Induction of dark keratinocytes by 12-O-tetradecanoylphorbol-13-acetate and mezerein as an indicator of tumor-promoting efficiency.
Induction of dark keratinocytes by 12-O-tetradecanoylphorbol-13-acetate and mezerein as an indicator of tumor-promoting efficiency.
复制标题
12-O-十四烷酰佛波醇-13-乙酸酯和 mezerein 诱导深色角质形成细胞作为肿瘤促进效率的指标。
作者：
Andres J Klein;S. Major;T. Slaga
12-O-十四烷酰佛波醇-13-乙酸酯 (TPA) 和 mezerein (MZ) 是结构相似的二萜酯，就其在小鼠皮肤中的增生、炎症和鸟氨酸脱羧酶活性诱导作用而言，在摩尔基础上大致等价。另一方面，TPA 作为肿瘤促进剂比 MZ 更有效。测定单次局部使用 1、2 或 4 微克 TPA 或 MZ 处理的小鼠毛囊间表皮 (IFE) 中深色基底角质形成细胞的百分比，并在其后 12、24、48、96 和 144 小时进行研究。结果表明，在 IFE 以及毛囊漏斗部中，TPA 诱导的暗细胞数量是 MZ 的 2 至 3 倍。在所有实验和对照情况下，后者上皮呈现出比 IFE 更多数量的深色角质形成细胞，并且在漏斗状表皮中 TPA 和 MZ 的效果之间的差异甚至比在 IFE 中更大。 TPA 诱导暗细胞数量比对照增加 5 至 11 倍（IFE 中约为 2%），局部应用 4 微克 TPA 24 小时后基底层达到最大值 21%。 MZ 仅产生了 3 至 6 倍的增量。两种化合物的基底层和深色基底细胞的标记指数均显着且类似地增加。不同的暗细胞诱导特征似乎是 TPA 和 MZ 产生的早期效应中唯一可检测到的差异，并且表明去分化暗细胞的产生在肿瘤促进的早期阶段的重要性。
12-O-Tetradecanoylphorbol-13-acetate (TPA) and mezerein (MZ) are diterpene esters of similar structure and approximately equipotent on a molar basis as far as their hyperplasiogenic, inflammatory, and induction of ornithine decarboxylase activity effects in mouse skin are concerned. On the other hand, TPA is much more effective than MZ as a tumor promoter. The percentage of dark basal keratinocytes was determined in the interfollicular epidermis (IFE) of mice topically treated with 1, 2, or 4 microgram of either TPA or MZ in a single application and studied at 12, 24, 48, 96, and 144 h thereafter. The results showed that TPA induced 2 to 3 times more dark cells than MZ in the IFE as well as in the infundibular portion of the hair follicle. The latter epithelium presented a larger number of dark keratinocytes than the IFE in all experimental and control situations, and the differences between the effects of TPA and MZ were even greater in the infundibular epidermis than in the IFE. TPA induced an increase of 5 to 11 times over the control number of dark cells (approximately 2% in IFE), reaching maximum values of 21% in the basal layer 24 h after topical application of 4 microgram of TPA. MZ only produced a 3- to 6-fold increment. The labeling indices of the basal layer and of the dark basal cells were markedly and similarly increased with both compounds. The different dark-cell inducing characteristics seem to be the only detectable difference in early effects produced by TPA and MZ and would point to the importance of the production of the dedifferentiated dark cells during early stages of tumor promotion.