Biochemical parameters of resistance of an adriamycin-resistant subline of P388 leukemia to emetine, an inhibitor of protein synthesis.
Biochemical parameters of resistance of an adriamycin-resistant subline of P388 leukemia to emetine, an inhibitor of protein synthesis.
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P388 白血病耐阿霉素亚系对蛋白质合成抑制剂依米丁的耐药生化参数。
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发表时间：
1978
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影响因子：
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通讯作者：
R. Johnson
中科院分区：
文献类型：
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作者：
M. Chitnis;R. Johnson
本研究比较了雌激素对P388白血病细胞（P388/S）和P388白血病阿霉素耐药亚系（P388/ADR）蛋白质和DNA合成的影响。P388/ADR细胞在体外对艾美替尼无明显抗性，P388/S和P388/ADR细胞在体外暴露于艾美替尼1小时和6小时后，细胞毒性无明显差异。在相同浓度的药物下，P388/S和P388/ADR细胞中蛋白质和DNA合成受到相似程度的抑制。然而，在P388/ADR细胞中，当细胞暴露于emglutamine并随后在添加标记的L-亮氨酸之前在无药物培养基中孵育1小时时，emglutamine对蛋白质合成的抑制比P388/S细胞中更可逆。P388/S和P388/ADR细胞之间的差异在体内是明显的。对荷瘤小鼠给予治疗剂量25 mg/kg艾美司汀后，P388/ADR细胞中蛋白质和DNA合成的抑制持续时间（大于90%）约为8小时，而P388/S细胞中为24小时。体内给药后24小时，P388/ADR细胞中的放射性水平仅为P388/S细胞中放射性水平的26%。提示P388/ADR耐药是由于药物滞留减少所致。
The effects of emetine on protein and DNA synthesis in vitro and in vivo were compared in P388 leukemia cells (P388/S) and in an adriamycin-resistant subline of P388 leukemia (P388/ADR), which was completely cross-resistant in vivo to emetine. In P388/ADR cells in vitro no apparent resistance to emetine was found; no difference in cytotoxicity was evident in P388/S or P388/ADR cells exposed to emetine in vitro for 1 or 6 hours. Protein and DNA synthesis was inhibited to a similar extent in P388/S and P388/ADR cells at equivalent concentrations of the drug. However, inhibition of protein synthesis by emetine in P388/ADR cells was more reversible than in P388/S cells when the cells were exposed to emetine and subsequently incubated in drug-free medium for 1 hour prior to addition of labeled L-leucine. Differences between P388/S and P388/ADR cells were evident in vivo. The duration of inhibition (greater than 90%) of protein and DNA synthesis in P388/ADR cells was about 8 hours compared to 24 hours in P388/S cells following administration of a therapeutic dose of 25 mg emetine/kg to tumor-bearing mice. The level of radioactivity in the P388/ADR cells 24 hours after in vivo administration of the emetine analog, (+/-)-[3'-14C]2,3-dehydroemetine, was only 26% of that in P388/S cells. This evidence suggests that the resistance of P388/ADR to emetine is due to decreased retention of the drug.