The role of p53 in death of IL-3-dependent cells in response to cytotoxic drugs

摘要: This report examines the cytotoxicity of chemotherapeutic agents to primary bone marrow-derived IL-3-dependent cells. Such cells derived from p53-null mice were resistant almost 100-fold higher concentrations inhibitors deoxyribonucleotide synthesis FUdR, methotrexate and hydroxyurea than with wild-type p53. In contrast, DNA damaging X-irradiation, cisplatin or bleomycin was p53-independent. The topoisomerase II inhibitor etoposide induced p53-dependent death, which suggests that damage may not be its mechanism in this cell type. An line expresses p53 used demonstrate ability cytotoxic drugs increase expression level does control their induce loss clonigenicity. Finally, comparison a show absence delays rate entry into apoptosis following treatment either synthesis. distinguishes short-term effects on role controlling ultimate survival.