Freeman S E, Hacham H, Gange R W, Maytum D J, Sutherland J C, Sutherland B M
Biology Department, Brookhaven National Laboratory, Upton, NY 11973.
Proc Natl Acad Sci U S A. 1989 Jul;86(14):5605-9. doi: 10.1073/pnas.86.14.5605.
The UV components of sunlight are believed to be a major cause of human skin cancer, and DNA is thought to be the principal molecular target. Alterations of the intensity and wavelength distribution of solar UV radiation reaching the surface of the earth, for example by depletion of stratospheric ozone, will change the effectiveness of solar radiation in damaging DNA in human skin. Evaluation of the magnitude of such effects requires knowledge of the altered sunlight spectrum and of the action spectrum for damaging DNA in human skin. We have determined an action spectrum for the frequency of pyrimidine dimer formation induced in the DNA of human skin per unit dose of UV incident on the skin surface. The peak of this action spectrum is near 300 nm and decreases rapidly at both longer and shorter wavelengths. The decrease in our action spectrum for wavelengths less than 300 nm is attributed to the absorption of the upper layers of the skin, an in situ effect that is inherently included in our measurements. Convolution of the dimer action spectrum with the solar spectra corresponding to a solar angle of 40 degrees under current levels of stratospheric ozone (0.32-cm O3 layer) and those for 50% ozone depletion (0.16-cm O3 layer), indicate about a 2.5-fold increase in dimer formation. If the action spectrum for DNA damage that results in skin cancer resembles that for dimer induction in skin, our results, combined with epidemiological data, suggest that a 50% decrease in stratospheric ozone would increase the incidence of nonmelanoma skin cancers among white males in Seattle, Washington, by 7.5- to 8-fold, to a higher incidence than is presently seen in the corresponding population of Albuquerque, New Mexico.
阳光中的紫外线成分被认为是人类皮肤癌的主要成因,而DNA被认为是主要的分子靶点。到达地球表面的太阳紫外线辐射强度和波长分布的改变,例如平流层臭氧的消耗,将改变太阳辐射对人类皮肤中DNA的损伤效果。评估此类影响的程度需要了解变化后的阳光光谱以及人类皮肤中DNA损伤的作用光谱。我们已经确定了每单位剂量紫外线照射到皮肤表面时,人类皮肤DNA中嘧啶二聚体形成频率的作用光谱。该作用光谱的峰值接近300纳米,在较长和较短波长处均迅速下降。我们的作用光谱在波长小于300纳米时的下降归因于皮肤上层的吸收,这是一种原位效应,在我们的测量中固有地包含在内。在当前平流层臭氧水平(0.32厘米臭氧层)和臭氧消耗50%(0.16厘米臭氧层)的情况下,将二聚体作用光谱与对应太阳角度为40度的太阳光谱进行卷积,结果表明二聚体形成增加了约2.5倍。如果导致皮肤癌的DNA损伤作用光谱与皮肤中二聚体诱导的作用光谱相似,我们的结果与流行病学数据相结合表明,平流层臭氧减少50%将使华盛顿州西雅图市白人男性非黑色素瘤皮肤癌的发病率增加7.5至8倍,达到高于新墨西哥州阿尔伯克基市相应人群目前所见的发病率。