Summary
Energy-dispersive X-ray microanalysis was performed on human biopsy materials taken during laryngoscopic intervention in 18 cases. The removed tissue pieces were divided into two parts. One of them was used for pathohistological studies, the other was processed for X-ray microanalysis by the freeze-fracture freeze-drying method. Of the cases investigated 4 proved to be of benign character, whereas the rest contained carcinoma planocellulare keratoides or nonkeratoides. Bulk specimen energy-dispersive X-ray microanalysis of 135 cells from the benign tissue samples revealed an average Na+/K+ molar ratio of 0.13±0.01 (SEM) in the intracellular space, with a regular Gaussian distribution. In the cases of carcinomas 641 cells were measured, the average of the same ratio was 0.67±0.03 (SEM) due mostly to an increase in the Na+ content. The distribution of data was apparently not normal in the cancerous samples. These observations and some theoretical considerations support the notion that the intracellular Na+/K+ ratio correlates with the proliferative capacity of tissues. The relevance of some recent biochemical results is also discussed in this respect.
Similar content being viewed by others
References
Adelman WJ Jr (1971) Electrical studies of internally perfused squid axons. In: Adelman WJ Jr (ed) Biophysics and physiology of excitable membranes. Van Nostrand Reinhold, New York, pp 274–319
Borgens RB, Vanable JW Jr, Jaffer LF (1977) Bioelectricity and regeneration. Initiation of frog limb regeneration by minute currents. J Exp Zool 200:403–416
Browning M, Bennett W, Lynch G (1979) Phosphorylase kinase phosphorylates a brain protein which is influenced by repetitive synaptic activation. Nature 278:273–275
Cameron IL, Smith NKR (1980) Energy dispersive X-ray micro-analysis of the concentrations of elements in relation to cell reproduction in normal and cancer cells. Scan Electron Microsc II:463–474
Cameron IL, Smith NKR, Pool TB, Sparks RL (1980a) Intracellular concentration of sodium and other elements as related to mitogenesis and oncogenesis in vivo. Cancer Res 40:1493–1500
Cameron IL, Smith NKR, Pool TB (1980b) Element concentration changes in mitotically active and postmitotic enterocytes. An X-ray microanalysis study. J Cell Biol 80:444–450
Cone CD Jr (1971) Unified theory on the basic mechanism of normal mitotic control and oncogenesis. J Theor Biol 30:151–181
Cone CD, Cone CM (1976) Induction of mitosis in mature neurons in central nervous system by sustained depolarization. Science 192:155–158
Cone CD Jr., Tongier M (1973) Contact inhibition of division: Involvement of the electrical transmembrane potential. J Cell Physiol 82:373–386
Douzou P, Maurel P (1977a) Ionic regulation in genetic translation systems. Proc Natl Acad Sci USA 74:1013–1015b
Douzou P, Maurel P (1977b) Ionic control of biochemical reactions. Trend Biochem Sci 2:14–17
Emmelot P, Scherer E (1980) The first relevant cell stage in rat liver carcinogenesis. A quantitative approach. Biochim Biophys Acta 605:247–304
Epel D (1980) Ionic triggers in the fertilization of sea urchin eggs. An NY Acad Sci 339:74–85
Forn J, Greergard P (1978) Depolarizing agents and cyclic nucleotides regulate the phosphorylation of specific neuronal proteins in rat cerebral cortex slices. Proc Natl Acad Sci USA 75:5195–5199
Hall TA, Clarke-Anderson H, Appleton T (1973) The use of thin specimens for X-ray microanalysis in biology. J Microsc 99:177–182
Holland R, Woodgett JR, Hardie DG (1983) Evidence that amiloride antagonises insulin-stimulated protein phosphorylation by inhibiting protein kinase activity. FEBS Lett 154:269–273
Hope AB (1971) Ion transport and Membranes. A biophysical outline. Butterworth, London
Ihlenfeldt M, Gantner G, Harrer M, Puschendorf P, Putzer H, Grunicke H (1981) Interaction of the alkylating antitumor agent 2,3,5-tris(ethyleneimino)benzoquinone with the plasma membrane of Ehrlich ascites tumor cells. Cancer Res. 41:289–293
Jaffe LF (1980) Calcium explosions as triggers of development. Ann NY Acad Sci 339:86–101
Koch KS, Leffert HL (1979) Increased sodium ion influx is necessary to initiate rat hepatocyte proliferation. Cell 18:153–163
Leffert HL, Koch KS (1979a) Regulation of growth of hepatocytes by sodium ions. In: Popper H, Schaffner F (eds) Progress in liver diseases. Grune and Stratton, New York, pp 123–134
Leffert HL, Koch KS (1979b) Ionic events at the membrane initiate rat liver regeneration. Ann NY Acad Sci 339:201–215
Lukács GL, Zs. -Nagy I, Lustyik Gy, Balázs Gy (1983) Microfluorimetric and X-ray microanalytic studies on the DNA content and Na+:K+ ratios of the cell nuclei in various types of thyroid tumors. J Cancer Res Clin Oncol 105:280–284
Maurel P, Douzou P (1976) Catalytic implications of electrostatic potentials: the lytic activity of lysozyme as a model. J Mol Biol 102:253–264
Mizukami Y, Matsubara F, Matsukawa S (1983) Changes in localization of ouabain-sensitive, potassium-dependent, p-nitrophenyl-phosphtase activity in human thyroid carcinoma cells. Lab Invest 48:411–418
Moolenaar WH, Mummery Cl, Van der Saag PT, De Laat SW (1981) Rapid ionic events and the initiation of growth in serum-stimulated neuroblastoma cells. Cell 23:789–798
Moscatelli D, Sanui H, Rubin HA (1979) Effects of depletion of K+, Na+ or Ca2+ on DNA synthesis and cell cation content in chick embryo fibroblasts. J Cell Physiol 101:117–128
Mummery CL, Boonstra J, Van der Saag PT, De Laat SW (1982) Modulations of Na+ transport during the cell cycle of neuroblastoma cells. J Cell Physiol 112:27–34
Owen NE, Villereal ML (1982) Evidence for a role of calmodulin in serum stimulation of Na+-Influx in human fibroblasts. Proc Natl Acad Sci USA 70:3537–3541
Prescott DM (1976) Cell surface changes during the cycle. In Prescott DM (ed) Reproduction of eukaryotic cells. Academic Press, New York, pp 47–106
Rodan GA, Bourret LA, Norton LA (1978) DNA synthesis in cartilage cells is stimulated by oscillating electric fields. Science 199:690–692
Sachs HG, Stambrook PJ, Ebert JD (1974) Changes in membrane potential during the cell cycle. Exp Cell Res 83:362–366
Sanui H, Rubin AH (1978) Membrane bound and cellular cationic changes associated with insulin stimulation of cultured cells. J Cell Physiol 96:265–278
Smith JB, Rozengurt E (1978) Serum stimulates the Na+−K+ pump in quiescent fibroblasts by increasing Na+ entry. Proc Natl Acad Sci USA 75:5560–5564
Smith NR, Sparks RL, Pool TB, Cameron IL (1978) Differences in the intracellular concentration of elements in normal and cancerous liver cells as determined by X-ray microanalysis. Cancer Res 38:1952–1959
Villereal ML (1981) Sodium fluxes in human fibroblasts: effect of serum, calcium and amiloride. J Cell Physiol 107:359–369
Villereal ML (1982) Inhibition of the serum-dependent, amiloridesensitive sodium transport pathway in human fibroblasts by extracellular divalent cations. J Cell Physiol 111:163–170
Von Hippel HP, Schleich T (1969) The effects of neutral salts on the structure and conformational stability of macromolecules in solution. In: Timaseff SH, Fasmann GD (eds) Structure and stability of biological macromolecules. Dekker New York, pp 417–574
Whitefield JF, Boynton AL, Macmanus JP, Rixon RH, Sikorska M, Tsang B, Walker PR (1980) The roles of calcium and cyclic AMP in cell proliferation. Ann NY Acad Sci 339:216–240
Zs. -Nagy I (1979) The role of membrane structure and function in cellular aging: a review. Mech Ageing Dev 9:237–246
Zs. -Nagy I (1983) Energy dispersive X-ray microanalysis of biological bulk specimens: a review on the method and its application to experimental gerontology and cancer research. Scan Electron Microsc III 1255–1268
Zs. -Nagy I, Pieri C, Giuli C, Bertoni-Freddari C, Zs.-Nagy V (1977) Energy dispersive X-ray microanalysis of the electrolytes in biological bulk specimens. I. Specimen preparation, beam penetration and quantitative analysis. J Ultrastruct Res 58:22–33
Zs. -Nagy I, Lustyik Gy, Zs.-Nagy V, Zarándi B, Bertoni-Freddari C (1981) Intracellular Na+/K+ ratios in human cancer cells as revealed by energy dispersive X-ray micronanalysis. J Cell Biol 90:769–777
Zs. -Nagy I, Lustyik Gy, Lukács G, Zs.-Nagy V, Balázs Gy (1983) Correlation of malignancy with the intracellular Na+/K+ ratio in human thyroid tumors. Cancer Res 43:5395–5402
Zs. -Nagy I, Lustyik Gy, Zs.-Nagy V (1984) On the possible role of sodium permeability of cell membrane in mitogenesis: a critical evaluation of some methodical approaches. Symp Biol Hung 26:353–377
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Zs. -Nagy, I., Tóth, L., Szállási, Z. et al. Energy-dispersive, bulk specimen X-ray microanalytical measurement of the intracellular Na+/K+ ratio in human laryngeal tumors. J Cancer Res Clin Oncol 113, 197–202 (1987). https://doi.org/10.1007/BF00391444
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00391444