Mechanism of DNA damage photosensitized by trisbipyrazyl ruthenium complex. Unusual role of Cu/Zn superoxide dismutase.
Trisbipyrazyl ruthenium(II) (Ru[bpz]3(2+)) was examined as DNA photosensitizer. Damage resulting from the photolysis of synthetic oligonucleotides has been monitored by polyacrylamide gel electrophoresis. Photoadduct formation is found on both single- and double-stranded oligonucleotides. On oligonucleotide duplex, oxidative damage occurs selectively at the 5'G of the 5'GG3' site and to a lesser extent at the 5'G of a GA sequence. These findings suggest the involvement of electron transfer and show that this mechanism is the main DNA damaging process involved in Ru(bpz)3(2+) photosensitization. In addition, photoadducts and oxidative damage are both highly affected by an increase of salt concentration in the reaction medium, stressing the importance of direct interactions between nucleic acid bases and the excited ruthenium complex for efficient electron transfer. On single-stranded oligonucleotides, all the guanines are oxidized to the same extent. In this case, oxidative damage, which is not affected by an increase of salt in the solution, has been attributed, in part, to singlet oxygen. More importantly, Cu/Zn superoxide dismutase (SOD) strongly enhances the yield of all damage, correlated to an increase of both electron transfer and singlet oxygen production. This original activity of SOD is the first example of bioactivation of a polyazaaromatic ruthenium complex.
Gicquel
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Laboratoire des Interactions Moléculaires, Reactivité Chimique et Photochimique, Université Paul Sabatier, Toulouse, France.
Paillous
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Vicendo
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P
D001483:Base Sequence; D004249:DNA Damage; D066298:In Vitro Techniques; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000528:radiation effects; D009942:Organometallic Compounds / Q000633:toxicity*; D010084:Oxidation-Reduction; D010782:Photolysis; D017319:Photosensitizing Agents / Q000633:toxicity*; D013482:Superoxide Dismutase / Q000378:metabolism*
D009838:Oligodeoxyribonucleotides; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; C419922:trisbipyrazyl ruthenium complex; D013482:Superoxide Dismutase