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. 1990 Jan;81(1):85-90.
doi: 10.1111/j.1349-7006.1990.tb02511.x.

Methotrexate cytotoxicity as related to irreversible S phase arrest in mouse L1210 leukemia cells

M Tsurusawa  1 , M Niwa, N Katano, T Fujimoto
Affiliations

Methotrexate cytotoxicity as related to irreversible S phase arrest in mouse L1210 leukemia cells

M Tsurusawa et al. Jpn J Cancer Res. 1990 Jan.

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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