title: The relationship of doxorubicin binding to membrane lipids with drug resistance.
abstract: Doxorubicin (DOX, Adriamycin) binds with high affinity to cellular membranes inflicting multiple lesions which are believed to be important in DOX-mediated neoplastic cell death. Using fluorescence and radioactive [14-14C-14]DOX assays for DOX, we have measured the partitioning of DOX between the cytosolic and membrane fractions of erythrocytes and of DOX-sensitive (V-79) and -resistant (LZ) Chinese hamster lung fibroblast cells. In both erythrocytes and fibroblasts, a significant fraction of DOX was associated with the membrane fraction. More significantly, the quantity of lipid-bound DOX in the fibroblasts correlated with the cell's susceptibility to DOX. The significance of these findings in the context of existing knowledge about DOX-membrane interactions is discussed.
authors.affiliation: University of Texas Southwestern Medical Center, Dallas.
authors.forename: S
authors.initials: S
authors.lastname: Awasthi
authors.forename: R
authors.initials: R
authors.lastname: Sharma
authors.forename: Y C
authors.initials: YC
authors.lastname: Awasthi
authors.forename: J A
authors.initials: JA
authors.lastname: Belli
authors.forename: E P
authors.initials: EP
authors.lastname: Frenkel
mesh_terms: D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D003600:Cytosol / Q000378:metabolism; D004317:Doxorubicin / Q000378:metabolism* / Q000494:pharmacology; D004351:Drug Resistance / Q000502:physiology*; D004910:Erythrocyte Membrane / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008563:Membrane Lipids / Q000097:blood / Q000378:metabolism*
chemical_list: D008563:Membrane Lipids; D004317:Doxorubicin