Selectivity of Very High Dose Methotrexate in Mcf-7 and Normal Cells Using a Priming and Non-Toxic 5-Fluorouracil Dose
Abstract
High-dose (10 micro-M) methotrexate (MTX) cytotoxicity is maintained in MCF-7 and MDA-MB-436 human breast cancer cells but reduced in Hs824.T human bone marrow by a priming-and nontoxic 5-fluorouracil (5-FU) dose (10 micro-M). The growth rates of MCF-7 and MDA-MB-436 cells in the presence of 5-FU, respectively are 97.59 +/- 0.97% and 94.89 +/- 1.35% of control rates; and the growth rate of bone marrow cells is 90.61% +/- 3.71%. The combinations of 5-FU 2h prior to MTX or MTX 2h prior to 5-FU followed by a 48h incubation, respectively, gave growth rates of: (1) 20.96% +/- 2.44% and 19.86 +/- 2.56% in MCF-7 cells, (2) 25.60% +/- 1.28% and 25.17% +/- 1.23% in MDA-MB-436 cells, and 3) 79.66% +/- 7.41% (a protective effect of 5-FU) and 31.39% +/- 1.77% in bone marrow. The % of control rates of MTX in MCF-7, MDA-MB-436, and bone marrow cells, respectively, are 21.81% +/- 3.33%, 22.54% +/- 1.56%, and 29.58% +/- 2.99%. A MTX level, at least 1 order of magnitude above 1 micro-M, is necessary for the cytotoxicity of 5-FU and MTX to be independent of sequence of administration. At equiconcentrations of trimetrexate (TMQ) and MTX, the nonplyglutamated antifolate TMQ or TMQ-5-FU combinations inhibited the growth of breast cancer cells less than MTX and MTX-5-FU combinations.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1998
- Accession Number
- ADB248375
Entities
People
- Donnell Bowen
Organizations
- Howard University