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Cellular and karyotypic characterization of two doxorubicin resistant cell lines isolated from the same parental human leukemia cell line
Author(s) -
Zalcberg John R.,
Hu Xiu F.,
Wall Dominic M.,
Mirski Shelagh,
Cole Susan,
Nadalin Gabrielle,
de Luise Mario,
Parkin John D.,
Vrazas Vickie,
Campbell Lynda,
Kantharidis Phillip
Publication year - 1994
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910570414
Subject(s) - cell culture , etoposide , vinca , biology , microbiology and biotechnology , leukemia , karyotype , topoisomerase , gene duplication , gene , chromosome , genetics , cancer research , dna , chemotherapy , pharmacology
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 μg/ml of Dox and maintained at 0.07 μg/ml. In contrast, the CEM/A5 line was selected using an initial concentration of 0.01 μg/ml and maintained in Dox at a concentration of 0.05 μg/ml. P‐glycoprotein expression was demonstrated in the CEM/A7 line but not the CEM/A5 line. Amplification of the mdr1 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 11 α and β in this line. Cytogenetic analyses of both lines revealed numerous karyotypk 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 mdr 1 gene, a finding not seen in the parental or CEM/AS line. CEM/AS, however, demonstrated an abnormality of chromosome 7, outside the region of the mdr 1 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. © 1994 Wiley‐Liss, Inc.