Cellular and karyotypic characterization of two doxorubicin resistant cell lines isolated from the same parental human leukemia cell line

John R. Zalcberg, Xiu F. Hu, Dominic M. Wall, Shelagh Mirski, Susan Cole, Gabrielle Nadalin, Mario de Luise, John D. Parkin, Vickie Vrazas, Lynda Campbell, Phillip Kantharidis

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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 mdr1 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 mdr1 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.

Original languageEnglish
Pages (from-to)522-528
Number of pages7
JournalInternational Journal of Cancer
Issue number4
Publication statusPublished - 1994
Externally publishedYes

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