Intracellular accumulation of thallium as a marker of cisplatin cytotoxicity in nonsmall cell lung carcinoma: an application of inductively coupled plasma mass spectrometry.
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.
Hanada
T
T
First Department of Medicine, School of Medicine, Hokkaido University, Sapporo, Japan.
Isobe
H
H
Saito
T
T
Ogura
S
S
Takekawa
H
H
Yamazaki
K
K
Tokuchi
Y
Y
Kawakami
Y
Y
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism; D002945:Cisplatin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D013058:Mass Spectrometry / Q000379:methods*; D013794:Thallium Radioisotopes / Q000493:pharmacokinetics; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D013794:Thallium Radioisotopes; D002945:Cisplatin