Drug-selected and retroviral-transduced P-gp^+ve cells are resistant to Fas-mediated, caspase-dependent DNA fragmentation and membrane lysis. CEM cell lines (A, B) (P-gp^−ve CCRF, 2H6; P-gp^+veA7⁺, IC10), parental 12D7 (P-gp^−ve), and retrovirus-transduced 12D7-MDR1 (P-gp^+ve) cells (E, F) were labeled with ¹²⁵IUdR and ⁵¹Cr for 1 hour, washed in growth media, and incubated for 16 hours in 96-well plates (2 × 10⁴ cells/well) with anti-human Fas IgM MoAb, CH-11 (0.01 μg/mL). In some wells, cells were preincubated for 30 minutes with 20 μmol/L ZVAD-fmk or control ZFA-fmk inhibitor and/or anti–P-gp MoAb MRK 16 (50 μg/mL) as indicated in Table 1. CCRF and A7⁺ cells (C), (D) were preincubated with the given concentrations of anti–P-gp MRK 16 MoAb (1 to 50 μg/mL) or UIC2 MoAb (0.1 to 5 μg/mL), then treated with 0.01 μg/mL anti-Fas MoAb for 16 hours. Data are calculated as the mean ± SE of triplicate samples and are representative of at least two different experiments.