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  • Title: Caspase-independent cell death without generation of reactive oxygen species in irradiated MOLT-4 human leukemia cells.
    Author: Yoshida K, Kubo Y, Kusunoki Y, Morishita Y, Nagamura H, Hayashi I, Kyoizumi S, Seyama T, Nakachi K, Hayashi T.
    Journal: Cell Immunol; 2009; 255(1-2):61-8. PubMed ID: 19081084.
    Abstract:
    To improve our understanding of ionizing radiation effects on immune cells, we investigated steps leading to radiation-induced cell death in MOLT-4, a thymus-derived human leukemia cell. After exposure of MOLT-4 cells to 4 Gy of X-rays, irradiated cells sequentially showed increase in intracellular reactive oxygen species (ROS), decrease in mitochondrial membrane potential, and eventually apoptotic cell death. In the presence of the caspase inhibitor z-VAD-fmk, irradiated cells exhibited necrotic characteristics such as mitochondrial swelling instead of apoptosis. ROS generation was not detected during this necrotic cell death process. These results indicate that radiation-induced apoptosis in MOLT-4 cells requires elevation of intracellular ROS as well as activation of a series of caspases, whereas the cryptic necrosis program--which is independent of intracellular ROS generation and caspase activation--is activated when the apoptosis pathway is blocked.
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