CYTOKINETIC AND CYTO-TOXIC EFFECTS OF ANTI-METABOLITES ON 9L RAT-BRAIN TUMOR-CELLS INVITRO

  • 1 January 1981
    • journal article
    • research article
    • Vol. 41  (10) , 3835-3839
Abstract
Treatment of exponentially growing 9L monolayer cells with graded concentrations of methotrexate or 5-fluorouracil (5-FUra) resulted in .apprx. 95% cell kill, corresponding to the percentage of cells in this system labeled by autoradiography (98%). Additional cell kill was obtained if 5-FUra was administered at a high concentration (7.7 .times. 10-4 M) and was partly reversed in the presence of 8.2 .times. 10-5 M uridine. When cell kill was measured as a function of time of exposure, a 3 h exposure to 2.2 .times. 10-4 M methotrexate or 7.7 .times. 10-6 or 7.7 .times. 10-4 M 5-FUra killed 30-50% of the cell population, which is equivalent to the percentage of the S-phase cells of the system. With both agents, additional cell kill was offset by division of unaffected G2 cells and a drug-induced block of G1 cells at the G1-S border; it depended on long drug exposure. Nontoxic concentrations of 5-FUra synchronized and increased the fraction of cells in the drug-sensitive S phase.