Resistance of human bone marrow CFUC to high-dose methotrexate cytotoxicity

We have studied the susceptibility of human bone marrow cells to the high-dose methotrexate (MTX) cytotoxicity by the in vitro cultures of the granulocyte precursor cells (CFUC) in a medium containing various concentrations of MTX. Cultures of cells were exposed to 10(-9) to 10(-2) M MTX for 2, 6, 24 h and 10 days. About 50% of CFUC were killed by a 10-day exposure to 10(-7) M MTX or more. However, there was no loss of CFUC even at a drug concentration of 10(-3) M MTX if the exposure time was kept for 24 h or less. Within a 2 h exposure time, CFUC was resistant to MTX at the concentration of 10(-2) M. Such a strong resistance of bone marrow cells to MTX may warrant clinical usefulness of the high-dose and short-time MTX therapy with leucovorin rescue, which has widely been used in the treatment of various malignant diseases.