Baxter C S, Chalfin K, Andringa A, Miller M L
Department of Environmental Health, University of Cincinnati College of Medicine, OH 45267-0056.
Carcinogenesis. 1988 Sep;9(9):1563-8. doi: 10.1093/carcin/9.9.1563.
Repeated twice-weekly applications of promoting doses of 12-O-tetradecanoylphorbol-13-acetate (TPA) to the dorsal skin of female adult SENCAR mice led to a reduction in numbers per unit area of epidermal Thy-1+ dendritic cells. Although no parallel effect was observed on Ia+ Langerhans cells, a concurrent reduction of dendritic morphology of both cell types was observed. Topical administration of TPA (2 micrograms) twice weekly for 4 or 8 weeks led to reductions in Thy-1+ cell numbers of 52 and 61%, respectively, whereas a single treatment was without effect. Similar effects were observed in animals initiated with 10 nmol 7,12-dimethylbenz[a]anthracene suggesting that the response was specific to the promotion, rather than the initiation, phase of two-stage tumorigenesis. All initiated animals bore tumors after 16 promoter treatments. In comparison with the potent promoter TPA, the weak overall, but stage-specific promoters 4-O-methylTPA and mezerein showed no effects on number or morphology of either dendritic cell type. These findings are therefore consistent with an important role for quantitative and qualitative alterations in epidermal non-keratinocytes of immune function in tumor promotion.
每周两次对成年雌性SENCAR小鼠背部皮肤涂抹促癌剂量的12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯（TPA），导致表皮Thy - 1 +树突状细胞每单位面积数量减少。虽然未观察到对Ia +朗格汉斯细胞有类似影响，但两种细胞类型的树突形态同时出现了减少。每周两次局部涂抹TPA（2微克），持续4周或8周，导致Thy - 1 +细胞数量分别减少52%和61%，而单次处理则无效果。在用10 nmol 7,12 - 二甲基苯并[a]蒽启动的动物中也观察到类似效果，这表明该反应是针对两阶段肿瘤发生的促癌阶段，而非启动阶段。所有启动的动物在接受16次促癌处理后都出现了肿瘤。与强效促癌剂TPA相比，总体较弱但具有阶段特异性的促癌剂4 - O - 甲基TPA和大戟二萜醇酯对两种树突状细胞类型的数量或形态均无影响。因此，这些发现与表皮非角质形成细胞在肿瘤促进过程中免疫功能的定量和定性改变所起的重要作用是一致的。
