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.