Nishigori Chikako
Division of Dermatology, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe University, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Photochem Photobiol Sci. 2006 Feb;5(2):208-14. doi: 10.1039/b507471a. Epub 2005 Dec 1.
Many aspects are involved in photocarcinogenesis. Historically, genetic change caused by UV-B-induced pyrimidine photoproducts have been paid much attention. Indeed they are very important factors. However, recent reports indicate the involvement of many other factors. First, UV-B induces not only pyrimidine photoproducts but also DNA lesions modified by reactive oxygen species (ROS). Several reports pointed out that types of mutations that are not theoretically caused by pyrimidine photoproducts are frequently observed in the human skin cancers of sun-exposed areas and UV-B-induced murine skin cancers. In addition to transition-type mutations at dipyrimidine sites, mutations which may be induced by the presence of oxidative DNA damage, are frequently observed in the ras oncogene and p53 tumor suppressor gene in human skin cancers of sun-exposed area and in UV-induced mouse skin cancers. Second, recent studies have shown that not only UV-B but also UV-A is involved in photocarcinogenesis based on animal experiments whereas UV-B has been considered mostly responsible. UV-A induces indirect DNA damage via ROS and lipid peroxidation. ROS have been associated not only with initiation, but promotion and progression in the multistage carcinogenesis model. Third, biological responses other than direct influence by UV such as inflammatory and immunological responses and oxidative modifications of DNA and proteins appears also responsible for carcinogenesis. Persistent oxidative stress in cancer may also cause activation of transcription factors and protooncogenes such as c-fos and c-jun as well as genetic instability. Such a stress may also contribute to maintain their malignant characteristics. An integrated model for photocarcinogenesis is proposed.
光致癌作用涉及多个方面。从历史上看，UV-B诱导的嘧啶光产物引起的基因变化备受关注。事实上，它们是非常重要的因素。然而，最近的报告表明还涉及许多其他因素。首先，UV-B不仅诱导嘧啶光产物，还诱导由活性氧（ROS）修饰的DNA损伤。几份报告指出，在暴露于阳光的区域的人类皮肤癌和UV-B诱导的小鼠皮肤癌中经常观察到理论上并非由嘧啶光产物引起的突变类型。除了二嘧啶位点的转换型突变外，在暴露于阳光区域的人类皮肤癌和UV诱导的小鼠皮肤癌的ras癌基因和p53肿瘤抑制基因中，经常观察到可能由氧化性DNA损伤引起的突变。其次，最近的研究表明，基于动物实验，不仅UV-B，而且UV-A也参与光致癌作用，而此前一直认为主要是UV-B的作用。UV-A通过ROS和脂质过氧化作用诱导间接DNA损伤。ROS不仅与多阶段致癌模型中的起始有关，还与促进和进展有关。第三，除了UV的直接影响之外的生物反应，如炎症和免疫反应以及DNA和蛋白质的氧化修饰，似乎也与致癌作用有关。癌症中持续的氧化应激还可能导致转录因子和原癌基因如c-fos和c-jun的激活以及基因不稳定。这种应激也可能有助于维持它们的恶性特征。本文提出了一个光致癌作用的综合模型。
