EFFECTS OF CADMIUM ON CELLULAR CALCIUM AND PROTOONCOGENE EXPRESSION

Effects of the carcinogenic metal cadmium on cellular calcium signalli ng and proto-oncogene expression were studied in mammalian cells. Cadm ium ions interfered with bradykinin- and adenosinetriphosphate (ATP)-s timulated calcium transients in rat pheocromocytoma PC12 cells, but Cd 2+ as such did not evoke intracellular Ca2+ spikes. At variance, cadmi um ions caused a sustained elevation of intracellular free Ca2+ by inh ibition of active calcium transport systems in various cell types. Pro blems of mutual interference of Ca2+ and Cd2+ analysis with the fluore scent probe Fura-2 could be overcome by the use of the fluorine 19 nuc lear magnetic resonance (F-19-NMR) probe acetoxymethyl ester of -amino -5-fluorophenoxy)ethane-N,N,N'N'-tetraacetic acid (5F-BAPTA), which al lows the measurement of free intracellular Ca2+, Cd2+ and other metal ions concurrently. Furthermore, the induction of the cellular protoonc ogenes c-fos and c-jun by Cd2+ was studied in PC12 cells. A dose of 0. 5 mu M Ca2+ sufficed to induce tile c-Fos and c-Jun proteins within 30 min. These results support a model which suggests that cadmium stimul ates cell proliferation by interference with intracellular calcium and induction of immediate early genes. .