The influence of hypoxia and acidity on the hyperthermic response of malignant cells in vitro.

Colony formation of JB-1-E tumor cells was studied after hyperthermic treatment (42.5 degrees C) at a pH of 6.4 or 7.2 under hypoxic and euoxic conditions. At a pH of 7.2 and normal oxygen tension, there was a moderate decrease in colony formation with increasing duration of hyperthermic treatment (To = 65 min.). This effect was slightly enhanced under hypoxic conditions (To = 36 min.). The hyperthermic effect was enhanced to a considerably greater degree when treatment was performed at a pH of 6.4 (To = 19 min.), with no observable difference between hypoxia and euoxia. These findings indicate that environmental acidity is a determining factor in the hyperthermic effect. The hypoxic effect at a pH of 7.2 is probably due to a slight decrease in the intracellular pH caused by increased production of lactic acid.