title: Supramolecular cationic tetraruthenated porphyrin induces single-strand breaks and 8-oxo-7,8-dihydro-2'-deoxyguanosine formation in DNA in the presence of light.
abstract: The aim of this investigation is the evaluation of DNA interaction of with tetraruthenated porphyrin (TRP) and of DNA damage in the presence of light. Direct-fluorescence and electronic absorption measurements after incubation of DNA with TRP indicate strong binding between pBR322 DNA or calf thymus DNA with the modified porphyrin. Exposure of pBR322 DNA to TRP (up to 3 microM) and light leads to single-strand break formation as determined by the conversion of the supercoiled form (form I) of the plasmid into the nicked circular form (form II). Oxidative DNA base damage was evaluated by the detection of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) after irradiation of calf thymus DNA in the presence of the TRP. The data demonstrated a dose and time dependence with each type of DNA damage. These data indicate (1) a specificity of the binding mode and (2) type I and II photoinduced mechanisms leading to strand scission activity and 8-oxodGuo formation. Accordingly, singlet molecular oxygen formation, after TRP excitation, was confirmed by near-infrared emission. From these investigations a potential application of TRP in photodynamic therapy is proposed.
authors.affiliation: Departamento de Bioquímica, Universidade de São Paulo, Brazil.
authors.forename: J
authors.initials: J
authors.lastname: Onuki
authors.forename: A V
authors.initials: AV
authors.lastname: Ribas
authors.forename: M H
authors.initials: MH
authors.lastname: Medeiros
authors.forename: K
authors.initials: K
authors.lastname: Araki
authors.forename: H E
authors.initials: HE
authors.lastname: Toma
authors.forename: L H
authors.initials: LH
authors.lastname: Catalani
authors.forename: P
authors.initials: P
authors.lastname: Di Mascio
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D002412:Cations; D002417:Cattle; D004247:DNA / Q000187:drug effects* / Q000378:metabolism* / Q000528:radiation effects; D004249:DNA Damage; D004277:DNA, Single-Stranded / Q000187:drug effects / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D008027:Light; D009942:Organometallic Compounds / Q000494:pharmacology*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011166:Porphyrins / Q000494:pharmacology*
chemical_list: D002412:Cations; D004277:DNA, Single-Stranded; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D011166:Porphyrins; C099070:tetraruthenated porphyrin; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D003849:Deoxyguanosine