摘要
目的:探讨单纯疱疹病毒Ⅰ型胸苷激酶基因工程化细胞(pLTKcSN/VPC)和更昔洛韦(GCV)系统的动物体内急、慢性毒性。方法:将pLTKcSN/VPC和(或)以β-半乳糖苷酶基因为报告基因的PA317细胞悬液注入小鼠、大鼠和灵长类动物体内,7d后部分动物再全身应用GCV。分批处死动物,观察pLTKcSN/VPC和GCV系统在不同种属动物的体内急、慢性毒性。采用PCR和原位杂交方法直接检测胸苷激酶基因在动物脑和全身各脏器内的整合及表达情况。结合原位杂交和X-gal染色结果,判断注射细胞在动物脑内的存活时间。结果:pLTKcSN/VPC和GCV系统对动物的心、肝、肺和肾有一定的急性损害作用。该细胞在大鼠和猴脑内的存活时间为3周。
Objective: To study the toxicities of the retroviralvector producer cells of herpes simplex virus thymidine kinase gene(pLTKcSN/VPC) and the ganciclovir(GCV) system in mice, rats and primates. Methods: pLTKcSN/VPC and/or the cell suspension of PA317 cells modified by the βgal reporter gene were injected into the animal bodies, and 7 d later, some of the animals were given GCV. The animals were then sacrificed as scheduled, and the acute and long term toxicities of this treatment system were evaluated through histological studies and direct detection of the transduction and expression of the thymidine kinase (TK) gene in animal brain and other organs. The survival interval of the xenogenic cells in rat and monkey brain was determined by the Xgal staining and the in situ hybridization of the TK gene in brain. Results: The pLTKcSN/VPC and GCV system had certain acute side effects on heart, liver, lung and kidney, but no long term toxicities could be detected. The survival time of pLTKcSN/VPC in the brain of rats and primates was 3 weeks. Conclusion: The pLTKcSN/VPC and GCV system has slight toxicities when applied in vivo.
出处
《第二军医大学学报》
CAS
CSCD
北大核心
1998年第2期137-139,共3页
Academic Journal of Second Military Medical University
基金
国家"863"计划生物领域"九五"重点课题