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
2014
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 O 2 ) 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 O 2 , 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 O 2 or with the formation of 8-oxodGuo by hydroxyl radical ( OH). We observed that when dGuo was oxidized by 1 O 2 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.
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