Threshold Level of p53 Required for the Induction of Apoptosis in X-Irradiated MOLT-4 Cells
- Department of Laboratory Animal Science, Tokyo Metropolitan Institute of Medical Science, Tokyo (Japan)
Purpose: To determine the threshold level for the initiation of apoptosis by studying the quantitative aspect of p53 response to DNA damage in individual cells, to better understand the process in X-ray-induced p53-dependent apoptosis. Methods and Materials: Time-sequential changes in p53 protein level were obtained for X-irradiated MOLT-4 cells using flow cytometry and analyzed. Results: The changes in the cellular frequency distribution pattern of p53 content could be divided into two parts at a certain p53 level. The p53 vs. side-scatter in flow cytometry showed the sequential changes of p53 increase followed by an increase in cell death. On the basis of these results we determined a threshold level of p53 for the initiation of apoptosis. The level was estimated to be (1.08 {+-} 0.05) x 10{sup 5} molecules per cell, which was approximately threefold higher than the mean content of control cells. The minimum times for p53 level to reach this threshold level were independent of X-ray dose and 1.4-1.6 h. The times for the signal transduction from the p53 accumulation to disruption of the mitochondrial membrane potential, caspase-3 activation, and cell death were 1.6, 2.1, and 2.8 h, respectively. Conclusions: The threshold level of p53 for the initiation of apoptosis and the time sequence in the course of apoptotic events were determined in X-irradiated MOLT-4 cells.
- OSTI ID:
- 20951719
- Journal Information:
- International Journal of Radiation Oncology, Biology and Physics, Vol. 68, Issue 3; Other Information: DOI: 10.1016/j.ijrobp.2007.03.007; PII: S0360-3016(07)00386-0; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0360-3016
- Country of Publication:
- United States
- Language:
- English
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