Turnell R W, Burton A F
Mol Cell Biochem. 1975 Dec 31;9(3):175-89. doi: 10.1007/BF01751312.
When cells of the thymus or mouse leukemias P288 and L1210 are exposed in vitro to the potent synthetic glucocorticoid, 3H-Triamcinolone acetonide, the steroid enters the cells passively and binds to macromolecules in the cytoplasm. At 37 degrees C this hormone-receptor complex enters the nucleus and associates with the chromatin. The association with chromatin occurs not only in the corticosteroid-sensitive rat thymocytes and mouse tumors P288 and P1798S but also in the corticosteroid-resistant mouse tumors L1210 and P1798R. An apparent correlation, although not absolute, exists between the content of glucocorticoid-binding macromolecule and the sensitivity of the lymphocytes studied to the lytic effect of glucocorticoids; the sensitive cells having more receptor than the resistant cells. The process of lysis is attributed to the release from the much larger stores of triglyceride in thymus and sensitive lymphoma cells, of a large pool of FFA which causes focal damage to the nuclear membrane resulting in karyorrhexis and, subsequently, to cytolysis. Resistance is attributed to the capacity for preventing the accumulation of greater than about 0.5 fmole FFA/cell. Resistant cells induced to accumulate greater amounts, even for a few minutes, ultimately undergo lysis. Most effective in accomplishing this are branched chain fatty acids of C-8 and higher, which block FFA metabolism, causing accumulation which results in cytolysis.
当胸腺细胞或小鼠白血病P288和L1210细胞在体外暴露于强效合成糖皮质激素3H-曲安奈德时，该类固醇被动进入细胞并与细胞质中的大分子结合。在37℃时，这种激素-受体复合物进入细胞核并与染色质结合。这种与染色质的结合不仅发生在对皮质类固醇敏感的大鼠胸腺细胞以及小鼠肿瘤P288和P1798S中，也发生在对皮质类固醇耐药的小鼠肿瘤L1210和P1798R中。糖皮质激素结合大分子的含量与所研究的淋巴细胞对糖皮质激素溶解作用的敏感性之间存在一种明显的相关性，尽管不是绝对的；敏感细胞比耐药细胞具有更多的受体。细胞溶解过程归因于胸腺和敏感淋巴瘤细胞中大量甘油三酯储存释放出大量游离脂肪酸（FFA），这些游离脂肪酸对核膜造成局部损伤，导致核碎裂，随后引起细胞溶解。耐药性归因于阻止细胞内积累大于约0.5飞摩尔游离脂肪酸的能力。诱导耐药细胞积累更多游离脂肪酸，即使仅几分钟，最终也会发生细胞溶解。最能实现这一点的是碳链长度为8及以上的支链脂肪酸，它们会阻断游离脂肪酸代谢，导致积累，从而引起细胞溶解。
