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

Abstract

An intraperitoneal injection of glucose (6mg/g) was made to induce hyperglycemia, causing low pH specifically to the tumor to study the degree of thermosensitivity and thermotolerance caused by the glucose administration in an ICR mouse with sarcoma-180 tumor transplanted under the skin of the thigh. Heating was with a controlled water bath of 43°C for 30 minutes. A second heating of the same temperature and duration was applied at various intervals. After administration of the glucose, hyperglycemia resulted. The pH value in the tumor area fell by 0.3 to 0.6, while normal tissue registered a reduction of 0 to 0.1pH, and the time required for recovery was significantly shorter for normal tissue. The drop in pH during hyperthermia was 0.2 to 0.3pH for both the tumor and the normal tissue, while with the combination of heating and glucose administration, pH values of the tumor changed from 6.9 to 6.5, while the change was from 7.2 to 6.9 for the normal tissue. The normal tissue recovered to initial levels immediately after heating, but recovery time of the tumor tissue was slow. Thermotolerance of the group administrated with glucose was maximum at 6 hours after heating, and decayed after 12 hours. Groups without glucose administration showed maximum thermal resistance after 12 hours, and did not show complete decay even after 72 hours. The speed of tumor growth of the group administrated with glucose was 4 days slower than for the group without glucose administration, and showed a 1 to 2 day delay regardless of the interval of heating, showing significant thermal enhancement from the glucose. Further, hyperglycemia induced by glucose administration lowers pH values selectively in tumor areas, making it possible to apply the thermal effect selectively to the tumor areas.