The relationship of increased nuclear protein content induced by hyperthermia to killing of HeLa S3 cells

The role of a heat-induced increase in nuclear protein mass in killing of cells by hyperthermia was investigated jointly by two groups that had previously reported apparently conflicting results. A correlation between the fraction of HeLa S3 cells killed and the protein content of nuclei isolated immediately after heat exposure was found. This correlation held when thermal sensitivity was modified by the sensitizers 0.41 M ethanol and 5 mM procaine or by the protector 0.6 M glycerol. However, when the HeLa cells were made thermotolerant by a priming heat exposure of 15 min at 45 degrees C followed by 5 h at 37 degrees C, the correlation no longer held. At the 10% survival level a 1.27-fold greater nuclear protein content was observed in tolerant cells relative to nontolerant cells. Thus no general correlation between initial heat-induced nuclear protein mass changes and hyperthermic cell killing exists. When heated cells were returned to 37 degrees C, a time-dependent reduction in the protein content was observed in nuclei isolated after incubation for various times at 37 degrees C. This rate of reduction in nuclear protein content was found to be accelerated in the tolerant cells. Heat-induced changes in cell-cycle progression had no significant effects on the data obtained. It is concluded from the total data base that not only the absolute increment in nuclear protein mass must be taken into account but also the duration of the binding expressed in the rate of recovery.(ABSTRACT TRUNCATED AT 250 WORDS)