title: Type II guanine oxidation photoinduced by the antibacterial fluoroquinolone Rufloxacin in isolated DNA and in 2'-deoxyguanosine.
abstract: The role played by type I (radical) and type II (singlet oxygen) mechanisms in the Rufloxacin (RFX)-photoinduced production of 8-hydroxy-2'-deoxyguanosine in DNA has been evaluated. This fluoroquinolone drug has been shown to be able to photoinduce increased levels of some DNA base oxidation products, such as 8-OH-dGuo, that are indicative of mutagenic and carcinogenic events, with probable implications in aging processes. The relative weight of the two photosensitization mechanisms was obtained via determination of two different photoproducts of 2'-deoxyguanosine (dGuo), which are diagnostic of the two different pathways, namely, (4R)- and (4S)-4,8-dihydro-4-hydroxy-8-oxo-2'-deoxyguanosine and 2,2-diamino-4-[(2-deoxy-beta-D-erythro-pentofuranosyl)amino]-2,5-dihydrooxazol-5-one. The observed predominance of type II reaction is in agreement with the fact that the triplet state of RFX is able to transfer with high efficiency its energy to molecular oxygen, giving rise to singlet oxygen. Photophysical measurements suggest that hydrated electrons produced by Rufloxacin photoionization react with dGuo, Thd, and DNA, whereas these biomolecules quench the RFX triplet state with low efficiency. Static quenching of Rufloxacin fluorescence indicates an interaction of this drug both with DNA and with dGuo. On the basis of these experimental data, Rufloxacin photosensitization of DNA is proposed to occur by a type II mechanism.
authors.affiliation: Dipartimento di Scienze Chimiche, Università di Catania, Viale A. Doria 6, I-95125 Catania, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Belvedere
authors.forename: Francisco
authors.initials: F
authors.lastname: Boscá
authors.forename: Alfio
authors.initials: A
authors.lastname: Catalfo
authors.forename: Maria C
authors.initials: MC
authors.lastname: Cuquerella
authors.forename: Guido
authors.initials: G
authors.lastname: de Guidi
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Miranda
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000737:chemistry*; D003849:Deoxyguanosine / Q000737:chemistry*; D024841:Fluoroquinolones; D006147:Guanine / Q000737:chemistry* / Q000528:radiation effects; D007700:Kinetics; D007834:Lasers; D008163:Luminescent Measurements; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry*; D010777:Photochemistry; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000494:pharmacology; D015363:Quinolones / Q000737:chemistry* / Q000494:pharmacology; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D017319:Photosensitizing Agents; D015363:Quinolones; D006147:Guanine; D004247:DNA; D003849:Deoxyguanosine; D010100:Oxygen; C060328:rufloxacin