Yamasaki H, Weinstein I B, Van Duuren B L
Carcinogenesis. 1981;2(6):537-43. doi: 10.1093/carcin/2.6.537.
A potent tumour promoter on mouse skin, phorbol-9-myristate-9a-acetate, induces certain clones of Friend erythroleukemia cells to become adhesive to the surface of tissue culture dishes, whereas in the absence of this compound, these cells grow in suspension. We have quantitatively tested 20 other phorbol esters and related compounds for this effect. When the results are expressed as the concentrations of compounds which show half-maximum effect on cell adhesion, the decreasing order of potency is: phorbol-9-myristate-9a-acetate (3.6 x 10(-10) M) approximately equal to gnilatimacrin greater than milliamine A approximately equal to phorbol-9,9a-didecanoate approximately equal to mezerein approximately equal to gnidilatin approximately equal to ingenol-3,20-dibenzoate greater than phorbol-9-myristate-9a-acetate greater than phorbol-9,9a-dibutyrate approximately equal to phorbol-9-9a-dibenzoate greater than 4a-O-methyl-phorbol-9-myristate-9a-acetate greater than phorbol-9-myristate-9a-acetate-3-aldehyde greater than phorbol-9,9a-diacetate greater than 2,3-dihydrophorbol-9-myristate-9a-acetate. Phorbol, 4a alpha-phorbol-9,9a-didecanoate, phorbol-3,9,9a-triacetate, phorbol-9-myristate, phorbol-9-monoacetate and phorbol-9a-monoacetate were inactive in this assay when tested at concentrations as high as 1 microgram/ml (10(-6) M). None of these 20 compounds induced adhesion when they were tested with a variant clone of Friend erythroleukemia cells which is resistant to the induction of adhesion and several other effects of phorbol-myristate-acetate. When the relative potencies of these compounds in the adhesion assay were compared to available in vivo data on tumour promoting activity on mouse skin, there was, in general, a good qualitative correlation. A better but not perfect quantitative correlation was obtained when the results from the adhesion assay were compared with reported inflammatory activity on mouse ear. When several other tumour promoters and cocarcinogens which differ structurally from the phorbol esters and related plant diterpenes were tested, none of these induced adhesion in this assay.
佛波醇 -9-肉豆蔻酸酯-9α-乙酸酯是一种强效的小鼠皮肤肿瘤促进剂，它能诱导Friend红白血病细胞的某些克隆贴附于组织培养皿表面，而在没有这种化合物的情况下，这些细胞呈悬浮生长。我们已经对其他20种佛波醇酯及相关化合物的这种作用进行了定量测试。当结果以对细胞黏附显示半数最大效应的化合物浓度表示时，效力递减顺序为：佛波醇 -9-肉豆蔻酸酯-9α-乙酸酯（3.6×10⁻¹⁰ M）≈格尼拉替马林＞米利亚明A≈佛波醇 -9,9α-二癸酸酯≈mezerein≈格尼地拉丁≈ingenol -3,20-二苯甲酸酯＞佛波醇 -9-肉豆蔻酸酯-9α-乙酸酯＞佛波醇 -9,9α-二丁酸酯≈佛波醇 -9,9α-二苯甲酸酯＞4a -O-甲基-佛波醇 -9-肉豆蔻酸酯-9α-乙酸酯＞佛波醇 -9-肉豆蔻酸酯-9α-乙酸酯-3-醛＞佛波醇 -9,9α-二乙酸酯＞2,3-二氢佛波醇 -9-肉豆蔻酸酯-9α-乙酸酯。佛波醇、4αα-佛波醇 -9,9α-二癸酸酯、佛波醇 -3,9,9α-三乙酸酯、佛波醇 -9-肉豆蔻酸酯、佛波醇 -9-单乙酸酯和佛波醇 -9α-单乙酸酯在高达1微克/毫升（10⁻⁶ M）的浓度下进行该试验时无活性。当用对佛波醇-肉豆蔻酸酯-乙酸酯诱导黏附及其他几种效应具有抗性的Friend红白血病细胞变异克隆进行测试时，这20种化合物均未诱导黏附。当将这些化合物在黏附试验中的相对效力与现有的关于对小鼠皮肤肿瘤促进活性的体内数据进行比较时，总体上存在良好的定性相关性。当将黏附试验结果与报道的对小鼠耳部的炎症活性进行比较时，获得了较好但并不完美的定量相关性。当测试其他几种在结构上与佛波醇酯及相关植物二萜不同的肿瘤促进剂和助致癌物时，在该试验中它们均未诱导黏附。
