The recovery from 5-FU–induced stress is delayed in Cul4A heterozygous mice. (A) Thirteen Cul4A^+/– and 12 wild-type littermates were treated with 150 mg/kg 5-FU and hematocrits were measured 0 to 20 days later. For wild-type (□) and Cul4A^+/– (▴) mice, the mean percentages ± SEM are plotted for the results from 3 independent experiments. At day 12, **P = .03, and for days 14 to 20, *P ≤ .04. For days 0 to 16, n = 6-12 mice, and for days 18-20, n = 3-5 mice. (B) Cul4A^+/– and wild-type littermates were treated with 5-FU as described in panel A, bone marrow was isolated from femurs 0, 4, or 7 days later and cultured for 7 days. BFU-Es, CFU-GEMMs, and granulocyte-macrophage colony-forming units (CFU-GMs), as well as total colonies, were counted, and the number of progenitors per femur was calculated and normalized with respect to untreated control mice of the same genotype (100%). The means (± SEM) for Cul4A^+/– and wild-type animals from 3 independent experiments are shown, where for the 0, 4, and 7 day time points, n = 13, 5, and 9 (respectively) each for wild-type (□) and Cul4A^+/– (▦) animals. For day 7, *P < .003. (C) Six Cul4A^+/– and 6 wild-type littermates were treated with 5-FU as described, and 7 days later bone marrow was isolated from femurs, stained with anti-Ter119 and anti-CD71 antibodies, and analyzed by flow cytometry to quantify the frequencies of proerythroblasts (PROERY), basophilic erythroblasts (BASO), late basophilic and polychromatophilic erythroblasts (LATE BASO, POLY), and orthochromatophilic erythroblasts (ORTHO) with respect to total erythroid precursors (see “Materials and methods”). The means (percent ± SEM) are graphed for the results from 2 independent experiments. For proerythroblasts (PROERY), *P = .03 and for basophilic erythroblasts (BASO), **P = .01.