Drug-selected and retroviral transduced P-gp^+ve cells are resistant to DOX-mediated, caspase-dependent DNA fragmentation and membrane lysis. Drug-selected CEM cell lines (P-gp^−ve CCRF, 2H6; P-gp^+veA7⁺, IC10) (A, B) and parental 12D7 (P-gp^−ve) and retrovirus transduced 12D7-MDR1 (P-gp^+ve) cells (E, F) were labeled with¹²⁵IUdR and ⁵¹Cr for 1 hour, washed in growth media, and incubated for 48 hours in 96-well plates (2 × 10⁴ cells/well) with DOX. In some wells, cells were preincubated for 30 minutes with 20 μmol/L ZVAD-fmk or control ZFA-fmk inhibitor as indicated in Table 1. P-gp^+ve cells were made sensitive to DOX-mediated DNA fragmentation (C) and membrane lysis (D) by preincubation with anti–P-gp MoAb, MRK 16 (50 μg/mL). DNA fragmentation and membrane lysis were reflected by¹²⁵I-DNA release (A, C, E) and ⁵¹Cr release (B, D, F), respectively. Data are calculated as the mean ± SE of triplicate samples and are representative of a least two different experiments.