[CANCER RESEARCH 43, 5395-5402,
November 1983]
Correlation of Malignancy with the Intracellular Na+:K+ Ratio in Human
Thyroid Tumors1
Imre Zs.-Nagy,2 GyörgyLustyik, GézaLukács, Valeria Zs.-Nagy, and GyörgyBalazs
F. Verzár International Laboratory for Experimental Gerontology (VILEG), Hungarian Section [I. Zs.-N., Gy. L, V. Zs.-N.], and First Department ol Surgery, University
Medical School [G. L, G. B.], H-4012 Debrecen, Hungary
ABSTRACT
Energy-dispersive X-ray microanalysis was applied on human
intraoperative biopsy materials of different thyroid tumors. To
ensure suitability of these tissue pieces for quantitative microa
nalysis in freeze-fractured, freeze-dried bulk specimens, sam
pling was carried out with strictly defined criteria. Benign aden
omas and differentiated and anaplastic carcinomas were se
lected for the studies on the basis of pathohistological investi
gations of the same specimen. The results of the tumor cells
were compared to those obtained in apparently normal human
epithelial cells. The number of normal cells analyzed was 349,
whereas in the tumors 408, 423, and 891 cells were measured
in the benign, differentiated, and anaplastic groups, respectively.
Intracellular monovalent contents were calculated as percentage
of cell dry mass; then, Na+:K+ molar ratios were calculated for
each cell individually. Due mostly to the increase of Na+ content,
the distribution histograms of the Na+:K+ molar ratio show an
increase in the number of cells with a higher Na+:K+ ratio with
increasing malignancy of the tumors studied. The differences
proved to be statistically highly significant by the x2 test. Thus,
in human thyroid, increasing malignancy is associated with in
creasing intracellular Na+:K+ ratio.
The results give further support to the theory of C. D. Cone
(J. Theor. Biol., 30: 151-181, 1971) according to which the
sustained depolarization of the cell membrane results in an
increased rate of cell division.
In 1971, Cone (5) formulated a "unified theory" on the basic
mechanism of normal mitotic control and oncogenesis. This
theory predicts that sustained depolarization of the cell mem
brane (i.e., an increase of the intracellular Na+:K+ in the resting
cell) is involved in the regulation of cell divisions during both
normal and malignant growth of tissues. Several studies pub
lished during the 1970s (2, 6, 7, 10, 18, 19, 23) demonstrated
an intimate correlation between cell membrane functions and the
regulation of mitotic activity. These studies have contributed
indirect and circumstantial support to Cone's (5) hypothesis.
Other investigators (15, 21, 22) doubt the theory of Cone (5).
The introduction of X-ray microanalytic methods in biology
allowed direct measurements of intracellular and intranuclear
elemental concentrations to be performed A correlation of in
creased proliferation with increased intracellular Na+:K+ ratio has
been described in various cell types: (a) normal animal cells; (b)
in part by Grants 144/79-11 and 360/82/3.1
of the Hungarian
Academy of Sciences.
2 To whom requests for reprints should be addressed, at VILEG Hungarian
Section, University Medical School, H-4012 Debrecen, Hungary.
Received March 4,1982; accepted July 27,1983.
NOVEMBER
phases of the cell cycle.
In light of the above results, the necessity of collecting more
data on human cancer cells of different origin and various levels
of malignancy is obvious. By means of an energy-dispersive Xray microanalytical method (27) applied by us formerly on human
urogenital invasive cancers (26), we measured the intranuclear
monovalent ion contents in samples of the human thyroid gland
removed under circumstances allowing us to perform a safe
quantitative analysis. The results described in this paper support
the idea that the increase of malignancy of human cancers is
correlated with the increase of the intranuclear Na+:K+ ratio due
mostly to a net increase of the sodium content.
INTRODUCTION
'Supported
transformed cells (hepatomas and mammary adenocarcinomas);
(c) normal rapidly or slowly dividing cells (3, 4,24); and (d) cancer
cells of invasively growing human urogenital tumors (26). Al
though these data support the hypothesis of Cone (5), obviously,
they still do not prove the causal role of high intranuclear sodium
content in the regulation of mitogenesis. Nevertheless, evidence
is accumulating nowadays for such a causal interrelationship.
Namely, Koch and Leffert (11 ) have shown in vitro in hepatocyte
cultures, and also in vivo in regenerating liver, that sodium influx
is a necessary prerequisite for the initiation of cell proliferation,
because a specific sodium influx inhibitor (amiloride) is able to
block the cell growth in both systems. Moolenaar ef al. (14)
published the same observations on serum-stimulated N1E-115
neuroblastoma cells. Furthermore, Mummery ef al. (16) have
demonstrated that amiloride specifically inhibits the transient
increase of Na+ influx at the d-S-phase transition of neuroblas
toma cells, whereas it has little effect on Na+ or K+ influx in other
MATERIALS AND METHODS
Sampling Criteria. Human tumors can be used for X-ray microanalysis
of the monovalent electrolytes (Na+, K+, Cl~) if the following criteria are
met: (a) sampling must be carried out before any cytostatic treatment
has been started; (b) the exact diagnosis can be established by detailed
pathohistological investigations (We always used parallel samples from
which the pathologist gave us the diagnosis.); (c) the biopsy material
must be mechanically and metabolically intact. Special care must be
taken by the surgeon to assure that the shortest possible time (less than
1 min) elapses between the closure of blood circulation and the deep
freezing of the sample; (d) sampling is allowed from humans only if the
surgical intervention is absolutely necessary in the interest of the patient;
(e) the removal of some normal tissue for control purposes is possible
without any damage to the patient. In the case of thyroid tumors, one
can obtain apparently intact thyroid tissue from those cases in which
lobectomy or total thyroidectomy must be performed due to the presence
of single or multiple nodules which are suspected to be malignant.
Materials. Sixteen patients suffering from thyroid tumors were in
volved in our studies (4 males, 12 females). The age of the patients was
between 36 and 67 years except 2 cases (12 and 26 years, respectively).
According to the pathohistological diagnoses, the patients could be
classified into 3 main groups: (a) benign adenomas (5 cases); (b) differ-
1983
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5395
/. Zs.-Nagy et al.
entiated carcinomas, including follicular, papillary, or mixed ones (5
cases); and (c) anaplastic carcinomas (6 cases). Sampling was carried
out in more cases; however, we used the samples for microanalysis only
if the pathologist established the above diagnoses. Cases of thyroiditis
were excluded from the present material.
Control tissue was obtained from 7 patients with benign adenomas
and differentiated carcinomas, in which we could find sufficiently large
tissue pieces containing no nodules or other pathologically altered parts.
The electron microscopic morphology of the tissue always documented
the normal state of the cells analyzed in the control group; only the
epithelial cells bordering the colloidal mass of the thyroid acini were
measured. However, it is conceivable that the adjacent pathological
process may have some influence on the nearby, apparently intact thyroid
tissue; i.e., our control cells may not be really "normal." Nevertheless,
450 cps. The distance between the specimen and the X-ray detector
we had to accept this compromise because intact normal human thyroid
tissue is not available.
X-Ray Microanalysis. The removed tissue samples were prepared
for energy-dispersive X-ray microanalysis by means of the freeze-fracture, freeze-drying technique described in detail elsewhere (27). Appli
cation of this method for human urogenital cancers has been described
by Zs.-Nagy ef al. (26). Identical preparative procedure and instrumen
tation were used for the present studies. The main steps of the procedure
are: (a) deep freezing of the resected sample in isopentane cooled by
liquid nitrogen to its freezing point; (o) fracture of the tissue samples by
cold scissors still in the deep-frozen state, in order to explore the intact
cell compartments inside the tissue; (c) freeze-drying of the samples; (d)
X-ray microanalysis of the nuclei at 10 kV accelerating voltage in a
scanning electron microscope with no coating layer (The incident beam
current was kept at 45 ^A, whereas the effective beam current in the
specimen was in the range of 1 to 2 pA, when obtaining a count rate of
cell nuclei of each individual, as well as 2 kinds of possibilities for further
handling of these data: (a) to calculate the average of the individual
averages with the respective standard deviation; (o) to pool together the
measured cells and give the average and standard deviation for the total
pool. Chart 1 clearly shows that pooling of the data represents the real
range in which the Na*:K+ ratios are scattered much better than the first
was 36 mm, and the takeoff angle was 28 degrees.); (e) computerized
evaluation of the X-ray spectra, obtained by using the mass fraction
method of Hall ef al. (9), extended for bulk specimens (27); (f) calculation
of the monovalent electrolyte concentrations of the nuclear water. For
additional technical or methodological details, see Refs. 26 and 27.
Statistical Evaluation of the Data. For each cell nucleus analyzed,
elemental concentrations of Na+, Cr, and K+, as well as Na+:K* molar
ratios, were calculated. In the first step of statistical elaboration of the
data, the individual averages of these parameters within the control and
each tumor group were calculated. It was evident that the basic data
displayed a fairly narrow Gaussian distribution in the normal thyroid cells
and that their scatter was considerably broader in the tumor samples.
For example, Chart 1 shows the Na+:K* ratios found in the normal thyroid
method mentioned above. This statistical approach appears to be even
more valid for the malignant tumors because, due to the much broader
scatter of the basic data, the average of the individual means may be
relatively more misleading. Pooling together the data is justified further
more by the fact that Student' f test did not reveal any significant
difference between the individual averages within each experimental
group. The pooled data of elemental concentrations were compared
again between different groups by using Student's i test (Table 1).
However, due to the fact that the distribution of the increasing malignancy
of the tumors, we applied the x2 test for the comaprison of histograms
(Chart 4).
-n
TOTAL POOL
RESULTS
AVERAGE OF MEANS
7
6
5
4
2
1
O
0.1
Chart!.
0.2
Demonstration
03
0.4
of the distribution
0.5
0.6 Na :K*(mol)
of Na*:K* ratios in normal thyroid
cells as individual means with the respective standard deviations. Right ordinate,
Cases 1 to 7. The average of means displays an unrealistically narrow standard
deviation, whereas the total pool gives a real range for the scatter of data. Note
that the average of means somewhat differs from the pool average due to some
differences in the number of cells measured per individual samples.
Morphology of the Normal and Cancerous Tissue Samples.
The freeze-fracture, freeze-drying method results in freeze-dried
bulk specimens with broken surfaces allowing exploration of the
internal compartments of cells which remained intact during the
dissection procedure. This method has been elaborated for the
purpose of X-ray microanalytical determination of intracellular
and intranuclear monovalent elemental concentrations; therefore,
the specimen quality is not ideal for morphological studies by
scanning electron microscopy (27). Nevertheless, the quality of
the obtainable image is sufficient for recognition of the main cell
compartments, such as nucleus, cytoplasm, cell borders, etc.
(Figs. 1 to 4). The normal thyroid epithelial cells forming the
thyroid acini can be distinguished readily, and the colloidal sub
stance also shows a characteristic morphology (Fig. 1). The cell
nuclei are always morphologically different from the cytoplasm.
This difference is due to the higher water content of the nuclear
substance demonstrated by immersion refractometry (1), result-
Table1
Monovalent electrolytes in cell nuclei of normal thyroid and tumorous cells
water)8K*2.921
water (mEq/kg
(%)cr0.389
mass
mon
ovalents
(mEq/kg)326.2
typeNormalCell
cells (349)"
±0.008C
+
±0.008
±1.1
±0.8
±1.7
47.6 + 2.1
0.328 + 0.014
45.6 ±1.4
239.6 ±2.1
Benign adenomas (408)
0.486 ±0.015
2.803 ±0.025
332.8
62.2 + 2.0
58.0 + 1.4
Differentiated cancers (423)
0.429 ±0.01 4
0.617 ±0.015
3.034 ±0.035
259.3 ±2.9
379.5
2.889 +0.022
246.9 + 2.1Total 410.1
0.592 ±0.014Dry 0.824 ±0.013Intranuclear
0.024Na*40.1
85.8 ±2.0cr36.5
77.4 ±1.3K*249.6
Anaplastic carcinomas (891)Na*0.277
a Calculated assuming 75 weight % intranuclear water content. All the monovalent concentrations of the tumor cells differ significantly with
p < 0.001 from the respective normal values except the Na* content of benign adenomas, where p < 0.01, and the K* content of the anaplastic
carcinomas, where the difference from the normal cells is not significant.
6 Numbers in parentheses, number of nuclei.
c Average ±S.E.
5396
CANCER
RESEARCH
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VOL. 43
Intracellular Na+:K+ Ratio in Thyroid Tumors
ing in a spongy structure of larger than average "hole size" than
e
40SEC 28297INT
VS : 580
H S : 20EV/CH
in the cytoplasm after freeze-drying. Also, one can recognize the
characteristic morphology of the cells in benign adenomas and
in differentiated and anaplastic carcinomas (Figs. 2 to 4).
X-Ray Microanalysis. The cell nuclei for microanalysis were
selected randomly in each type of tumor. The only parameter
that we considered was nuclear size. Obviously, the plane of
breaking could pass at different heights through the nearly
spherical nucleus, and if this plane was far from the equatorial
one, the nucleus was broken into a smaller and a larger segment.
Since in the bulk specimen we can see only the surface, it is
impossible to decide whether at a given place the smaller or the
larger segment of the nucleus will be found below the surface.
Unfortunately, one cannot completely avoid the danger of overpenetration of the nucleus by selecting the largest ones, if the
average nuclear diameter is below about 8 ^m. Evidence has
been published elsewhere (25, 27) regarding the penetration
depth of the 10-kV electron beam into the freeze-dried biological
mass. Since most of the nuclei of the normal thyroid epithelium
are smaller than 8 urn (Fig. 1), it is certain that some part of the
X-ray counts collected over the nucleus come from the cytoplasm
below the broken nuclei. However, this does not represent any
difficulty for determination of Na+:K+ ratios, since the nuclear
membrane does not play a barrier role for the light elements
such as Na+ and K+ (17). Therefore, the mean ratio of these
elements must be equal in the nucleus and the cytoplasm. On
the other hand, the phenomenon of the possible overpenetration
of the nucleus represents a difficulty if our data were to be
converted to absolute concentrations, since the nuclei contain
somewhat more water than does the cytoplasm (1). As we shall
point out later, absolute concentrations cannot be calculated
without knowing the exact water content of the analyzed cell
compartment.
A further possibility of error in measuring normal thyroid epi
thelial cells may be that, if due to special topographical circum
stances of breaking the tissue, the colloidal substance lies very
near the analyzed cell, resulting in analysis of colloid. Such cases,
however, are easily recognized on the following basis. Chart 2
demonstrates a typical X-ray spectrum taken from a normal
thyroid epithelial cell (Chart 2A) and one taken from the central
part of the colloid substance of an acinus (Chart 2B). It is clear
from these spectra that the colloid substance contains almost
no phosphorus and a very low concentration of K+, whereas it
is extremely rich in sulfur. At the same time, the sulfur content
of the cells is rather low. If we obtained a considerably increased
sulfur content accompanied by unusually low phosphorus and
K* peaks over an epithelial cell, the beam overpenetrated the
cell into the colloid, and such spectra were discarded. The form
of such spectra was so characteristic that it was not necessary
to establish any numerical cutoff point for the selection of un
suitable spectra.
It is very important to perform analysis only on living cells.
Although the tumor samples were always taken from regions of
tissue where no apparent macroscopic signs of necrosis could
be observed, we cannot exclude a priori the presence of some
necrotic cells in our samples. However, on the basis of the
criteria that we elaborated and described in detail elsewhere
(26), one can safely distinguish and exclude from analysis the
necrotic cells from the living ones. The main signs of necrosis
apart from the morphological appearance are the absence of any
NOVEMBER
1983
EDfiX
B
0
vs
40SEC
14297 INT
250
HS: 20EV/CH
06
|08
EDfiX
Chart 2. Typical X-ray spectra recorded from the nucleus of a thyroid epithelial
cell (A) and from the colloidal substance (B) of the same acinus. Arrows, peaks (left
to right). Na", phosphorus, sulfur, Cr, K*. Note that the vertical scale (VS) is
different for the 2 spectra.
ion gradient (as compared to the extracellular space) and the
accumulation of Ca2+ ions.
Chart 3 shows a typical X-ray spectrum recorded from the
nucleus of an anaplastic cancer cell. The high sodium peak is
evident, accompanied by some increase in Cl~ content and
decrease of the K* peak.
Table 1 summarizes the results obtained in the normal epithe
lial cells and 3 different classes of thyroid tumors. Since the
method of quantitation used by us (26, 27) gives mass fraction
values in the dry mass of the cells for the measured elements,
we present here these values as percentages by weight. At least
40 to 50 cells were measured, usually from 2 to 3 different tissue
pieces prepared from the biopsy material of each patient.
5397
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/.
Zs.-Nagy
etal.
8
VS:
48SEC
259
HS
creased Na*:K+ ratios, and the proportion of these cells increases
13877INT
20EV/CH
parallel with the malignancy of the tumors. One might assume
that cells with extremely high Na+:K* ratios (e.g., 1.5 or above)
may be injured or seriously disturbed, even if they are not dead
cells according to our criteria mentioned above. However, even
if we exclude these cells from consideration, the mean values
may be somewhat lower, but neither the shape of the histograms
nor the significance levels will be altered considerably.
The Na+:K+ ratios presented in the histograms were calculated
for each nucleus individually, and the averages of these ratios
are shown in Chart 4. For mathematical reasons, this average of
the ratios is not equal to the ratio of the average molar concen
trations presented in Table 1. However, the latter values show
similar tendencies.
DISCUSSION
The applicability, reliability, and limitations of the bulk specimen
Chart 3. X-ray spectrum of a cell nucleus in anaplastic carcinoma. Arrows are
defined in Chart 2. Note the considerably increased Na* and Cl~ peaks and the
somewhat decreased K* peaks. VS, vertical scale.
It is evident from the data of Table 1 that the Na+ and Cr
contents of the nuclear dry mass increase parallel with the
increased malignancy of the tumors studied. At the same time,
the 1C content, although displaying some statistically significant
changes, varies relatively little and does not show any clear
tendency.
Table 1 reports also the concentrations of the monovalent ions
calculated for the intranuclear water in mEq/kg units. In order to
calculate these concentrations, the actual dry mass content (;'.e.,
the water content) of the nuclei must be determined. Since this
parameter was not measured in the present material, we as
sumed uniformly a value of 25% by weight for the dry mass (i.e.,
75% by weight for water) for the values reported in Table 1. We
should like to stress, however, that our calculated values cannot
be taken as true absolute concentrations, since differences in
the nuclear dry mass content may influence the figures obtained
very strongly. For example, if the dry mass content of the nuclei
is only 20% instead of the assumed 25%, all the monovalent
concentrations calculated for the water will be lowered to 75%
of the values shown [for details, see Equation 1 of BertoniFreddari et al. (1)]. Differences of several percentage points in
the total dry mass may well exist between the normal and tumor
cells, bringing the absolute values of the monovalent concentra
tions back into the physiologically accepted range of approxi
mately 300 mEq/kg water.
Chart 4 shows the distribution histograms of the Na+:K+ ratios
calculated individually for each nucleus. It should be stressed
that this parameter does not depend at all on the actual dry
mass content of the cells; therefore, its increase from the normal
value toward the anaplastic carcinomas may represent real dif
ferences between various states of the thyroid tissue. It is
noteworthy that the x2 test of statistical comparison revealed
very highly significant differences between
grams (p < 0.001). It is obvious from the
that each type of tumor studied contains
having Na+:K+ ratios in the normal range.
additional cell population
5398
any pair of the histo
histogram of Chart 4
a population of cells
However, there is an
in the tumors with considerably
in
1C•
NORMALTHYROIDCELLS
349 nuclei
( Teases)
12
1.0
16-
NO.-/K
15
(mol)
BENIGN ADENOMAS
406 nuclei
(5cases)
12-
n-.
to
Na /K
(mol)
DIFFERENTIATED CARCINOMAS
423 nuclei
(5 cases)
12
oA
*'•
12-
1.5
•
2.0*/.
"l r-,
-mro7sN<T/K*
005-"
(mol)
ANAPLASTIC CARCINOMAS
891 nuclei
(6 cases)
10
15
Na /K
(mol)
Chart 4. Distribution histograms of the Na*:K* molar ratios in normal thyroid
epithelium and 3 types of thyroid tumors. Perpendicular broken lines, site of average
values (±S.E.). Numbers at right, above arrows, total percentages of cells display
ing Na*:K* ratios higher than 1.6. (The differences between any pair of the
histograms proved to be statistically highly significant by the x2 test. For more
details, see the text.)
CANCER
RESEARCH
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VOL. 43
Intracellular A/a+:K+ Ratio in Thyroid Tumors
X-ray microanalysis for human unogenital tumor cell nuclei have
been discussed in detail in our earlier paper (26). Therefore, we
shall not discuss the validity of the approach further. We are of
the opinion that this method is also valid for human thyroid
tumors, since the sampling criteria were met.
The present results demonstrate that the malignancy of the
thyroid tumors is correlated with their intracellular Na+:K+ ratio.
As used here, malignancy is a clinical term which describes the
proliferative capacity of the tumors, the invasive character of the
tumor, and the tendency to form métastases.
The possible mechanisms of action by which an increased
Na+:K+ ratio may affect regulation of cell division are still not
quite clear. We listed some theoretical possibilities in our earlier
paper (26). Even if the theory of Cone (5) is true, the absolute
value of the Na+:K+ ratio cannot be regarded as the only factor
regulating cell division, since even physiologically normal cells
display a variation in this parameter. For example, normal thyroid
cells have a Na+:K+ ratio twice as high as that of urinary bladder
epithelial cells (26). The membrane potential of any cell type is
determined by the actual Na+:K+ ratios in the extra- and intra
cellular spaces, as well as by the permeability ratio of the cell
membrane for these ions. In normal resting cells, these param
eters are regulated according to the state of differentiation and
type of the cells, resulting in some variations between the differ
ent cell types. Nevertheless, the increase of the intracellular
Na+:IC ratio and the increase of the PNa:PKratio lead to the
depolarization of the cell membrane as described by the Goldman
equation. Therefore, if we detect an increased Na*:K+ ratio, it
will contribute toward relative depolarization of the cell mem
brane. It is also possible that the chromatin of differentiated cells
binds less Na+.
The mechanism of the increase in intracellular Na+ content in
the tumor cells is unknown. Theoretically, one can assume 2
basic phenomena, either of which (or their combination) may
result in this increase: (a) it is possible that the Na+ permeability
of the cell membrane remains normal, but that the membranebound Na+-K+-dependent ATPase (the "pump enzyme") is defec
tive, thereby allowing the extra- and intracellular space to equili
brate more or less quickly the concentration gradient for Na+; (ó)
the Na+ permeability of the resting cell membrane may be higher
(being much lower normally than that for K+). As a consequence
of increased Na+ influx, the pump enzyme will be activated but
may not be able to pump out the excess Na+, since the influx is
too high. It is interesting to note that both of these mechanisms
may be associated with cancerous growth. For instance, in
chemically induced liver cancers, the disappearance of the pump
enzyme was shown to be the very first and persisting detectable
histochemical alteration (for details, see Ref. 8). On the other
hand, our preliminary histochemical studies on the thyroid tumors
revealed a marked increase of the pump enzyme activity in the
anaplastic cancer cells as compared to the normal thyroid cells
or to the less malignant thyroid tumor cells.3 Although this fact
still does not directly prove an increased sodium permeability of
the cell membrane, it offers strong support for such an assump
tion. Similarly, Rozengurt and Mendoza (20) have demonstrated
an increased sodium permeability of serum-stimulated fibroblasts
compared to quiescent cells and of transformed compared to
normal cells. The possibility that human carcinogenesis may
result from an increased sodium permeability of the cell mem
3 Unpublished observation.
NOVEMBER
brane is not merely of theoretical significance. It seems to be
reasonable to assume that sodium channel-blocking drugs, such
as amiloride, may inhibit the growth of cancer cells in humans as
they inhibit cell proliferation in experimental systems (11,14,16).
In earlier observations (12), we showed that the DNA content
of cell nuclei in thyroid cancers is very aneuploid, whereas benign
adenomas are less aneuploid. Recently, we performed parallel
measurements of DNA content and the intranuclear Na+:K+ ratios
on the thyroid biopsy material presented in this report. The
results of these studies revealed a strong correlation between
increased aneuploidy and increased intracellular Na+:K* ratio
(13). These data give further support to the hypothesis of Cone
(5) that sustained membrane depolarization increases DNA syn
thesis and cell division.
Some previously published reports deny a regulatory role for
intracellular Na+ in mitogenesis (15, 22). The intracellular Na+
content in those experiments was determined by atomic absorp
tion spectroscopy, the reuslts of which are subject to extensive
alterations due to the preparative steps applied to cultured
fibroblasts. The methodical controversy, however, will be treated
elsewhere."
Note Added in Proof
Since this manuscript was completed. Mizukami et al. (Lab. Invest., 48:411 -418,
1983) published data on the ouabain-sensitive, potassium-dependent p-Nitrophenylphosphatase activity in human thyroid carcinoma cells. It has been shown that
this enzyme shows a marked change in its localization in the thyroid papillary
carcinomas and the biochemically measured activity of it was 10 times higher, as
expressed per mg of DNA, than that in the normal thyroid cells.
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Fig. 1. Detail of a thyroid acinus in a secondary electron image of the freeze-fractured, freeze-dried bulk specimen. Due to the uncoated surface, the quality of the
image is poor. Although there is some electrostatic charging, it is not able to displace the beam. £,epithelialcell layer;N, nucleusof an epithelialcells; C, colloid substance
of the acinus, x 2800.
Fig. 2. Low-power scanning image of a detail from a benign adenoma. The follicular character of this tumor can be recognized. Preparation method as described in
Fig. 1. Bar, 10 ¡¡m.
x 2000.
Fig. 3. Details of several cancer cells from a differentiated carcinoma at higher magnification in a secondary electron image. Uncoated bulk specimen. Bar 10 ^m
x 5800.
Fig. 4. Cancer cells from an anaplastic carcinoma. Uncoated bulk specimen. Secondary electron image. Bar, 10 jim. x 5200.
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VOL. 43
Intracellular Na*:K+ Ratio in Thyroid Tumors
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VOL. 43
Correlation of Malignancy with the Intracellular Na+:K+ Ratio in
Human Thyroid Tumors
Imre Zs.-Nagy, György Lustyik, Géza Lukács, et al.
Cancer Res 1983;43:5395-5402.
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