Two distinct modes of hyperthermic cell death

Plateau-phase Chinese hamster ovary cells sterilized by heat died one of two distinct modes of death. A "rapid" mode, which predominated during the first few days postheating, was characterized by cell detachment and inhibited rates of protein, RNA, and DNA synthesis. A "slow" mode of death became evident after the cells had fully recovered from the heat-induced inhibition of macromolecular synthesis and cell detachment had ceased. These populations had reduced plating efficiencies relative to nonheated populations and contained a large fraction of cells with multiple nuclei. The multinucleated cells did not form colonies, but heated populations also contained increased numbers of uninucleated cells which were nonclonogenic. As the heat dose was increased and the surviving fraction decreased, the rapid mode of death predominated. These data show that heat damage is expressed in two distinct ways. This might result from the existence of two separate targets for heat killing, or a single target which manifests its effects in different ways as the damage it sustains increases.