Artigo Acesso aberto Produção Nacional Revisado por pares

Novel properties of melanins include promotion of DNA strand breaks, impairment of repair, and reduced ability to damage DNA after quenching of singlet oxygen

2012; Elsevier BV; Volume: 52; Issue: 9 Linguagem: Inglês

10.1016/j.freeradbiomed.2012.02.039

ISSN

1873-4596

Autores

Andréia Akemi Suzukawa, Alessandra Vieira, Sheila Maria Brochado Winnischofer, Alexsandra Cristina Scalfo, Paolo Di Mascio, Ana Maria da Costa Ferreira, Jean‐Luc Ravanat, Daniela de Luna Martins, Maria Eliane Merlin Rocha, Gláucia Regina Martinez,

Tópico(s)

Skin Protection and Aging

Resumo

Melanins have been associated with the development of melanoma and its resistance to photodynamic therapy (PDT). Singlet molecular oxygen ((1)O(2)), 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 (1)O(2), 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.

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