De Fabo Edward C
Department of Environmental & Occupational Health, The School of Public Health & Health Services, The George Washington University, Washington, DC 20817, USA.
Prog Biophys Mol Biol. 2006 Sep;92(1):97-104. doi: 10.1016/j.pbiomolbio.2006.02.024. Epub 2006 Mar 20.
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.
维生素D的产生始于皮肤中的7-脱氢胆固醇暴露于阳光中的UVB(280 - 320纳米)成分,从而形成光产物,随后这些光产物在一系列暗反应中被代谢激活为生物活性部分,本研讨会其他地方对此有描述。然而,用UVB照射皮肤还有其他影响,并非所有这些影响都是有益的。最显著的是引发皮肤癌。非黑色素瘤皮肤癌显然是由UVB引发的,但对于最致命的皮肤癌——皮肤恶性黑色素瘤,尽管与阳光照射有关,但尚未明确确定其致病波长。使用紫外线诱导黑色素瘤的小鼠模型,我们最近表明,引发黑色素瘤的也是UVB,而非UVA(320 - 400纳米)。因此,需要在阳光中UVB照射的健康效应——维生素D形成——与其中最具潜在严重性的有害效应——黑色素瘤引发之间取得平衡。确定这种平衡的一个有力工具是了解每种效应的作用光谱或波长依赖性。在此,我们描述了作用光谱测定的方法、途径和潜在陷阱,并以我们在紫外线诱导黑色素瘤的HGF/SF转基因小鼠模型中的经验为例进行说明。