Similar Heat-Induced Cell Cycle Delays in the Clonogenic and Nonclonogenic Fractions of a Thermotolerant Population

We have tested the theory that a faster rate of recovery from thermal damage in thermotolerant cells relative to nontolerant cells is the critical factor which confers heat resistance. We measured the rate of recovery from the heat-induced cell cycle delay in Chinese hamster ovary cells, since this delay is shortened in thermotolerant cells (i.e., exhibits thermotolerance) and can be measured in individual cells. Individual thermotolerant cells were followed by discontinuous microscopic observation from shortly after heating, through the first mitosis after heating, until a colony formed or failed to form by 8 days. The heat-induced delay in the clonogenic and nonclonogenic fractions was the same. This shows that the rate of recovery from the cell cycle delay was not the determining factor as to whether or not a cell survived to form a colony. Either additional factors are involved or the rate of recovery from the cell cycle delay plays no role in cell survival. These data show the importance of determining whether a faster rate of repair of thermal damage is specific for the clonogenic fraction, since most if not all types of thermal damage are likely to be repaired more quickly when thermotolerant and nontolerant cells are compared at isodose.