Odaka C, Toyoda E, Nemoto K
Department of Bacterial and Blood Products, National Institute of Infectious Diseases, Tokyo, Japan.
Immunology. 1998 Nov;95(3):370-6. doi: 10.1046/j.1365-2567.1998.00606.x.
Deoxyspergualin (DSG) has been found to have an antitumour and immunosuppressive activity. However, the precise mechanism of action of DSG has not been clarified. We have used its analogue, methyldeoxyspergualin (MeDSG) for in vitro culture studies of DSG since it shows good stability in aqueous solution and retains strong immunosuppressive activity. In the present study, we found that MeDSG inhibited proliferation of rapidly dividing murine T-cell hybridomas, resulting in cell death. The cell death was accompanied by chromatin condensation and DNA cleavage at the linker regions between nucleosomes. Furthermore, MeDSG induced a reduction in mitochondrial transmembrane potential. When murine thymocytes were treated with MeDSG for 48 hr, a slight increase of DNA fragmentation was constantly observed, and selective depletion of CD4- CD8- cells was noticed. In contrast, CD4+ CD8+ cells were hardly affected. Moreover, splenic T-cells are resistant to MeDSG-induced apoptosis, as evaluated by measuring DNA cleavage. Our findings may account for the immunosuppressive and antitumour properties of DSG which were described in a number of previous studies.
去氧精胍菌素（DSG）已被发现具有抗肿瘤和免疫抑制活性。然而，DSG的确切作用机制尚未阐明。我们使用其类似物甲基去氧精胍菌素（MeDSG）进行DSG的体外培养研究，因为它在水溶液中表现出良好的稳定性并保留了强大的免疫抑制活性。在本研究中，我们发现MeDSG抑制快速分裂的小鼠T细胞杂交瘤的增殖，导致细胞死亡。细胞死亡伴随着染色质浓缩和核小体间连接区域的DNA裂解。此外，MeDSG诱导线粒体跨膜电位降低。当用MeDSG处理小鼠胸腺细胞48小时时，持续观察到DNA片段化略有增加，并注意到CD4-CD8-细胞的选择性耗竭。相比之下，CD4+CD8+细胞几乎不受影响。此外，通过测量DNA裂解评估，脾T细胞对MeDSG诱导的凋亡具有抗性。我们的发现可能解释了先前许多研究中描述的DSG的免疫抑制和抗肿瘤特性。
