Mitchel R E, McCann R
Health Sciences and Services Division, AECL Research, Chalk River, Ontario, Canada.
Carcinogenesis. 1993 Apr;14(4):659-62. doi: 10.1093/carcin/14.4.659.
The dorsal skins of 6-8 week old female SENCAR mice were initiated with a single application of 10 nmol of 7,12-dimethylbenz[a]anthracene (DMBA) and subsequently promoted twice/week with topical applications of vitamin E (dl-alpha-tocopherol, 80 mumol/treatment). Vitamin E from two separate commercial suppliers was tested. For comparison, a group of similar mice, also initiated with DMBA, was promoted twice/week with the known tumor promoter 12-O-tetradecanoylphorbol-13- acetate (TPA, 2 micrograms/treatment). Papillomas appeared 39 and 50 days respectively after promotion began with vitamin E from the two different sources, as compared with 32 days in the group receiving TPA promoted. Hundred per cent of TPA-promoted animals and 92-96% of the vitamin E-promoted mice developed tumors. A maximum of 15 papillomas/animal appeared in the TPA-promoted mice. The two vitamin E preparations were somewhat less effective than TPA and showed different relative potencies, producing about seven and 12 papillomas per animal respectively. Unlike TPA, vitamin E showed very little ability to produce an inflammatory response in skin. To test whether initiated cells that did not appear as papillomas after vitamin E promotion were still viable, and had proceeded past stage I of promotion (conversion), the group that developed 12 papillomas/animal from vitamin E promotion was further promoted with mezerein, a stage II promoter. In this group, the papilloma frequency then increased to approximately 17/animal. The animals were followed over the course of their lifespan and monitored for skin carcinomas. In the TPA-promoted group 64% of the mice developed carcinomas, while the two vitamin E-promoted groups showed 48 and 60% incidence respectively. These results indicate that topically applied vitamin E acts as a complete tumor promoter in DMBA-initiated mouse skin, with an efficiency approaching that of TPA. Since vitamin E is a powerful antioxidant, they also suggest that reduction of cellular oxidant levels may trigger the tumor promotional process, and it may therefore be prudent to avoid repetitive or prolonged topical exposure of human skin to antioxidants like vitamin E.
对6 - 8周龄雌性SENCAR小鼠的背部皮肤单次涂抹10 nmol的7,12 - 二甲基苯并[a]蒽（DMBA）进行启动，随后每周两次局部涂抹维生素E（dl-α-生育酚，每次治疗80 μmol）进行促癌。测试了来自两个不同商业供应商的维生素E。作为对照，一组同样用DMBA启动的相似小鼠，每周两次用已知的肿瘤促癌剂12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯（TPA，每次治疗2 μg）进行促癌。分别用来自两种不同来源的维生素E促癌开始后39天和50天出现乳头瘤，而接受TPA促癌的组在32天出现乳头瘤。100%接受TPA促癌的动物和92 - 96%接受维生素E促癌的小鼠发生了肿瘤。接受TPA促癌的小鼠每只动物最多出现15个乳头瘤。两种维生素E制剂的效果略低于TPA，且显示出不同的相对效力，每只动物分别产生约7个和12个乳头瘤。与TPA不同，维生素E在皮肤中引发炎症反应的能力非常小。为了测试在维生素E促癌后未表现为乳头瘤的启动细胞是否仍然存活，并且是否已经经过促癌的I期（转化），对从维生素E促癌中每只动物产生12个乳头瘤的组进一步用II期促癌剂大戟二萜醇酯进行促癌。在该组中，乳头瘤频率随后增加到约每只动物17个。在动物的整个生命周期内对其进行跟踪，并监测皮肤癌情况。在接受TPA促癌的组中，64%的小鼠发生了皮肤癌，而两个接受维生素E促癌的组的发病率分别为48%和60%。这些结果表明，局部应用的维生素E在DMBA启动的小鼠皮肤中作为一种完全的肿瘤促癌剂起作用，其效率接近TPA。由于维生素E是一种强大的抗氧化剂，这些结果还表明细胞氧化剂水平的降低可能触发肿瘤促癌过程，因此谨慎的做法可能是避免人类皮肤反复或长期局部接触像维生素E这样的抗氧化剂。
