Volsen S G, Barrass N, Scott M P, Miller K
Immunotoxicology Department, British Industrial Biological Research Association, Carshalton, Surrey, U.K.
Int J Immunopharmacol. 1989;11(6):703-15. doi: 10.1016/0192-0561(89)90157-4.
Experiments have been performed to characterise early changes in the proliferative capacity and phenotypic makeup of thymocytes obtained from DOTC-treated PVG rats. The analysis of density gradient-separated thymocytes demonstrated that within 72 h of oral dosing, spontaneous in vitro thymocyte proliferation was markedly suppressed. A concomitant depletion of an MRC OX18 positive thymocyte population was also observed. These events occurred prior to both overt thymic weight loss and characteristic, treatment-induced histopathological changes. Since recent evidences suggest that the growth factor interleukin-2 (IL-2) may play an important role in thymocyte proliferation, additional molecular biological studies were performed to evaluate whether DOTC may exert its anti-proliferative effects by compromising IL-2 production. Using a mRNA cytoplasmic dot blot technique, the examination of thymocyte lysates from treated and control animals revealed that DOTC markedly down regulated and at high doses abolished, the normal expression of the IL-2 gene. The high turnover gene alpha-actin was, however, unaffected by its action, thus demonstrating the selective effects of DOTC.
已开展实验来表征从经DOTC处理的PVG大鼠获得的胸腺细胞在增殖能力和表型构成方面的早期变化。对密度梯度分离的胸腺细胞的分析表明，口服给药72小时内，体外自发胸腺细胞增殖受到显著抑制。还观察到MRC OX18阳性胸腺细胞群体同时减少。这些事件发生在明显的胸腺重量减轻和特征性的、治疗诱导的组织病理学变化之前。由于最近的证据表明生长因子白细胞介素-2（IL-2）可能在胸腺细胞增殖中起重要作用，因此进行了额外的分子生物学研究，以评估DOTC是否可能通过损害IL-2的产生来发挥其抗增殖作用。使用mRNA细胞质斑点印迹技术，对处理组和对照组动物的胸腺细胞裂解物进行检测，结果显示DOTC显著下调并在高剂量时消除了IL-2基因的正常表达。然而，高周转率基因α-肌动蛋白不受其作用影响，从而证明了DOTC的选择性作用。
