Influence of a prior heat treatment on the enhancement by hyperthermia of X-ray-induced inactivation of cultured mammalian cells.

The effect of prior heat treatment on thermal enhancement of radiation effects in treatments of cultured M8013S cells, derived from a transplantable murine mammary carcinoma, combining X-irradiation and 30 min at 43 degrees C up to 45 min at 45 degrees C in medium without serum have been studied. Prior heat treatment induces resistance to combined heat-irradiation treatments. A treatment of 30 min at 43 degrees C without prior heat treatment led to a thermal enhancement ratio of 2.2. With a prior 30 min at 43 degrees C treatment 6 hours before the combined heat-irradiation treatment, this ratio was decreased to 1.6. The relative resistance to combined treatments is very probably the result of the thermotolerant state of the cells induced by the prior heat treatment. The effects seem to be predominantly on the shoulder of the radiation survival curve. The resistance decays when the prior heat treatment is given longer than 24 hours before the combined heat-irradiation treatment. However, in the thermotolerant state large thermal enhancement ratios can be observed, this in spite of the resistance. A treatment of 45 min at 45 degrees C, 6 hours after a prior 30 min 43 degrees C treatment, led to an enhancement ratio of 6.0 both in medium with and without serum. Without prior heat treatment, the relative survival after 45 min at 45 degrees C is too low to enable determination of thermal enhancement of radiation effects. The sensitivity of the cells to a single heat treatment appeared to be dependent on nutritional conditions. Cells treated in medium without serum were more sensitive to heat. The sensitivity of preheated thermotolerant cells to a relatively short (up to 3 hours at 43 degrees C) heat treatment appeared to be rather independent of nutritional conditions, but the sensitivity of these cells to prolonged heat treatment (longer than 4 hours at 43 degrees C) was very dependent on the nutritional state. The presence of serum (and possibly other components in complete culture medium) made thermotolerant cells much more resistant to these long heat treatments. The present results may be important for clinical application of hyperthermia in combination with radiotherapy. They may provide guidelines concerning the intervals to be applied in fractionated treatments.