Heat-induced thermal tolerance and radiation resistance to apoptosis in human lymphocytes

We have investigated heat- and radiation-induced apoptosis in human lymphocytes in vitro. We have previously shown that apoptosis was induced by radiation at doses as low as 0.05 Gy. Here we report that heat induced apoptosis in human lymphocytes in a temperature- and time-dependent manner. Temperatures at or below 42 degrees C, for up to 90 min, did not cause lymphocytes to undergo apoptosis, whereas temperatures at or above 43 degrees C, for 30 min and longer, did induce apoptosis. Lymphocytes were protected against apoptosis induced by 44 degrees C heat by a prior heat shock of 42 degrees C for 30 min. Heat-induced thermal tolerance developed immediately following the inducing heat shock, was greater after 4 h, and persisted for at least 24 h. While heat also induced radiation resistance, this change was minor and not apparent until about 24 h after the heat shock. Prior to the development of radiation resistance, heat shock sensitized lymphocytes to radiation-induced apoptosis. We have previously shown that radiation-induced apoptosis in lymphocytes varies between donors and therefore may be useful in assessing individual radiosensitivity. We report here that heat also induced variable levels of apoptosis in lymphocytes from different donors, although the range of responses was not as large as those observed with radiation-induced apoptosis. In summary, heat shock induces tolerance to heat-induced apoptosis and results first in sensitization and then protection of lymphocytes against radiation-induced apoptosis.