INVESTIGADORES
CABRERIZO Franco Martin
congresos y reuniones científicas
Título:
Oxidation of 2'-deoxyguanosine-5'-monophosphate photoinduced by pterin: Type I versus type II mechanism
Autor/es:
GABRIELA PETROSELLI; FRANCO M. CABRERIZO; ALBERTO L. CAPPARELLI; CAROLINA LORENTE; ESTHER OLIVEROS; ANDRÉS H. THOMAS
Lugar:
Los Cocos, Córdoba, Argentina
Reunión:
Congreso; 9th Latin American Conference on Physical Organic Chemistry; 2007
Resumen:
Solar radiation is a genotoxic agent that induces modifications to genomic DNA and is implicated in the induction of human skin cancers. UV-B radiation (280-320 nm) damages DNA through the direct excitation of the nucleobases. On the other hand, the main processes responsible for the DNA damage induced by UV-A radiation (320-400 nm) are photosensitized oxidations.This indirect action,  mediated by a photosensitizer (endogenous or exogenous) which is excited by UV-A radiation, involve an electron abstraction (type I) and/or the production of singlet molecular oxygen (O2(1Dg), denoted throughout as 1O2) (type II). The nucleobases are the preferential DNA substrates of type I oxidation. Among the DNA bases, guanine that exhibits the lowest ionization potential is the preferential target for one-electron oxidation reactions over adenine and pyrimidine bases. On the other hand, guanine is the only DNA constituent that significantly reacts with 1O2 (1). Pterins are a family of heterocyclic compounds present in human cells, and in some diseases, like vitiligo, they are accumulated in zones of the skin devoid of melanin and, therefore, with a deficiency of protection against UV radiation. Electronically excited states of pterins can be generated by radiation in the UV-A and visible spectral domain and are able to produce reactive oxygen species, such as singlet oxygen (1O2) that can oxidize DNA and other biomolecules (2). In this work we describe the photosensitization of 2'-deoxyguanosine-5'-monophosphate (dGMP) by PT in aqueous solution under UV-A radiation. Kinetic analysis was employed to evaluate the participation of both types of mechanism under different pH conditions. Steady-state methods were performed to determine the rate constant of 1O2 total quenching (kt) by dGMP, as well as the rate constant of the chemical reaction between 1O2 and dGMP (kr). We found that the reactivity of dGMP towards 1O2 is much higher in alkaline media (kr = (9.6 ± 0.8) x107 M-1s-1 at pH= 10.5 and (1.7 ± 0.3) x 107 M-1s-1 at pH=5.5). Participation of singlet and triplet excited states of pterin are discussed.   1) J. Cadet, M. Berger, T. Douki, B. Morin, S. Raoul, J. -L. Ravanat, S. Spinelli, Effects of UV and visible radiation on DNA – final base damage, Biol. Chem. (1997) 378, 1275-1286. 2) Lorente, C.; Thomas, A. H. Photophysics and photochemistry of pterins in aqueous solution, Acc. Chem. Res., (2006) 39, 395-402.