Initial studies on an in vivo action spectrum for melanoma induction.
Vitamin D production is initiated by exposure of 7-dehydrocholesterol in the skin to the UVB (280-320 nm) component of sunlight, resulting in the formation of photoproducts, which are subsequently metabolically activated to biologically active moieties in a series of dark reactions as described elsewhere in this symposium. Irradiation of the skin with UVB has, however, other effects not all of which are beneficial. Most notable is the initiation of skin cancer. Non-melanoma skin cancer is clearly initiated by UVB but for the most lethal of the skin cancers, cutaneous malignant melanoma, although associated with sunlight exposure, the wavelengths responsible have not been clearly identified. Using a mouse model for UV-induced melanoma, we have recently shown that UVB, not UVA (320-400 nm), is also responsible for melanoma initiation. A balance therefore needs to be struck between the healthy effects of exposure to UVB in sunlight--vitamin D formation--and the deleterious effects of which the most potentially serious is melanoma initiation. A powerful tool in determining this balance would be an understanding of the action spectra or wavelength dependence for each of these effects. Here we describe methodologies, approaches and potential pitfalls for action spectra determination illustrated by our experience with the HGF/SF transgenic mouse model for UV-induced melanoma.
De Fabo
Edward C
EC
Department of Environmental & Occupational Health, The School of Public Health & Health Services, The George Washington University, Washington, DC 20817, USA.
D000818:Animals; D001822:Body Burden; D004307:Dose-Response Relationship, Radiation; D008545:Melanoma / Q000209:etiology* / Q000503:physiopathology*; D051379:Mice; D009381:Neoplasms, Radiation-Induced / Q000209:etiology / Q000503:physiopathology*; D011829:Radiation Dosage; D012062:Relative Biological Effectiveness; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D012878:Skin Neoplasms / Q000209:etiology* / Q000503:physiopathology*; D013056:Spectrophotometry, Ultraviolet; D014466:Ultraviolet Rays / Q000009:adverse effects* / Q000145:classification*