Upregulation of P-glycoprotein in rat hepatoma ρ° cells: Implications for drug–DNA interactions

✍ Scribed by Vinochani Pillay; Ryan D. Martinus; John S. Hill; Don R. Phillips

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 438 KB
• Volume: 69
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/(sici)1097-4644(19980615)69:4<463::aid-jcb7>3.0.co;2-l

✦ Synopsis

Rat hepatoma cells lacking mitochondrial DNA (°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 °c ells were 45-fold less sensitive to Adriamycin than the parental ϩ 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 °cells. This was indicated by confocal microscopy where ϩ cells exhibited thirteenfold higher cellular levels of Adriamycin than °cells. Upregulation (tenfold) of P-glycoprotein in °cells was also confirmed by Northern dot blot analysis. Since the MDR phenotype is present in °cells and upregulation of P-glycoprotein is maintained in these cells, °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.