STUDY OF MECHANISMS OF DIFFERENTIATION AND RESISTANCE TO ANTI-CANCER AGENT OF EMBRYONAL CARCINOMA CELLS

(1)我们证明了顺铂在畸胎癌F9细胞中诱导生长抑制并随后诱导分化。本研究以p34^<cdc2>的改变为重点，探讨顺铂对F9细胞周期进程的影响机制。经处理后，cdc2 mRNA的表达水平没有变化，但p34^<cdc2>的半衰期大大缩短，导致细胞周期阻滞在S晚期至G2/M。(2)哺乳动物Rad51基因是酵母Rad5l和大肠杆菌RecA基因的同源基因，与DNA双链断裂修复有关，也参与g辐照和抗癌剂等烷基化剂对DNA损伤的重组修复和各种SOS反应。在本研究中，我们证明了Rad51反义寡核苷酸在体内和体外增强小鼠恶性胶质瘤的放射敏感性，提示通过抑制DNA双链断裂修复来增强恶性胶质瘤的放射治疗。

(1) We demonstrated that cisplatin induced growth suppression followed by induction of differentiation in teratocarcinoma F9 cells. In this study, we investigated the mechanism of the effect of cisplatin for cell cycle progression in F9 cells focusing on the change of p34^<cdc2>. By the treatment, the level of the expressionof cdc2 mRNA did not change, but the half life of p34^<cdc2> was greatly reduced, which would result in the arrest the cell cycle at the late S to G2/M.(2) The mammalian Rad51 gene is a homolog of the yeast Rad5l and E.coli RecA genes, which are related to the repair of DNA double-strand breaks and are also involved in recombination repair and various SOS responses to DNA damage by g-irradiation and alkylating agent like anticancer agent. In this study, we demonstrated that Rad51 antisense oligonucleotides enhances the radiosensityivity of mouse malignant gliomas in vivo and in vitro, suggesting the potentiation for radiation therapy in malignant gliomas by inhibiting DNA double-strand break repair.