Enhanced efflux of actinomycin D, vincristine, and vinblastine in adriamycin-resistant subline of P388 leukemia.
In vitro cross-resistance of adriamycin-resistant subline of P388 leukemia to non-anthracycline agents-actinomycin D, vincristine and vinblastine was elucidated. Decreased uptake of these 3 drugs was observed with the resistant cells. In addition, 2,4-dinitrophenol, a metabolic inhibitor, greatly enhanced the uptake of these drugs by the sensitive and resistant cell lines, particularly by the latter, abolishing a difference in drug uptake between the 2 which was observed under the normal condition. These results suggest that adriamycin-resistant cells are endowed with an enhanced capacity for outward transport of not only anthracycline antibiotics, but chemically and pharmacologically dissimilar agents such as the aforementioned agents.
D000818:Animals; D002460:Cell Line; D003609:Dactinomycin / Q000378:metabolism*; D004317:Doxorubicin / Q000494:pharmacology*; D004351:Drug Resistance; D007941:Leukemia P388 / Q000188:drug therapy / Q000378:metabolism*; D007942:Leukemia, Experimental / Q000378:metabolism*; D051379:Mice; D014747:Vinblastine / Q000378:metabolism*; D014750:Vincristine / Q000378:metabolism*
D003609:Dactinomycin; D014750:Vincristine; D014747:Vinblastine; D004317:Doxorubicin