Extracellular glutamine level reduction enhances 5-fluorouracil cytotoxicity.

Cultured P388 (murine) and CEM (human) leukemia cells were exposed to medium including either 5-fluorouracil (5-FU) or methotorexate (MTX). The level of drug was less than the ID50 value obtained in RPMI 1640 medium (control). Enhancement of drug cytotoxicity was determined with medium in which asparagine or glutamine level had been reduced to 60% of the level of the control. Proliferation of both types of cells for 3 days showed the cytotoxicities of the drugs. Asparagine reduced medium showed no enhancement of cytotoxicity in comparison with control, while glutamine reduced medium enhanced the cytotoxicity of 5-FU, but not that of MTX. Regulation of extracellular glutamine level seemed to affect stage G1 of the cell cycle, as found in the previous result with adriamycin.