CPX inhibits ribonucleotide reductase. (A) MDAY-D2 and OCI-M2 leukemia cells were treated with CPX (5 and 10 μM) or buffer control for 24 hours. After incubation, cells were harvested, rapidly frozen, and the tyrosyl radical activity (↑) was measured by EPR at a microwave frequency of 9.12 GHz and 77 Kelvin. The averaged of 9 scans is presented. One of 2 representative experiments is shown. (Insets) Mean percentage viability of cells treated with increasing concentrations of CPX. (B) HeLa cervical cancer cells were transfected with cDNA corresponding to RRM2 or vector control and incubated with CPX at increasing concentrations. Seventy-two hours after incubation, cell viability was assessed by the MTS assay. Data represent the mean ± SD percentage viable cells from 1 of 3 representative experiments performed in triplicate; *P < .05 (Student t test). (C) U937 leukemia and KMS18 myeloma cells were treated with increasing concentrations of CPX or hydroxyurea (HU). Seventy-two hours after incubation, cell growth and viability were measured by the MTS assay. Data represent the mean percentage ± SD relative to control cells of 1 of 3 representative experiments performed in triplicate.