Intracellular Na+:K+ ratios in human cancer cells as revealed by energy dispersive x-ray microanalysis.

Abstract

Intranuclear sodium, potassium, and chloride contents were measured by energydispersive x-ray microanalysis in freeze-fractured, freeze-dried, bulk-tumor samples taken from 10 patients suffering from invasive urogenital cancers. Human biopsies were carried out during the first diagnostic interventions before any cytostatic treatment had been applied. Pathohistological diagnosis established the malignancy in each case . The cancers were classified in three types: keratinizing, transitional cell, and hypernephroid carcinoma. More than 250 cell nuclei were measured from each type of cancer . The results were compared with those obtained in intact human urothelium taken from patients having no malignant processes. Proximal and distal tubular epithelial cell nuclei representing the origin of human hypernephroid cancer were also measured in rat kidney because corresponding healthy human material cannot be obtained . The analyses revealed, in all three types of cancer cells, that the average intranuclear sodium content increased more than three-fold, the potassium content decreased 32, 16, and 13%, respectively; meanwhile the chloride content increased, but to a lesser extent than did the sodium . The intranuclear Na + :K + ratios were more than five-fold higher in the cancer cells on the average, and their distribution histograms were much broader than in the normal human urothelium and in the tubular cell nuclei of the rat kidney . The results obtained fit well with the theory of Cone, C. D., Jr . 1971 . J. Theor. Biol. 30 : 151-181 according to which the sustained depolarization of the cell membrane may be of mitogenic effect .

Intracellular BKCa (iBKCa) channels

“… Intracellular organelles and potassium flow A schematic diagram depicting the major intracellular organelles with their inner K + concentrations [K + ]. [K + ] inside the mitochondrion (Mito) is ∼15 m m (Zoeteweij et al 1994), in the nucleus (Nu) is estimated as ∼214 m m (Nagy et al 1981), and in the Golgi apparatus (Ga) is estimated as ∼107 m m (Schapiro & Grinstein, 2000). [K + ] in the ER is assumed to be similar to that in the cytoplasm, in analogy to the concentrations found in toadfish (Somlyo et al 1977).…”

Combined imaging biomarkers for therapy evaluation in glioblastoma multiforme: correlating sodium MRI and F-18 FLT PET on a voxel-wise basis

“…In neoplastic tissue, sustained depolarization of the cell membrane precedes the high rate of mitotic activity that characterizes abnormal cell growth [14,15] and leads to an increase in Na i that has been demonstrated in a number of human neoplasms [2,16,17]. Further characterization of Na i rise in several types of human carcinomas [16,17] and glial cell lines [18,19] has established a positive correlation between proliferative activity and increased intracellular Na+:K+ ratio (mostly due to an increase in Na i ).…”

“…Further characterization of Na i rise in several types of human carcinomas [16,17] and glial cell lines [18,19] has established a positive correlation between proliferative activity and increased intracellular Na+:K+ ratio (mostly due to an increase in Na i ). Once neoplastic changes are set in the tissue, a decrease in CVF is observed due to the different morphology of neoplastic cells.…”

In vivo sodium MR imaging of the abdomen at 3T

“…It has shown to aid in the diagnosis of hepatitis- and cirrhosis-producing changes in intracellular [Na + ] and extracellular matrix structure [12] in the liver. 23 Na MRI has also proved useful for distinguishing between benign and malignant tumor since rapidly proliferating tumor cells are shown to have a high intracellular [Na + ] [13] and is expected to be useful for diagnosis of many acute and chronic renal diseases [10], [14, 15]. Applications of 23 Na MRI could be applied in cardiac imaging to evaluate the elevation of myocardial TSC in acute ischemia models [16–18] and its potential has been explored in human hearts on 7T [17].…”