INVESTIGADORES
CABRERIZO Franco Martin
congresos y reuniones científicas
Título:
Cell-free DNA damage photoinduced by harmine and 6-chloro-harmine
Autor/es:
FEDERICO A. O. RASSE-SURIANI; MARCO SEIFERMANN; JUAN G. YAÑUK; FRANCISCO SIMON; VALERIA E. ALVAREZ; M. PAULA DENOFRIO; M. MICAELA GONZALEZ; ROSA ERRA-BALSELLS; BERND EPE; FRANCO M. CABRERIZO
Lugar:
Córdoba
Reunión:
Congreso; 16th International Congress of Photobiology; 2014
Resumen:
The photosensitizing properties of β-carboline (βC) alkaloids and some related derivatives have been recently well studied and documented. On cell-free DNA, photoexcited βCs induce single strand-breaks (SSB), 8-oxo-7,8-dihydroguanine and pyrimidine dimers formation (CPDs) [1,2]. The extent and type of photosensitized damage depends not only on the nature of the βC 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 βCs 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 βCs are used as photosensitizers. [1] M.M. Gonzalez, F.A.O. Rasse-Suriani, C.A. Franca, R. Pis Diez, Y. Gholipour, H. Nonami, R. Erra-Balsells, F.M. Cabrerizo, Org. Biomol. Chem., 2012, 10, 9359. [2] M.M. Gonzalez, M. Vignoni, M. Pellon-Maison, M.A. Ales-Gandolfo, M.R. Gonzalez-Baro, R. Erra-Balsells, B. Epe, F.M. Cabrerizo, Org. Biomol. Chem., 2012, 10, 1807. [3] M. Vignoni, F.A.O. Rasse-Suriani, K. Butzbach, R. Erra-Balsells, B. Epe, F.M. Cabrerizo, Org. Biomol. Chem., 2013, 11, 5300. [4] M. Vignoni, R. Erra-Balsells, B. Epe, F.M. Cabrerizo, J. Photochem. Photobiol. B Biol., 2014, 132, 66.