PMID- 24893147 OWN - NLM STAT- MEDLINE DCOM- 20140915 LR - 20140722 IS - 1096-0384 (Electronic) IS - 0003-9861 (Linking) VI - 557 DP - 2014 Sep 1 TI - 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. PG - 55-64 LID - S0003-9861(14)00189-1 [pii] LID - 10.1016/j.abb.2014.05.024 [doi] AB - 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 approximately 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. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Pellosi, Maria Carolina AU - Pellosi MC AD - Programa de Pos-graduacao em Ciencias (Bioquimica), Departamento de Bioquimica e Biologia Molecular, Universidade Federal do Parana, Curitiba, PR, Brazil. FAU - Suzukawa, Andreia Akemi AU - Suzukawa AA AD - Programa de Pos-graduacao em Ciencias (Bioquimica), Departamento de Bioquimica e Biologia Molecular, Universidade Federal do Parana, Curitiba, PR, Brazil. FAU - Scalfo, Alexsandra Cristina AU - Scalfo AC AD - Departamento de Bioquimica, Instituto de Quimica, Universidade de Sao Paulo, Sao Paulo, SP, Brazil. FAU - Di Mascio, Paolo AU - Di Mascio P AD - Departamento de Bioquimica, Instituto de Quimica, Universidade de Sao Paulo, Sao Paulo, SP, Brazil. FAU - Martins Pereira, Carolina Parga AU - Martins Pereira CP AD - Departamento de Bioquimica, Instituto de Quimica, Universidade de Sao Paulo, Sao Paulo, SP, Brazil. FAU - de Souza Pinto, Nadja Cristhina AU - de Souza Pinto NC AD - Departamento de Bioquimica, Instituto de Quimica, Universidade de Sao Paulo, Sao Paulo, SP, Brazil. FAU - de Luna Martins, Daniela AU - de Luna Martins D AD - Instituto de Quimica, Universidade Federal Fluminense, Rio de Janeiro, RJ, Brazil. FAU - Martinez, Glaucia Regina AU - Martinez GR AD - Programa de Pos-graduacao em Ciencias (Bioquimica), Departamento de Bioquimica e Biologia Molecular, Universidade Federal do Parana, Curitiba, PR, Brazil. Electronic address: grmartinez@pq.cnpq.br. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140602 PL - United States TA - Arch Biochem Biophys JT - Archives of biochemistry and biophysics JID - 0372430 RN - 0 (Indoles) RN - 0 (Reactive Oxygen Species) RN - 4790-08-3 (5,6-dihydroxy-2-indolylcarboxylic acid) SB - IM MH - *DNA Damage MH - *DNA Repair MH - Indoles/*chemistry MH - Reactive Oxygen Species/*chemistry OTO - NOTNLM OT - DHICA OT - DNA damage OT - DNA repair OT - Fpg OT - Hydroxyl radical OT - Singlet oxygen OT - Strand breaks EDAT- 2014/06/04 06:00 MHDA- 2014/09/16 06:00 CRDT- 2014/06/04 06:00 PHST- 2014/01/14 00:00 [received] PHST- 2014/05/15 00:00 [revised] PHST- 2014/05/26 00:00 [accepted] PHST- 2014/06/04 06:00 [entrez] PHST- 2014/06/04 06:00 [pubmed] PHST- 2014/09/16 06:00 [medline] AID - S0003-9861(14)00189-1 [pii] AID - 10.1016/j.abb.2014.05.024 [doi] PST - ppublish SO - Arch Biochem Biophys. 2014 Sep 1;557:55-64. doi: 10.1016/j.abb.2014.05.024. Epub 2014 Jun 2.