DECREASED CYTO-TOXICITY OF 1-BETA-D-ARABINOFURANOSYLCYTOSINE IN 9L RAT-BRAIN TUMOR-CELLS PRETREATED WITH ALPHA-DIFLUOROMETHYLORNITHINE INVITRO

  • 1 January 1983
    • journal article
    • research article
    • Vol. 43  (6) , 2541-2544
Abstract
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 cyotoxicity 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 cytoxocity. Flow cytometric analysis showed that cells treated with ara-C alone entered S phase semisynchronously within 8 h 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.