Photosensitization of DNA by b-carbolines: Kinetic analysis and photoproduct characterization

M. MICAELA GONZALEZ; MARIANA VIGNONI; MAGALI PELLON-MAISON,; MATIAS A. ALES-GANDOLFO; MARIA R. GONZALEZ-BARO; ROSA ERRA-BALSELLS; BERND EPE; FRANCO M. CABRERIZO

ORGANIC & BIOMOLECULAR CHEMISTRY

ROYAL SOC CHEMISTRY

Lugar: CAMBRIDGE; Año: 2012 vol. 10 p. 1807 - 1819

1477-0520

b-Carbolines (bCs) 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 wellestablished 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 bCs(norharmane, harmane and harmine) and two of its derivatives (N-methyl-norharmane and N-methylharmane) 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 bCs after nonintercalative 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 D2O 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 bCs, while only photoexcited harmine gives rise to the formation of cyclobutane pyrimidine dimers as well.