组织型纤溶酶原激活剂（t—PA）工程细胞系遗传特性及成瘤性分析

组织型纤溶酶原激活剂(t-PA)因其在防止血栓形成中起重要作用而受到人们的重视。但由于t-PA在血液中半衰期很短,作为溶栓药,一时难于推广。为了延长半衰期、增强其特异活性,本组构建了t-PA突变体并在CHO-dhfr~-细胞中获得了高效表达。我们在细胞培养基中加入秋水仙素,通过低张、固定、染色,进行染色体分析,结果表明,t-PA工程细胞系染色体条数为20条,畸变类型有异着丝粒。四倍体、裂隙、断片,畸变率为15％,属于正常范围。同时我们对该细胞系进行成瘤性试验,选用4周龄裸鼠作为试验鼠,以Hela细胞为阳性对照,CHO-dhfr~-细胞为阴性对照,试验表明:t-PA工程细胞及表达产物对裸鼠均无成瘤性。

THE ANALYSIS OF HEREDITARY FEATURE AND ON- COGENICITY FOR THE TISSUE-TYPE PLASMINO- GEN ACTIVATOR (T-PA) ENGINEERING CELL LINE

Recombinant t-PA is a new thrombolytic agent, it has a high affinity for fibrin. But as a new thrombolytic agent, it has some disadvantages, such as rapidly eliminated by the hepatic cells from the circulation and inhibited by plasmiriogen activator inhibitor-l, these results in its shorter half-life in human plasma and needing a high concentration in vein by contin-ous infusion. In order to prolong its half-life fand increase resistance to PAl-1, We constructed t-PA engineering cell line. The results of hereditary feature and oncogenic analysis show that t-PA engineering cell line have normal hereditary feature and don't produce tumour in nude mice.