title: Novel properties of melanins include promotion of DNA strand breaks, impairment of repair, and reduced ability to damage DNA after quenching of singlet oxygen.
abstract: 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.
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, 81.531-980 Curitiba, PR, Brazil.
authors.forename: Andréia Akemi
authors.initials: AA
authors.lastname: Suzukawa
authors.forename: Alessandra
authors.initials: A
authors.lastname: Vieira
authors.forename: Sheila Maria Brochado
authors.initials: SM
authors.lastname: Winnischofer
authors.forename: Alexsandra Cristina
authors.initials: AC
authors.lastname: Scalfo
authors.forename: Paolo
authors.initials: P
authors.lastname: Di Mascio
authors.forename: Ana Maria da Costa
authors.initials: AM
authors.lastname: Ferreira
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Ravanat
authors.forename: Daniela de Luna
authors.initials: Dde L
authors.lastname: Martins
authors.forename: Maria Eliane Merlin
authors.initials: ME
authors.lastname: Rocha
authors.forename: Glaucia Regina
authors.initials: GR
authors.lastname: Martinez
mesh_terms: D004249:DNA Damage; D004260:DNA Repair; D004578:Electron Spin Resonance Spectroscopy; D005293:Ferritins / Q000378:metabolism; D008543:Melanins / Q000502:physiology; D026082:Singlet Oxygen / Q000378:metabolism*
chemical_list: D008543:Melanins; D026082:Singlet Oxygen; D005293:Ferritins