目的：以P388/DBA小鼠白血病模型，探讨新型自杀基因YCD的体内治疗作用。方法：用逆转录病毒载体将YCD基因导入，筛选P388-YCD-eGFP细胞克隆，以P388-eGFP和野生性（wt）P388细胞为对照。（1）3组细胞腹腔接种给DBA小鼠（n=5），5×10 6/只（下同），观察致病性；（2）3组细胞腹腔接种给DBA小鼠（n=5），分别以5-FC治疗2周，观察疗效；（3）2组×5只小鼠腹腔接种P388-YCD-eGFP，5-FC 5 μmol/L·d-1×2 d或PBS治疗，根据小鼠存活时间推算杀伤效率。以流式细胞仪、冰冻切片和HE切片检测各脏器中白血病细胞的分布和变化。结果：基因导入对细胞的生物学特性影响不显著；5-FC治疗2周，YCD组小鼠存活(17.8±1.89) d，而eGFP组和wtP388组分别存活(7.8±1.10) d 和(7.7±1.15) d （P<005）；5-FC治疗2 d的杀伤率达99.6%。结论：YCD转基因细胞在体内可被5-FC有效杀灭，该系统具有应用前景。

Objective: To explore therapeutic effect of a novel yeast cytosine deaminase (YCD) suicide gene in vivo on P388/DBA murine leukemia model. Methods: P388-YCD-eGFP clone was selected after retrovirus transduction by limiting dilution, P388-eGFP and wild type (wt) P388 were used as control. (1) Tumorigenesis study: DBA mice were inoculated with P388-YCD-eGFP, P388-eGFP or wt P388, 5×10 6/each i.p. (n=5). (2) 5-FC therapy study: After inoculation with P388-YCD-eGFP, P388-eGFP and wt P388 respectively (n=5)，each mouse was given 5-FC with a dose of 5 μmol/d×2 w. (3) 5-FC killing effect study: 2 groups (n=5) of mice inoculated with P388-YCD-eGFP were treated with 5-FC×2 d or PBS. Results: Mice in YCD, eGFP and wtP388 group developed leukemia and survived for (8±1.0) d, (7.6±0.89) d and (7.8±1.64) d (P>0.05), respectively. After 5-FC-2w-treatment, mice in YCD group survived (17.8±1.89) d (P<0.05) vs (7.8±1.10) d (eGFP) and (7.7±1.15) d (wtP388) group, respectively. Mice of YCD group with 5-FC-2 d-treatment survived for (13.3±2.36) d，while PBS group (8.0±1.15) d. Flow cytometry and pathological examinations suggested mice of in YCD group died of leukemia relapse. Conclusion: YCD/5-FC is an efficient suicide gene system in vivo.

国家自然基金（30172347）和上海市卫生系统百名跨世纪优秀学科带头人培养计划（98 BR029）资助