ANTHRACYCLINE RESISTANCE IN P388 MURINE LEUKEMIA AND ITS CIRCUMVENTION BY CALCIUM-ANTAGONISTS

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  • 1 January 1985
    • journal article
    • research article
    • Vol. 45  (4) , 1687-1691
Abstract
Daunorubicin transport was compared in P388 murine leukemia and in P388/Adramycin (ADR), an anthracycline-resistant subline. An energy-dependent outward transport system in P388/ADR which limits drug accumulation can be demonstrated. Although no Ca requirement for the outward transport process could be shown, several Ca antagonists inhibited outward transport of daunorubicin in P388/ADR and modified the drug resistance pattern. But these agents failed to alter Ca fluxes in either cell line, suggesting that their mode of action in these studies, was not related to interactions with C dependent processes. Accumulation differences could not account for the level of daunorubicin resistance observed in the P388/ADR cell line, nor could resistance be wholly circumvented by calcium antagonists.