Unequal modification of the thermal survival responses of clonal human colon carcinoma cell lines by decreased pH.

We have investigated the responses of two closely related human colon tumour lines (clone A and clone D) to hyperthermic cell killing in vitro under two conditions of environmental acidity (pH values 7.40 and 6.75). At pH 7.40, under prolonged exposure to 42.5 degrees C, both lines exhibited biphasic response curves with thermotolerance appearing at about 4 h of continuous heating. It was found that the clone D human tumour line was more resistant to hyperthermic inactivation than the clone A line. At pH 6.75, both lines exhibited increased sensitivity to heating killing at 42.5 degrees C, but it was found that the effect was unequally demonstrated by the two human tumour lines (i.e. decreased pH was not acting simply as a dose modifying agent). Specifically, clone A exhibited a much greater hyperthermic sensitivity in the thermotolerant region of survival (i.e. a heating time of 4 h or more) than did clone D. Clinically, this result would suggest that although potential pH sensitization of heterogeneous tumours to hyperthermic cell killing may vary in a random manner among tumour cell subpopulations within a given tumour, the increased heat sensitivity found may produce isosurvival results for equal heating times for the different subpopulations.