Berton T R, Conti C J, Mitchell D L, Aldaz C M, Lubet R A, Fischer S M
Division of Nutritional Sciences, The University of Texas at Austin, USA.
Mol Carcinog. 1998 Nov;23(3):175-84. doi: 10.1002/(sici)1098-2744(199811)23:3<175::aid-mc6>3.0.co;2-b.
Despite the benefits of sunscreens, ultraviolet (UV) exposure can still lead to skin cancer. In this study we investigated the effect of topical application of the antioxidant vitamin E acetate (VEA) on the inhibition of UV-induced carcinogenesis. Hairless SKH-1 mice received 5.2 mg of VEA 30 min before (VEA/UV) or after (UV/ VEA) a single minimal erythemic dose of UV light. Vehicle-control animals received acetone 30 min before UV exposure (Ace/UV). After 24 h, cyclobutane dimer repair was twofold and 1.5-fold greater in the UVNEA and VEA/UV groups, respectively. Expression of p53 protein in the UV/VEA group was maximum at 12 h after UV exposure, whereas in the Ace/UV- and VEA/UV-treated mice, maximum p53 immunostaining was statistically higher at 15 h (P = 0.03). DNA synthesis as determined by 5-bromo-2'-deoxyuridine incorporation was twofold higher after 15 h in all groups but was not statistically different among treatment groups. Protein levels of cyclin D1 and p21 were increased in both VEA groups by 6 h. In addition, VEA treatments delayed tumor formation and yield for the first 20 wk, although this difference was lost by 30 wk. The telomerase activity of carcinomas from the UV/VEA-treated mice was statistically lower than that of the Ace/UV-treated mice (P = 0.05). This study showed that although VEA may mitigate some of the initial events associated with UV irradiation such as DNA damage and p53 expression, it has limited potential in preventing UV-induced proliferation and tumor formation.
尽管防晒霜有诸多益处，但紫外线（UV）照射仍可导致皮肤癌。在本研究中，我们调查了局部应用抗氧化剂维生素E醋酸酯（VEA）对抑制紫外线诱导的致癌作用的影响。无毛SKH-1小鼠在单次最小红斑剂量紫外线照射前30分钟（VEA/UV）或照射后30分钟（UV/VEA）接受5.2毫克VEA。载体对照动物在紫外线照射前30分钟接受丙酮（Ace/UV）。24小时后，UVNEA组和VEA/UV组的环丁烷二聚体修复分别增加了两倍和1.5倍。UV/VEA组中p53蛋白的表达在紫外线照射后12小时达到最大值，而在Ace/UV和VEA/UV处理的小鼠中，最大p53免疫染色在15小时时在统计学上更高（P = 0.03）。通过5-溴-2'-脱氧尿苷掺入法测定的DNA合成在15小时后在所有组中均增加了两倍，但各治疗组之间无统计学差异。两个VEA组中细胞周期蛋白D1和p21的蛋白水平在6小时时均升高。此外，VEA处理在前20周延迟了肿瘤形成和产量，尽管这种差异在30周时消失。UV/VEA处理小鼠的癌组织端粒酶活性在统计学上低于Ace/UV处理的小鼠（P = 0.05）。本研究表明，尽管VEA可能减轻一些与紫外线照射相关的初始事件，如DNA损伤和p53表达，但它在预防紫外线诱导的增殖和肿瘤形成方面的潜力有限。
