title: Long-range and short-range oxidative damage to DNA: photoinduced damage to guanines in ethidium-DNA assemblies.
abstract: Short-range and long-range photoreactions between ethidium and DNA have been characterized. While no DNA reaction is observed upon excitation into the visible absorption band of ethidium, higher-energy irradiation (313-340 nm) leads both to direct strand cleavage at the 5'-G of 5'-GG-3' doublets and to piperidine-sensitive lesions at guanine. This reactivity is not consistent with oxidation of guanine by either electron transfer or singlet oxygen as shown by comparison with reactions of a rhodium intercalator and methylene blue, respectively. By covalently tethering ethidium to one end of a DNA duplex, we demonstrate the presence of two distinct reactions, one short-range and the other long-range. The short-range reaction involves a covalent modification of guanine by ethidium, based upon HPLC analysis of the nucleoside products and studies with ethidium derivatives. The long-range reaction is entirely consistent with oxidation of guanine by DNA-mediated electron transfer. The yield of this electron-transfer reaction is not attenuated with distance; equal yields of guanine damage are observed at a proximal (17 A Et-GG separation) and distal (44 A Et-GG separation) site. These results are quite similar to those previously observed with a covalently tethered rhodium photooxidant and underscore the unique ability of the DNA base stack to facilitate long-range electron transfer so as to effect oxidative damage from a distance.
authors.affiliation: Department of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena 91125, USA.
authors.forename: D B
authors.initials: DB
authors.lastname: Hall
authors.forename: S O
authors.initials: SO
authors.lastname: Kelley
authors.forename: J K
authors.initials: JK
authors.lastname: Barton
mesh_terms: D000478:Alkylation; D002851:Chromatography, High Pressure Liquid; D018736:DNA Adducts / Q000378:metabolism* / Q000528:radiation effects; D004249:DNA Damage / Q000187:drug effects / Q000528:radiation effects*; D004579:Electron Transport / Q000187:drug effects / Q000528:radiation effects; D004996:Ethidium / Q000378:metabolism* / Q000494:pharmacology / Q000528:radiation effects; D006147:Guanine / Q000378:metabolism / Q000528:radiation effects*; D007364:Intercalating Agents / Q000494:pharmacology; D009841:Oligonucleotides / Q000378:metabolism / Q000528:radiation effects; D016877:Oxidants / Q000494:pharmacology*; D010100:Oxygen / Q000494:pharmacology; D010777:Photochemistry; D012997:Solvents
chemical_list: D018736:DNA Adducts; D007364:Intercalating Agents; D009841:Oligonucleotides; D016877:Oxidants; D012997:Solvents; D006147:Guanine; D004996:Ethidium; D010100:Oxygen