title: Effects of the melanin precursor 5,6-dihydroxy-indole-2-carboxylic acid (DHICA) on DNA damage and repair in the presence of reactive oxygen species.
abstract: Eumelanin is a heterogeneous polymer composed of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) and 5,6-dihydroxyindole (DHI). Studies have shown that DHICA promotes single strand breaks in plasmid DNA exposed to ultraviolet B radiation (UVB, 313 nm) and in DNA from human keratinocytes exposed to ultraviolet A radiation (UVA, 340-400 nm). Singlet molecular oxygen ((1)O2) is the main reactive species formed by UVA radiation on the skin. In this context, we now report that DHICA can cause single strand breaks in plasmid DNA even in the absence of light radiation. Interestingly, when DHICA was pre-oxidized by (1)O2, it lost this harmful capacity. It was also found that DHICA could interact with DNA, disturbing Fpg activity and decreasing its recognition of lesions by ∼50%. Additionally, the free nucleoside deoxyguanosine (dGuo) was used to evaluate whether DHICA would interfere with the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) and spiroiminodihydantoin (dSp) by (1)O2 or with the formation of 8-oxodGuo by hydroxyl radical (OH). We observed that when dGuo was oxidized by (1)O2 in the presence of DHICA, 8-oxodGuo formation was increased. However, when dGuo was oxidized by OH in the presence of DHICA, 8-oxodGuo levels were lower than in the absence of the precursor. Overall, our data reveal an important role for this eumelanin precursor in both the promotion and the protection of DNA damage and imply that it can impair DNA repair.
authors.affiliation: Programa de Pós-graduação em Ciências (Bioquímica), Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, PR, Brazil.
authors.forename: Maria Carolina
authors.initials: MC
authors.lastname: Pellosi
authors.affiliation: Programa de Pós-graduação em Ciências (Bioquímica), Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, PR, Brazil.
authors.forename: Andréia Akemi
authors.initials: AA
authors.lastname: Suzukawa
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Alexsandra Cristina
authors.initials: AC
authors.lastname: Scalfo
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Paolo
authors.initials: P
authors.lastname: Di Mascio
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Carolina Parga
authors.initials: CP
authors.lastname: Martins Pereira
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Nadja Cristhina
authors.initials: NC
authors.lastname: de Souza Pinto
authors.affiliation: Instituto de Química, Universidade Federal Fluminense, Rio de Janeiro, RJ, Brazil.
authors.forename: Daniela
authors.initials: D
authors.lastname: de Luna Martins
authors.affiliation: Programa de Pós-graduação em Ciências (Bioquímica), Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, PR, Brazil. Electronic address: grmartinez@pq.cnpq.br.
authors.forename: Glaucia Regina
authors.initials: GR
authors.lastname: Martinez
mesh_terms: D004249:DNA Damage; D004260:DNA Repair; D007211:Indoles / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000737:chemistry*
chemical_list: D007211:Indoles; D017382:Reactive Oxygen Species; C030692:5,6-dihydroxy-2-indolylcarboxylic acid
keywords: DHICA; DNA damage; DNA repair; Fpg; Hydroxyl radical; Singlet oxygen; Strand breaks