HEAT-INDUCED THERMAL TOLERANCE AND RADIATION-RESISTANCE TO APOPTOSIS IN HUMAN-LYMPHOCYTES

We have investigated heat- and radiation-induced apoptosis in human ly mphocytes in vitro. We have previously shown that apoptosis was induce d by radiation at doses as ion as 0.05 Gy. Here we report that heat in duced apoptosis in human lymphocytes in a temperature-and time-depende nt manner. Temperatures at or below 42 degrees C, for up to 90 min, di d not cause lymphocytes to undergo apoptosis, whereas temperatures at or above 43 degrees C, for 30 min and longer, did induce apoptosis. Ly mphocytes were protected against apoptosis induced by 44 degrees C hea t by a prior heat shock of 42 degrees C for 30 min. Heat-induced therm al tolerance developed immediately following the inducing heat shock, was greater after 4 h, and persisted for at least 24 h. While heat als o induced radiation resistance, this change was minor and not apparent until about 24 h after the heat shock. Prior to the development of ra diation resistance, heat shock sensitized lymphocytes to radiation-ind uced apoptosis. We have previously shown that radiation-induced apopto sis in lymphocytes varies between donors and therefore may be useful i n assessing individual radiosensitivity. We report here that heat also induced variable levels of apoptosis in lymphocytes from different do nors, although the range of responses was not as large as those observ ed with radiation-induced apoptosis. in summary, heat shock induces to lerance to heat-induced apoptosis and results first in sensitization a nd then protection of lymphocytes against radiation-induced apoptosis.