de Gruijl F R, Sterenborg H J, Forbes P D, Davies R E, Cole C, Kelfkens G, van Weelden H, Slaper H, van der Leun J C
Department of Dermatology, University of Utrecht, The Netherlands.
Cancer Res. 1993 Jan 1;53(1):53-60.
Information on the variation in carcinogenicity with wavelength is crucial in risk assessments for skin cancers induced by UV radiation. Until recently the wavelength (lambda) dependencies of other detrimental UV effects, such as sunburn, have been used as substitutes. Direct information on the lambda dependency can only be obtained from animal experiments. To this end we accumulated a large data set on skin tumors induced by chronic UV exposure of albino SKH:HR1 mice (14 different broadband UV sources and about 1100 mice); the data come from the Photobiology Unit of the former Skin and Cancer Hospital in Philadelphia and from the Department of Dermatology of the University of Utrecht. The lambda dependency was extracted from this data set (a statistically satisfactory description with chi 2 = 13.4, df = 7) and represented by the Skin Cancer Utrecht-Philadelphia action spectrum, i.e., a set of factors to weight the exposures at different wavelengths according to their respective effectiveness (inversely proportional to the daily exposure required for a median tumor induction time of 300 days). The fits obtained with other already available action spectra proved to be poor (chi 2 > 60, df = 11). The maximum effectiveness was found at 293 nm, and above 340 nm the effectiveness showed a shoulder at about 10(-4) of the maximum. A sensitivity analysis of the final solution for the lambda dependency showed a large margin of uncertainty above 340 nm and an information gap below 280 nm. The large variation in tumor responses in the present data set can be transformed to a coherent, common dose-response relationship by proper spectral weighting with this single action spectrum.
紫外线辐射诱发皮肤癌的风险评估中,致癌性随波长变化的信息至关重要。直到最近,其他有害紫外线效应(如晒伤)的波长(λ)依赖性一直被用作替代。关于λ依赖性的直接信息只能从动物实验中获得。为此,我们积累了大量关于白化病SKH:HR1小鼠长期紫外线照射诱发皮肤肿瘤的数据集(14种不同的宽带紫外线源和约1100只小鼠);这些数据来自费城 former Skin and Cancer Hospital 的光生物学部门以及乌得勒支大学皮肤科。从该数据集中提取了λ依赖性(卡方 = 13.4,自由度 = 7,统计上令人满意的描述),并由乌得勒支 - 费城皮肤癌作用光谱表示,即一组根据不同波长各自的有效性对暴露进行加权的因子(与诱导中位肿瘤时间为300天所需的每日暴露量成反比)。用其他已有的作用光谱得到的拟合结果很差(卡方 > 60,自由度 = 11)。最大有效性在293 nm处被发现,在340 nm以上,有效性在最大值的约10^(-4)处出现一个平台。对λ依赖性最终解决方案的敏感性分析表明,在340 nm以上存在很大的不确定性范围,在280 nm以下存在信息空白。通过用这个单一作用光谱进行适当的光谱加权,本数据集中肿瘤反应的巨大差异可以转化为连贯的、通用的剂量反应关系。