The photosensitizing activity of lumazine using 2´-deoxyguanosine 5´-monophosphate and HeLa cells as targets

M. PAULA DENOFRIO; SONJA HATZ; CAROLINA LORENTE; FRANCO M. CABRERIZO; PETER R. OGILBY; ANDRÉS H. THOMAS

Photochemical and Photobiological Sciences

RSC

Año: 2009 vol. 8 p. 1539 - 1549

1474-905X

Lumazines are a family of heterocyclic compounds present in biological systems as biosynthetic precursors or products of the metabolic degradation of pterins. Upon UV irradiation, the specific compound called lumazine (pteridine-2,4(1,3H)-dione, Lum) is able to generate singlet oxygen (1O2), which is one of the main chemical species responsible for photodynamic effects. In order to assess the photosensitizing capability of Lum, we performed experiments using the nucleotide 2?-deoxyguanosine 5?-monophosphate (dGMP) and cervical cancer cells (HeLa cell line) as targets. Analysis of irradiated solutions by UV/VIS spectrophotometry, HPLC and electrochemical measurement of dissolved O2 revealed that dGMP undergoes oxidation photoinduced by Lum. In this process, Lum is not consumed. Studies performed with cells included fluorescence analysis of cell extracts and phototoxicity experiments (Rhodamine 123 and Trypan Blue assays). Results showed that, upon Lum uptake and irradiation, photodynamic effects occur. In particular, the mitochondria and cell membrane were perturbed, both of which reflect key stages in cell death.