DIFFERENTIAL POTENTIATION OF 1,3-BIS(2-CHLOROETHYL)-1-NITROSOUREA BY ALPHA-DIFLUOROMETHYLORNITHINE IN CHLOROETHYLNITROSOUREA-SENSITIVE AND CHLOROETHYLNITROSOUREA-RESISTANT 9L-RAT BRAIN-TUMOR CELLS-INVITRO

  • 1 January 1983
    • journal article
    • research article
    • Vol. 43  (8) , 3576-3578
Abstract
.alpha.-Difluoromethylornithine [DFMO], an enzyme-activated, irreversible inhibitor of ornithine decarboxylase, inhibited the growth of both chloroethylnitrosourea-sensitive and-resistant 9L rat brain tumor cells in vitro. After 48 h of treatment with 10 mM DFMO, the putrescine and spermidine contents of both resistant and sensitive cells were < 5% of control levels, but the spermine level was slightly elevated. The cytotoxicity of 1,3-bis(2-chloroethyl)-nitrosourea [BCNU], as measured by a colony-forming efficiency assay, was significantly increased in DFMO-pretreated sensitive cells, but not in resistant cells treated with this polyamine inhibitor. With the sister chromatid exchange assay, it was found that DFMO pretreatment increased BCNU-induced damage to chromosomes in sensitive, but not in resistant cells.

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