Sukemori S, Sugimura K
Rokkou Bio-Scientific Research Laboratory Co., Ltd., Saitama.
Cancer Biochem Biophys. 1994 Sep;14(2):99-105.
The effect of a singular amino acid, asparagine (Asn), glutamine (Gln), or proline deletion in a cultured medium (RPMI 1640 supplemented with 10% fetal calf serum and other ingredients) on adriamycin (ADR) cytotoxicity 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 values under the amino acid deleted condition. Singular deletion of Gln or Asn from ADR-free medium apparently inhibited the proliferation of both 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 other of them in stepwise levels varied at 80, 60, 40, 20 and 0% of the ordinary level. Change of Asn level caused a difference in ADR toxicity; also, the change of Gln level, especially the 60% level caused ADR toxicity of 5 nM, which is less than the IC50 value, in the proliferation of both cells. This suggested the usefulness of glutamine level modification on the enhancement of ADR cytotoxicity.
在含有10%胎牛血清和其他成分的培养基(RPMI 1640)中,单一氨基酸天冬酰胺(Asn)、谷氨酰胺(Gln)或脯氨酸缺失对阿霉素(ADR)细胞毒性的影响,在3天时间内对P388小鼠白血病细胞和CEM人急性淋巴细胞白血病细胞的生长进行了评估。在氨基酸缺失条件下的IC50值测定中,未观察到ADR细胞毒性增强。在无ADR培养基中单独缺失Gln或Asn明显抑制了两种细胞的增殖,即两种细胞系都强烈需要它们。然后在培养基中检测5 nM ADR的细胞毒性,该培养基中逐步改变Gln或Asn的含量,分别为正常水平的80%、60%、40%、20%和0%。Asn水平变化导致ADR毒性存在差异;同样,Gln水平变化,尤其是60%水平,导致5 nM ADR在两种细胞增殖中的毒性低于IC50值。这表明改变谷氨酰胺水平对增强ADR细胞毒性有用。