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Title: Rapid up-regulation of mdr1 expression by anthracyclines in a classical multidrug-resistant cell line.
Austin Authors: Hu, X F;Slater, A;Wall, D M;Kantharidis, P;Parkin, John Desmond;Cowman, A;Zalcberg, John R
Affiliation: Department of Medical Oncology, Heidelberg Repatriation Hospital, Victoria, Australia
Issue Date: 1-May-1995
Publication information: British Journal of Cancer; 71(5): 931-6
Abstract: Studies were carried out in a variant human multidrug-resistant (MDR) cell line CEM/A7R, which expresses very low levels of mdr1 mRNA and P-glycoprotein (P-gp). The induction of mdr1 RNA expression by three anthracyclines, (doxorubicin, daunorubicin, epirubicin), VP-16 and two vinca alkaloids (vincristine, vinblastine) was semiquantitatively assessed by scanning Northern blots on a phosphorimager. The relative level of mdr1 expression was expressed as ratio of mdr1 to the internal RNA (actin). A significant increase (P < 0.02) in expression of mdr1 was noted within 4 hrs of exposure to 1.5 micrograms ml-1 daunorubicin or epirubicin. Neither vinblastine nor vincristine had any effect on mdr1 levels after an 8 h exposure. With increasing concentrations of daunorubicin or epirubicin in a fixed 24 h time period, mdr1 expression increased, although a biphasic response was seen. Based on MRK 16 binding, an increase in P-gp levels was seen in the CEM/A7R line after a 24 h exposure to 1 microgram ml-1 daunorubicin or epirubicin. The rapid increase in mdr1 expression after a short period of exposure to doxorubicin, daunorubicin or epirubicin suggests that induction of mdr1 expression may have an important role in the development of drug-resistant tumours.
Gov't Doc #: 7734315
Journal: British Journal of Cancer
Type: Journal Article
Subjects: Antibiotics, Antineoplastic.pharmacology
Blotting, Northern
Drug Resistance, Multiple.genetics
Flow Cytometry
Gene Expression Regulation, Leukemic.drug effects
Leukemia-Lymphoma, Adult T-Cell.drug therapy.genetics.metabolism
RNA, Messenger.genetics.metabolism
Tumor Cells, Cultured
Up-Regulation.drug effects
Appears in Collections:Journal articles

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