胞苷脱氨酶基因对小鼠大剂量化疗的保护作用

Protection of cytidine deaminase gene gainst toxicity of high-dose chemotherapy in mice

AIM: To observe the tolerance to high-dose cytarabine (Ara-C) in mice after the cytidine deaminase (CD) gene is trans-fected into mouse bone marrow cells, and to explore the feasibility of chemotherapy combined with the tolerance of myelosuppression. METHODS: Human cytidine deaminase gene was trans-fected into mouse bone marrow cells by retroviral vector. Then the colony-forming unit granulocyte-macrophage (CFU-GM) was observed in the cells of marrow donor and acceptor mice treated with Ara-C. DNA was extracted from the cells and the drug-resistant genes were detected by polymerase chain reaction (PCR). The blood cell count, weight and survival rate of the mice treated with Ara-C were analyzed. RESULTS: Drug-resistant colonies appeared both in the bone marrow cells of donor and acceptor mice treated with Ara-C, and the CFU-GMs were 52% and 54% respectively, which were significantly higher than those of the controls (X2 = 124.62,126.26; both P<0.01). The survival rate was significantly higher in CD-transfected mice as compared with that in the controls (X2 = 7.42, P<0.01), and the blood cell count and body weight decreased less and recovered sooner. CD gene was expressed in the bone marrow cells of transfected mice. CONCLUSION: Drug-resistant gene can not only integrate and express in mouse bone marrow cells, but also promote the tolerance to high-dose Ara-C.