Abstract
Objective
To explore the feasibility of transfecting cytidine deaminase (CD) gene into mouse bone marrow cells in order to observe the drug resistance of high dose Ara-C and improve the tolerance of myelosuppression following combination chemotherapy.
Methods
Human cytidine deaminase gene was transfected into mice bone marrow cells by retroviral vector. Resistant colony-forming unit granulocyte-macrophage (CFU-GM) assay was performed after the transfected mice bone marrow cells treated by the Ara-C. DNA was extracted from mice bone marrow cells. The drug resistant gene in mice bone marrow cells after transfection was detected by PCR.
Results
Bone marrow cells of the donor mice cultured with the retroviral producer cells showed the drug resistant colonies and resistance to Ara-C, so did accept mice transplanted with the CD gene (CFU-GM of donor mice was 52%, χ2 = 124.62, P < 0.01; accept mice was 54%, χ2 = 126.26, P < 0.01, both compared with the contrast group). The animal survival rate was significantly higher in gene transfected group than that of the control (χ2 = 7.42, P < 0.01). CD gene of transfected bone marrow cells was confirmed by PCR.
Conclusion
CD gene can be transfected into bone marrow cells of mice efficiently and increase the drug resistance to Ara-C.
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References
Takebe N, Zhao SC, Ural AU, et al. Retroviral transduction of human dihydropyrimidine dehydrogenase cDNA confers resistance to 5-fluorouracil in murine hematopoietic progenitor cells and human CD34+-enriched peripheral blood progenitor cells. Cancer Gene Ther, 2001, 8: 966–973.
Belur LR, Boelk-Galvan D, Diers MD, et al. Methotrexate accumulates to similar levels in animals transplanted with normal versus drug-resistant transgenic marrow. Cancer Res, 2001, 61: 1522–1526.
Takebe N, Xu LC, MacKenzie KL, et al. Methotrexate selection of long-term culture initiating cells following transduction of CD34(+) cells with a retrovirus containing a mutated human dihydrofolate reductase gene. Cancer Gene Ther, 2002, 9: 308–320.
Capiaux GM, Budak-Alpdogan T, Takebe N, et al. Retroviral transduction of a mutant dihydrofolate reductase-thymidylate synthase fusion gene into murine marrow cells confers resistance to both methotrexate and 5-fluorouracil. Hum Gene Ther, 2003, 14: 435–446.
Eliopoulos N, Al-Khaldi A, Beausejour CM, et al. Human cytidine deaminase as an ex vivo drug selectable marker in gene-modified primary bone marrow stromal cells. Gene Ther, 2002, 9: 452–462.
Gourdeau H, Bibeau L, Ouellet F, et al. Comparative study of a novel nucleoside analogue (Troxatyl, troxacitabine, BCH-4556) and AraC against leukemic human tumor xenografts expressing high or low cytidine deaminase activity. Cancer Chemother Pharmacol, 2001, 47: 236–240.
Beausejour CM, Eliopoulos N, Momparler L, et al. Selection of drug-resistant transduced cells with cytosine nucleoside analogs using the human cytidine deaminase gene. Cancer Gene Ther, 2001, 8: 669–676.
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Supported by a grant from the National Natural Science Foundation of China (No. 30471678).
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Chen, B., Liu, C., Lu, Y. et al. Protection of a cytidine deaminase gene gainst toxicity of high dose chemotherapy in mice. Chin. -Ger. J. Clin. Oncol. 7, 358–360 (2008). https://doi.org/10.1007/s10330-008-0039-6
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DOI: https://doi.org/10.1007/s10330-008-0039-6