Blewitt R W, Abbott A C, Bird C C
Br J Cancer. 1983 Apr;47(4):477-86. doi: 10.1038/bjc.1983.77.
The kinetics, specificity and morphology of cytolethal responses have been studied in human glucocorticoid-sensitive and -insensitive lymphoid cell lines (HLCL) and fibroblasts following treatment with high (10(-3)M) and low (10(-6)M) doses of steroid. The high dose cytolethal response appears non-specific occurring in all cell lines with every steroid tested. By contrast, the low dose (pharmacological) cytolethal response requires an active glucocorticoid and a sensitive HLCL. However, both high and low concentrations of steroid induce virtually identical morphological changes in dying cells and similar changes can be induced in cells killed by deliberate feed exhaustion. Although the morphological features in each case resemble apoptosis, the "programmed" physiological form of cell death, the intracellular events leading to cytolysis seem likely to differ. The earliest morphological changes presaging cell death comprise rounding up of cells and condensation of nuclear chromatin. Nuclear changes progress rapidly thereafter and appear to result from detachment of chromatin from the nuclear matrix. The low dose cytolethal response requires the continuous presence of glucocorticoid for periods in excess of 24h, prior to which cell growth appears unaffected. The constancy of this latent interval suggests glucocorticoids may influence some replication control mechanism unrelated initially to macromolecular biosynthesis.
在用高剂量（10⁻³M）和低剂量（10⁻⁶M）类固醇处理后，已对人糖皮质激素敏感和不敏感的淋巴细胞系（HLCL）及成纤维细胞的细胞致死反应的动力学、特异性和形态学进行了研究。高剂量细胞致死反应似乎是非特异性的，在所测试的每种类固醇作用下，所有细胞系都会出现这种反应。相比之下，低剂量（药理学上的）细胞致死反应需要活性糖皮质激素和敏感的HLCL。然而，高浓度和低浓度的类固醇在垂死细胞中诱导的形态变化实际上是相同的，并且在因故意耗尽营养物质而死亡的细胞中也能诱导出类似的变化。尽管每种情况下的形态特征都类似于凋亡，即细胞死亡的“程序性”生理形式，但导致细胞溶解的细胞内事件似乎可能不同。预示细胞死亡的最早形态变化包括细胞变圆和核染色质凝聚。此后核变化迅速进展，似乎是由于染色质与核基质分离所致。低剂量细胞致死反应需要糖皮质激素持续存在超过24小时，在此之前细胞生长似乎未受影响。这个潜伏间隔的恒定表明糖皮质激素可能会影响一些最初与大分子生物合成无关的复制控制机制。
