Selectivity of Very High Dose Methotrexate in MCF-7 and Normal Cells Using a Priming and Non-Toxic 5-Fluorouracil Dose

Abstract

Utilizing the fluoropyrimidine 5-fluorouracil (5-FU) and the classical and nonclassical antifolates methotrexate (MTX) and trimetrexate (TMQ), respectively, the goal of this research project is to illustrate how these agents may improve the quality of life by: exploiting differences in the biochemical pharmacology of MTX in human breast cancer cells and human bone marrow cells and providing a clear basis for the rescue or protection of normal host cells, such as bone marrow, from MTX toxicity when high-dose MTX is used in combination with 5-FU. The aim of this work is to provide support for the hypothesis that breast cancer cells tend to synthesize significant higher levels of MTX-polyglutamates (MTXPGs) than normal cells. A priming-and nontoxic dose of 5-FU by conserving cellular reduced-folates protects against the effects of MTX but not MTXPGs and, therefore, should provide a greater protective effect to normal cells than to cancer cells.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 1999
Accession Number
ADA381717

Entities

People

  • Donnell Bowen

Organizations

  • Howard University

Tags

DTIC Thesaurus Topics

  • Blood
  • Blood Cells
  • Bone Marrow
  • Bone Marrow Cells
  • Bones
  • Breast Cancer
  • Cardiovascular System
  • Cells
  • Chemistry
  • Enzyme Inhibitors
  • Hematopoietic Cells
  • Hematopoietic System
  • Incubation
  • Materials
  • Methotrexate
  • Neoplasms
  • Tumor Cell Line

Readers

  • Materials Science.
  • Oncology (Cancer Research).