Tumor-selective modification of cellular microenvironment in vivo: effect of glucose infusion on the pH in normal and malignant rat tissues

Abstract

The pH distributions in transplanted neural (TV1A, BT1A) and hepatic (HV1A3) tumors and in brain and kidney of BDIX rats were analyzed as a function of serum glucose concentration (SGC), tumor size, and tissue architecture. Tissue damage during pH measurements in vivo could be minimized by the use of pH microelectrodes with tip diameters of less than or equal to 10 micrometers. In normoglycemic rats, the pH in TV1A tumors was only slightly lower than in brain or kidney. However, at 6 hr after the induction of hyperglycemia by continuous i.v. infusion of glucose, the average pH in TV1A tumors had fallen to 6.7 at an SGC of 27 mM and to 6.1 at an SGC of 50 mM. A similar glucose-mediated pH reduction was observed in BT1A and HV1A3 tumors. No significant increase in tissue acidity occurred in brain and kidney. The pH in tumors had reached its minimum at 2 hr after the onset of high-dose glucose infusion (SGC, 50 mM) and could be maintained at this level in hyperglycemic rats for at least 48 hr. In hyperglycemic hosts, an increased retention of acidic metabolites in the tumor tissue with decreasing vascular density was reflected by a tumor size (age)-dependent pH reduction and a higher degree of intratumoral pH variation. In partially necrotic tumors, pH values as low as 5.2 were recorded. Oral administration of NaHCO3 to tumor-bearing rats had no effect on the average pH in TV1A tumors.