Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/13023
Title: Cellular and karyotypic characterization of two doxorubicin resistant cell lines isolated from the same parental human leukemia cell line.
Authors: Zalcberg, John R;Hu, X F;Wall, D M;Mirski, S;Cole, S;Nadalin, G;De Luise, M;Parkin, John Desmond;Vrazas, V;Campbell, L
Affiliation: Department of Medical Oncology, Heidelberg Repatriation Hospital, Australia.
Issue Date: 15-May-1994
Citation: International Journal of Cancer. Journal International Du Cancer; 57(4): 522-8
Abstract: Separate mechanisms underlying the multidrug resistant (MDR) phenotype were identified in 2 independent approaches to select tumour cells resistant to low concentrations of doxorubicin (Dox) from the sensitive T cell leukemia cell line CCRF-CEM. The CEM/A7 cell line was selected at an initial concentration of 0.005 microgram/ml of Dox and maintained at 0.07 microgram/ml. In contrast, the CEM/A5 line was selected using an initial concentration of 0.01 microgram/ml and maintained in Dox at a concentration of 0.05 microgram/ml. P-glycoprotein expression was demonstrated in the CEM/A7 line but not the CEM/A5 line. Amplification of the mdrI gene was not observed in the CEM/A7 cell line. Both cell lines showed cross-resistance to a number of structurally unrelated cytotoxic drugs including anthracyclines and etoposide (VP-16), although only the CEM/A7 line was cross resistant to Vinca alkaloids. Immunoblots of total cell lysates of the CEM/A5 line have revealed almost undetectable levels of topoisomerase II alpha and beta in this line. Cytogenetic analyses of both lines revealed numerous karyotypic abnormalities which were present in the parental cell line as well as both resistant cell lines. The CEM/A7 line also demonstrated a duplication of part of the long arm of chromosome 7 which included the region containing the mdrI gene, a finding not seen in the parental or CEM/A5 line. CEM/A5, however, demonstrated an abnormality of chromosome 7, outside the region of the mdrI gene, and it also contained a deletion of the short arm of chromosome 2. Abnormalities in this latter region of genome have been associated with non-P-glycoprotein-mediated MDR.
Internal ID Number: 7514153
URI: http://ahro.austin.org.au/austinjspui/handle/1/13023
URL: http://www.ncbi.nlm.nih.gov/pubmed/7514153
Type: Journal Article
Subjects: Antibodies.metabolism
Antineoplastic Agents.pharmacokinetics.pharmacology
Carrier Proteins.physiology
DNA Topoisomerases, Type II.metabolism
Doxorubicin.pharmacokinetics.pharmacology
Drug Resistance.genetics
Flow Cytometry
Gene Amplification
Humans
Immunoblotting
Karyotyping
Leukemia.drug therapy.genetics.pathology
Membrane Glycoproteins.physiology
Models, Biological
P-Glycoprotein
Phenotype
RNA.genetics
Tumor Cells, Cultured.drug effects
Appears in Collections:Journal articles

Files in This Item:
There are no files associated with this item.


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.