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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Decreased cell kill of vincristine and methotrexate against 9L rat brain tumor cells in vitro caused by alpha-difluoromethylornithine-induced polyamine depletion.

The effect of polyamine depletion on the cell kill caused by the cell cycle-specific agents vincristine (VCR) and methotrexate (MTX) was studied in 9L rat brain tumor cells in vitro using a colony-forming efficiency assay as the experimental end point. The cell kill produced by a 24-hr treatment with VCR or MTX was decreased in 9L cells pretreated with 1 mM alpha-difluoromethylornithine, an irreversible inhibitor of ornithine decarboxylase. Reversal of the alpha-difluoromethylornithine-induced polyamine depletion with 1 mM exogenous putrescine prevented the decrease in VCR and MTX cytotoxicity. After a 48-hr treatment with 1 mM alpha-difluoromethylornithine, the number of mitotic cells in asynchronously growing 9L cell cultures was reduced markedly. The decreased cell kill of VCR and MTX appeared to be the result of polyamine depletion-induced inhibition of 9L cell cycle traverse, which reduced the number of cells in drug-sensitive phases of the cell cycle and thereby reduced the cell kill caused by the drugs.[1]


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