Decreased cytotoxicity of 1-beta-D-arabinofuranosylcytosine in 9L rat brain tumor cells pretreated with alpha-difluoromethylornithine in vitro.
The effect of pretreating 9L rat brain tumor cells in vitro with 10 mM alpha-difluoromethylornithine (DFMO), an enzyme-activated, irreversible inhibitor of ornithine decarboxylase, on the cytotoxicity of 1-beta-D-arabinofuranosylcytosine (ara-C) was investigated using a colony-forming assay. DFMO-mediated polyamine depletion significantly decreased the cytotoxicity of ara-C. The addition of putrescine to DFMO-pretreated cells replenishes intracellular polyamine levels and prevents the decrease in ara-C cytotoxicity. Flow cytometric analysis showed that cells treated with ara-C alone entered S phase semisynchronously within 8 hr after the end of treatment. This phenomenon was virtually eliminated by DFMO pretreatment. Addition of putrescine to DFMO-pretreated cells before treatment with ara-C prevented this DFMO-induced cell cycle kinetic effect.
D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003561:Cytarabine / Q000633:toxicity*; D004247:DNA / Q000032:analysis; D004357:Drug Synergism; D000518:Eflornithine; D009952:Ornithine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D013997:Time Factors
D003561:Cytarabine; D004247:DNA; D009952:Ornithine; D000518:Eflornithine