Cycle Progression and Division of Viable and Nonviable Chinese Hamster Ovary Cells following Acute Hyperthermia and Their Relationship to Thermal Tolerance Decay¹ Free

Cell cycle progression delays and subsequent growth kinetics of viable and nonviable Chinese hamster cells following acute (45.5°) 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° 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° 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.