Zinc-induced structural effects enhance oxygen consumption and superoxide generation in synthetic pheomelanins on UVA/visible light irradiation

The abnormal susceptibility of red-haired individuals to UV-induced inflammation and skin cancers is commonly attributed to the marked photoreactivity of pheomelanin pigments, which would be responsible for the sustained generation of reactive oxygen species in the skin following sun exposure. The structural factors detg. pheomelanin photolability remain mostly unknown. Here, we describe the effects of zinc ions, typically found at high levels in red hair, in enhancing both oxygen consumption and superoxide prodn. in model pheomelanin pigments following irradn. with UVA and visible light. ESR (EPR) oximetry and EPR-spin trapping expts. with synthetic pheomelanins, prepd. by oxidn. of dopa and cysteine or isomeric cysteinyldopas under different conditions, indicate a higher photoreactivity of the pigments prepd. in the presence of zinc ions compared with those obtained in the absence of the metal. Quant. anal. of thiazole-contg. structural markers of the synthetic pheomelanins provides evidence that the effect of zinc ions is due to modification of the formation pathway and structural features of the pigments. Overall, these results point to a hitherto unrecognized crit. role of zinc ions in pheomelanogenesis, which may affect the intrinsic photoreactivity of the pigment.