title: Base-selective oxidation and cleavage of DNA by photochemical cosensitized electron transfer.
abstract: A photochemical mechanism for single-strand cleavage of DNA is proposed in which a photoexcited intercalator transfers an electron to an externally bound cosensitizer. Once formed, the oxidized intercalator oxidizes an adjacent base, creating a charge-separated complex from which reactions leading to cleavage of the sugar-phosphate backbone occur in competition with back electron transfer. Using ethidium bromide (EB) as the intercalator and methyl viologen (MV) as the externally bound cosensitizer, a 10-fold enhancement in the rate of single-strand break formation was found in pBR322 DNA over that for EB alone using 488-nm excitation. The rate of cleavage correlated with the amount of MV bound to DNA. In accord with the expected redox properties of the one-electron-oxidized EB and the DNA bases, cleavage occurs selectively at guanines. Although the reaction proceeds in nitrogen-purged solutions, the rate of cleavage in air-saturated solutions was enhanced 2-fold. Treatment of irradiated samples with alkali leads to a 2-fold increase in the yield of single-strand breaks. These results support a mechanism in which cleavage occurs by selective oxidation of guanines in DNA, initiated by photochemical cosensitized electron transfer from intercalated EB to externally bound MV, and may provide a basis for the development of light-activated base-selective DNA cleaving agents.
authors.affiliation: Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston 02114.
authors.forename: D A
authors.initials: DA
authors.lastname: Dunn
authors.forename: V H
authors.initials: VH
authors.lastname: Lin
authors.forename: I E
authors.initials: IE
authors.lastname: Kochevar
mesh_terms: D004247:DNA / Q000187:drug effects*; D004579:Electron Transport; D004591:Electrophoresis, Polyacrylamide Gel; D004996:Ethidium / Q000737:chemistry; D007364:Intercalating Agents / Q000737:chemistry; D010084:Oxidation-Reduction; D010269:Paraquat / Q000737:chemistry; D010777:Photochemistry
chemical_list: D007364:Intercalating Agents; D004247:DNA; D004996:Ethidium; D010269:Paraquat