Induction of quiescent S-phase cells by irradiation and/or hyperthermia. II. Correlation with colony forming ability

Quiescent S-phase cells, i.e. cells with an S-phase DNA content that do not show BrdU incorporation, can be induced in a dose-dependent manner by irradiation and/or hyperthermia (Zölzer et al. 1992). As they begin to appear only 48-72 h after treatment, they do not seem to be related to early cell cycle disturbances, but rather to late events involved with cell death. We therefore determined colony forming ability under the same conditions, and tried to correlate the two parameters. Although, in general, higher frequencies of unlabelled S-phase cells were associated with lower survival, there were interesting differences. At the same level of survival, for instance, quiescent cells were induced more efficiently by hyperthermia than by irradiation. Additional experiments with split dose protocols showed that while cell killing was reduced by fractionation, the frequency of unlabelled S-phase cells increased. This further corroborates our conclusion that there is no simple relationship between the two parameters. Quiescence in S-phase is not just an expression of cell death irrespective of the treatment by which it may have been caused.