Damages of DNA synthesis in normal and tumor cells with sugar alcohol derivatives.
The rates of incorporation of 2-14C-thymidine into DNA of melanoma B16, bone marrow, gastrointestinal mucosa, spleen and liver at various time after administration of dianhydrogalactitol (DAG), 3,4-diacetyldianhydrogalactitol (DiacDAG) and 3,4-disuccinyldianhydrogalactitol (DisuDAG) at maxima nonlethal single doses to tumor-bearing mice were studied. The sugar alcohol derivatives induced the stable inhibition in DNA synthesis of tumor cells. DNA synthesis in normal dividing cells was shown to recover more rapidly than in melanoma B16 cells after administration of all drugs. DisuDAG is characterized by stronger inhibitory effect on DNA synthesis in melanoma B16 cells at the half of the single maxima nonlethal dose compared with DAG and DiacDAG. Differing from DAG, DiacDAG and DisuDAG did not effect the incorporation of 2-14C-thymidine into DNA of liver cells. In vivo inhibition of DNA synthesis in melanoma B16 cells with DiacDAG was not due to damage of the TCA soluble fraction.
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001853:Bone Marrow / Q000378:metabolism; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis*; D003961:Dianhydrogalactitol / Q000031:analogs & derivatives / Q000627:therapeutic use; D007274:Injections, Intraperitoneal; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D009092:Mucous Membrane / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D013402:Sugar Alcohols / Q000009:adverse effects / Q000627:therapeutic use*; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors
D000970:Antineoplastic Agents; D013402:Sugar Alcohols; D003961:Dianhydrogalactitol; C027991:dianhydro-3,4-diacetylgalactitol; C044246:3,4-disuccinyl 1,2-5,6-dianhydrogalactitol; D004247:DNA; D013936:Thymidine