INHIBITION OF CULTURED LEUKEMIA-CELL GROWTH BY ENHANCED ADRIAMYCIN CYTOTOXICITY WITH REDUCTION OF GLUTAMINE OR ASPARAGINE LEVEL IN MEDIUM

The effect of a singular amino acid, asparagine (Asn), glutamine (Gin) , or proline deletion in a cultured medium (RPMI 1640 supplemented wit h 10% fetal calf serum and other ingredients) on adriamycin (ADR) cyto toxicity was evaluated in the growth of P388 murine leukemia cells and CEM human acute lymphoblastic leukemia cells over a 3 day period. No enhancement of ADR cytotoxicity was observed in the assay of IC50 valu es under the amino acid deleted condition. Singular deletion of Gin or Asn from ADR-free medium apparently inhibited the proliferation of bo th cells, i.e. both cell lines strongly require them. The cytotoxicity of 5 nM ADR was then examined in medium which included one or the oth er of them in stepwise levels varied at 80, 60, 40, 20 and 0% of the o rdinary level. Change of Asn level caused a difference in ADR toxicity ; also, the change of Gin level, especially the 60% level caused ADR t oxicity of 5 nM, which is less than the IC50 value, in the proliferati on of both cells. This suggested the usefulness of glutamine level mod ification on the enhancement of ADR cytotoxicity.