Gensler H L, Aickin M, Peng Y M, Xu M
Cancer Prevention and Control Program, Arizona Cancer Center, Tucson 85724, USA.
Nutr Cancer. 1996;26(2):183-91. doi: 10.1080/01635589609514474.
With increasing solar ultraviolet (UV)-B radiation reaching the Earth's surface and the incidence of skin cancer rising steadily, there is an ever-increasing need to determine agents that modulate photocarcinogenesis and to understand the mechanisms underlying this modulation. Our laboratory has demonstrated that topical application of the dl-alpha-tocopherol form of vitamin E to mice prevents skin cancer and the immunosuppression induced by UVB irradiation. However, dl-alpha-tocopherol has limited stability at room temperature. The current study was designed to ask whether the thermostable esters of vitamin E, alpha-tocopheryl acetate, or alpha-tocopheryl succinate prevent skin cancer and immunosuppression induced in mice by UV radiation. In the alpha-tocopheryl acetate study, skin cancers developed in 70% of UVB-irradiated control mice and in 90%, 73%, and 90% of mice receiving topical applications of 12.5, 25, and 50 mg of dl-alpha-tocopheryl acetate, respectively. In the alpha-tocopheryl succinate study, skin cancer developed in 59.3% of control UVB-irradiated mice and in 82%, 100%, and 81.5% of mice treated with 2.5, 12.5, and 25 mg d-alpha-tocopheryl succinate, respectively. Thus neither alpha-tocopheryl acetate nor alpha-tocopheryl succinate prevented photocarcinogenesis. At 12.5 and 25 mg/treatment, alpha-tocopheryl acetate and alpha-tocopheryl succinate, respectively, enhanced photocarcinogenesis (p = 0.0114 and 0.0262, respectively, log rank test). On the basis of high-performance liquid chromatography analysis at 16-17 weeks after the first vitamin E treatment, the esterified forms of vitamin E applied epicutaneously accumulated in the skin, but the levels of free alpha-tocopherol remained low. Neither alpha-tocopheryl acetate nor alpha-tocopheryl succinate prevented the induction by UV radiation of immunosusceptibility to implanted syngeneic antigenic UV-induced tumor cells. Thus alpha-tocopheryl acetate or alpha-tocopheryl succinate not only failed to prevent photocarcinogenesis, but may have enhanced to process. Considering that alpha-tocopherol esters are included in many skin lotions, cosmetics, and sunscreens, further studies are needed to determine the conditions under which topical alpha-tocopheryl acetate and alpha-tocopheryl succinate enhance photocarcinogenesis.
随着到达地球表面的太阳紫外线（UV）-B辐射增加以及皮肤癌发病率稳步上升，确定能够调节光致癌作用的物质并了解这种调节作用背后的机制的需求日益增长。我们实验室已证明，将维生素E的dl-α-生育酚形式局部应用于小鼠可预防皮肤癌以及UVB照射诱导的免疫抑制。然而，dl-α-生育酚在室温下稳定性有限。当前研究旨在探究维生素E的热稳定酯类，即α-生育酚乙酸酯或α-生育酚琥珀酸酯，是否能预防UV辐射诱导的小鼠皮肤癌和免疫抑制。在α-生育酚乙酸酯研究中，70%接受UVB照射的对照小鼠发生了皮肤癌，而分别接受12.5、25和50mg dl-α-生育酚乙酸酯局部应用的小鼠中，皮肤癌发生率分别为90%、73%和90%。在α-生育酚琥珀酸酯研究中，59.3%接受UVB照射的对照小鼠发生了皮肤癌，而分别用2.5、12.5和25mg d-α-生育酚琥珀酸酯处理的小鼠中，皮肤癌发生率分别为82%、100%和81.5%。因此，α-生育酚乙酸酯和α-生育酚琥珀酸酯均未能预防光致癌作用。在每次处理剂量为12.5和25mg时，α-生育酚乙酸酯和α-生育酚琥珀酸酯分别增强了光致癌作用（对数秩检验，p值分别为0.0114和0.0262）。在首次给予维生素E处理后16 - 17周进行的高效液相色谱分析表明，经皮应用的维生素E酯化形式在皮肤中蓄积，但游离α-生育酚水平仍然较低。α-生育酚乙酸酯和α-生育酚琥珀酸酯均未能预防UV辐射诱导的对植入的同基因抗原性UV诱导肿瘤细胞的免疫易感性。因此，α-生育酚乙酸酯或α-生育酚琥珀酸酯不仅未能预防光致癌作用，反而可能增强了这一过程。鉴于许多护肤液、化妆品和防晒剂中都含有α-生育酚酯类，需要进一步研究以确定局部应用α-生育酚乙酸酯和α-生育酚琥珀酸酯增强光致癌作用的条件。
