Changes in pH and blood flow induced by glucose, and their effects on hyperthermia with or without BCNU in RIF-1...

The changes in pH and blood flow of tumours caused by hyperglycaemia, and their effects on hyperthermia with BCNU, were investigated using RIF-1 tumours which grew intradermally in the thigh of C3H mice. The pH of the tumour was measured by inserting a microelectrode into the tumour. The blood flow in the tumour was estimated by flow cytometry from the uptake of the bisbenzamide fluorochrome Hoechst 33342 into the tumour. Administration of glucose resulted in a transient drop of both pH and blood flow of the tumour. The change in blood flow appeared earlier than that in pH. The response of the tumour to heat was enhanced by the administration of glucose in a time- and dose-dependent fashion, and closely correlated to the change in tumour pH. Glucose administration reduced the cytotoxicity of BCNU. This can be explained by the inhibitory effect of glucose on tumour blood flow. The effect of BCNU was enhanced by hyperthermia. This combined effect of heat and BCNU was further enhanced by the addition of glucose, but this effect was not dramatic. Because glucose inhibits blood flow in the RIF system at least, glucose is more effective for thermotherapy than for thermochemotherapy.