Cycle progression and division of viable and nonviable Chinese hamster ovary cells following acute hyperthermia and their relationship to thermal tolerance decay.

Cell cycle progression delays and subsequent growth kinetics of viable and nonviable Chinese hamster cells following acute (45.5 degrees) hyperthermia were documented in an attempt to correlate these changes with the decay of thermal tolerance. Following heating for various lengths of time, cells exhibited a delay in subsequent division which was related to cell survival by a power function relationship. A cell was considered to be viable if it retained the ability to divide to form a colony of 50 or more cells. The components of the delay in cycle transit for viable cells heated in G1 for a treatment of 20 min at 45.5 degrees were approximately 28 hr in G1 and 20 hr in S and G2-M. This represents a 7-fold decrease in the rate progression through G1 and a 2-fold decrease through S and G2-M relative to control rates. The doubling times of viable cells, in subsequent generations, were significantly decreased to a rate 61% of that of control up to 120 hr after heating. This reduction was in part due to lethal sectoring, i.e., a division which produces only one daughter that is capable of forming a viable subclone, within the viable progeny. Within a viable subclone, up to 30% of the cells that divided from 48 to 91 hr after a heat treatment of 20 min at 45.5 degrees were found to be nonclonogenic. Following resumption of division, nonviable cells slowly lost their capacity for proliferation. Nearly all thermal tolerance development induced by a 20-min pretreatment occurred while the viable cells remained in G1. Subsequent progression into heat-sensitive S and G2-M phases modulated thermal tolerance only slightly. Finally, maximal loss of thermal tolerance was exhibited at the time corresponding to the resumption of viable cell division.