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

Abstract

The goal of this research project is (a) designed to improve the quality of life by exploiting differences in the biochemical pharmacology of methotrexate (MTX) in MCF-7 breast cancer cells versus normal tissues and (b) provide one clear basis for intracellular rescue of only host cells from MTX toxicity when high dose MTX is used in combination with 5-fluorouracil (5-FU). The major findings are: (1) High dose MU toxicity is reduced by a (priming - and non-toxic -)5-FU dose. 5-FU reverses high dose MU acute toxicity on bone marrow. The erythroid cells appear to be more sensitive than the myeloid cells to the acute adverse effect of MU. (2) A 50% reduction in the priming-dose of 5-FU was effective in providing marked protection against weight loss from an acute MU dose 6 times the lethal dose. (3) Cytotoxicity to MCF-7 human breast cells may be the resultant of higher intracellular of methotrexate polyglutamate (MU PGs) than MU.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 1997
Accession Number
ADA338760

Entities

People

  • Donnell Brown

Organizations

  • Howard University

Tags

DTIC Thesaurus Topics

  • Animals
  • Blood
  • Body Weight
  • Bone Marrow
  • Bones
  • Breast Cancer
  • Cells
  • Erythroid Cells
  • Lethal Dosage
  • Materials
  • Methotrexate
  • Myeloid Cells
  • Neoplasms
  • Pharmacology
  • Quality Of Life
  • Skin Diseases
  • Toxicity

Fields of Study

  • Medicine

Readers

  • Immunology and Pathology
  • Toxicology/Environmental Toxicology