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铊的细胞内蓄积作为非小细胞肺癌中顺铂细胞毒性的标志物:电感耦合等离子体质谱法的应用

Intracellular accumulation of thallium as a marker of cisplatin cytotoxicity in nonsmall cell lung carcinoma: an application of inductively coupled plasma mass spectrometry.

作者信息

Hanada T, Isobe H, Saito T, Ogura S, Takekawa H, Yamazaki K, Tokuchi Y, Kawakami Y

机构信息

First Department of Medicine, School of Medicine, Hokkaido University, Sapporo, Japan.

出版信息

Cancer. 1998 Sep 1;83(5):930-5. doi: 10.1002/(sici)1097-0142(19980901)83:5<930::aid-cncr19>3.0.co;2-w.

DOI:10.1002/(sici)1097-0142(19980901)83:5<930::aid-cncr19>3.0.co;2-w
PMID:9731897
Abstract

BACKGROUND

Thallium-201 (201Tl) scintigraphy has been used to detect malignant pulmonary disease. The mechanism of Tl influx in tumor cells is believed to be similar to that of cisplatin (CDDP) mediated by sodium- and potassium-activated adenosine triphosphatase (Na-K ATPase), and the Na-K ATPase activity may determine the cellular CDDP accumulation and sensitivity to CDDP. The objective of this study was to determine the accumulation of CDDP and Tl in vitro by using inductively coupled plasma mass spectrometry (ICP-MS), a new analytic technique for detecting ultra trace elements, and to evaluate the correlations between cellular CDDP and Tl accumulation, between CDDP 50% inhibitory concentration (IC50) values and cellular CDDP accumulation, and between CDDP IC50 values and cellular Tl accumulation.

METHODS

Eight nonsmall cell lung carcinoma (NSCLC) cell lines were used (five adenocarcinomas and three squamous cell carcinomas). The cell lines were exposed to CDDP or Tl for 1 hour, and the resulting cellular accumulation of platinum and Tl was determined by ICP-MS. CDDP IC50 values were determined by a soluble tetrazolium/formazan assay.

RESULTS

The authors were able to measure cellular CDDP and Tl accumulation precisely, and heterogeneity in the cellular accumulation of CDDP and Tl existed among the NSCLC cell lines. A significant inverse correlation was observed between CDDP IC50 values and the cellular accumulation of both CDDP and Tl.

CONCLUSIONS

ICP-MS is suitable for the determination of cellular CDDP and Tl accumulation in NSCLC cell lines. Cellular Tl accumulation determined by ICP-MS may reflect CDDP cytotoxicity rather than cellular CDDP accumulation.

摘要

背景

铊 - 201(201Tl)闪烁扫描术已用于检测恶性肺部疾病。据信肿瘤细胞中铊的流入机制与由钠钾激活的三磷酸腺苷酶(Na - K ATPase)介导的顺铂(CDDP)相似,且Na - K ATPase活性可能决定细胞内顺铂的积累及对顺铂的敏感性。本研究的目的是通过使用电感耦合等离子体质谱法(ICP - MS)(一种检测超微量元素的新分析技术)来测定体外顺铂和铊的积累,并评估细胞内顺铂和铊积累之间、顺铂50%抑制浓度(IC50)值与细胞内顺铂积累之间以及顺铂IC50值与细胞内铊积累之间的相关性。

方法

使用了8种非小细胞肺癌(NSCLC)细胞系(5种腺癌和3种鳞癌)。将细胞系暴露于顺铂或铊1小时,然后通过ICP - MS测定所得细胞内铂和铊的积累。通过可溶性四氮唑/甲臜测定法测定顺铂IC50值。

结果

作者能够精确测量细胞内顺铂和铊的积累,且NSCLC细胞系之间顺铂和铊的细胞内积累存在异质性。观察到顺铂IC50值与顺铂和铊的细胞内积累之间存在显著的负相关。

结论

ICP - MS适用于测定NSCLC细胞系中细胞内顺铂和铊的积累。通过ICP - MS测定的细胞内铊积累可能反映顺铂的细胞毒性而非细胞内顺铂的积累。

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