Pro-Oxidant Properties of Melanosomal Melanin from Melanoma Origin

Author(s): Meyskens, FL; Gidanian, S; Farmer, P | Editor(s): Davies, K | Abstract: Melanoma cells, in comparison to normal melanocytes, contain higher concentrations of redox active species and yet are inefficient in mediating oxidative stress. We attribute these features to changes of intracellular melanosomes and melanin reactivity during the pathogenic process. Eumelanins are redox active pigments containing hydroquinone, semiquinone, quinone and quinone-imine functionalities within their structure. We have previously shown that pro-oxidant properties of synthetic melanin are enhanced by stabilization of the oxidized form of melanin as a result of metal chelation. Chemical studies using DNA clipping activity of isolated melanosomes from different sources indicated enhanced pro-oxidant properties of melanosomes from melanoma origin compared to melanin from normal melanocytes and sepia origin. Electron paramagnetic resonance spin trapping studies confirm these results both in electrochemically polymerized dihydroquinones and in intact human melanoma cells and suggested generation of superoxide and hydroxyl radicals. Ultrastructural investigations of melanosomes by electron microscopy revealed abnormalities in melanin deposition and membrane of the melanoma melanosomes compared to melanocyte melanosomes, which may play a part in higher reactivity of melanoma melanosomes. in related experiments exposure of normal human melanocytes to ultraviolet light radiation –B plus copper and cadmium (but not zinc) salts led to cells that phenotypically resembled dysplastic nevus cells in culture.