Teicher B A, Holden S A, Jacobs J L, Abrams M J, Jones A G
Biochem Pharmacol. 1986 Oct 1;35(19):3365-9. doi: 10.1016/0006-2952(86)90437-5.
The platinum(II) tetrachlorodianion and two molecules of rhodamine-123 associate to form a neutral tight ion pair. To examine the intracellular fate of this ionic complex, the levels of uptake after a 1-hr exposure to a 100 microM concentration of each component of the complex, the complex itself and cis-diamminedichloroplatinum(II) (CDDP) were measured in SCC-25 cells. The uptake of Pt(Rh-123)2 was measured by two independent methods: fluorescence and 195mPt gamma-counting. There was excellent agreement between these two methods as to the amount of Pt(Rh-123)2 which was taken up by the cells, indicating that the Pt(Rh-123)2 is probably entering cell intact. Association with Rh-123 increased the amount of platinum which entered the cells by about 70-fold compared to CDDP and increased by about 700-fold the amount of platinum which entered the cells compared to K2PtCl4. The subcellular distributions of Pt(Rh-123)2, Rh-123, CDDP and K2PtCl4 were also examined. When measured by fluorescence or 195mPt gamma-counting, 40-54% of the Pt(Rh-123)2 was in the nuclei of the SCC-25 or SCC-25/CP cells and 27-35% was in the cytosol of the cells. There was excellent agreement between the findings of fluorescence and 195mPt gamma-counting regarding the amount of Pt(Rh-123)2 in each of the subcellular fractions immediately after incubation with the drug and over the time course of observation after drug removal, indicating that the Pt(Rh-123)2 is probably remaining largely intact intracellularly. On a per mg protein basis, there was about a 55-fold greater amount of platinum in the nuclei of the SCC-25 cells exposed to Pt(Rh-123)2 compared to cells exposed to CDDP. In the SCC-25/CP cells, there was about 258-fold greater platinum in the nuclei of cells exposed to Pt(Rh-123)2 than those exposed to CDDP because CDDP was taken up to a much lesser extent by the SCC-25/CP cells. Association of Rh-123 with potassium tetrachlorodianion forms a tight ion pair, which enters cells in relatively high amounts and is selectively concentrated in the nuclei of the cells.
二价铂四氯二阴离子与两个罗丹明 - 123分子缔合形成一个中性紧密离子对。为了研究这种离子复合物在细胞内的命运，在SCC - 25细胞中测量了在1小时内暴露于复合物各组分、复合物本身和顺 - 二氯二氨铂（II）（CDDP）100 microM浓度后的摄取水平。通过两种独立方法测量Pt（Rh - 123）₂的摄取：荧光法和¹⁹⁵mPtγ计数法。这两种方法在细胞摄取的Pt（Rh - 123）₂量方面具有极好的一致性，表明Pt（Rh - 123）₂可能完整地进入细胞。与Rh - 123缔合使进入细胞的铂量相比CDDP增加了约70倍，相比K₂PtCl₄增加了约700倍。还研究了Pt（Rh - 123）₂、Rh - 123、CDDP和K₂PtCl₄的亚细胞分布。通过荧光或¹⁹⁵mPtγ计数法测量时，40 - 54%的Pt（Rh - 123）₂存在于SCC - 25或SCC - 25/CP细胞的细胞核中，27 - 35%存在于细胞的细胞质中。在与药物孵育后立即以及去除药物后的观察时间过程中，荧光和¹⁹⁵mPtγ计数法关于每个亚细胞组分中Pt（Rh - 123）₂量的结果具有极好的一致性，表明Pt（Rh - 123）₂可能在细胞内大部分保持完整。以每毫克蛋白质计，与暴露于CDDP的细胞相比，暴露于Pt（Rh - 123）₂的SCC - 25细胞细胞核中的铂量大约多55倍。在SCC - 25/CP细胞中，暴露于Pt（Rh - 123）₂的细胞细胞核中的铂比暴露于CDDP的细胞大约多258倍，因为CDDP被SCC - 25/CP细胞摄取的程度要小得多。Rh - 123与四氯二阴离子钾缔合形成紧密离子对，该离子对以相对较高的量进入细胞并选择性地集中在细胞核中。
