Cytokinetic and cytotoxic effects of antimetabolites on 9L rat brain tumor cells in vitro.
Treatment of exponentially growing 9L monolayer cells with graded concentrations of methotrexate or 5-fluorouracil (5-FUra) resulted in approximately 95% cell kill, corresponding to the percentage of cells in this system labeled by autoradiography (98%). Additional cell kill could be obtained if 5-FUra was administered at a high concentration (7.7 x 10(-4) M) and could be partly reversed in the presence of 8.2 x 10(-5) M uridine. When cell kill was measured as a function of time of exposure, a 3-hr exposure to 2.2 x 10(-4) M methotrexate or 7.7 x 10(-6) or 10(-4) M 5-FUra killed 30 to 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, and it depended on long drug exposure. Nontoxic concentrations of 5-FUra could synchronize and increase the fraction of cells in the drug-sensitive S phase.
D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002453:Cell Cycle; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005472:Fluorouracil / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D008727:Methotrexate / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D013997:Time Factors
D005472:Fluorouracil; D008727:Methotrexate