Figure 5.

AICAr increases the level of orotate and decreases the level of UMP; exogenous orotate prevents brequinar effects and has no effects on AICAr. A, U937 cells were incubated with AICAr (0.2 or 0.5 mm) or brequinar (0.5 μm) for 24 h. The levels of orotate and UMP were determined as described under “Experimental procedures.” B and C, U937 cells were incubated with AICAr (0.2 or 0.5 mm) or brequinar (0.5 μm) for 72 h. Orotates (0.3 mm) were added 5–15 min after agents, and control cells were treated with vehicle (DMSO). B, representative histograms of propidium-labeled cells from three independent experiments analyzed by flow cytometry. C, the number of viable cells and the expression of differentiation markers were determined as described under “Experimental procedures.” Results are mean ± S.E. (error bars) of at least three independent experiments. *, p < 0.05 compared with control (ctrl).