Bailly C, Beauvillain J C, Bernier J L, Hénichart J P
INSERM U 16, Lille, France.
Cancer Res. 1990 Jan 15;50(2):385-92.
The effect of the anticancer drug bleomycin on acyl chain order of KB cell membranes was examined by electron paramagnetic resonance and fluorescence polarization spectroscopies using respectively, the 5-doxyl stearic acid spin probe and the 1,6-diphenyl-1,3,5-hexatriene and the 1-[4-(trimethylammonio)phenyl]-6-phenyl-1,3,5-hexatriene fluorescent probes. Measurements of the order parameter, S, by the two techniques showed a perturbation of the plasma membrane fluidity with bleomycin-iron, while no effect was observed with bleomycin or iron alone. A kinetic study of the location of the 1,6-diphenyl-1,3,5-hexatriene fluorescent probe into the cell was followed by fluorescence microscopy. Lipid peroxidation measurements were also performed using isolated unsaturated lipids, intact cells, or isolated plasma membranes whose purity was checked by electronic microscopy. These membrane perturbation effects not observed with bleomycin-iron in the presence of a hydroxyl radical scavenger, dimethyl thiourea, or a chelating agent, desferrioxamine, were correlated with the ability of the complex to generate highly reactive oxygen species.
利用电子顺磁共振和荧光偏振光谱法，分别使用5-硬脂酸-二氧代硬脂酸自旋探针、1,6-二苯基-1,3,5-己三烯和1-[4-(三甲基铵基)苯基]-6-苯基-1,3,5-己三烯荧光探针，研究了抗癌药物博来霉素对KB细胞膜酰基链有序性的影响。通过这两种技术对有序参数S的测量表明，博来霉素-铁会干扰质膜流动性，而单独使用博来霉素或铁则未观察到影响。通过荧光显微镜对1,6-二苯基-1,3,5-己三烯荧光探针在细胞内的定位进行了动力学研究。还使用分离的不饱和脂质、完整细胞或通过电子显微镜检查纯度的分离质膜进行了脂质过氧化测量。在存在羟基自由基清除剂二甲基硫脲或螯合剂去铁胺的情况下，博来霉素-铁未观察到这些膜扰动效应，这与该复合物产生高活性氧物种的能力相关。
