目的:探讨组织特异性胞嘧啶脱氨酶/5氟胞嘧啶(CD/5FC)系统热化疗对裸鼠结肠癌肝转移模型治疗的安全性。方法： 30只裸鼠经门静脉注射转染CD基因的人结肠癌LOVO细胞，建立结肠癌肝转移模型，随机分为对照组、热化疗组和化疗组，分别经腹腔注射生理盐水、43 ℃前药5FC和室温前药5FC\[均为500 mg/（kg·d）\]进行治疗。治疗21 d后处死裸鼠,取各组裸鼠肝脏转移瘤组织、正常肝组织及胃、肺、胰腺、小肠及大肠组织作病理检测； RTPCR检测各组织的CD基因表达。结果：常规病理检测显示对照组肝转移瘤组织细胞生长活跃，热化疗组较化疗组肝转移瘤细胞生长受抑制更明显；3组裸鼠正常肝组织及胃、肺、胰腺、小肠和大肠组织均呈正常形态，无明显病理改变。RTPCR检测显示，3组肝脏转移瘤组织CD基因表达稳定，均见154 bp条带；显示3组裸鼠正常肝组织及胃、肺、胰腺、小肠和大肠组织均无CD基因表达。结论：组织特异性CD/5FC系统热化疗明显提高了CD基因表达的靶向性，减少了热化疗引起的正常组织损伤，该治疗系统有较好的安全性。

Objective: To study the safety of tissuespecific cytosine deaminase /5fluorocytosine (CD/5FC) system thermochemotherapy in treatment of a liver metastasis model of colon cancer in nude mice. Methods: Liver metastasis model was established by intravenously injection of LOVO cell lines harboring tissuespecific CD gene in 30 nude mice. The mice were then randomly divide into three groups, namely, a control group, a thermochemotherapy group, and a chemotherapy group; the three groups were intraperitoneally injected with sodium saline, 43 ℃ prodrug 5 FC or prodrug 5FC, respectively. After 21 days, the animals were sacrificed and the pathological changes of liver, stomach, lung, pancreas, small intestine, and large intestine were examined by HE staining. RTPCR was used to study the expression of CD gene. Results: The growth of tumor cells in the control group grew actively, and the growth in the 43 ℃ prodrug 5 FC group was greatly inhibited compared with those in the prodrug 5FC and normal saline groups. The normal liver, stomach, lung, pancreas, small intestine and large intestine tissues showed no pathological changes and no CD expression. RTPCR examination revealed stable CD gene expression in the 3 groups. Conclusion: Tissuespecific CD/5FC system thermochemotherapy can improve the specificity of CD gene expression, and reduces the damages to the normal tissues by the thermochemotherapy.

福建省自然科学基金资助项目（No.C0410045）