Abstract
Combined effects of ACNU and 5-Fu on rat glioma clone-6 cells grown exponentially as monolayers and in multicell spheroids (500-600 micron in diameter) were analyzed by the colony-forming assay. Cells in spheroids with central necroses were more sensitive to ACNU than cells in monolayer, although a large fraction of the cells in these spheroids was resistant to 5-Fu. The effect of ACNU was enhanced by the combined treatment with 5-Fu for cells in both spheroids and monolayers, and was more remarkable when 5-Fu was administered 24 hr prior to ACNU treatment. The enhancement was mainly due to a decrease in the number of spheroid-cells resistant to 5-Fu. Isobologram analysis indicated that the enhancement was supra-additive when a low concentration of 5-Fu was combined with a high concentration of ACNU. It is suggested that a low dose of 5-Fu combined with a high dose of ACNU may preferentially kill more cells in solid tumors.
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