CEM cell lines genetically deficient in either nucleoside transport or deoxycytidine kinase activity
OHSU # 1626
Two nucleoside transport-deficient cell lines were developed through isolation from a hypoxanthine-guanine phosphoribosyltransferase-deficient derivative of wild type CEM cells (a human T lymphoblast cell line originally derived from a patient with acute lymphocytic leukemia). The Ara-C/8C and TUB-4D clones were isolated by virtue of their resistance to 8 µM arabinosylcytosine and 4µM tubercidin, respectively. One cell line completely deficient in deoxycytidine kinase activity, the Ara-C/8D clone, is a clonal derivative of an hypoxanthine-guanine phosphoribosyltransferase-deficient parent CEM cell line originally isolated in semi-solid agarose containing 8µM arabinosylcytosine. The Ara-C/8C and TUB-4D cell lines are cross-resistant to a spectrum of cytotoxic nucleosides to which parental and Ara-C/8D cell are sensitive.
Cytarabine (Ara-C), a pyrimidine analog, is a conventional anti-cancer chemotherapeutic commonly used for the treatment of acute myeloid leukemia. Although Ara-C treatment often induces partial or complete remission of cancerous tissue, many patients eventually develop resistance. Ara-C/8C cells demonstrate cross-resistance to gemcitabine and 2’, 3’-dideoxycytidine. Therefore, this cell line may be useful for research into nucleoside transport deficiencies as well as anti-cancer chemotherapeutic analysis.
The Arac-C/8D cell line has been studied in detail for some time and found to express negligible deoxycytidine kinase activity and increased resistance to 2’-deoxyadenosine and 2’-deoxyguanosine-induced cytotoxicity as well as marked resistance to dideoxycytidine. The Ara-C/8D cell line has been found to contain two DNA mutations within the 2’-deoxycytidein kinase gene conferring its resistance.
Links/Publications: Ulllman et al., J Biol Chem. 1988 Sep 5;263(25):12391-6. Owens et al., Cancer Res. 1992 May 1;52(9):2389-93.
Licensing Opportunity: The cell lines are available for non-exclusive licensing.
- Buddy Ullman, SM.Biochemistry & Molecular Biology
- OHSU # 1626-C — ARAC-8D cell line
- OHSU # 1626-A — ARAC-8C cell line
- OHSU # 1626-B — TUB-4D cell line
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