Effect of glucocorticoid hormones in vitro on the structural integrity of nuclei in corticosteroid-sensitive and -resistant lines of lymphosarcoma P1798.
Effect of glucocorticoid hormones in vitro on the structural integrity of nuclei in corticosteroid-sensitive and -resistant lines of lymphosarcoma P1798.
复制标题
体外糖皮质激素对淋巴肉瘤 P1798 皮质类固醇敏感和耐药系细胞核结构完整性的影响。
作者：
M. Nicholson;D. Young
大鼠胸腺细胞暴露于糖皮质激素导致细胞核在低渗休克裂解全细胞后存活的能力下降。在这项研究中，一个类似的糖皮质激素诱导的“核脆性”增加被发现在两个皮质激素敏感和耐药系的P1798小鼠淋巴肉瘤细胞。皮质醇（10（-6）M）暴露2小时后，皮质激素敏感细胞的核脆性略有增加; 3小时时，核脆性比对照值高20%至40%。这种作用似乎是一种特异性糖皮质激素反应。皮质醇和地塞米松在10（-7）M时都产生作用，10（-6）M睾酮无活性，与糖皮质激素受体结合的皮质醇酮降低了这种作用。环己酰亚胺，在抑制蛋白质合成的浓度，也阻断这种作用。虽然皮质激素抗性系也表现出类似程度的效果，但它需要更长的激素暴露时间（6小时）。在没有激素的情况下可测量的两种细胞系（皮质激素抗性系的细胞核较不脆弱）的“耐寒性”的明显差异似乎解释了对类固醇的差异敏感性。在此基础上提出了新的抗性理论，其中抗性的出现与细胞的结构差异有关。
Exposure of rat thymus cells to glucocorticoids leads to a decreased ability of nuclei to survive the lysis of whole cells by hypotonic shock. In this study, a similar glucocorticoid-induced increase in "nuclear fragility" was found in both corticoid-sensitive and -resistant lines of P1798 mouse lymphosarcoma cells. In corticoid-sensitive cells a small increase in nuclear fragility is seen after a 2-hr exposure to cortisol (10(-6) M); by 3 hr it is 20 to 40% above control values. This effect appears to be a specific glucocorticoid response. Both cortisol and dexamethasone at 10(-7) M produce an effect, 10(-6) M testosterone is inactive, and cortexolone, which binds to glucocorticoid receptors, reduces the effect. Cycloheximide, at concentrations that inhibit protein synthesis, also blocks this effect. While the corticoid-resistant line also demonstrates an effect of similar magnitude, it requires a much longer exposure to the hormone (6 hr). Distinct differences in the "hardiness" of the two cell lines (nuclei of the corticoid-resistant line are less fragile) measurable in the absence of hormones appears to account for the differential susceptibility to steroids. On this basis a new theory of resistance is advanced where the emergence of resistance is related to structural differences in the cells.