Liebler D C, Burr J A
Department of Pharmacology and Toxicology and Southwest Environmental Health Sciences Center, College of Pharmacy, The University of Arizona, Tucson, AZ 85721-0207, USA.
Carcinogenesis. 2000 Feb;21(2):221-5. doi: 10.1093/carcin/21.2.221.
Recent reports indicate that both orally administered and topically applied alpha-tocopherol (vitamin E, TH) prevent UVB-induced skin carcinogenesis in mice. Because UVB exposure causes the formation of oxidants associated with tumor promotion, epidermal TH status may be an important determinant of susceptibility to photocarcinogenesis. To test this hypothesis, we studied the status of epidermal TH in C3H mice following exposure to single and repeated UVB exposures at doses typical of chronic photocarcinogenesis protocols. Exposure of mice to a single 13 kJ/m(2) dose over 60 min resulted in no acute depletion of epidermal TH and a modest increase in TH within 6-12 h. Daily exposure to 6.5 kJ/m(2) over 30 min resulted in a gradual increase in epidermal TH, which reached 5-fold after five daily exposures. The increase in epidermal TH was accompanied by an increase in the TH oxidation products alpha-tocopherolquinone (TQ) and alpha-tocopherolhydroquinone (THQ). We also studied the effect of the prooxidant chemical tumor promoter benzoyl peroxide and the prooxidant azo initiators azobis(amidinopropane HCl) and azobis(2, 4-dimethylvaleronitrile). Topical application of these prooxidant chemicals acutely oxidized epidermal TH to TQ and THQ. Topical treatments with the phorbol ester tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) increased epidermal TH levels without producing a significant accumulation of TH oxidation products. The results indicate that UVB and tumor promoting chemicals all exert qualitatively different effects on epidermal TH status and that UVB and TPA trigger an adaptive response involving epidermal TH accumulation.
最近的报告表明，口服和局部应用的α-生育酚（维生素E，TH）均可预防紫外线B（UVB）诱导的小鼠皮肤癌发生。由于UVB照射会导致与肿瘤促进相关的氧化剂形成，表皮TH状态可能是光致癌易感性的重要决定因素。为了验证这一假设，我们研究了C3H小鼠在按照慢性光致癌方案的典型剂量进行单次和重复UVB照射后的表皮TH状态。小鼠在60分钟内接受单次13 kJ/m²剂量的照射后，表皮TH没有急性耗竭，且在6 - 12小时内TH有适度增加。每天在30分钟内接受6.5 kJ/m²的照射会导致表皮TH逐渐增加，在每日照射五次后达到5倍。表皮TH的增加伴随着TH氧化产物α-生育醌（TQ）和α-生育氢醌（THQ）的增加。我们还研究了促氧化化学肿瘤启动剂过氧化苯甲酰以及促氧化偶氮引发剂偶氮双（脒基丙烷盐酸盐）和偶氮双（2,4 - 二甲基戊腈）的作用。局部应用这些促氧化化学物质会使表皮TH急性氧化为TQ和THQ。用佛波酯肿瘤启动剂12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯（TPA）进行局部处理可增加表皮TH水平，但不会产生TH氧化产物的显著积累。结果表明，UVB和肿瘤促进化学物质对表皮TH状态均产生质的不同影响，且UVB和TPA会引发涉及表皮TH积累的适应性反应。
