Send to

Choose Destination
See comment in PubMed Commons below
Cancer Res. 1988 Apr 15;48(8):2149-55.

Impaired polyglutamylation of methotrexate as a cause of resistance in CCRF-CEM cells after short-term, high-dose treatment with this drug.

Author information

  • 1Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510.


Two methotrexate-resistant sublines, CCRF-CEM R3/7 and CCRF-CEM R30/6, were selected from the human leukemia T-lymphoblast cell line, CCRF-CEM, after repeated exposures (7 and 6 times, respectively) for 24 h to constant concentrations (3 and 30 microM) of the drug. Analysis of the mechanism of resistance revealed no differences in levels of dihydrofolate reductase activity, its binding affinity for methotrexate, or in methotrexate transport between the CCRF-CEM parent and methotrexate-resistant cell lines. The development of resistance to methotrexate was associated with a marked decrease in the intracellular level of methotrexate polyglutamates. Although the resistant sublines were able to form substantial amounts of folate polyglutamates when measured with [3H]folic acid, the level of polyglutamates formed was decreased to about 50% of that formed by the parent cell line. No qualitative differences in folate polyglutamates formed were noted between the parental and resistant sublines. This is the first example of a cell line which displays resistance which is solely attributable to defective methotrexate polyglutamate synthesis.

[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Write to the Help Desk