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 .
Phytohemagglutinin P (PHA-P) was administered in form of intralumbar injection to old (24–27 months) female Wistar rats. PHA-P has an inductive effect also on the nerve cells. The thermal denaturation characteristics of the DNA in situ as well as the numerical density of perichromatin granules being connected to the extranucleolar RNA synthesis returned practically to the young levels in the large brain cortical cells and in the cerebellar granular cells 20 h after the injection. The reversal of these aging phenomena was accompanied by a significant decrease of intranuclear and intracytoplasmic K+ content measured by X-ray microanalysis in the dry mass, whereas Na+ and Cl- remained unchanged. If PHA-P causes also some (1–2%) rehydration of the old neurons, the total ionic strength in the cell due to the monovalents may even reach the young level. The possible regulatory role of the ionic strength and the Na+/K+ ratio in the chromatin function is discussed on the basis of experimental data. It is the first time that the reversibility of some cytological aging parameters has been demonstrated in vivo.
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