Voest E E, Van Faassen E, Neijt J P, Marx J J, Van Asbeck B S
Department of Internal Medicine, University Hospital Utrecht, The Netherlands.
Magn Reson Med. 1993 Sep;30(3):283-8. doi: 10.1002/mrm.1910300303.
The decay of nitroxide spin label electron paramagnetic resonance (EPR) absorption intensity was used to investigate the doxorubicin-mediated intracellular generation of free radicals. The effects of 50-500 micrograms/ml doxorubicin on human tumor cells (MCF-7, breast cancer cells, and HL-60, promyelocytic leukemia, cells) were studied by measuring 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) absorption intensity decay (TAID) at a TEMPO concentration of 10 microM. Doxorubicin accelerated the TAID in both cell lines with a detection limit of 50 micrograms/ml for MCF-7 cells and 500 micrograms/ml doxorubicin for HL-60 cells. Preincubation of cells with the iron chelating agent, deferoxamine (5 mM), partially prevented the effects of doxorubicin on the TAID. Catalase and copper, zinc-superoxide dismutase (Cu,Zn-SOD) had no influence on the effects of doxorubicin on the TAID in intact cells. However, Cu,Zn-SOD completely abolished the effects of doxorubicin on the TAID in a MCF-7 cell-free system. Our findings suggest that doxorubicin mediates the intracellular generation of O2.- and that iron is involved in this process.
利用氮氧化物自旋标记电子顺磁共振（EPR）吸收强度的衰减来研究阿霉素介导的细胞内自由基生成。通过在10微摩尔/升的2,2,6,6-四甲基哌啶-1-氧基（TEMPO）浓度下测量TEMPO吸收强度衰减（TAID），研究了50-500微克/毫升阿霉素对人肿瘤细胞（MCF-7乳腺癌细胞和HL-60早幼粒细胞白血病细胞）的影响。阿霉素在两种细胞系中均加速了TAID，MCF-7细胞的检测限为50微克/毫升，HL-60细胞为500微克/毫升阿霉素。用铁螯合剂去铁胺（5毫摩尔）对细胞进行预孵育，部分阻止了阿霉素对TAID的影响。过氧化氢酶和铜锌超氧化物歧化酶（Cu,Zn-SOD）对完整细胞中阿霉素对TAID的影响没有作用。然而，在无MCF-7细胞的体系中，Cu,Zn-SOD完全消除了阿霉素对TAID的影响。我们的研究结果表明，阿霉素介导细胞内超氧阴离子的生成，且铁参与了这一过程。
