Chemiexcitation of melanin derivatives induces DNA photoproducts long after UV exposure

Autor(es)

Premi, Sanjay ^[1] ; Wallisch, Silvia ^[1] ; Mano, Camila M. ^{[2, 1]} ; Weiner, Adam B. ^[1] ; Bacchiocchi, Antonella ^[3] ; Wakamatsu, Kazumasa ^[4] ; Bechara, Etelvino J. H. ^{[2, 5]} ; Halaban, Ruth ^{[6, 3]} ; Douki, Thierry ^[7] ; Brash, Douglas E. ^{[1, 6]}

Afiliação do(s) autor(es)

^[1] Yale Univ, Sch Med, Dept Therapeut Radiol, New Haven, CT 06520 - USA

^[2] Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-05513970 Sao Paulo - Brazil

^[3] Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06520 - USA

^[4] Fujita Hlth Univ, Sch Hlth Sci, Dept Chem, Toyoake, Aichi 4701192 - Japan

^[5] Univ Fed Sao Carlos, Dept Ciencias Exatas & Terra, BR-09972270 Sao Paulo - Brazil

^[6] Yale Univ, Sch Med, Yale Comprehens Canc Ctr, New Haven, CT 06520 - USA

^[7] CEA Grenoble, INAC, LCIB UMR CEA UJF E3, F-38054 Grenoble 9 - France

• Tipo de documento: Artigo Científico
• Fonte: Science; v. 347, n. 6224, p. 842-847, FEB 20 2015.
• Citações Web of Science: 145

Resumo

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. (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