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源自抗肿瘤金属茂的金属分布的细胞内图谱分析。

Intracellular mapping of the distribution of metals derived from the antitumor metallocenes.

作者信息

Waern Jenny B, Harris Hugh H, Lai Barry, Cai Zhonghou, Harding Margaret M, Dillon Carolyn T

机构信息

School of Chemistry, The University of Sydney, Sydney, NSW 2006, Australia.

出版信息

J Biol Inorg Chem. 2005 Aug;10(5):443-52. doi: 10.1007/s00775-005-0649-1. Epub 2005 Sep 23.

DOI:10.1007/s00775-005-0649-1
PMID:15906108
Abstract

The intracellular distribution of transition metals in V79 Chinese hamster lung cells treated with subtoxic doses of the organometallic anticancer complexes Cp(2)MCl(2), where Cp is eta (5) -cyclopentadienyl and M is Mo, Nb, Ti, or V, has been studied by synchrotron-based X-ray fluorescence (XRF). While significantly higher concentrations of Mo and Nb were found in treated cells compared with control cells, distinct differences in the cellular distribution of each metal were observed. Analysis of thin sections of cells was consistent with some localization of Mo in the nucleus. Studies with a noncytotoxic thiol derivative of molybdocene dichloride showed an uneven distribution of Mo in the cells. For comparison, the low levels of Ti and V in cells treated with the more toxic titanocene and vanadocene complexes, respectively, resulted in metal concentrations at the detection limit of XRF. The results agree with independent chemical studies that have concluded that the biological chemistry of each of the metallocene dihalides is unique.

摘要

利用基于同步加速器的X射线荧光(XRF)技术,研究了用亚毒性剂量的有机金属抗癌配合物Cp(2)MCl(2)处理的V79中国仓鼠肺细胞中过渡金属的细胞内分布,其中Cp为η(5)-环戊二烯基,M为Mo、Nb、Ti或V。与对照细胞相比,处理后的细胞中Mo和Nb的浓度显著更高,但观察到每种金属的细胞分布存在明显差异。对细胞薄片的分析与Mo在细胞核中的一些定位一致。用二氯茂钼的一种无细胞毒性的硫醇衍生物进行的研究表明,Mo在细胞中的分布不均匀。作为比较,分别用毒性更强的二氯钛茂和二氯钒茂配合物处理的细胞中Ti和V的含量较低,导致金属浓度处于XRF的检测限。这些结果与独立的化学研究一致,这些研究得出结论,每种二卤茂金属的生物化学性质是独特的。

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