Cellular radiosensitivity and cell-type-specific activation of apoptosis signaling pathways

Abstract We have examined the cell-type-dependent sensitivity to UV-induced apoptosis using mouse lymphoma 3SB and human leukemic Jurkat cells and three human carcinoma cell lines (HeLa S3, HeLa SC and MCF-7). Exposure of 3SB and Jurkat cells resulted in large amounts of cytochrome c being released into the cytosol, and a clear laddering pattern of DNA fragments and morphological changes characteristic of apoptosis were detected within 3 h of incubation after irradiation. HeLa S3, HeLa SC and MCF-7 cells also showed extensive release of cytochrome c at 4–6 h after exposure, but apoptotic morphologic changes appeared much later. Similar differences in induction of apoptosis after γ irradiation were observed between two kinds of cells. Interestingly, 3SB cells that express wild-type p53 protein showed a steep increase in number of apoptotic cells when irradiated with low doses of γ-rays, and the dose response of apoptosis induction was not influenced by radiation dose rate. This result suggests that signaling for radiation-induced apoptosis in hematopoietic cells showing rapid apoptosis can be triggered by initial DNA damage, and not determined by DNA repair.