Biomaterial Database

Active efflux of daunorubicin and adriamycin in sensitive and resistant sublines of P388 leukemia. 1979

M Inaba, and H Kobayashi, and Y Sakurai, and R K Johnson

Significantly decreased uptake and retention of daunorubicin (DAU) and Adriamycin (ADR) have been reported in sublines of P388 leukemia resistant to these anthracyclines. We studied the effects of inhibitors of oxidative phosphorylation on uptake and retention of DAU and ADR in order to characterize the transport process for these anthracyclines and to clarify further the alteration in resistant cells. In glucose-free medium, uptake of DAU and ADR was accelerated by metabolic inhibitors to a greater extent in resistant cells than in sensitive cells. Under these conditions, drug uptake was similar in sensitive and resistant cells. When glucose was added to the incubation medium in the presence of 2,4-dinitrophenol, efflux of DAU from both sensitive and resistant cells was observed. Net efflux of ADR was also observed with the resistant cells, whereas glucose markedly inhibited 2,4-dinitrophenol-stimulated uptake of ADR by the sensitive cells. Furthermore, in sensitive and resistant cells preloaded with ADR and DAU, efflux of the drugs was inhibited by the addition of 2,4-dinitrophenol. These results suggest that there is an active outward transport mechanism for anthracyclines in P388 leukemia cells and that enhanced activity of this efflux process renders cells highly resistant to the cytostatic and cytotoxic effects of ADR and DAU.

UI	MeSH Term	Description	Entries
D007942	Leukemia, Experimental	Leukemia induced experimentally in animals by exposure to leukemogenic agents, such as VIRUSES; RADIATION; or by TRANSPLANTATION of leukemic tissues.	Experimental Leukemia,Experimental Leukemias,Leukemia Model, Animal,Leukemias, Experimental,Animal Leukemia Model,Animal Leukemia Models,Leukemia Models, Animal
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D003630	Daunorubicin	A very toxic anthracycline aminoglycoside antineoplastic isolated from Streptomyces peucetius and others, used in treatment of LEUKEMIA and other NEOPLASMS.	Daunomycin,Rubidomycin,Rubomycin,Cerubidine,Dauno-Rubidomycine,Daunoblastin,Daunoblastine,Daunorubicin Hydrochloride,NSC-82151,Dauno Rubidomycine,Hydrochloride, Daunorubicin,NSC 82151,NSC82151
D004140	Dinitrophenols	Organic compounds that contain two nitro groups attached to a phenol.
D004317	Doxorubicin	Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.	Adriamycin,Adriablastin,Adriablastine,Adriblastin,Adriblastina,Adriblastine,Adrimedac,DOXO-cell,Doxolem,Doxorubicin Hexal,Doxorubicin Hydrochloride,Doxorubicin NC,Doxorubicina Ferrer Farm,Doxorubicina Funk,Doxorubicina Tedec,Doxorubicine Baxter,Doxotec,Farmiblastina,Myocet,Onkodox,Ribodoxo,Rubex,Urokit Doxo-cell,DOXO cell,Hydrochloride, Doxorubicin,Urokit Doxo cell
D004351	Drug Resistance	Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration.	Resistance, Drug
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000963	Antimetabolites	Drugs that are chemically similar to naturally occurring metabolites, but differ enough to interfere with normal metabolic pathways. (From AMA Drug Evaluations Annual, 1994, p2033)	Antimetabolite
D001693	Biological Transport, Active	The movement of materials across cell membranes and epithelial layers against an electrochemical gradient, requiring the expenditure of metabolic energy.	Active Transport,Uphill Transport,Active Biological Transport,Biologic Transport, Active,Transport, Active Biological,Active Biologic Transport,Transport, Active,Transport, Active Biologic,Transport, Uphill
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus