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This review contends that “healthy” water in terms of electrolyte balance is as important as “pure” water in promoting public health. It considers the growing use of desalination (demineralization) technologies in drinking water treatment which often results in tap water with very low concentrations of sodium, potassium, magnesium and calcium. Ingestion of such water can lead to electrolyte abnormalities marked by hyponatremia, hypokalemia, hypomagnesemia and hypocalcemia which are among the most common and recognizable features in cancer patients. The causal relationships between exposure to demineralized water and malignancies are poorly understood. This review highlights some of the epidemiological and in vivo evidence that link dysregulated electrolyte metabolism with carcinogenesis and the development of cancer hallmarks. It discusses how ingestion of demineralized water can have a procarcinogenic effect through mediating some of the critical pathways and processes in the cancer microenvironment such as angiogenesis, genomic instability, resistance to programmed cell death, sustained proliferative signaling, cell immortalization and tumorigenic inflammation. Evidence that hypoosmotic stress-response processes can upregulate a number of potential oncogenes is well supported by a number studies. In view of the rising production and consumption of demineralized water in most parts of the world, there is a strong need for further research on the biological importance and protean roles of electrolyte abnormalities in promoting, antagonizing or otherwise enabling the development of cancer. The countries of the Gulf Cooperative Council (GCC) where most people consume desalinated water would be a logical place to start this research. [ABSTRACT FROM AUTHOR]

Abstract: Acid-sensing ion channels (ASICs) are strong candidates for mammalian mechanoreceptors. We investigated whether mouse acid-sensing ion channel-1b (ASIC1b) is sensitive to mechanical stimuli using oocyte electrophysiology, because ASIC1b is located in the mechanosensory stereocilia of cochlear hair cells. Hypotonic stimuli that induced membrane stretch of oocytes evoked no significant current in ASIC1b-expressing oocytes at pH 7.5. However, acid (pH 4.0 or 5.0)-evoked currents in the oocytes were substantially enhanced by the hypotonicity, showing mechanosensitivity of ASIC1b and possible mechanogating of the channel in the presence of other components. Interestingly, the ASIC1b channel was permeable to K+ (a principal charge carrier for cochlear sensory transduction) and the affinity of the channel for amiloride (IC50 (inhibition constant)=approximately 48.3μM) was quite similar to that described for the mouse hair cell mechanotransducer current. Taken together, these data raise the possibility that ASIC1b participates in cochlear mechanoelectrical transduction. [Copyright &y& Elsevier]

TonEBP (NFAT5) is a newly identified member of the Rel family of transcriptional activators that include NF-κB and NFAT1 to NFAT4. Activated in response to hypertonicity, TonEBP stimulates transcription of transporters of organic osmolytes, certain cytokines, and a molecular chaperone. We provide biochemical data demonstrating that full-length TonEBP dimerizes via the C-terminus of the Rel-homology domain (CRHD). The two polyglutamine motifs were not involved. The dimerization was not affected by nucleocytoplasmic shifts in TonEBP in response to changes in ambient tonicity. Preventing the dimer formation by deleting the CRHD did not affect the nucleocytoplasmic shifts. On the other hand, deletion of the CRHD prevented DNA binding and eliminated the dominant negative activity of a C-terminal truncated TonEBP. Furthermore, phosphorylation was dramatically reduced especially in hypertonic conditions by deletion of the CRHD. We conclude that dimerization is required for proper phosphorylation of TonEBP as well as DNA binding. [Copyright &y& Elsevier]