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A differential low pH effect on tumour cells grown in vivo and in vitro when treated with hyperthermia.

The effectiveness of low extracellular pH in sensitizing cells to heat was studied using SCK mammary carcinoma cells of A/J mice. Solid tumours of 400-600 mg or cells grown in vitro for less than 13 weeks were dispersed to single cells and the in vivo- or in vitro-derived cells were suspended in a medium of pH 7.2 or 5.5-6.6 and then heated at 41-44 degrees C in vitro using a water bath. The dispersion procedure did not alter the heat sensitivity of these cells, but acidic medium of pH below 6.6 caused an increase in heat sensitivity. This effect of low pH decreased with increasing temperature of heating for both cell types. However, the effect was much smaller on in vivo-derived cells than that on in vitro-derived cells for any heating temperature tested. This reduction of the pH effect was also observed for cells derived from larger tumours as well as tumours at an early stage of growth in which the internal milieu was not acidic. This indicates that cellular adaptation to low intratumour pH was not the cause of the reduced pH effect; instead, factors other than low pH must cause the reduced pH effect seen in tumour-derived cells.