Modulation of 5-Fluorouracil Toxicity via Estrogen Receptor

  • Chris Benz
  • Ed Cadman
Part of the NATO Advanced Science Institutes Series book series (NSSA, volume 57)


Modulation of 5-fluorouracil (FUra) metabolism and toxicity by methotrexate (MTX) and other antimetabolites occurs in many cultured tumor cell lines, including the estrogen receptor positive human mammary carcinoma, 47-DN. The growth rate of this cell line depends on exogenously administered insulin and estradiol, and can be reversibly inhibited by the antiestrogen, tamoxifen (TAM).

47-DN cell-cycle kinetics are altered by doses of TAM which suppress the synthesis of estrogen and progesterone receptors. In cloning assays, TAM is synergistic with FUra and sequentially combined MTX-KFUra; in biochemical assays, TAM inhibits FUra intracellular accumulation and incorporation into RNA. This unique form of drug modulation may represent a form of “complementary inhibition,” and supports clinical trials in breast cancer suggesting that TAM + FUra-containing chemotherapy is superior to chemotherapy alone.


Intracellular Accumulation Clonal Growth Complementary Inhibition Antiestrogen Action Cloning Assay 
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Copyright information

© Springer Science+Business Media New York 1983

Authors and Affiliations

  • Chris Benz
    • 1
  • Ed Cadman
    • 1
  1. 1.Departments of Medicine and PharmacologyYale School of MedicineNew HavenUSA

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