Cutaneous Biology Research Center, Massachusetts General Hospital, Charlestown, MA, USA.
Bioessays. 2013 Aug;35(8):672-6. doi: 10.1002/bies.201300020. Epub 2013 May 7.
Recently, we reported that melanoma risk in redheads is linked not only to pale skin, but also to the synthesis of the pigment - called pheomelanin - that gives red hair its color. We demonstrated that pheomelanin synthesis is associated with increased oxidative stress in the skin, yet we have not uncovered the chemical pathway between the molecule pheomelanin and the DNA damage that drives melanoma formation. Here, we hypothesize two possible pathways. On one hand, pheomelanin might generate reactive oxygen species (ROS) that directly or indirectly cause oxidative DNA damage. On the other hand, pheomelanin synthesis might consume cellular antioxidant stores and make the cell nucleus more vulnerable to other endogenous ROS. Uncovering the mechanistic pathway between pheomelanin and oxidative DNA damage will be an important step in developing strategies to lower melanoma risk in redheads.
最近，我们报告称，红发人群的黑色素瘤风险不仅与白皙的皮肤有关，还与合成一种名为“真黑色素”的色素有关，这种色素赋予红发颜色。我们证明了真黑色素的合成与皮肤中氧化应激的增加有关，但我们还没有发现真黑色素分子与驱动黑色素瘤形成的 DNA 损伤之间的化学途径。在这里，我们假设了两种可能的途径。一方面，真黑色素可能会产生活性氧（ROS），这些 ROS 会直接或间接地导致氧化 DNA 损伤。另一方面，真黑色素的合成可能会消耗细胞内的抗氧化剂储存，使细胞核更容易受到其他内源性 ROS 的影响。揭示真黑色素和氧化 DNA 损伤之间的机制途径将是制定降低红发人群黑色素瘤风险策略的重要一步。
