[In vitro cytotoxicity of methotrexate]

Five murine tumor cells (sarcoma 1509a, Gc-4, YAC-1, Dunn osteosarcoma, Lewis lung carcinoma) were exposed to methotrexate (MTX) at concentrations of 10(-1)-10(-9) mg/ml for 4-72 hours in vitro and then assayed for their viability. The effect of cell killing by MTX was dependent on both exposure time and concentration of the agent. MTX at a concentration of 10(-5) mg/ml killed the entire cell population in 72 hours, whereas the agent was not particularly effective even at a concentration of 10(-1) mg/ml on exposure for 4 hours. There was a close relation between doubling time of tumor cells and exposure time to MTX for killing entire populations of the tumor cells. The longer doubling time of the tumor cells was, the longer exposure time to MTX was needed to kill them. Lewis lung carcinoma was less sensitive to MTX than other sarcomas. The effect of citovorum factor (CF) on tumor cell killing by MTX was studied on sarcoma 1509a. After exposure to MTX sarcoma 1509a populations could not be rescued by the treatment of CF.