Artículos de revistas
Novel properties of melanins include promotion of DNA strand breaks, impairment of repair, and reduced ability to damage DNA after quenching of singlet oxygen
Fecha
2012Registro en:
FREE RADICAL BIOLOGY AND MEDICINE, NEW YORK, v. 52, n. 9, pp. 1945-1953, MAY 1, 2012
0891-5849
10.1016/j.freeradbiomed.2012.02.039
Autor
Suzukawa, Andreia Akemi
Vieira, Alessandra
Winnischofer, Sheila Maria Brochado
Scalfo, Alexsandra Cristina
Di Mascio, Paolo
Ferreira, Ana Maria da Costa
Ravanat, Jean-Luc
Martins, Daniela de Luna
Rocha, Maria Eliane Merlin
Martinez, Glaucia Regina
Institución
Resumen
Melanins have been associated with the development of melanoma and its resistance to photodynamic therapy (PDT). Singlet molecular oxygen (102), which is produced by ultraviolet A solar radiation and the PDT system, is also involved. Here, we investigated the effects that these factors have on DNA damage and repair. Our results show that both types of melanin (eumelanin and pheomelanin) lead to DNA breakage in the absence of light irradiation and that eumelanin is more harmful than pheomelanin. Interestingly, melanins were found to bind to the minor grooves of DNA, guaranteeing close proximity to DNA and potentially causing the observed high levels of strand breaks. We also show that the interaction of melanins with DNA can impair the access of repair enzymes to lesions, contributing to the perpetuation of DNA damage. Moreover, we found that after melanins interact with 102, they exhibit a lower ability to induce DNA breakage; we propose that these effects are due to modifications of their structure. Together, our data highlight the different modes of action of the two types of melanin. Our results may have profound implications for cellular redox homeostasis, under conditions of induced melanin synthesis and irradiation with solar light. These results may also be applied to the development of protocols to sensitize melanoma cells to PDT. (c) 2012 Elsevier Inc. All rights reserved.