DNA photosensitization by pterin

SANDRA ESTÉBANEZ; VIRGINIE LHIAUBET; MIGUEL A. MIRANDA; CAROLINA LORENTE; ANDRÉS H. THOMAS

Santiago de Chile

Congreso; 25st Inter American Photochemical Society Conference (25st I-APS conference); 2016

Inter American Photochemical Society

Most of thesolar radiation incident on the surface of Earth corresponds to UV-A radiation(320 ? 400 nm), which is not absorbed significantly by DNA, therefore does notaffect directly the biomacromolecules. Nevertheless, UV-A radiation actsindirectly by photosensitized reactions and is recognize as a class Icarcinogen [1]. A photosensitized reaction is a photochemical modificationoccurring in a molecular entity as a result of the initial absorption of radiationby a photosensitizer [2]. Pterins belong to a family of heterocyclic compoundspresent in a wide range of living systems and participate in relevantbiological functions. Under UV-A excitation (320 - 400 nm), pterins canfluoresce, undergo photooxidation and generate reactive oxygen species (ROS) [3].In the presence of oxygen, pterin (Ptr) act as photosensitizer through type I(electron abstraction) and/or type II (1O2-mediatedoxidation) mechanisms [4-5].Thephotosensitized degradation of pyrimidine nucleotide of 2´-deoxythymidine (dT)by Ptr were studied in acidic aqueous solutions upon UV-A irradiation (350 nm)at room temperature, under different experimental conditions. The photochemicalreactions were followed by UV-Vis spectrophotometry and HPLC. Under anaerobicconditions, the formation of an adduct between the substrate and the sensitizerwas observed. This adduct was isolated, and the emission spectrum and thelifetime were recorded. The fluorescence properties of the adduct are similar tothose of Ptr itself.On the otherhand, the degradation of DNA of Calf Thymus by Ptr was studied in neutralaqueous solutions upon UV-A irradiation (350 nm) at room temperature, underdifferent experimental conditions. The photochemical reactions were followed byUV-Vis and fluorescence spectrophotometry. An increase of fluorescence emissionwith the irradiation time under anaerobic conditions was observed. Thisemission remains even when samples were denatured. A covalent bond between Ptrand DNA occurs, most probably in the thymidine moiety. [1] F. El Ghissassi, R. Baan and K. Straif, Lancet Oncol., 2009, 10, 51?52. [2] Braslavsky, S. E.; Pure App. Chem. 2007, 79,293.[3] Lorente, C.; et. al.; Acc. Chem. Res. 2006, 39, 395.[4] Petroselli, G.; et. al.; J. Am. Chem. Soc.2008, 130, 3001.[5] Petroselli, G.; et. al.; Org. Biomol. Chem. 2007, 5, 2792.