title: Photosensitization of DNA by β-carbolines: kinetic analysis and photoproduct characterization.
abstract: β-Carbolines (βCs) are a group of alkaloids present in many plants and animals. It has been suggested that these alkaloids participate in a variety of significant photosensitized processes. Despite their well-established natural occurrence, the main biological role of these alkaloids and the mechanisms involved are, to date, poorly understood. In the present work, we examined the capability of three important βCs (norharmane, harmane and harmine) and two of its derivatives (N-methyl-norharmane and N-methyl-harmane) to induce DNA damage upon UV-A excitation, correlating the type and extent of the damage with the photophysical characteristics and DNA binding properties of the compounds. The results indicate that DNA damage is mostly mediated by a direct type-I photoreaction of the protonated βCs after non-intercalative electrostatic binding. Reactive oxygen species such as singlet oxygen and superoxide are not involved to a major extent, as indicated by the only small influence of D(2)O and of superoxide dismutase on damage generation. An analysis with repair enzymes revealed that oxidative purine modifications such as 8-oxo-7,8-dihydroguanine, sites of base loss and single-strand breaks (SSB) are generated by all βCs, while only photoexcited harmine gives rise to the formation of cyclobutane pyrimidine dimers as well.
authors.affiliation: CIHIDECAR-CONICET, Universidad de Buenos Aires, Pabellón 2, 3p, Ciudad Universitaria, Buenos Aires, Argentina.
authors.forename: M Micaela
authors.initials: MM
authors.lastname: Gonzalez
authors.forename: Mariana
authors.initials: M
authors.lastname: Vignoni
authors.forename: Magali
authors.initials: M
authors.lastname: Pellon-Maison
authors.forename: Matias A
authors.initials: MA
authors.lastname: Ales-Gandolfo
authors.forename: Maria R
authors.initials: MR
authors.lastname: Gonzalez-Baro
authors.forename: Rosa
authors.initials: R
authors.lastname: Erra-Balsells
authors.forename: Bernd
authors.initials: B
authors.lastname: Epe
authors.forename: Franco M
authors.initials: FM
authors.lastname: Cabrerizo
mesh_terms: D002243:Carbolines / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D007700:Kinetics; D015394:Molecular Structure; D055668:Photochemical Processes; D017319:Photosensitizing Agents / Q000737:chemistry*; D017382:Reactive Oxygen Species; D013936:Thymidine / Q000737:chemistry
chemical_list: D002243:Carbolines; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; D004247:DNA; D013936:Thymidine