Effects of Hyperthermia-Induced Changes in pH Value on Tumor Response and Thermotolerance

Summary

After inducing hyperglycemia by intraperitoneally injecting 6mg/kg glucose in C3H mice transplanted with a FM3A tumor subcutaneously in the thigh, a selective decrease of tumor tissue pH was seen.The frequency of appearance of thermal hypersensitivity and thermotolerance in response to glucose administration was studied. Heating was conducted by placing the animals in a thermostatic water bath at 43°C for 30 min, followed by a repeat of the same treatment after various intervals. After inducing hyperglycemia by glucose administration, nonheated tumor tissue pH decreased by 0.3 to 0.6, whereas pH of nonheated normal tissue fell by only 0.1 to 0.2, with a slower recovery to the previous level than the tumor tissue. On heating after glucose administration, tumor tissue pH fell from 6.9 to 6.5 immediately after heating with a delay of recovery time after heating. In normal tissue, tissue pH of 7.2 before heating fell to 6.9, rapidly recovering to a level higher than the baseline after the heat treatment. Thermotolerance reached a maximum 6h after the first heat treatment in the group given glucose and disappeared after 12 h. In the group not given glucose, thermotolerance reached a maximum 12 h after the first treatment, and no complete loss of thermotolerance occurred even after 72 h. Tumor growth rate in the group given glucose was 4 days slower than in that not given glucose when the interval between heat treatment was 12 h, indicating an antitumor effect. At all intervals after the first, the group given glucose showed a delay of tumor growth by 1–2 days compared to the group not given glucose, indicating augmented heat sensitivity. Hyperglycemia caused by glcose administration induced a selective decrease of tumor tissue pH, indicating the possibility of inducing selective heat sensitivity in tumors.