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 (Tl-201) scintigraphy has been used to detect malignant pulmonary disease. The mechanism of Tl influx in tumor cell s is believed to be similar to that of cisplatin (CDDP) mediated by so dium- and potassium-activated adenosine triphosphatase (Na-K ATPase), and the Na-K ATPase activity may determine the cellular CDDP accumulat ion and sensitivity to CDDP. The objective of this study was to determ ine the accumulation of CDDP and Tl in vitro by using inductively coup led plasma mass spectrometry (ICP-Ms;), a new analytic technique for d etecting ultra trace elements, and to evaluate the correlations betwee n cellular CDDP and Tl accumulation, between CDDP 50% inhibitory conce ntration (IC50) values and cellular CDDP accumulation, and between CDD P IC50 values and cellular Tl accumulation. METHODS. Eight nonsmall ce ll lung carcinoma (NSCLC:) cell lines were used (five adenocarcinomas and three squamous cell carcinomas). The cell lines were exposed to CD DP or Tl for 1 hour, and the resulting cellular accumulation of platin um and Tl was determined by ICP-MS. CDDP IC,, values were determined b y a soluble tetrazolium/formazan assay. RESULTS. The authors were able to measure cellular CDDP and Tl accumulation precisely, and heterogen eity in the cellular accumulation of CDDP and Tl existed among the NSC LC cell lines. A significant inverse correlation was observed between CDDP IC,, values and the cellular accumulation of both CDDP and Tl. CO NCLUSIONS. ICP-MS is suitable for the determination of cellular CDDP a nd Tl accumulation in NSCLC cell lines. Cellular Tl accumulation deter mined by ICP-MS may reflect CDDP cytotoxicity rather than cellular CDD P accumulation. (C) 1998 American Cancer Society.