Most of malignant lymphomas have been shown to be relatively radiosensitive clinically, but some, especially recurrent ones, are frequently highly radioresistant. To clarify the origin of the difference, we examined ionizing radiation (IR)-induced apoptosis in three closely related human lymphoma cell lines (DL-40, DL-95, and DL-110) that differ in p53 status. DL-95 and DL-110 cells have a wild-type p53, whereas DL-40 cells carry a T to G transition in exon 5 of the p53 gene, resulting in a change of Cys to Phe at codon 176. Irradiation of DL-40 cells (mutant-type p53) with 5 Gy gamma-rays resulted in delayed apoptosis with membrane changes (annexin-V expression) 13 h after IR, and caspase-3 activation 23 h after IR, whereas apoptotic response was not identified in DL-95 cells until 48 h after IR in spite of their normal p53 status. Concerning DL-110 cells, delayed and reduced apoptotic response was revealed both microscopically and by DNA fragmentation assay. These results suggested that IR-induced apoptosis in DL-40 cells is mediated by a mechanism involving the caspase-3 cascade of the p53-independent pathway, and that some unknown mechanism inhibited IR-induced apoptosis in existence of wild-type p53, especially for DL-95 cells.