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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

UV-induced Melanin Chemiexcitation: A New Mode of Melanoma Pathogenesis

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Brash, Douglas E.
Total Authors: 1
Document type: Journal article
Source: TOXICOLOGIC PATHOLOGY; v. 44, n. 4, p. 552-554, JUN 2016.
Web of Science Citations: 5

Mutations in sunlight-induced melanoma arise from cyclobutane pyrimidine dimers (CPDs), DNA photoproducts usually created picoseconds after an ultraviolet (UV) photon is absorbed at thymine or cytosine. Surprisingly, we found that, in melanocytes, CPDs were generated for hours after UVA or UVB exposure. These dark CPDs constituted the majority of CPDs in cultured human and murine melanocytes and in mouse skin, and they were most prominent in skin containing pheomelanin, the melanin responsible for blonde and red hair. The mechanism was also a surprise. Dark cyclobutane pyrimidine dimers (CPDs) arise when ultraviolet (UV)-induced superoxide and nitric oxide combine to form peroxynitrite, one of the few biological molecules capable of exciting an electron. This process, termed chemiexcitation, is the source of bioluminescence in lower organisms. Excitation occurred in fragments of melanin, creating a quantum triplet state that had the energy of a UV photon but which induced CPDs by radiationless energy transfer to DNA. UVA and peroxynitrite also solubilized melanin and permeabilized the nuclear membrane, allowing melanin to enter. Melanin is evidently carcinogenic as well as protective. Chemiexcitation may also trigger pathogenesis in internal tissues because the same chemistry should arise wherever superoxide and nitric oxide arise near cells that contain melanin. (AU)

FAPESP's process: 09/02062-8 - Triplet excited species in biological systems
Grantee:Camila Marinho Mano
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 06/56530-4 - Carbonilic and redox stress associated with alpha-aminoketones and endogenous beta-ketoacids: mechanisms and biomarkers.
Grantee:Etelvino José Henriques Bechara
Support type: Research Projects - Thematic Grants