title: Ultraviolet B but not ultraviolet A radiation initiates melanoma.
abstract: Cutaneous malignant melanoma is one of the fastest increasing cancers with an incidence that has more than doubled in the last 25 years. Sunlight exposure is strongly implicated in the etiology of cutaneous malignant melanoma and the UV portion of the sunlight spectrum is considered responsible. Data are, however, conflicting on the roles of ultraviolet B [UVB; 280-320 nanometers (nm)] and ultraviolet A (UVA; 320-400 nm), which differ in their ability to initiate DNA damage, cell signaling pathways and immune alterations. To address this issue, we have used specialized optical sources, emitting isolated or combined UVB or UVA wavebands or solar simulating radiation, together with our hepatocyte growth factor/scatter factor-transgenic mouse model of UV-induced melanoma that uniquely recapitulates human disease. Only UVB-containing sources initiated melanoma. These were the isolated UVB waveband (>96% 280-320 nm), the unfiltered F40 sunlamp (250-800 nm) and the solar simulator (290-800 nm). Kaplan-Meier survival analysis indicated that the isolated UVB waveband was more effective in initiating melanoma than either the F40 sunlamp or the solar simulator (modified log rank P < 0.02). The latter two sources showed similar melanoma effectiveness (P = 0.38). In contrast, transgenic mice irradiated with either the isolated UVA waveband (>99.9% 320-400 nm, 150 kJ/m2), or an F40 sunlamp filtered to remove > 96% of the UVB, responded like unirradiated control animals. We conclude that, within the constraints of this animal model, UVB is responsible for the induction of mammalian cutaneous malignant melanoma whereas UVA is ineffective even at doses considered physiologically relevant. This finding may have major implications with respect both to risk assessment from exposure to solar and artificial UVB, and to development of effective protection strategies against melanoma induction by UVB. Moreover, these differences in wavelength effectiveness can now be exploited to identify UV pathways relevant to melanomagenesis.
authors.affiliation: Laboratory of Photobiology and Photoimmunology, Department of Environmental and Occupational Health, School of Public Health and Health Services, The George Washington University Medical Center, Washington, DC 20037, USA. drmecd@gwumc.edu
authors.forename: Edward C
authors.initials: EC
authors.lastname: De Fabo
authors.forename: Frances P
authors.initials: FP
authors.lastname: Noonan
authors.forename: Thomas
authors.initials: T
authors.lastname: Fears
authors.forename: Glenn
authors.initials: G
authors.lastname: Merlino
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D008546:Melanoma, Experimental / Q000209:etiology*; D051379:Mice; D008822:Mice, Transgenic; D009381:Neoplasms, Radiation-Induced / Q000209:etiology*; D012878:Skin Neoplasms / Q000209:etiology*; D014466:Ultraviolet Rays / Q000009:adverse effects*