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Heat Sensitivity, Thermotolerance, and Profile of Protein Synthesis of Human Bone Marrow Progenitors¹

Division of Radiation Oncology, Department of Radiation Research, City of Hope National Medical Center, Duarte, California 91010

Hyperthermic sensitivity, kinetics of thermotolerance induction and decay, and profile of heat shock protein synthesis were studied in human granulocyte-macrophage progenitors and nucleated bone marrow cells, respectively. The D₀ of the heat survival curves of human granulocyte-macrophage colony-forming cells at 43°C, 44°C, and 45°C were 23, 12, and 5 min, respectively.

The kinetics of thermotolerance induction was measured with a triggering dose of 44°C/20 min, 45°C/10 min, 41°C/2 h, and 42°C/1 and 4 h. The cells were then challenged with 44°C or 45°C after incubation for 2, 4, 6, 24, and 48 h at 37°C. In all cases, except for 41°C/2 h, thermotolerance was maximum at 2 to 6 h, began to decay at 24 h, and decayed completely by 48 h. At the 41°C/2-h triggering dose, the thermotolerance decayed completely by 24 h. The heat shock protein synthesis was measured after a triggering dose of 44°C/20 min or 45°C/10 min. Synthesis of M_r 70,000 and 87,000 heat shock proteins in the total nucleated bone marrow cells was evident at least for 8 h after the initial heating.

¹ This work was supported by NIH Grant CA 33572 from the National Cancer Institute.

Received 10/ 7/87. Revised 4/ 4/88. Accepted 4/ 5/88.