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Mechanisms of resistance to daunorubicin in Ehrlich ascites tumor cells.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Skovsgaard, Torben |
| Copyright Year | 1978 |
| Abstract | Uptake and binding of daunorubicin were studied in a sensitive (EHR 2) and in a resistant (EHR 2/DNR+) subline of Ehrlich ascites tumor cells. At steady state, the cell:medium ratio of daunorubicin was about 10-fold higher in EHR 2 than in EHR 2/DNR+. The bindings of daunorubicin to cell homogenate of the two cell lines were equal when the concentration at equilibrium was below 0.7 µg/ml, whereas homogenate of EHR 2 bound significantly more daunorubicin at higher concentrations. Based on the binding affinity for cell homogenate, the cytoplasm:medium ratio at steady state was estimated to be below 0.15 in EHR 2/DNR+, while the ratio in EHR 2 was 0.6 to 1.0. Omission of glucose together with the addition of sodium azide resulted in a considerable increase in drug uptake and in an equalization of the cytoplasm: medium gradient in EHR 2/DNR+. If glycolysis was restored by the addition of glucose to cells treated with sodium azide and loaded with daunorubicin, and uphill exodus of the drug was induced in EHR 2/DNR+. In both cell lines omission of glucose together with sodium azide increased the initial rate of uptake. However, the increment was three times as high for EHR 2/DNR+ as for EHR 2. In the medium without glucose but with sodium azide, the influx followed simple saturation kinetics in both cell lines, indicating carrier-mediated transport. As a consequence of a lower Vmax, the influx was significantly lower in EHR 2/DNR+ than in EHR 2. The data indicate that lower drug uptake in cells resistant to daunorubicin may be a result of at least three different mechanisms: a lower influx, a higher active extrusion, and a lower affinity for intracellular binding sites. |
| File Format | PDF HTM / HTML |
| PubMed reference number | 647687 |
| Journal | Medline |
| Volume Number | 38 |
| Issue Number | 6 |
| Alternate Webpage(s) | http://cancerres.aacrjournals.org/content/canres/38/6/1785.full.pdf |
| Journal | Cancer research |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
