Back to Search
Start Over
Comparative effects of selected antifolates on transforming human lymphocytes and on established human lymphoblastic cell lines
- Source :
- Biochemical Pharmacology. 25:1947-1954
- Publication Year :
- 1976
- Publisher :
- Elsevier BV, 1976.
-
Abstract
- When 15 nM methotrexate was added to the medium in which human peripheral lymphocytes stimulated with phytohemagglutinin were incubated, it caused a 50 per cent decrease in the maximum number of blasts produced, in the number of cells in mitosis and in the incorporation of [ 3 H]deoxyuridine into DNA. However, [ 3 H]thymidine incorporation into DNA was increased by methotrexate concentrations up to 0.5 mM. When 50 nM methotrexate was present continuously, blast formation, mitosis and deoxyuridine incorporation were virtually abolished, but if this concentration was present only during the induction phase (the first 24 hr), the subsequent effect on blast proliferation was slight. In contrast, 24-hr exposure during the proliferative phase (days 3–5) severely affected blast proliferation. The effects of methotrexate were largely reversible by thymidine, but hypoxanthine or purine nucleosides had no significant effect so that the metabolic block appears to be entirely at thymidylate synthetase under the experimental conditions. The inhibitory effects of ten other antifolates on transforming lymphocytes were determined and, with one exception, their relative effectiveness was found to be as predicted from inhibitory effects on highly purified bovine dihydrofolate reductase. The growth of four established lines of human lymphoblastic cells was inhibited to essentially the same extent by six of the antifolates, and these cells were only slightly less sensitive to the antifolates than were the transforming normal lymphocytes.
- Subjects :
- Time Factors
Mitosis
In Vitro Techniques
Lymphocyte Activation
Biochemistry
Thymidylate synthase
Cell Line
chemistry.chemical_compound
Lectins
Dihydrofolate reductase
medicine
Animals
Humans
Hypoxanthine
Pharmacology
biology
Deoxyuridine
Stimulation, Chemical
Methotrexate
Liver
chemistry
Cell culture
biology.protein
Folic Acid Antagonists
Cattle
Thymidine
medicine.drug
Subjects
Details
- ISSN :
- 00062952
- Volume :
- 25
- Database :
- OpenAIRE
- Journal :
- Biochemical Pharmacology
- Accession number :
- edsair.doi.dedup.....0b0d9674101594cb146455b564f957fc