Reduction of streptozotocin toxicity by 3-O-methyl-D-glucose with enhancement of antitumor activity in murine L1210 leukemia.

3-O-Methyl-D-glucose (3-OMG), a nontoxic nonmetabolizable derivative of glucose, is effective in reducing the toxicity of streptozotocin (SZ). In mice the administration of 3-OMG prior to SZ increased the dose that killed 50% of the animals from 240 to 340 mg/kg. Furthermore, the combination of 3-OMG plus nicotinamide (also effective in reducing SZ toxicity) increased the dose that killed 50% of the animals to 540 mg/kg. In L1210 leukemic mice treated with SZ, there was a 2-fold increase in the median survival of animals pretreated with 3-OMG and a 3-fold increase in that of animals pretreated with the combination of 3-OMG and nicotinamide. Neither 3-OMG nor nicotinamide alone enhanced the survival of the leukemic mice. Pretreatment of normal mice with 3-OMG partially prevented the expected fall in hepatic nicotinamide adenine dinucleotide content. This study suggests that 3-OMG, by protecting normal tissue, will permit the administration of larger therapeutic doses of SZ in leukemic L1210 mice. The protective effect of 3-OMG against SZ toxicity appears to be partially mediated through conservation of the nicotinamide adenine dinucleotide content in the tissue.