Polet H
J Pharmacol Exp Ther. 1975 Feb;192(2):270-9.
The characteristics of the uptake of 3H-Actinomycin D (3H-AMD) by mammalian cells was studied in vitro. Chang liver (CH) cells accululated 3H-AMD over 100 times above extracellular levels. CH cells accumulated and released 3H-AMD at a slow rate. Treatment of cells with ethanol-acetone or Tween 80 significantly increased the rates of drug uptake and release by cells, indicating that the cell membrane effectively slows down passage of 3H-AMD in and out of cells. Cellular 3H-AMD uptake is temperature dependent and not energy dependent. The rates of 3H-AMD uptake after short and prolonged incubation suggest that AMD entry into cells consists of two phases, an initial phase of rate-limiting diffusion process followed by a second phase of binding to deoxyribonucleic acid. Although lymphocytes take up less 3H-AMD than CH cells, the differential inhibitory effect of AMD on nucleic acid synthesis in the two cell types is small. The time required for cells to be fully saturated with 3H-AMD varies with the cell type and is based on permeability differences of the cell membrane for 3H-AMD. The time required for lymphocytes and CH cells to be fully saturated with 3H-AMD is reflected in the differential effect of the drug on nucleic acid synthesis. The physiological basis of AMD resistance can be explained on the basis of impaired diffusion of the drug into cells.
在体外研究了哺乳动物细胞摄取3H-放线菌素D（3H-AMD）的特性。张氏肝细胞（CH细胞）积累的3H-AMD超过细胞外水平100倍以上。CH细胞以缓慢的速率积累和释放3H-AMD。用乙醇-丙酮或吐温80处理细胞可显著提高细胞摄取和释放药物的速率，这表明细胞膜有效地减缓了3H-AMD进出细胞的过程。细胞摄取3H-AMD与温度有关，与能量无关。短期和长期孵育后3H-AMD的摄取速率表明，AMD进入细胞包括两个阶段，一个是限速扩散过程的初始阶段，随后是与脱氧核糖核酸结合的第二阶段。虽然淋巴细胞摄取的3H-AMD比CH细胞少，但AMD对两种细胞类型核酸合成的差异抑制作用较小。细胞被3H-AMD完全饱和所需的时间因细胞类型而异，并且基于细胞膜对3H-AMD的通透性差异。淋巴细胞和CH细胞被3H-AMD完全饱和所需的时间反映在药物对核酸合成的差异作用上。AMD耐药性的生理基础可以基于药物向细胞内扩散受损来解释。
