Hyperthermic Radiosensitization of Synchronous Chinese Hamster Cells: Relationship between Lethality and Chromosomal Aberrations

Synchronous Chinese hamster cells in vitro were obtained by mitotic selection. The cells were heated at 45.5°C for 4 min in mitosis, 11 min in G1, or 7 min in S sphase and then X-irradiated immediately thereafter. Colony survival from heat alone was 0.30 to 0.45, and the frequency of chromosomal aberrations induced by heat was 0.00, 0.14, or 0.97 for heat treatments during M, G1, or S, respectively. As shown previously, lethality from hyperthermia alone is due to chromosomal aberrations only when the cells are heated during S phase. The log survival $(D_{0}^{\sim}=80\ \text{rad})$ and aberration frequency curves for cells irradiated during mitosis were linear, and the only effect of hyperthermia was to shift the curves in accord with the effect from heat alone. Thus, hyperthermia did not radiosensitize the mitotic cells. The cells irradiated in G1 were more resistant $(D_{0}^{\sim}=100\ \text{rad})$ than those irradiated in mitosis, and the survival and aberration frequency curves both had shoulders. The primary effect of hyperthermia was to greatly reduce the shoulders of the curves and to increase the slopes by about 23%. The cells irradiated in S were the most resistant $(D_{0}^{\sim}=140\ \text{rad})$, and the survival and aberration frequency curves both had large shoulders. For both end points of lethality and chromosomal aberrations, heat selectively radiosensitized S-phase cells relative to G1 cells by removing most of the shoulder and increasing the slope by about 45%. In fact, a treatment of heat plus X irradiation produced more lethal and chromosomal damage in cells treated in S than in those treated in G1. Furthermore, for both G1 and S-phase cells, the radiosensitization for lethality was almost identical to that for induction of aberrations. This positive correlation can be illustrated by a plot of log survival versus aberration frequency, in which the points for cells irradiated in M, G1, or S, with or without heat treatment, fell on a straight line having a $D_{0}^{\sim}$ of 0.9 aberrations per cell. Thus, for cells treated in G1 or S, the increase in radiosensitization following hyperthermia can be accounted for by an increase in the frequency of chromosomal aberrations.