Failure of 2-deoxy-D-glucose and 5-thio-D-glucose to kill hypoxic cells of two murine tumors.

We have administered the glycolysis inhibitors 2-deoxy-D-glucose and 5-thio-D-glucose to C3H/HeJ mice bearing KHT or 16/C transplantable tumors to seek evidence for hypoxic cell toxicity in vivo. The drugs were given (a) with or without insulin, (b) as large single doses or as multiple hourly injections, and (c) alone or immediately after the tumors had received radiation to kill most of the aerobic cell population. Tumor response was assessed by growth delay or by lung colony assay. Limiting toxicity of 2-deoxy-D-glucose and 5-thio-D-glucose was neurological, leading to seizures and/or death, and this toxicity was increased by insulin. The drugs had at most minimal effects on the growth of either untreated or irradiated tumors at maximal tolerated doses. Despite the known selective toxicity of these glucose analogues for hypoxic cells in tissue culture, we have found them to be ineffective in killing hypoxic cells of two murine tumors.