Pillay V, Martinus R D, Hill J S, Phillips D R
School of Biochemistry, La Trobe University, Bundoora, Australia.
J Cell Biochem. 1998 Jun 15;69(4):463-9.
Rat hepatoma cells lacking mitochondrial DNA (rho(o) cells) were used as a model system to examine the possible roles of mitochondrial DNA as a target for the DNA-acting anticancer drug Adriamycin (doxorubicin). The rho(o) cells were 45-fold less sensitive to Adriamycin than the parental rho+ cells containing mitochondrial DNA. Other non-DNA-acting drugs also exhibited similar behaviour, and this was shown to be due to a multidrug resistance (MDR) phenotype in the rho(o) cells. This was indicated by confocal microscopy where rho+ cells exhibited thirteenfold higher cellular levels of Adriamycin than rho(o) cells. Upregulation (tenfold) of P-glycoprotein in rho(o) cells was also confirmed by Northern dot blot analysis. Since the MDR phenotype is present in rho(o) cells and upregulation of P-glycoprotein is maintained in these cells, rho(o) cells are not a good model system for drug-DNA studies (where the drug is susceptible to extrusion by P-glycoprotein), and any such results obtained with this system must be treated with considerable caution.
缺乏线粒体DNA的大鼠肝癌细胞（ρ⁰细胞）被用作模型系统，以研究线粒体DNA作为DNA作用抗癌药物阿霉素（多柔比星）靶点的可能作用。ρ⁰细胞对阿霉素的敏感性比含有线粒体DNA的亲代ρ⁺细胞低45倍。其他非DNA作用药物也表现出类似行为，这被证明是由于ρ⁰细胞中的多药耐药（MDR）表型所致。共聚焦显微镜显示，ρ⁺细胞中阿霉素的细胞水平比ρ⁰细胞高13倍，表明了这一点。Northern斑点印迹分析也证实了ρ⁰细胞中P-糖蛋白上调（10倍）。由于ρ⁰细胞中存在MDR表型且这些细胞中P-糖蛋白维持上调，所以ρ⁰细胞不是用于药物-DNA研究（药物易被P-糖蛋白挤出）的良好模型系统，用该系统获得的任何此类结果都必须极其谨慎地对待。
