Baxter C S, Andringa A, Chalfin K, Miller M L
University of Cincinnati Medical Center, Department of Environmental Health, Cincinnati, OH 45267-0056.
Carcinogenesis. 1991 Jun;12(6):1017-21. doi: 10.1093/carcin/12.6.1017.
Topical application of tumor-promoting agents to the dorsal skin of female SENCAR mice on a twice-weekly basis resulted in a reduction in density per unit area of bone marrow-derived Thy-1+ dendritic cells. Activity was observed for well-established tumor-promoting doses of promoting agents of several different chemical types, including 12-O-tetradecanoylphorbol-13-acetate (TPA, diterpene diester), anthralin (dihydroxyanthrone), and n-dodecane (n-alkane). A reduction in density of the same cells was also observed on the basis of the asialoGM1 lipid as a surface marker after TPA treatment. No parallel effect was observed for epidermal Langerhans (Ia+) cells, the second major epidermal immunofunctional cell type, except in the case of anthralin, a finding which is consistent with the reported toxicity of this agent. The stage 2 promoting agent mezerein was unique in inducing a consistent increase in Langerhans cell densities, but did not affect the density of Thy-1+ cells when applied for a prolonged period unless applied following four doses of TPA. In contrast to the SENCAR strain, the promotion-resistant Balb/c and C56BL/6 strains showed no response with respect to TPA-induced reduction of Thy-1+ cell density. In addition to effects on density, the above tumor-promoting agents induced morphological changes in both Thy-1+ and Langerhans cells. When these changes were placed on a quantitative basis by the calculation of shape and area fraction parameters, marked and significant effects were observed for the above agents, but not for the partial promoting agent mezerein nor the non-promoting phorbol diester 4-O-methyl-TPA. The effects of TPA were largely blocked by the potent anti-promoting agent fluocinolone acetonide, moreover. These findings further support an important role for quantitative and qualitative alterations in dendritic epidermal cells in tumor promotion.
每周两次将促癌剂局部涂抹于雌性SENCAR小鼠的背部皮肤，导致骨髓来源的Thy-1⁺树突状细胞的单位面积密度降低。观察到几种不同化学类型的促癌剂在已确定的促癌剂量下具有活性，包括12-O-十四酰佛波醇-13-乙酸酯（TPA，二萜二酯）、蒽林（二羟基蒽酮）和正十二烷（正烷烃）。TPA处理后，基于去唾液酸GM1脂质作为表面标志物，也观察到相同细胞的密度降低。除蒽林外，未观察到表皮朗格汉斯（Ia⁺）细胞（第二种主要的表皮免疫功能细胞类型）有平行效应，这一发现与该试剂已报道的毒性一致。2期促癌剂斑蝥素在诱导朗格汉斯细胞密度持续增加方面是独特的，但长期应用时除非在四剂TPA之后应用，否则不会影响Thy-1⁺细胞的密度。与SENCAR品系相反，促癌抗性Balb/c和C56BL/6品系对TPA诱导的Thy-1⁺细胞密度降低无反应。除了对密度的影响外，上述促癌剂还诱导了Thy-1⁺和朗格汉斯细胞的形态变化。当通过计算形状和面积分数参数将这些变化进行定量时，观察到上述试剂有显著且明显的影响，但对部分促癌剂斑蝥素和非促癌佛波醇二酯4-O-甲基-TPA则没有影响。此外，TPA的作用在很大程度上被强效抗促癌剂醋酸氟轻松所阻断。这些发现进一步支持了树突状表皮细胞的定量和定性改变在肿瘤促进中的重要作用。
