Photosensitization of DNA by b-carbolines: Kinetic analysis and

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 thatthese alkaloids participate in a variety of significant photosensitized processes. Despite their wellestablishednatural occurrence, the main biological role of these alkaloids and the mechanisms involvedare, 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 damagewith the photophysical characteristics and DNA binding properties of the compounds. The results indicatethat DNA damage is mostly mediated by a direct type-I photoreaction of the protonated âCs after nonintercalativeelectrostatic binding. Reactive oxygen species such as singlet oxygen and superoxide are notinvolved to a major extent, as indicated by the only small influence of D2O and of superoxide dismutaseon damage generation. An analysis with repair enzymes revealed that oxidative purine modifications suchas 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.