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: Sanjay Premi, Silvia Wallisch, Camila M Mano, Adam B Weiner, Antonella Bacchiocchi, Kazumasa Wakamatsu, Etelvino J H Bechara, Ruth Halaban, Thierry Douki, Douglas E Brash
• Journal: Science (New York, N.Y.) (Science) Vol. 347 Issue 6224 Pg. 842-7 (Feb 20 2015) ISSN: 1095-9203 [Electronic] United States
• PMID: 25700512 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2015, American Association for the Advancement of Science.

Chemical References

• Melanins
• Pyrimidine Dimers
• Receptor, Melanocortin, Type 1
• Cytosine
• DNA
• Thymine

Topics

• Animals
• Cells, Cultured
• Cytosine (metabolism)
• DNA (chemistry, genetics, radiation effects)
• DNA Damage (genetics)
• Energy Transfer
• Humans
• Melanins (chemistry, metabolism)
• Melanocytes (metabolism, radiation effects)
• Melanoma (genetics)
• Mice
• Mice, Inbred C57BL
• Mutagenesis
• Mutation
• Neoplasms, Radiation-Induced (genetics)
• Photons
• Pyrimidine Dimers (metabolism)
• Receptor, Melanocortin, Type 1 (genetics)
• Skin Neoplasms (genetics)
• Sunlight (adverse effects)
• Thymine (metabolism)
• Ultraviolet Rays