DUAL ROLE OF MELANINS AND MELANIN PRECURSORS AS PHOTOPROTECTIVE AND PHOTOTOXIC AGENTS - INHIBITION OF ULTRAVIOLET RADIATION-INDUCED LIPID-PEROXIDATION

Ultraviolet radiation (UVR) is one of the risk factors for skin cancer and the main inducer of melanin pigmentation, the major protective me chanism of mammalian skin against radiation damage. The melanin pigmen ts, eumelanin and pheomelanin, are likely to be important in protectio n against UVR, but their precursors are generally considered as photot oxic. The available data suggest DNA damage as the mechanism of photot oxicity. However, the effect of melanin precursors on membrane damage through lipid peroxidation, another important and probably more releva nt (from the point-of-view of the melanosomal confinement of these mol ecules) mechanism of phototoxicity, is net known. As a model system fo r UVR-melanin-membrane interactions. we irradiated liposomes in the pr esence of eumelanin, pheomelanin and two of their major precursors, 5, 6-dihydroxyindole (DHI) and 5-S-cysteinyldopa (SCD), The presence of t he two melanin precursors substantially reduced the formation of lipid peroxidation products resulting from UVR exposure, The antioxidant ac tivity of the melanin precursors was diminished under strong prooxidan t conditions (presence of Fe3+). These results suggest that melanin pr ecursors may have an important role in the protection of skin against the harmful effects of UVR including photocarcinogenesis.