McLachlin J R, Eglitis M A, Ueda K, Kantoff P W, Pastan I H, Anderson W F, Gottesman M M
Laboratory of Molecular Hematology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
J Natl Cancer Inst. 1990 Aug 1;82(15):1260-3. doi: 10.1093/jnci/82.15.1260.
In multidrug resistance, cells become simultaneously resistant to anthracyclines, vinca alkaloids, epipodophyllotoxins, and certain other natural product cytotoxic drugs. Resistance results from synthesis of a multidrug transporter (P-glycoprotein) encoded by the MDR1 gene (also known as the PGY1 gene). In the present study, a retrovirus vector containing a complementary DNA for the human multidrug resistance gene HaMDR1/A was used to transfer the multidrug resistance phenotype to bone marrow cells of the DBA/2J mouse. A high proportion of transduced bone marrow cells showed resistance to both colchicine and vinblastine, as determined by in vitro colony formation of hematopoietic precursor cells. In addition, brief culturing of the cells in a cytotoxic drug following exposure to the retrovirus vector could be used to increase the proportion of bone marrow cell colonies that were resistant. These results may serve as a model for the generation and selection of bone marrow cells resistant to the toxic effects of chemotherapeutic agents in vivo.
在多药耐药中，细胞会同时对蒽环类药物、长春花生物碱、表鬼臼毒素以及某些其他天然产物细胞毒性药物产生耐药性。耐药性是由MDR1基因（也称为PGY1基因）编码的多药转运蛋白（P-糖蛋白）合成所致。在本研究中，使用一种含有人类多药耐药基因HaMDR1/A互补DNA的逆转录病毒载体，将多药耐药表型转移到DBA/2J小鼠的骨髓细胞中。通过造血前体细胞的体外集落形成测定，高比例的转导骨髓细胞对秋水仙碱和长春花碱均表现出耐药性。此外，在暴露于逆转录病毒载体后，将细胞在细胞毒性药物中短暂培养，可用于增加耐药骨髓细胞集落的比例。这些结果可作为体内产生和选择对化疗药物毒性具有抗性的骨髓细胞的模型。
