[Protection of hematopoietic cells against toxicity of anticancer agents by transfecting mdr1 gene into bone marrow cells].

OBJECTIVE

To investigate whether the hematopoietic cells can be protected from the toxic effect of anticancer agents by transfecting mdr1 gene into bone marrow cells.

METHODS

The mdr1 gene was transfected into murine and human bone marrow cells by Lipofectin. Expression of mdr1 was assessed by RT-PCR and flow cytometry. The functional activity of mdr1 in transfected cells was examined by rhodamine retention assay. Resistance to chemotherapeutic drugs of human and murine mdr1 gene transfected bone marrow cells was ascertained in vivo and that of murine cells was assessed in vivo in a bone marrow transplantation model.

RESULTS

Multidrug resistance 1 gene was successfully transfected into and expressed in murine and human bone marrow cells. The transfected cells were resistant to doxorubicin; Vp-16, vincristine and colchicine. Bone marrow cells transfected with mdr1 gene reconstituted the hematopoietic function and offered resistance to doxorubicin in recipient mice.

CONCLUSION

To transfect mdr1 gene into bone marrow cells is a promissing approach to protect bone marrow cells from the myelosuppressive effect of chemotherapeutic agents.