UV causation of melanoma in Xiphophorus is dominated by melanin photosensitized oxidant production.
Controversy continues both as to which wavelengths of sunlight cause melanoma and the mechanisms by which these different wavelengths act. Direct absorption of UVB by DNA is central in albino animal models, but melanin-pigmented models have shown major contributions by wavelengths longer than UVB that are thought to be mediated by photosensitized oxidant production. The only model for which the action spectrum of melanoma causation is known is a genetically melanoma-susceptible specific cross of Xiphophorus fish. We used electron paramagnetic resonance to quantitatively detect the UV induction of reactive melanin radicals in situ in the melanin-containing cells in the skin of this model and derived the action spectrum for melanin-photosensitized oxidant production (Phi(ox)). This action spectrum was identical to that for melanoma induction (Phi(mel)). These results confirm the hypothesis that melanin-photosensitized radical production is the major causative step of melanoma in this model and demonstrate that the wavelengths and mechanisms of melanoma causation in different models are dependent on the presence of melanin. This approach should be applicable to humans, thus providing an accurate surrogate for Phi(mel) for prevention studies.
Wood
Simon R
SR
Division of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
Berwick
Marianne
M
Ley
Ronald D
RD
Walter
Ronald B
RB
Setlow
Richard B
RB
Timmins
Graham S
GS
D000818:Animals; D055592:Biophysical Phenomena; D001703:Biophysics; D003532:Cyprinodontiformes; D004195:Disease Models, Animal; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D008543:Melanins / Q000378:metabolism* / Q000528:radiation effects; D008546:Melanoma, Experimental / Q000209:etiology* / Q000378:metabolism; D009381:Neoplasms, Radiation-Induced / Q000209:etiology / Q000378:metabolism; D018462:Photobiology; D014466:Ultraviolet Rays / Q000009:adverse effects
D005609:Free Radicals; D008543:Melanins