c-MYC retrovirus-driven lymphomas lacking Puma, Noxa, and Bim are as drug resistant as those lacking p53. (A-B) Cell lines derived from rv c-MYC–driven lymphomas of the different genotypes were treated with etoposide (0.04, 0.2, or 1.0 μg/mL for 6 (A) or 24 hours (B). Data represent mean ± SEM from at least 3 independent experiments (each independent cell line represented by an individual line). (C) Induction of p53 protein following DNA damage with etoposide. More p53 protein is evident at 6 hours postexposure to etoposide in rv c-MYC-Noxa^−/−Puma^−/−Bim^−/−, consistent with the fact that cell death is not as great at this time point in this genotype, relative to the rv c-MYC-Puma^−/−Bim^−/− cell line. (D) Induction of the p53 target genes, p21 and Mdm2, following exposure to etoposide relative to untreated controls. Data for individual lymphoma cell lines represent mean ± SEM 3 independent experiments).