Ramu A, Glaubiger D, Magrath I T, Joshi A
Cancer Res. 1983 Nov;43(11):5533-7.
We have studied the structural order of the lipid phase of plasma membranes from P388 murine leukemia cells and from a Doxorubicin-resistant subline, P388/ADR, using electron spin resonance spectroscopy and fluorescence depolarization measurements. Measurements of the order parameter, S, following incubation of cells from both lines with the N-oxyl-4'-4'-dimethyloxazolidine derivative of 5-ketostearic acid show higher values for the resistant cells at all temperatures where S was measured (4-37 degrees). Fluorescence depolarization measurements following incubation of the cells, or cell fractions, with 1,6-diphenylhexatriene indicate more restricted motion of the probe in resistant cells. These measurements also show increased amounts of cytoplasmic lipid in the resistant cells. The higher degree of structural order in the lipid phase of the plasma membranes of P388/ADR cells and their larger intracellular lipid content may account for the decreased rate of intracellular accumulation of anthracycline drugs (and other compounds) seen in these cells and, in part, for their relative resistance to the cytotoxic effects of these drugs.
我们使用电子自旋共振光谱法和荧光去极化测量法，研究了P388小鼠白血病细胞以及多柔比星耐药亚系P388/ADR细胞膜脂质相的结构有序性。用5-酮硬脂酸的N-氧基-4'-4'-二甲基恶唑烷衍生物孵育这两种细胞系的细胞后，对有序参数S进行测量，结果表明，在所有测量S的温度下（4-37摄氏度），耐药细胞的S值都更高。用1,6-二苯基己三烯孵育细胞或细胞组分后进行荧光去极化测量，结果表明探针在耐药细胞中的运动受到更多限制。这些测量还表明，耐药细胞中的细胞质脂质含量增加。P388/ADR细胞膜脂质相更高程度的结构有序性及其更大的细胞内脂质含量，可能解释了这些细胞中蒽环类药物（以及其他化合物）细胞内积累速率降低的原因，部分解释了它们对这些药物细胞毒性作用的相对抗性。
