Influence of pH and thermotolerance on the enhancement of X-ray induced inactivation of cultured mammalian cells by hyperthermia.

The influence of pH and thermotolerance on thermal enhancement of radiation effects have been studied with M8013 cells, derived from a transplantable murine mammary carcinoma. The effect of combined heat-irradiation treatment of cells at different pH of the medium clearly shows an influence of the pH. Thermal enhancement of the effectiveness of radiation is relatively strong below pH 7.0 and above pH 7.75. In the physiological range pH 6.7-7.4 the influence of pH is not very large. This implies that combination of hyperthermia and radiotherapy in cancer treatment would not give much therapeutic advantage from low pH which is often observed in solid tumours as this low pH is rarely below pH 6.7. Sensitization of cells to the effects of heat treatment alone at a low pH of the cellular medium is greatly decreased when thermotolerance is induced in the cells by a prior heat treatment 4-6 hours before the final treatment. When the cells are in the thermotolerant state, induced by a prior heat treatment, not only resistance to heat treatment, but also resistance to combined heat-irradiation treatment is observed. The degree of this latter resistance is independent of the pH of the cellular medium during the combined heat-irradiation treatment. In spite of the resistance, strong thermal enhancement of radiation effects can be observed when cells are treated in the thermotolerant state by a strong heat treatment. Without thermotolerance such a strong heat treatment, whether combined with irradiation or not, caused so much effect that it was impossible to determine relative cellular survival. The enhancement of radiation effects by a strong heat treatment with cells in the thermotolerant state is largely independent of the pH of the cellular medium.