Potten C S, Chadwick C A, Cohen A J, Nikaido O, Matsunaga T, Schipper N W, Young A R
Department of Epithelial Biology, Paterson Institute for Cancer Research, Christie Hospital (NHS) Trust, Manchester, UK.
Int J Radiat Biol. 1993 Mar;63(3):313-24. doi: 10.1080/09553009314550421.
The incidence of the various types of skin cancer in the general population has been increasing at an annual rate of 2-8% over the past 2 decades. In spite of considerable media coverage on the risk of skin cancer the acquisition of a suntan is still very popular. Thus the UV exposures required for tanning pose a serious carcinogenic risk, particularly to individuals who tan poorly. On the other hand, the presence of natural skin pigment, or the ability to tan easily can protect the skin against some of the harmful effects of subsequent UV exposures (Kollias et al. 1991). We have recently shown (Young et al. 1991) in human volunteers, using an indirect measurement of DNA damage (unscheduled DNA synthesis (UDS) detected by autoradiography), that a tan induced by UV in the presence of a UVB sunscreen (Parsol MCX) preparation containing 5-methoxypsoralen (5-MOP) is more effective at protecting the skin against a subsequent DNA-damaging challenge dose of UV than a tan induced by UV alone, particularly in individuals who tan poorly. No such protection was seen with the same sunscreen lacking 5-MOP. 5-MOP is an ingredient in natural citrus oils and in many other plants. Here we show the same pattern of protective action when measuring, for the first time, DNA damage directly using a monoclonal antibody to thymine dimers (a major category of DNA lesion induced by UV radiation) on fixed human skin sections and automated image analysis. There is a good correlation between UV exposure dose and the levels of thymine dimers in epidermal nuclei. The levels of thymine dimers (measured as absorption by the mean integrated optical density (IOD)) also correlated well with the levels of UDS (grains per nucleus). These findings are of importance in the comparative risk-benefit assessment of sunscreens with and without 5-MOP. The techniques described have applications for measuring other DNA lesions following UV and other exposures.
在过去20年中，普通人群中各类皮肤癌的发病率以每年2% - 8%的速度增长。尽管媒体对皮肤癌风险进行了大量报道，但晒黑仍然很受欢迎。因此，晒黑所需的紫外线暴露会带来严重的致癌风险，尤其是对于那些不容易晒黑的人。另一方面，天然皮肤色素的存在或容易晒黑的能力可以保护皮肤免受后续紫外线暴露的一些有害影响（科利亚斯等人，1991年）。我们最近在人类志愿者中发现（杨等人，1991年），通过间接测量DNA损伤（用放射自显影检测的非预定DNA合成（UDS）），在含有5 - 甲氧基补骨脂素（5 - MOP）的UVB防晒霜（帕索MCX）制剂存在的情况下，紫外线诱导的晒黑比单独紫外线诱导的晒黑更有效地保护皮肤免受后续DNA损伤性紫外线激发剂量的伤害，尤其是对于那些不容易晒黑的人。缺乏5 - MOP的相同防晒霜则没有这种保护作用。5 - MOP是天然柑橘油和许多其他植物中的一种成分。在这里，当我们首次在固定的人体皮肤切片上使用针对胸腺嘧啶二聚体（紫外线辐射诱导的主要DNA损伤类型）的单克隆抗体并通过自动图像分析直接测量DNA损伤时，发现了相同的保护作用模式。紫外线暴露剂量与表皮细胞核中胸腺嘧啶二聚体的水平之间存在良好的相关性。胸腺嘧啶二聚体的水平（以平均积分光密度（IOD）的吸光度测量）也与UDS的水平（每核颗粒数）密切相关。这些发现对于评估含5 - MOP和不含5 - MOP的防晒霜相对风险效益具有重要意义。所描述的技术可用于测量紫外线和其他暴露后其他DNA损伤。
