CROSS-RESISTANCE TO RHODAMINE-123 IN ADRIAMYCIN-RESISTANT AND DAUNORUBICIN-RESISTANT FRIEND-LEUKEMIA CELL VARIANTS

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  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (12) , 5544-5549
Abstract
Cross-resistance to rhodamine 123 (Rho-123) was found in Adriamycin(ADM)-resistant and daunorubicin(DNR)-resistant Friend leukemia cell variants. Cytotoxicity in sensitive cells correlates with the intracellular amount of Rho-123, as determined by high-pressure liquid chromatography. Differential resistance coincides with Rho-123 acumulation which in sensitive cells was 20-fold higher than in resistant cells after 180 min of treatment. Sodium azide, which has been shown to inhibit ADM-resistant cells, did not inhibit Rho-123 efflux. The difference in Rho-123 accumulation between sensitive and resistant cells correlates with cytotoxicity, which is in contrast to what has been found in these cells when treated with either ADM or DNR. In contrast to the known effects of ADM and DNR on macromolecular synthesis, Rho-123 in sensitive cells was found to inhibit protein synthesis but had no effect on DNA or RNA synthesis. At Rho-123 doses which inhibited protein synthesis, drug localization changed from mitochondrial specific to generalized cytoplasmic. This effect was never achieved in reistant cells even with prolonged drug exposure. Thus, different mechanisms of resistance to different drug types can be identified in the same cells even though similar resistance occurs. The similarity in resistance need not share a common mechanism. Although the drugs were effluxed more efficiently in resistant cells, the mechanisms for resistance in each case seem to differ. In the case of ADM or DNR, it appears to be multifactorial, whereas with Rho-123, total intracellular accumulation seems to be most important.