title: Photochemistry. Chemiexcitation of melanin derivatives induces DNA photoproducts long after UV exposure.
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.
authors.affiliation: Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Premi
authors.affiliation: Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Silvia
authors.initials: S
authors.lastname: Wallisch
authors.affiliation: 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.
authors.forename: Camila M
authors.initials: CM
authors.lastname: Mano
authors.affiliation: Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Adam B
authors.initials: AB
authors.lastname: Weiner
authors.affiliation: Department of Dermatology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Antonella
authors.initials: A
authors.lastname: Bacchiocchi
authors.affiliation: Department of Chemistry, Fujita Health University School of Health Sciences, Toyoake, Aichi 470-1192, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Wakamatsu
authors.affiliation: 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.
authors.forename: Etelvino J H
authors.initials: EJ
authors.lastname: Bechara
authors.affiliation: 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.
authors.forename: Ruth
authors.initials: R
authors.lastname: Halaban
authors.affiliation: INAC/LCIB UMR-E3 CEA-UJF/Commissariat à l'Energie Atomique (CEA), 38054 Grenoble Cedex 9, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Douki
authors.affiliation: 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.
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Brash
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003596:Cytosine / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000528:radiation effects*; D004249:DNA Damage / Q000235:genetics*; D004735:Energy Transfer; D006801:Humans; D008543:Melanins / Q000737:chemistry / Q000378:metabolism*; D008544:Melanocytes / Q000378:metabolism / Q000528:radiation effects*; D008545:Melanoma / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D016296:Mutagenesis; D009154:Mutation; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D017785:Photons; D011740:Pyrimidine Dimers / Q000378:metabolism*; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics*; D013472:Sunlight / Q000009:adverse effects; D013941:Thymine / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D008543:Melanins; D011740:Pyrimidine Dimers; D044102:Receptor, Melanocortin, Type 1; D003596:Cytosine; D004247:DNA; D013941:Thymine