Chemiexcitation of melanin derivatives induces DNA photoproducts long after UV exposure

Author(s)

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]}

Affiliation

^[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

• Document type: Journal article
• Source: Science; v. 347, n. 6224, p. 842-847, FEB 20 2015.
• Web of Science Citations: 145

Abstract

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)

• 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 Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 09/02062-8 - Triplet Excited Species in Biological Systems
• Grantee: Camila Marinho Mano
• Support Opportunities: Scholarships in Brazil - Doctorate