Tumor Oxygenation and Acidification are Increased in Melanoma Xenografts after Exposure to Hyperglycemia and meta-Iodo-benzylguanidine

Burd, R., Lavorgna, S. N., Daskalakis, C., Wachsberger, P. R., Wahl, M. L., Biaglow, J. E., Stevens, C. W. and Leeper, D. B. Tumor Oxygenation and Acidification are Increased in Melanoma Xenografts after Exposure to Hyperglycemia and meta-Iodo-benzylguanidine. Radiat. Res. 159, 328–335 (2003). Tumor oxygen tension and extracellular pH (pHe) are physiological parameters that can be manipulated to improve current cancer therapies. Many human tumors consist of cells that are chronically exposed to low pHe. Exposure of tumor cells in culture to glucose decreases oxygen consumption (oxygen sparing or Crabtree effect), and while this effect is absent in low pH-adapted tumor cells, it can be restored by combining the respiratory inhibitor meta-iodo-benzylguanidine (MIBG) with glucose (Burd et al., Cancer Res. 61, 5630–5635, 2001). The effects of hyperglycemia and MIBG on tumor oxygen tension and on pHe were investigated in human melanoma xenografts in SCID mice. An oral gavage of 1 M glucose (2 g/kg) increased the average blood glucose concentration from