Effects of cadmium on cellular calcium and proto-oncogene expression
Hechtenberg, S.; Schäfer, T.; Benters, J.; Beyersmann, D.
Annals of Clinical and Laboratory Science 26(6): 512-521
1996
ISSN/ISBN: 0091-7370 PMID: 8908321 Document Number: 467589
Effects of the carcinogenic metal cadmium on cellular calcium signalling and proto-oncogene expression were studied in mammalian cells. Cadmium ions interfered with bradykinin- and adenosinetriphosphate (ATP)-stimulated calcium transients in rat pheocromocytoma PC12 cells, but Cd-2+ as such did not evoke intracellular Ca-2+ spikes. At variance, cadmium ions caused a sustained elevation of intracellular free Ca-2+ by inhibition of active calcium transport systems in various cell types. Problems of mutual interference of Ca-2+ and Cd-2+ analysis with the fluorescent probe Fura-2 could be overcome by the use of the fluorine 19 nuclear magnetic resonance (19F-NMR) probe acetoxymethyl ester of 1,2-bis(2-amino-5-fluorophenoxy)ethane-N,N,N'N'-tetraacetic acid (5F-BAPTA), which allows the measurement of free intracellular Ca-2+, Cd-2+ and other metal ions concurrently. Furthermore, the induction of the cellular proto-oncogenes c-fos and c-jun by Cd-2+ was studied in PC12 cells. A dose of 0.5 mu-M Ca-2+ sufficed to induce the c-Fos and c-Jun proteins within 30 min. These results support a model which suggests that cadmium stimulates cell proliferation by interference with intracellular calcium and induction of immediate early genes.