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

FEDERICO RASSE SURIANI; MARCO SEIFERMANN; J. GABRIEL YAÑUK; FRANCISCO SIMÓN; VALERIA ALVAREZ; M. LIS ALOMAR; M. PAULA DENOFRIO; ROSA ERRA-BALSELLS; BERND EPE; FRANCO M. CABRERIZO

Congreso; 16th International Congress on Photobiology; 2014

The photosensitizing properties of b-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), 8-oxo-7,8-dihydroguanine (8-oxoGua) and pyrimidine dimers formation (CPDs) [1,2]. 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 [3]. 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 [4]. 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. Our results show that 6-chloro-harmine photoinduce a quite disctintive damage profile in comparison with other bCs investigated: i.e., SSB are the main DNA photoproducts when 6-chloro-harmine is used, whereas oxidative purine modifications, such as 8-oxoGua, FapyGua and FapyAde, and also AP sites, are the most frequent products generated when other bCs are used as photosensitizers. Scheme 1: Chemical structure of harmine (R = H) and 6-chloro-harmine (R = Cl).