Wagner B A, Buettner G R, Burns C P
Department of Medicine, University of Iowa College of Medicine, Iowa City 52242.
Cancer Res. 1993 Feb 15;53(4):711-3.
Using the spin trap alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone, we have detected a lipid-derived carbon-centered free radical generated from intact L1210 lymphoblastic leukemia cells that were exposed to 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (edelfosine or ET-18-OCH3) and oxidative stress. The spectral characteristics, including hyperfine splitting constants of aN = 15.61G and aH = 2.65G, were consistent with the spin trapping of an alkyl radical. Radical detection required iron and prior enrichment of cellular components with the polyunsaturated fatty acid docosahexaenoic acid; unmodified cells failed to generate detectable free radical. Ascorbate further enhanced radical generation. The detection of lipid-derived free radicals when intact cells are exposed to edelfosine provides further evidence that oxidative stress may play an important role in the cytotoxic mechanism of this class of anticancer drug.
使用自旋捕获剂α-(4-吡啶基-1-氧化物)-N-叔丁基硝酮，我们检测到完整的L1210淋巴细胞白血病细胞在暴露于1-O-十八烷基-2-O-甲基-rac-甘油-3-磷酸胆碱（依地福新或ET-18-OCH3）和氧化应激时产生的一种脂质衍生的碳中心自由基。其光谱特征，包括超精细分裂常数aN = 15.61G和aH = 2.65G，与烷基自由基的自旋捕获一致。自由基检测需要铁以及事先用多不饱和脂肪酸二十二碳六烯酸富集细胞成分；未修饰的细胞未能产生可检测到的自由基。抗坏血酸进一步增强了自由基的产生。当完整细胞暴露于依地福新时检测到脂质衍生自由基，这进一步证明氧化应激可能在这类抗癌药物的细胞毒性机制中起重要作用。
