UV-induced Melanin Chemiexcitation: A New Mode of Melanoma Pathogenesis.
Toxicol Pathol
; 44(4): 552-4, 2016 06.
Article
en En
| MEDLINE
| ID: mdl-26951162
ABSTRACT
Mutations in sunlight-induced melanoma arise from cyclobutane pyrimidine dimers (CPDs), DNA photoproducts usually created picoseconds after an ultraviolet (UV) photon is absorbed at thymine or cytosine. Surprisingly, we found that, in melanocytes, CPDs were generated for hours after UVA or UVB exposure. These "dark CPDs" constituted the majority of CPDs in cultured human and murine melanocytes and in mouse skin, and they were most prominent in skin containing pheomelanin, the melanin responsible for blonde and red hair. The mechanism was also a surprise. Dark cyclobutane pyrimidine dimers (CPDs) arise when ultraviolet (UV)-induced superoxide and nitric oxide combine to form peroxynitrite, one of the few biological molecules capable of exciting an electron. This process, termed "chemiexcitation," is the source of bioluminescence in lower organisms. Excitation occurred in fragments of melanin, creating a quantum triplet state that had the energy of a UV photon but which induced CPDs by radiationless energy transfer to DNA. UVA and peroxynitrite also solubilized melanin and permeabilized the nuclear membrane, allowing melanin to enter. Melanin is evidently carcinogenic as well as protective. Chemiexcitation may also trigger pathogenesis in internal tissues because the same chemistry should arise wherever superoxide and nitric oxide arise near cells that contain melanin.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Cutáneas
/
Rayos Ultravioleta
/
Melaninas
/
Melanocitos
/
Melanoma
Tipo de estudio:
Etiology_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Toxicol Pathol
Año:
2016
Tipo del documento:
Article
País de afiliación:
Estados Unidos