Abstract |
The association between cytotoxicity and cell cycle perturbation caused by methotrexate (MTX) was investigated in mouse L1210 leukemia cells by flow cytometric bromodeoxyuridine/ DNA assay. In the range of concentrations of MTX from 10(-7) M to 10-6) M, in vitro exposure to the drug for 6 h caused a dose-dependent suppression of clonal growth of the tumor cells and S phase arrest in the cycle progression, resulting in an accumulation of cells in early S phase, in which they showed no definite increase of DNA content above G1 levels. The surviving fraction of the clonogenic cells corresponded with the fraction of cells which recovered from the S phase arrest in MTX-free medium. In mice bearing L1210 ascites tumors, a bolus injection of MTX caused the S phase arrest of the tumor cells as shown in suspension cultures, and cytokinetic recovery was observed in parallel with the regrowth of the tumor. These results showed that irreversible S phase arrest is a critical cytokinetic event associated with the cytotoxicity of MTX.
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Authors | M Tsurusawa, M Niwa, N Katano, T Fujimoto |
Journal | Japanese journal of cancer research : Gann
(Jpn J Cancer Res)
Vol. 81
Issue 1
Pg. 85-90
(Jan 1990)
ISSN: 0910-5050 [Print] Japan |
PMID | 2108951
(Publication Type: Journal Article)
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Chemical References |
- DNA
- Bromodeoxyuridine
- Methotrexate
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Topics |
- Animals
- Bromodeoxyuridine
(metabolism)
- DNA
(biosynthesis)
- Flow Cytometry
- Interphase
(drug effects)
- Leukemia L1210
(drug therapy)
- Methotrexate
(pharmacology, therapeutic use)
- Mice
- Tumor Cells, Cultured
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