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The dark side of melanin exposed
Sun worshippers may have more to worry about than the DNA damage that occurs while they're relaxing on the beach. It seems that the DNA photoproducts responsible for cancer-causing mutations in skin cells continue to be generated for hours after sunlight exposure. Premi et al. find that a key mediator of this delayed damage is melanin, a pigment thought to protect against cancer (see the Perspective by Taylor). They propose a “chemiexcitation” model in which reactive oxygen and nitrogen species induced by ultraviolet light excite an electron in melanin fragments. This energy is then transferred to DNA, inducing the same damage as ultraviolet light, but in the dark. Conceivably, this energy could be dissipated by adding quenchers to sunscreens.
Mutations in sunlight-induced melanoma arise from cyclobutane pyrimidine dimers (CPDs), DNA photoproducts that are typically created picoseconds after an ultraviolet (UV) photon is absorbed at thymine or cytosine. We found that in melanocytes, CPDs are generated for >3 hours after exposure to UVA, a major component of the radiation in sunlight and in tanning beds. These “dark CPDs” constitute the majority of CPDs and include the cytosine-containing CPDs that initiate UV-signature C→T mutations. Dark CPDs arise when UV-induced reactive oxygen and nitrogen species combine to excite an electron in fragments of the pigment melanin. This creates a quantum triplet state that has the energy of a UV photon but induces CPDs by energy transfer to DNA in a radiation-independent manner. Melanin may thus be carcinogenic as well as protective against cancer. These findings also validate the long-standing suggestion that chemically generated excited electronic states are relevant to mammalian biology.