RESEARCH ON MDR1 GENE TRANSFERRING INTO MURINE BONE MARROW HEMATOPOIETIC CELLS AND ITS EFFECT OF CHEMOPROTECTION IN VIVO

Wang S, Kang Q, Jin XQ, Li YC, Xu JL.

Dept. of Surgery, Children¡¯s Hospital, Chongqing University of Medical Sciences, China

 

Objective: To investigate the protective effect of mdr1 gene on hematopoietic cells in chemotherapy and to explore an effective approach to prevent myelosuppression due to anticancer agents.

Methods: mdr1gene was transferred into hematopoietic cells of murine bone marrow with plasmid pHaMDR1/A by the mediation of retrovirus vecter.  The resistance of mdr1 gene transferred murine bone marrow cells to anticancer agents was tested in vivo by bone marrow transplantation murine model. Also, the function and the expression of mdr1gene detected by PCR method, IC method and DNR extrusion test in vitro and in vivo.

Results: (1) mdr1 gene was successfully transferred into hematopoietic cells of murine bone marrow and its transfection ratio was up to 35%. The expression production of exogenous mdr1 gene had itself physical function. The expression of exogenous gene was still got in vivo. (2) The death ratio of control group mice was 92.9% and the group of mdr1 gene transfection mice was 32.5% after undergoing high-dose chemotherapy. (3) The resistance level of mdr1 gene transfection mice to taxol was increased 4-6 times and to CTX was increased 6-8 times contrasting to common dose.

Conclusion: These results show transferring mdr1 gene into bone marrow hematopoietic cells can protect bone marrow hematopoietic cells against the toxicities of anticancer agents. These results as a basement date is important for further phase I clinical trial.

 

 
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