Accession Number : ADA338760

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

Descriptive Note : Annual rept. 16 Sep 96-15 Sep 97

Corporate Author : HOWARD UNIV WASHINGTON DC

Personal Author(s) : Brown, Donnell

PDF Url : ADA338760

Report Date : OCT 1997

Pagination or Media Count : 13

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.

Descriptors :   *TOXICITY, *CELLS(BIOLOGY), *LETHAL DOSAGE, *METHOTREXATE, TISSUES(BIOLOGY), BIOCHEMISTRY, RESCUES, QUALITY, ADVERSE CONDITIONS, DOSAGE, ERYTHROCYTES, WEIGHT REDUCTION, BONE MARROW, PHARMACOLOGY, HOSTS(BIOLOGY), LIVING STANDARDS, BONES, NORMALITY.

Subject Categories : Medicine and Medical Research
      Toxicology
      Pharmacology

Distribution Statement : APPROVED FOR PUBLIC RELEASE