Melanoma induction by ultraviolet A but not ultraviolet B radiation requires melanin pigment.
Malignant melanoma of the skin (CMM) is associated with ultraviolet radiation exposure, but the mechanisms and even the wavelengths responsible are unclear. Here we use a mammalian model to investigate melanoma formed in response to precise spectrally defined ultraviolet wavelengths and biologically relevant doses. We show that melanoma induction by ultraviolet A (320-400 nm) requires the presence of melanin pigment and is associated with oxidative DNA damage within melanocytes. In contrast, ultraviolet B radiation (280-320 nm) initiates melanoma in a pigment-independent manner associated with direct ultraviolet B DNA damage. Thus, we identified two ultraviolet wavelength-dependent pathways for the induction of CMM and describe an unexpected and significant role for melanin within the melanocyte in melanomagenesis.
Laboratory of Photobiology and Photoimmunology, Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, District of Columbia 20037, USA.
Frances P
FP
Noonan
M Raza
MR
Zaidi
Agnieszka
A
Wolnicka-Glubisz
Miriam R
MR
Anver
Jesse
J
Bahn
Albert
A
Wielgus
Jean
J
Cadet
Thierry
T
Douki
Stephane
S
Mouret
Margaret A
MA
Tucker
Anastas
A
Popratiloff
Glenn
G
Merlino
Edward C
EC
De Fabo
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004249:DNA Damage / Q000187:drug effects; D004578:Electron Spin Resonance Spectroscopy; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D008543:Melanins / Q000235:genetics / Q000378:metabolism*; D008544:Melanocytes / Q000187:drug effects* / Q000378:metabolism*; D008545:Melanoma / Q000209:etiology*; D051379:Mice; D018613:Microscopy, Confocal; D009381:Neoplasms, Radiation-Induced / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000209:etiology* / Q000378:metabolism*; D014466:Ultraviolet Rays / Q000009:adverse effects*
D008543:Melanins