SYNERGISTIC CELL-CYCLE KINETIC EFFECT OF LOW-DOSES OF HYPERTHERMIA AND RADIATION ON TUMOR-CELLS

In the present work asynchronous PNJ cells, an in vitro line of a mouse mammary tumour, were treated with small doses of heat (41.5°C for 60 min) and radiation (200 rad), either alone or in combination with variable sequence and when no and a 24-hr interval was interposed between the treatments. The effects were evaluated by growth curves, the relative survival and cell cycle kinetic changes by means of flow cytometry. When hyperthermia preceded radiation, a more lethal effect was observed than when the opposite sequence was used. An interval of up to 24 hr did not change the effect of the combined treatment. When the cells were treated with either hyperthermia or radiation, the alteration of the cell cycle was found to be only small and short-lived, while the combined treatment induced a considerable accumulation of cells with G2 DNA content which could be traced in the DNA histograms for several days. The kinetic effect was at least as pronounced and extended in time when a 24-hr interval was introduced between the treatments as when one treatment was immediately followed by the other. The results suggest that different heat- and radiation-sensitive mechanisms are involved in the progression of cells through the cell cycle and in the lethal damage of the cells. Another explanation is that changes in the cell cycle distribution occur at a lower treatment level than changes in the survival. © 1979.