Inhibition of specific binding of [3H]phorbol-12,13-dipropionate to an epidermal fraction by certain irritants and irritant promoters of mouse skin.
Inhibition of specific binding of [3H]phorbol-12,13-dipropionate to an epidermal fraction by certain irritants and irritant promoters of mouse skin.
复制标题
小鼠皮肤的某些刺激物和刺激促进剂抑制[3H]佛波醇-12,13-二丙酸酯与表皮部分的特异性结合。
DOI：
10.1093/carcin/4.1.77
复制
发表时间：
1983
期刊：
影响因子：
4.7
通讯作者：
Hecker,E
中科院分区：
文献类型：
--
作者：
Schmidt,R;Adolf,W;Marston,A;Roeser,H;Sorg,B;Fujiki,H;Sugimura,T;Moore,RE;Hecker,E
证明了[3 H]佛波醇-12，13-二丙酸酯（[3 H]PDPr）与小鼠皮肤的参与部分的特异性结合（KD= 35 nM; Rt= 1.2 pmol/mg蛋白质）。一系列具有不同程度活性的二萜酯、吲哚生物碱和聚乙酸酯类型的化合物作为皮肤肿瘤促进剂和/或刺激物，已经测试了它们抑制特异性[3 H]PDPr结合的能力。发现了三个主要类别：（i）在它们作为体内刺激物和促进剂的效力与它们在体外抑制特异性结合之间表现出正相关性的化合物：12-O-十四酰基佛波醇-13-乙酸酯、3-O-十四酰基巨大戟二萜醇、庚二烯因子P2、“杀鱼素”、二氢杀鱼素B和银环蛇毒素在体内和体外都有活性，而佛波醇和巨大戟二萜醇是无活性的，4-O-甲基-12-C）-十四酰基-佛波醇-13-乙酸酯是弱活性的;（ii）是强刺激剂和结合抑制剂但是弱或实际上非促进剂的化合物：mezerein，12-O-视黄酰基佛波醇-13-乙酸酯和milliamine C;（iii）强刺激物，其为弱或轻微活性的结合抑制剂：脱溴阿托伐他汀和树脂毒素。这些研究结果与肿瘤促进的生化机制的解释的一些后果进行了讨论。
Specific binding of [3H]phorbol-12,13-dipropionate ([3H]PDPr) to a participate fraction of mouse skin is demonstrated (KD= 35 nM; Rt= 1.2 pmol/mg protein). A series of compounds of the diterpene ester, indole akaloid and polyacetate types with different degrees of activity as skin tumor promoters and/or irritants have been tested for their capacity to inhibit specific [3H]PDPr binding. Three main categories are found: (i) compounds which exhibit a positive correlation between their potency as irritants and promotersin vivoand their inhibition of specific bindingin vitro: 12-O-tetradecanoyiphorbol-13-acetate, 3-O-tetradecanoylingenol, pimelea factor P2, ‘teleocidin’, dihydroteleocidin B, and iyngbyatoxin are activein vivoandin vitro, whereas phorbol and ingenol are inactive and 4-O-methyl-12-C)-tetradecanoyl-phorbol-13-acetate is weakly active; (ii) compounds which are strong irritants and inhibitors of binding but are weak or practically non-promoters: mezerein, 12-O-retinoylphorbol-13-acetate and milliamine C; (iii) strong irritants which are weak or marginally active inhibitors of binding: debromoaplysiatoxin and resiniferatoxin. Some consequences of these findings with respect to interpretations of the biochemical mechanism(s) of tumor promotion are discussed.