RESISTANCE OF RESTING 3T6 MOUSE FIBROBLASTS TO METHOTREXATE CYTOTOXICITY

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  • 1 January 1978
    • journal article
    • research article
    • Vol. 38  (8) , 2408-2412
Abstract
The relative susceptibility of resting (GO) vs. exponentially growing mouse fibroblasts (line 3T6) to methotrexate (MTX) [an antineoplastic drug] cytotoxicity was compared. Culture of cells were exposed to different levels of MTX for various intervals. Cloning efficiencies of the cells were then determined in medium containing hypoxanthine and thymidine. Growing 3T6 cells exhibited time- and dose-dependent cytotoxicity. Greater than 95% of the cells were killed by a 24 h exposure to 10-6 M MTX. Resting cells showed no loss of cloning efficiency even at drug concentrations of 10-3 M and exposure times of 7 days. The resistance of resting cells was not the result of a MTX transport deficiency since extracellular MTX was taken up by resting and growing cells. Intracellular dihydrofolate reductase activity was abolished in resting and growing cells at similar extracellular MTX dosages.