Sensitization of clonogenic malignant cells to hyperthermia by glucose-mediated, tumor-selective pH reduction.

The fraction of clonogenic cells (as assayed by colony formation in semisolid agar medium) in neurogenic TV1A tumor transplants carried subcutaneously by hyperglycemic BDIX rats (serum glucose concentration 50 mmoles/1; average intratumoral pH 6.1) was reduced by a factor of approximately 2.5 X 10(3) after in vivo exposure to 42.2 degrees C for 1 h. The corresponding reduction factor for TV1A tumors in normoglycemic rats was about 20 (serum glucose concentration 6 mmoles/1; average intratumoral pH 6.9). Hyperglycemia without hyperthermic treatment reduced clonogenicity by a factor of about 18 ("glucose-mediated suicide").