Smart R C, Huang M T, Han Z T, Kaplan M C, Focella A, Conney A H
Laboratory of Experimental Carcinogenesis and Metabolism, Roche Institute of Molecular Biology, Hoffmann-La Roche Inc., Nutley, New Jersey 07110.
Cancer Res. 1987 Dec 15;47(24 Pt 1):6633-8.
The effects of topically applied 12-O-tetradecanoylphorbol-13-acetate (TPA) on the level of ascorbic acid in the epidermis and the effects of topically applied ascorbic acid, ascorbyl palmitate (a synthetic lipophilic derivative of ascorbic acid), palmitic acid and sorbitan monopalmitate on TPA-induced epidermal ornithine decarboxylase activity, epidermal DNA synthesis, and the promotion of skin tumors were evaluated in female CD-1 mice. Topical application of 5 or 16 nmol of TPA resulted in a 45-50% decrease in the amount of ascorbic acid per mg protein in mouse epidermis at 5 h after TPA application. Large topical doses of ascorbic acid inhibited TPA-induced tumor promotion in mouse epidermis, but smaller doses were inactive. The topical application of relatively small doses of ascorbyl palmitate had a marked inhibitory effect on TPA-induced ornithine decarboxylase activity, DNA synthesis, and tumor promotion in mouse epidermis. Ascorbic acid, palmitic acid, and sorbitan monopalmitate were less effective than ascorbyl palmitate as inhibitors of tumor promotion. The topical application of 4 mumol of ascorbyl palmitate inhibited by 60-76% the induction of epidermal ornithine decarboxylase activity and DNA synthesis that occurred after a single topical application of 2 nmol of TPA whereas similar doses of ascorbic acid had no inhibitory effect. The topical application of 4 mumol of ascorbyl palmitate together with 5 nmol of TPA twice weekly for 20 weeks to previously initiated mice inhibited by 91% the number of tumors per mouse.
在雌性CD-1小鼠中，评估了局部应用12-O-十四烷酰佛波醇-13-乙酸酯（TPA）对表皮中抗坏血酸水平的影响，以及局部应用抗坏血酸、抗坏血酸棕榈酸酯（抗坏血酸的一种合成亲脂性衍生物）、棕榈酸和山梨醇单棕榈酸酯对TPA诱导的表皮鸟氨酸脱羧酶活性、表皮DNA合成和皮肤肿瘤促进作用的影响。局部应用5或16 nmol的TPA导致在应用TPA后5小时，小鼠表皮中每毫克蛋白质的抗坏血酸量减少45 - 50%。大剂量局部应用抗坏血酸可抑制TPA诱导的小鼠表皮肿瘤促进作用，但小剂量则无活性。局部应用相对小剂量的抗坏血酸棕榈酸酯对TPA诱导的小鼠表皮鸟氨酸脱羧酶活性、DNA合成和肿瘤促进作用有显著抑制作用。抗坏血酸、棕榈酸和山梨醇单棕榈酸酯作为肿瘤促进抑制剂的效果不如抗坏血酸棕榈酸酯。局部应用4 μmol的抗坏血酸棕榈酸酯可抑制单次局部应用2 nmol TPA后发生的表皮鸟氨酸脱羧酶活性和DNA合成的诱导，抑制率为60 - 76%，而相似剂量的抗坏血酸则无抑制作用。对先前已启动的小鼠，每周两次局部应用4 μmol的抗坏血酸棕榈酸酯与5 nmol的TPA，持续20周，可使每只小鼠的肿瘤数量减少91%。
