Rapid stimulation of phospholipid metabolism in bovine lymphocytes by tumor-promoting phorbol esters.
Rapid stimulation of phospholipid metabolism in bovine lymphocytes by tumor-promoting phorbol esters.
复制标题
促进肿瘤的佛波酯快速刺激牛淋巴细胞中的磷脂代谢。
作者：
P. Wertz;G. Mueller
12-O-Tetradecanoylphorbol-13-acetate (TPA) 是一种高活性的肿瘤促进剂和淋巴细胞促分裂剂，可加速[甲基-3H]胆碱氯化物（[3H-Me]胆碱）掺入牛淋巴细胞的磷脂中。
在 [3H-Me]胆碱存在下，对暴露于 10-8 m TPA 不同时间间隔的淋巴细胞的磷脂进行色谱分析，显示大约 20 分钟的滞后期，此后磷脂酰胆碱、溶血磷脂酰胆碱和鞘磷脂的标记率均有所增强。结构-活性研究表明佛波二酯加速[3H-Me]胆碱掺入的能力与其作为淋巴细胞促分裂原和肿瘤促进剂的效力平行。对 TPA 的反应分别对放线菌素 D 和放线菌酮对 RNA 和蛋白质合成的抑制不敏感，对细胞松弛素 B 对膜运动的抑制也不敏感。视黄酸是 TPA 促进肿瘤和促卵裂作用的拮抗剂，也可阻断 TPA 加速 [3H-Me] 胆碱掺入磷脂中。这些观察结果表明，牛淋巴细胞系统可能有助于研究促进肿瘤的佛波酯及其类维生素A拮抗剂的分子作用机制。
12- O -Tetradecanoylphorbol-13-acetate (TPA), a highly active tumor-promoting agent and lymphocyte comitogen, accelerates the incorporation of [ methyl -3H]choline chloride ([3H-Me]choline) into the phospholipids of bovine lymphocytes.
Chromatographic analysis of the phospholipids from lymphocytes exposed to 10-8 m TPA for varying intervals in the presence of [3H-Me]choline reveals a lag period of about 20 min, after which the rate of labeling of phosphatidylcholine, lysophosphatidylcholine, and sphingomyelin are all enhanced. Structure-activity studies show that the ability of phorbol diesters to accelerate [3H-Me]choline incorporation runs parallel to their potency as lymphocyte comitogens and as tumor promoters. The response to TPA is insensitive to the inhibition of RNA and protein synthesis by actinomycin D and cycloheximide, respectively, and is also insensitive to the inhibition of membrane movement by cytochalasin B. Retinoic acid, an antagonist of the tumor-promoting and comitogenic actions of TPA, also blocks the acceleration of [3H-Me]choline incorporation into phospholipids by TPA. These observations suggest that the bovine lymphocyte system may be useful for studies of the molecular mechanisms of action of tumor-promoting phorbol esters and their retinoid antagonists.