Synergistic cell cycle kinetic effect of low doses of hyperthermia and radiation on tumour cells

Asynchronous mouse mammary PNJ tumour cells were treated with heat and radiation (200 rad), either alone or in combination with variable sequence and with or without a 24-hr interval 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 for several days. The kinetic effect was at least as pronounced and extended in time whether or nor a 24-hour interval was introduced between treatments. The results suggested that different heat- and radiation-sensitive mechanisms were involved in the progression of cells through the cell cycle and in the lethal damage of the cells. Another explanation was that changes in the cell cycle distribution occurred at a lower treatment level than changes in the survival. (author)