Protection of murine progenitor cells in vitro from the cytotoxic effects of Trimetrexate, Tomudex, or LY231 514 together with NBMPR.

Murine BM cells were transduced with retroviral vectors expressing only the GFP gene, an L22YF31R trimetrexate (TMTX)-insensitive variant of the DHFR gene, or the NBMPR-insensitive nucleoside transporterei gene. Cells were then treated in suspension culture for 4 days in dialyzed FBS supplemented with myeloid cytokines in the presence or absence of 100 nmol/L Thd and 100 μmol/L hypoxanthine. 150 nmol/L TMTX (A), 100 nmol/L Tomudex (B), and 1 μmol/L LY231514 (C) were added to the suspension cultures in the presence or absence of 100 nmol/L NBMPR or 10 μmol/L DIP as indicated. After 4 days of drug treatment, cells were washed and plated in drug-free semisolid media, and the myeloid progenitor counts were determined. The progenitor cell counts in drug-treated cultures are expressed as a percentage of the colony number observed in untreated cultures.