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

Autor(es)

Brash, Douglas E.

• Tipo de documento: Artigo Científico
• Fonte: TOXICOLOGIC PATHOLOGY; v. 44, n. 4, p. 552-554, JUN 2016.
• Citações Web of Science: 5

Resumo

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)

• Processo FAPESP: 06/56530-4 - Estresse redox e carbonílico associado a alfa-aminocetonas e beta-cetoácidos endógenos: mecanismos e biomarcadores
• Beneficiário: Etelvino José Henriques Bechara
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 09/02062-8 - Espécies Excitadas Tripletes em Sistemas Biológicos
• Beneficiário: Camila Marinho Mano
• Modalidade de apoio: Bolsas no Brasil - Doutorado