DNA spectral changes un- der the conditions of oxidative DNA damage, indi- cating a conformational change of the DNA strand by dopamine and copper. The DNA conformational change was suppressed by adding a Cu(I)-specific chelator bathocuproine. Therefore, the conforma- tional change can be explained by a rearrangement of the copper-coordination geometry in DNA through Cu(II) reduction to Cu(I). Thus, changes in DNA con- formation could be involved in metal-mediated geno- toxicity as well as oxidative damage but via different mechanism.

journal of health science

Involvement of DNA Conformational Change Induced by Rearrangement of Copper-coordination Geometry in Oxidative DNA Damages Caused by Copper and Dopamine