Intracellular Distributions of the Anthracycline 4′-iodo-4′-deoxy-Doxorubicin and Essential Trace Metals Using Nuclear Microprobe Analysis
Intracellular Distributions of the Anthracycline 4′-iodo-4′-deoxy-Doxorubicin and Essential Trace Metals Using Nuclear Microprobe Analysis
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使用核微探针分析蒽环类 4-碘-4-脱氧阿霉素和必需微量金属的细胞内分布
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发表时间：
2000
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影响因子：
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通讯作者：
R. Ortega
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作者：
R. Ortega
摘要 核探针是一种具有显微成像功能的多元素分析仪器。对暴露于抗肿瘤剂蒽环类 4'-碘-4'-脱氧阿霉素 (IDX) 的培养癌细胞同时进行粒子诱导 X 射线发射 (PIXE) 和卢瑟福背散射光谱 (RBS)。元素图谱显示，碘和铁的空间分布密切相关，表明蒽环类药物在细胞内螯合铁。通常在细胞核区域内观察到铁和碘的共定位。微量元素浓度的定量测定表明，暴露于 20 μM IDX 两小时后，细胞中内源微量金属的平均量没有变化。这表明在 IDX 摄取过程中没有细胞外铁被输入到细胞中。从这些结果可以得出结论，铁-IDX复合物可能在细胞内形成，至少当IDX以20μM施用时，并且可能参与蒽环类抗肿瘤药物的各种生物效应。
Abstract The nuclear microprobe is an instrument of multi-elemental analysis with micro-imaging capabilities. Particle Induced X-ray Emission (PIXE) and Rutherford Backscattering Spectrometry (RBS) were performed simultaneously on cultured cancer cells exposed to an antitumor agent, the anthracycline 4′-iodo-4′-deoxy-doxorubicin (IDX). Element mapping revealed that iodine and iron spatial distributions were strongly correlated, suggesting iron intracellular chelation by the anthracycline. Iron and iodine co-localizations were generally observed within the nucleus region. Quantitative determination of trace element concentrations shown that the average amount of endogenous trace metals did not change in cells after two hours exposure to 20 μM IDX. It suggests that no extra-cellular iron was imported into the cells during IDX uptake. From these results, it can be concluded that iron-IDX complexes might be formed in the intracellular space, at least when IDX is administered at 20 μM, and could participate to the various biological effects of anthracyclines antitumor drugs.