Intracellular accumulation of [¹⁴C]STI571 mesylate, doxorubicin, and mitoxantrone. (A) The intracellular [¹⁴C]STI571 accumulation (mean ± SD) in BCRP-overexpressing MCF7 sublines and (B) BCRP-transfected HEK293 cells. The relative accumulation of [¹⁴C]STI571, after a 2-hour exposure to this radioactive compound, is based on the mean of at least 3 independent experiments and is expressed as a fraction of that found in parental BCRP-negative cells (% control). (C) Relative accumulation of doxorubicin and (D) mitoxantrone in HEK293 cells, transfected with pcDNA3 (HEK293/Neo), wt-BCRP (HEK293/R), or mt-BCRP variants at residue 482 (HEK293/G and HEK293/T). Intracellular accumulation was measured by flow cytometry. Relative accumulation of these drugs, shown as fluorescence intensity (peak value) of at least 20 000 events, is shown as fraction relative to that found in control HEK293/Neo cells (% control). (E) The effect of 200 nM Ko-143 on the steady-state accumulation of [¹⁴C]STI571 in the panel of HEK293 cells. HEK293 BCRP variants were preincubated with Ko143 (200 nM) for 1 hour and then exposed to ¹⁴C-labeled imatinib (0.21 μM) for an additional 2 hours. Betaradiation (dpm) was used as a measure of the intracellular [¹⁴C]STI571 accumulation.