Photosensitization of DNA by b-carbolines: kinetic analysis and photoproducts characterization

M. MICAELA GONZALEZ, MARIANA VIGNONI, MATÍAS ALÉS-GANDOLFO, MAGALI PELLÓN-MAISÓN, M. GONZALEZ-BARÓ, ROSA ERRA-BALSELLS, BERND EPE, FRANCO M. CABRERIZO

ORGANIC & BIOMOLECULAR CHEMISTRY

ROYAL SOC CHEMISTRY

Año: 2012

1477-0520

b-Carbolines (bCs) are a group of alkaloids present in many plants and animals. It has beensuggested that these alkaloids participate in a variety of significant photosensitized processes. Despite their well-established importance, 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-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 the DNA damage is mostly mediated by a direct type-I photoreaction of the protonated βCs after nonintercalative,non-covalent binding. Reactive oxygen species such as singlet oxygen and superoxide arenot involved to a major extent, as indicated by the only small influence of D2O and of superoxidedismutase on damage generation. An analysis with repair enzymes revealed that oxidative purinemodifications 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.