Open AccessMethotrexate Cytotoxicity as Related to Irreversible S Phase Arrest in Mouse L1210 Leukemia Cells
Author(s) -
Tsurusawa Masahito,
Niwa Makoto,
Katano Naoyuki,
Fujimoto Takeo
Publication year - 1990
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1990.tb02511.x
Subject(s) - cytotoxicity , methotrexate , leukemia , cancer research , l1210 cells , neoplasm , chemistry , medicine , in vitro , biology , immunology , pathology , biochemistry
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.