Cell-free DNA damage photoinduced by harmine and 6-chloro-harmine

FEDERICO A. O. RASSE-SURIANI; MARCO SEIFERMANN; JUAN G. YAÑUK; FRANCISCO SIMON; VALERIA E. ALVAREZ; ALOMAR, M.LIS; M.PAULA DENOFRIO; ROSA ERRA-BALSELLS; BERND EPE; FRANCO M CABRERIZO

Cordoba

Congreso; 16 th International Congress on photobiology; 2014

International Union of Photobiology

Introduction The photosensitizing properties of beta carboline (bC) alkaloids and some related derivatives have been recently well studied and documented. On cell-free DNA, photoexcited bCs induce single strand-breaks (SSB), 8oxo7,8dihydroguanine (8-oxoGua), formamidopyrimidines (FapyAde and FapyGua, ring-opened purines), apurinic/apyrimidinic sites (AP sites), and also pyrimidine dimers formation (CPDs). The extent and type of photosensitized damage depends not only on the nature of the bC substituent but also on their DNA binding affinity to DNA. In a recent study, we have also demonstrated that the DNA damage profile generated in mammalian cells shows major differences compared with that observed in cell-free DNA. In the present work, we examine the capability of harmine and 6-chloro-harmine (Scheme 1) to photoinduce damage in cell-free DNA. The type (damage spectrum) and extent of the damage is analyzed together with photochemical, photophysical and binding properties of the investigated compounds.