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Science. 2015 Feb 20;347(6224):842-7. doi: 10.1126/science.1256022.

Photochemistry. Chemiexcitation of melanin derivatives induces DNA photoproducts long after UV exposure.

Author information

1
Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA.
2
Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA. Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo 05513-970 SP, Brazil.
3
Department of Dermatology, Yale University School of Medicine, New Haven, CT 06520, USA.
4
Department of Chemistry, Fujita Health University School of Health Sciences, Toyoake, Aichi 470-1192, Japan.
5
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo 05513-970 SP, Brazil. Departamento de Ciências Exatas e da Terra, Universidade Federal de São Paulo, Diadema, São Paulo 09972-270 SP, Brazil.
6
Department of Dermatology, Yale University School of Medicine, New Haven, CT 06520, USA. Yale Comprehensive Cancer Center, Yale University School of Medicine, New Haven, CT 06520, USA.
7
INAC/LCIB UMR-E3 CEA-UJF/Commissariat à l'Energie Atomique (CEA), 38054 Grenoble Cedex 9, France.
8
Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA. Yale Comprehensive Cancer Center, Yale University School of Medicine, New Haven, CT 06520, USA. douglas.brash@yale.edu.

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.

PMID:
25700512
PMCID:
PMC4432913
DOI:
10.1126/science.1256022
[Indexed for MEDLINE]
Free PMC Article

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