Afaq Farrukh, Adhami Vaqar M, Mukhtar Hasan
Department of Dermatology, University of Wisconsin, Medical Sciences Center, Room #B25, 1300 University Avenue, Madison, WI 53706, USA.
Mutat Res. 2005 Apr 1;571(1-2):153-73. doi: 10.1016/j.mrfmmm.2004.07.019. Epub 2005 Jan 23.
Exposure to solar radiation, particularly its ultraviolet (UV) B component, has a variety of harmful effects on human health. Some of these effects include sunburn cell formation, basal and squamous cell cancers, melanoma, cataracts, photoaging of the skin, and immune suppression. Amongst these various adverse effects of UV radiation, skin cancer is of the greatest concern. Over the years, changes in lifestyle has led to a significant increase in the amount of UV radiation that people receive, and this consequently has led to a surge in the incidence of skin cancer. The development of skin cancer is a complex multistage phenomenon involving three distinct stages exemplified by initiation, promotion and progression stages. Each of these stages is mediated via alterations in various cellular, biochemical, and molecular changes. Initiation, the first step in the carcinogenesis process is essentially an irreversible step in which genetic alterations occur in genes that ultimately leads to DNA modification and fixation of mutation. Tumor promotion is the essential process in cancer development involving clonal expansion of initiated cells giving rise to pre-malignant and then to malignant lesions, essentially by alterations in signal transduction pathways. Tumor progression involves the conversion of pre-malignant and malignant lesions into an invasive and potentially metastatic malignant tumor. All these processes for skin cancer development involve stimulation of DNA synthesis, DNA damage and proliferation, inflammation, immunosuppression, epidermal hyperplasia, cell cycle dysregulation, depletion of antioxidant defenses, impairment of signal transduction pathways, induction of cyclooxygenase, increase in prostaglandin synthesis, and induction of ornithine decarboxylase. Photochemoprevention has been appreciated as a viable approach to reduce the occurrence of skin cancer and in recent years, the use of agents, especially botanical antioxidants, present in the common diet and beverages consumed by human population have gained considerable attention as photochemopreventive agents for human use. Many such agents have also found a place in skin care products. Although this is more common in oriental countries, its popularity is significantly growing in western countries. In this article, we have summarized the available information of laboratory studies on UVB-mediated signaling that can be exploited as targets for photochemoprevention. We suggest that the use of skin care products supplemented with proven chemopreventive agents in conjunction with the use of sunscreens along with educational efforts may be an effective strategy for reducing UV-induced photodamage and skin cancer in humans. The mechanistic basis for the use of such products is discussed.
暴露于太阳辐射，尤其是其紫外线（UV）B成分，对人类健康有多种有害影响。其中一些影响包括晒伤细胞形成、基底细胞癌和鳞状细胞癌、黑色素瘤、白内障、皮肤光老化以及免疫抑制。在紫外线辐射的这些各种不利影响中，皮肤癌是最令人担忧的。多年来，生活方式的改变导致人们接受的紫外线辐射量显著增加，这 consequently 导致皮肤癌发病率激增。皮肤癌的发展是一个复杂的多阶段现象，涉及三个不同阶段，以起始、促进和进展阶段为例。这些阶段中的每一个都通过各种细胞、生化和分子变化的改变来介导。起始是致癌过程的第一步，本质上是一个不可逆的步骤，其中基因发生遗传改变，最终导致DNA修饰和突变固定。肿瘤促进是癌症发展中的关键过程，涉及起始细胞的克隆扩增，通过信号转导途径的改变，产生癌前病变，然后发展为恶性病变。肿瘤进展涉及将癌前病变和恶性病变转化为侵袭性且可能转移的恶性肿瘤。皮肤癌发展的所有这些过程都涉及DNA合成、DNA损伤和增殖、炎症、免疫抑制、表皮增生、细胞周期失调、抗氧化防御的消耗、信号转导途径的损害、环氧化酶的诱导、前列腺素合成的增加以及鸟氨酸脱羧酶的诱导。光化学预防已被视为减少皮肤癌发生的一种可行方法，近年来，人类日常饮食和饮料中存在的 agents，尤其是植物性抗氧化剂，作为人类光化学预防剂受到了相当大的关注。许多此类 agents 在护肤品中也有一席之地。虽然这在东方国家更为常见，但在西方国家其受欢迎程度正在显著增长。在本文中，我们总结了关于UVB介导的信号传导的实验室研究的现有信息，这些信息可被用作光化学预防的靶点。我们建议，使用添加了经过验证的化学预防剂的护肤品，结合使用防晒霜以及开展教育工作，可能是减少紫外线诱导的光损伤和人类皮肤癌的有效策略。讨论了使用此类产品的机制基础。
