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.
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000517:prevention & control; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D007939:Leukemia L1210 / Q000188:drug therapy* / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008757:Methylglucosides / Q000494:pharmacology*; D008759:Methylglycosides / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009243:NAD / Q000378:metabolism; D009536:Niacinamide / Q000494:pharmacology; D013311:Streptozocin / Q000009:adverse effects*
D008757:Methylglucosides; D008759:Methylglycosides; D009243:NAD; D009536:Niacinamide; D013311:Streptozocin