Skin 
Retracting fibrous material 
Hydropic"B"-zone 
+''Retraction oedema" 
strUctures extending to the cutis will retract the skin and en­
hance the accumulation of elcctroosmotically transported 
warer in the skin. Thc "circular .. structure (lower right) cur­
responds internally 10 the external "skin thickening". Re· 
traction forces of the radiating structures in this region are 
counterbalanced by retraction forces of the normal tissue dis· 
tal to the Hcircular" structure. The thickness of the Hc-irc-u­
lar" structure is the same as that of the "skin [hickening ", 
funher suggesting their common pathoge.nesis as hydropic 
"8" zones. straight (Fig. XVI: 27 b). One's lim impression may 
be that the underlying fibres represent artefacts of 
preparation. This explanation, however, is highly un· 
likely because identical appearances of undulating 
structures are seen irrespective of the direction of 
cutting the specimen. This observation was experi· 
mentally ch<-cked as follows; 
Tissue surrounding a scirrhous breast cancer was 
excised and divided into four pieces. Two pieces (a+b) 
were placed in saline solution and frozen. The remain· 
ing two pieces (<+d) were kept in a dry place in a 
refrigerator overnight in order to become slightly de· 
hydrated. Frozen sections were .then prepared of the 
four pieces. Pieces a+c were cut as closely as possible 
BCEC in cancer of the breast 229 Fig. XVI: 28. Dehydration shrinks hydrophilic components 
of fibrotic tissue between nonhydrophilic , birefringem colla­
gen fibres. Histclogic frozen sections (haematoxylin~in , 
a-<i, same magnification ). ArroWll indicate directions of cut­
ting. (a, b) Two specimens of fibrous tissue from a breast 
230 BCEC in cancer of the breast Pig. XVI: 27. Variable ap­
pearances of fibrous strands 
radiating from a scirrhous 
carcinoma of the breast (his­
tologic sections, haematoxy­
lin-eosin). (a) Undulating 
course of panly birefringen< 
fibres. (b) Straight course of 
fibres in another part of the 
same specimen. The undu· 
lating fibrous sttuctures are 
not necessarily artefacts of 
preparation. Identical ap­
pearances can be obtained 
regardless of the direction of 
culling the specimen (see 
further Fig. XV! : 28). cancer after soaking in saline solution overnight . The colla· 
gen fibres are straight, regardless of the di.recrjon of cuttinr. (c, d) Corresponding fibrous tissue after overnight dehydra­
tion of the mate.rial. The collagen fibres undulate, regardless 
of the direction of cutting. Fig. XV/:29. "Skin tltick­
eningJ' near a mammary 
carcinoma (40-year-old 
woman, I. J. in Table 
XVI: 3). Mammogram, 
mAstectomy specimen. (a) a 
The tumour is surrounded b 
by fibrous radiating struc­
tures and poo.sibly an u A" 
zone with some circular 
structures . (b) The same 
specimen. Radiograp h of 
the skin, which is tltick­
ened to the right and be­
low the retracted nipple 
but is of normal tltickness 
to the left. along the extensions of the fibrous radiating material, 
pieces b+d perpendicular to the extensions. The sec­
tions were mounted and stained. Fig. XVI: 28 a and b 
shows the material which had been kept in saline 
solution. All the birefringent collagenous material in 
these two specimens appeared rather straight and no­
where undulated. This finding was interpreted as an 
indication that the hygroscopic fibrous material be­
tween the collageno us fibres was hydrated and contri­
buted to the straight appearance. The dehydrated ma­
terial (Fig. XVI: 28c and d), on the other hand, 
showed a characteristic undulating course of birefrin­
gent nonhygroscopic collagen fibres, which was inter­
preted as produced by shrinkage of the adjacent hy­
groscopic fibrous material. ln none of the sections was 
there any correlation between the direction of cutting 
and the appearance of the fibrous material. It seems likely that undulating courses of fibrous 
tissue around a breast cancer may be caused by local 
dehydration of hygroscopic components of fibrous tis­
sue. Local dehydration may in turn result from elec­
troosmotic outflow of water, leading to shrinking of 
the hygroscopic material of the fibrous tissue strands 
and retraction of the skin. In such areas the "skin 
thickening" should be called a local oedema of the 
skin, which in certain parts could also be called retrac­
tion oedema. We may now recognize the equivalence 
of these structural changes around a breast cancer and the previously described pleural retraction pocket near 
a peripheral lung cancer (Chapter III, Fig. III: 35). Fat and water content were also analyzed quantita­
tively for the so-called "skin thickening " over two 
breast carcinomas and for skin from parts of the breast 
specimens which appeared radiologically normal. Fig. XVI: 29a shows the mammogram of one of them, 
patient I. 1. This carcinoma is surrounded by numer­
ous thin radiating structures and possibly a radioluceot 
"A" zone. Fig. XVI: 29b shows "skin thickening " 
both to the right and under the retracted nipple. Table 
XVI: 3 presents the analytica.l values for the two pa­
tients. Table XVI: 3. Fat-wattr content of "skin tltick~ning " over 
breast cancm and Mrmal skin 
"SIOn Nonnal Normal 
Parient thickening'' skin I s!On II 
l. j. H,O 77.5 62.6 63.5 
Fat 0.2 3.9 3.9 
RcsiduaJ 21.0 32.9 3 t. 7 
lost l.3 0.6 0.9 
A. C. H,O 79.5 71.3 
Residual 18.0 25.6 
Lost 2.S 2.1 
BCEC in cancer of the breast 231 The results indicate that so-called "skin thickening " 
correlates with a relative increase of water content 
(local oedema), explaining the local increases in x-ray 
anenuation seen in the mammogram. K. Closed circuit production 
of fibrous radiating 
structures: cathodic and 
anodic types of fibrosis 
Fibrous radiating structures often develop around car­
cinomas in the lung as well as in the breast. This 
observation has here been interpreted as a conse­
quence of two phenomena: physicochemical polariza­
tion of the lesions and the existence of biologically 
closed electric circuits. Radiating structures were pre­
viously also produced experimentally in vitro and in 
vivo (Chapters X, XI). A closed electric circuit is a 
necessity for their experimental production. This sec­
tion will show experimentally that radiating structures 
can be produced very efficiently over closed circuits 
even in "dead" tissue and also that material in these 
structures looks like and may possibly be identical 
with the fibrous material around tumours. One prerequisite for the development of radiating 
structures is the presence of so-called electric edge 
enhancement {Chapter X). To utilize this phenom­
enon, circular electrode plates of platinum were there­
fore perforated at multiple sites with a needle. Small 
protrusions of the metal were produced in this way on 
the side of the electrode plate facing the tissue speci­
men. A piece of human breast fat in a plastic 10 ml 
syringe between two plungers, each provided with a 
platinum electrode, is shown in the soft tissue radio­
graphs of Fig. XVI: 30. Platinum strings were con­
nected to the electrode plates and to a generator of 
direct current. Fig. XVI: 30a shows the specimen 
before any current was applied. Some already existent 
fibrous structures can be seen in the fat, which is 
essentially free from such material close to the elec­
trodes. Fig. XVI: 30 b shows the specimen after 10 
days (25 coulombs) and Fig. XVI: 30c after 17 days 
(30 coulombs), during application of 10 volts over the 
material. During the ftrst hour a current of a few rnA 
flowed with increasing intensity through the speci­
men. The current then usually decreased to very low 
values (a few pA). As days passed, radiopaque struc­
tures developed in the fat. In the cathodic part of the 
chamber, clear linear structures were seen after I 0 
days. More cathodic and anodic material is seen after 
17 days than after 10 days. After 17 days the anodic 
232 BCEC in cancer of the breast b 
10V 
25C 
+ c 
10V 
30C 
+ 
Fig. XVI: 30. Direct current treatment of human breast fat 
in a plastic chamber between two platinum electrodes with 
protruding edges. Soft tissue racliographs . (a) Before electro­
phoresis, practicaiJy no fibrous tissue in parts of the speci­
men immecliately adjacent to the electrodes. (b) Mter 10 
days, 25 coulombs at 10 V. (c) SJiahtly different projection, 
after 17 days, 30coulombs at 10 V. Fibrous tissue is pro­
duced as "radiating structures" due to field enhancement at 
some of the electrode protrusions. These structures are not 
straight, which is explained by preferential pathways for cur­
rent in the tissue. Note macroscopic differences of cathodic 
(-)and anodic (+)fibrous tissue as well as many small 
"dots" in the anodic part of the specimen. part of the specimen ( +) showed some very small dark 
dots and more delicate irregular structures than the 
cathodic portion (-). The newly formed linear structures in the cathodic 
and anodic regions close to the electrodes were easy to 
identify in histological sections because no or only 
Fig. XV I: 31. Histopathologi c appearances of radiating • 
structures experimentally induced in cathodic and anodic re­
gions of breast fat (a-f), compared with fibrotic tissues aris-
ing in vivo around a breast cancer (g--J). (a""') Cathodic, (d-/) 
anodic newly formed racliating structures. Same specimen as 
in Fig. XVI: 30. Cathodic fibrosis looks like a Stretched mesh 
of fibres (a, b) which never shows any fibroblasts . During 
development some groups of fat cells diminish in size (c) and 
form a central "nucleus'' before they disappear {sec further 
on development of cathodic fibrosis, Figs. XVI: 33, 36). An­
odic fibrosis shows dense, irregular fibrous material with fi­
broblast-like cells (d, e) and seanered groups of ceiJs of an 
epithelial type (t,/). (g, h) Some fibrous tissue from the sur­
roundings of a breast cancer appears as a mesh, similar to ex­
perimentally produced cathodic fibrous tissue. It contains 
cellular structures of variable appearance. Some are flat and 
of a fibroblast type. Others appear with rounded cellular 
nuclei (arrows). (i-J) Tissue from another part of the tissues 
surrounding the same tumour. This fibrous tissue is particu· 
larly irregular and dense. It contains a large number of fi­
broblasts and looks like experimentally produced anodic fi­
brous tissue (a, b, d, t van Gieson, c,f-j naematoxylin-eosin 
stain). a-f 
g-j 
233 minimal amounts of fibrous tissue were there before 
the application of current. Histologic sections of the 
newly formed radiating structures are shown in Fig. XVI: 31 from close to the cathodic electrode (a, b, c) 
and the anodic electrode (d, e, f). The cathodic and 
anodic structures resemble elements of spontaneously 
developed fibrous tissue material. They also show dis­
tinct internal structural differences. Both materials 
contain birefringent and nonbirefringent components. The cathodic material shows a net-like loose mesh 
mainly oriented in the direction between the elec­
trodes. The anodic material is more compact and irreg­
ular in appearance and shows islands of what will later 
be shown as epithelial -like cells and many spool­
shaped small structures which look like fibroblasts. No fibroblast -like structures were seen in cathodic 
fibrous material. Both "cathodic" and "anodic" rypes of fibrosis now 
can be recognized in the radiating scar tissue around a 
breast carcinoma, as shown in Fig. XVI: 31 g-j. The 
experimentally produced cathodic, mesh-like fibrous 
tissue (Fig. XVI: 31 a, b, c) may be compared with the 
endogenously developed fibrous mesh-like tissue of 
Fig. XVI: 31 g, h. This endogenous tissue, however, 
does contain some fibroblast-like cells, unlike the ex­
perimental cathodic fibrous tissue. The experimenta lly produced anodic, dense fibrous 
tissue contains large amounts of fibroblast -like cells 
(Fig. XVI:31 d, e, /).The endogenous anodic rype of 
fibrous tissue also contains large amounts of fibro­
blasts (Fig. XVI: 31 i, J). The groups of epithelial cells 
seen in Fig. XVI: 31 d, e, f will be discussed later. A 
mixture of anodic and cathodic rypes of endogenously 
developed fibrosis around a tumour is in agreement 
with the conception of fluctuating changes of polarity 
of a degrading tissue, and hence the direction of flow 
of current. Production of fibrosis is, in this view, a 
result of the flow of current over BCEC channels. This 
far-reaching statement will, however, shortly be fur­
ther supported by other observations. Recently the opinion has been expressed that fibro­
sis in breast cancer might be a primary carcinogenic 
factor (67). In the author's opinion this conclusion is 
not very plausible. Formation of scar tissue is a com­
mon reaction in various tissues to different kinds of 
injury. Desenerative changes or traumatic injuries are 
frequently encountered in normal breast tissue. Very 
often, spontaneous necrosis and haemorrhage occur in 
breast cancers. In the following it will be seen that 
many of the structural modificat ions of cells and tissue 
which can be seen inside and around breast cancers 
can be induced by direct current. Even the possibiliry 
of carcinogmic effects by endogenous or induced cur­
rents in tissue might be considered in future research. The closed circuit treatment of tissue samples shows 
that it is possible to produce newly structured material 
234 BCEC in cancer of the breast in both the cathodic and the anodic fields even in a 
"dead'", excised piece of tissue. Radiating "fibrous" 
tissue structures can be produced in tissue samples of 
mammary fat by direct current when the electrodes arc: 
provided with small protrusions causing local spots of 
high current density. The sites where the fibrous tis· 
sue structures develop depend not only on the loca­
tions of the protrusions on the electrodes. At some 
protrusions no structures will develop. This phenom­
enon has been interpreted as an effect of inhomogene­
ity with regard to conducting properties of the tissues. Preferentia l pathways of current in tissue, even if it 
looks histologically homogeneous, can fully explain 
such a phenomenon. The experimentally produced fibrous material very 
much resembles scar tissue, although it is apparently 
different in the cathodic and anodic fie lds. This result 
is not surprising as long as a unidirectional mode of 
current has been applied. Evidence has been present­
ed, both experimentally and theoretically , that a spon­
taneous tissue injury will produce a fluctuating poten­
tial o,·er BCEC, thus allowing anions as well as 
cations to contribute to the healing process and conse­
quently also to the formation of complete or "mixed" 
fibrous tissue. Experiments were therefore also arranged to fluctu­
ate the electric potential over samples of fat tissue. Before these experiments are described, we will, how­
ever, extend the present experiments of producing 
radiating structures into attempts to produce mem­
branes with unidirectional current. L. Closed circuit production 
of fibrous membrane s 
A tentative explanation for the production of fibrous 
organ capsules was given in Chapter XII. It was 
assumed, for example, that the liver and its sur­
rounding organs will produce asynchronous, physio­
logic fluctuations of potential, which should lead to 
"ebb and flow" movements of anions and cations to 
the organs• surfaces. A depOsidon of material should 
then lead to the production of fibrous capsules as long 
as the driving force over the BCEC is strong enough to 
induce the ionic movements. The thickness of an or­
gan's capsule should then correspond exactly to the 
physiologic driving force over the BCEC. The capsules 
of organs may consequently be regarded as analogues 
to the products of polarization at electrode surfaces. Thi; section contains experiment s showing how fi­
brous membranes can be produced by the use of this 
principle, but in a simplified way. We will again make use of the eloctrophoretic cham-a 
II' 
''f' 
'-f 
~ t . 
' ') } . "'I ,.'-,--,f-...... -' 'j ...... , ,, 
Fig. XVT:U. Pmciucr1nn 
by direct current in vitro 
of(a, b) cathodic and (c, d) 
anodic membranes using 
flal platinum electrodes 
against human fat tissue. Photomicrographs show 
the cathodic membrane to 
be thin and covered with a 
thin layer of a brown-black 
ma<erial. The anodic 
membrane is thicker and 
more irregular (haematox · 
ylin-=in). ~\ 
ber. This time we will use fl•t electrodes without 
protrusions on their surfaces. As always, deposition of 
material will take place on electrode surfaces when 
they are immersed in an electrolyte and current flows 
through the circuit. Such material on an electrode 
surface is difficult to retrieve undestroyed for histolo­
gic studies. We will, however, make use of a tissue 
matrix as a supporting medium between the electrodes 
to take care of this problem. At sufficiently high densi­
ties of current, gas produced at the metal surfaces will 
"lift off" nongaseous deposited materiaL Such materi­
al will adhere to the matrix by interface adsorption and 
thus become available for histologic studies. I 
\ ) 
--..... \ 
7 
\ 
Thus, histologic sec-tions of cathodic and anodic 
membranes produced on breast fat are seen in Fig. XVI: 32. These membranes consist of birefringent rna· 
terial structured differently from the material of radi­
ating structures in the cathodic and anodic fields, as 
shown in the previous section. The cathodic mem­
brane is thinner and smoother than the anodic. On its 
surface lies a deposition of some dark material, which 
is absent on the anodic side. In the cathodic and 
anodic fields there were also several membranous 
structures in the fat tissue, parallel with the electrode 
surface. BCEC in caoce.r of the breast 235 c 
( Fig. XV/:33. Developme nt 
of cathodic fibrous tissue. (a) The cathodic membrane 
adjacent to fat tissue con· 
tains islands of ''atrophic" 
and modified fat ceUs. (b) Modified fat cells of var­
ious sizes show formation of 
a reticulum . (c) A region of 
gradual transformation of 
atrophic fat ccUs, which oth· 
crwisc appear normal, shows 
reticulum strucru.res and 
thickened cell membranes. (d) A row of fat ceUs with re· 
ticulum shows from top to 
bottom gradual disappear­
ance of cell content and 
thickening of ceU mcm· 
brancs, leading to mesh-like 
cathodic fibrosis without fi. ~~}~~)[ij~~~~t\~~ broblasts(a, b, von Kossa, "'"'J•'"''' c. d, haematoxylin·eosin 
M. Closed circuit production 
of cathodic and anodic 
fibrous tissue 
Detailed analysis of the background biokinetics of the 
development of radiating structures and membranes is 
beyond the scope of the present study. Neverthe less, 
236 BCEC in cancer of the breast stains). the reader may be interested in some preliminary ob­
servations of the transformation of fat material close to 
the electrodes, as affected by current applied unidirec­
tionally. An overview (Fig. XVI: 33 a, von Kossa stain) of a 
piece of a fibrous c.athodic membrane reveals a number 
of small fat cells, appearing relatively normal. Many 
cells inside the membrane structure have been inter· 
preted as fat cells undergoing transformation. These Fig. XV I: 34. Development 
of anodic fibrosis. (a) Over· 
view of dense, anodic fibro· 
sis containing numerous fi­
broblast-like cell elements. Some of these elements form 
circular groups, while a few 
are positioned at the edge of 
the fibrotic tissue and in a 
thickened intercellular 
space. (b) Magnified view of 
a. A thin, fibrotic, inter­
cellular structure contains 
"fibroblasts" (arrows) adja· 
cent to some fat cells. The 
membranes of the fat cells 
are of normal thickness . Such findings suggest that 
anodic fibrosis with "fibro· 
blasts" develops interstitial· 
ly (haematoxylin-eosin ). .. 
• ~;[/ r 
·=~ i, .-, 
......... ~# , '. ' ·' 
cells, seen under higher magnification in Fig. XVI: 33 b, are of varying size and contain a delicate 
reticulum. Such cells under the same magnification 
but stained with haematoxylin ·eosin are shown in Fig. XVI: 33 c. The upper part of this figure contains small 
normal fat cells, cells which partly contain reticular 
structures and some cells which are filled with reticu· 
lar structures. The latter have thick cellular walls. Fig. XVI: 33 d shows a row of thick-walled fat cells with 
some reticular structures (upper part of figure). The 
lower part of Fig. XVI: 33 d shows that the cells are 
elongated and have lost their reticular content. The 
elongated and thicke.ned fat cell membranes seem 10 
fuse and produce a fibrous tissue which looks like a 
stretched mesh, as was also shown in Fig. XVI: 31 a, b 
in the description of cathodic radiating fibrous struc· 
lUres. Anodic fibrous tissue contains fibroblast-like cell 
elements, which do not appear in the cathodic fibrous 
tissue. The anodic fibrous tissue seems to develop 
between fat cells in the interstitial tissue. When a thin 
fibrous tissue strand is seen at the edge of a large 
anodic fibrous complex, a chain of "fibroblasts" can 
be seen together with some fibrous tissue in the inter· 
stitial space (Fig. XVI: 34). Because fibrous tissue can 
be produced in "dead" fat tissue under the influence 
of direct current, it seems likely that the fibrous t 
! . , 
I .. • • , 
j 0.2mm 
/ -
50J.Jm 
strand, containing fibroblast -like cell elements (Fig. XVI: 34 b, arrows) represents a preferential pathway of 
current between the electrodes. Fibrous tissue is a 
poor electric conductor. A flow of current in intersti· 
tial spaces, producing interstitial fibrosis, can never· 
theless be possible if the current is flowing in the space 
between cells and the surface of the developing inter­
stitial fibrous strand. The following observations may 
serve as a support for this hypothesis: 
When a supporting matrix is used in the membrane 
experiments , as is the case with specimens of fat tis· 
sue, membrane structures are produced not only at the 
electrode surfaces. Fibrous membrane s also develop 
parallel to the electrodes at several sites in each fat 
specimen (Fig. XVI: 35a, van Gieson, b, Alizarin 
stain, with anodic sides to the right). Because fibrous 
tissue is a relatively insulating electric material, it can 
be expected to be a barrier to the flow of current. Current might then flow along the surface of the bar· 
rier in the interstitial conducting medium. When it 
reaches the edge of the fibrous barrier, the current 
should tend to take new pathways in the specimen. The edge of the fibrous tissue and its surrounding 
conducting medium then represent a region of modi­
fied conductivity. Hence the pattern of flow of current 
should be modified. An anticipated resulting modifica· 
tion of tissue structure by such a mechanism is shown 
BCEC in cancer of the breast 237 a 
. -
..., . \ . a 
b / 
' ,.. 
• 
I 
238 BCEC in cancer of the breast 50}Jm 
I Fig. XV/:35. Membranous 
fibrous structure produced 
by direct current in a fat 
spocimen . Cathodic sick to 
tbe left and anodic sick to 
tbe rilbt. (o) This mem­
brane has 1 direction more 
or less perpendicular to tbe 
main direction of current 
between the electrodes. Be­
cause fibrous tissue is a poor 
conductor, current should 
flow along its surface. At tbe 
edge or the membrane, are-­
gioll of modified conductiv­
ity is entered. (6) At tbc 
edge of a fibrous membrane , 
fat ce.lls are small and pos­
sas tortuous membranes. Observe also small bush-like 
structures to the right of the 
fibrous tissue in a and 
around the edge of the fi­
brous tissue in 6. (a) van 
Gieson stain, (6) AJi22rin 
slain . Fig. XVI: 36. (a) Experi­
mcntslly produced, fully de­
veloped ca1/wdic fil>rous titnu 
from human breast fat. The 
mesh-like fibrous tissue is 
now dense but contains 
(.TCViccs with irregular, bire­
fringent borderli11es. No fi­
broblasts or other cells are 
present. (6) Fully developed 
GMdic jil>rous timu from 
same preparations as a. This fibrous tissue is homo­
geneous and dmse, with ir· 
regularly arranged, thin, 
partly birefringent fibres. Large areas do not contain 
fibroblastS. Other areas con­
tain fibroblasts, either scat· 
tcn:d or in dense collections. The lack or fibrobwts inca­
thodic fibrosis and the lack 
or correlation between the 
amount of anodic fibrous 
tissue and the numbtrs and 
locations of fibroblasts is 
striking (haematoxylin·eo-­
sin). Fig. XVI: 37. Intermediate mem· 
branes produced by unidirectional and 
revtrs<d direct current. (a) Soft tissue 
radiograph of original fat and glandu· 
Jar breast tissue material. (b) An inter­
mediate fat zone appeared after 31 
coulombs at 10 V for three days. Gas is 
produced at the electrode surfaces. (c) After removal of gas a thin cathodic 
membrane (arrow) is seen adjacent to 
!he intermediate fot zone. (d) Polarity 
was then reversed. After 39 additional 
coulombs over a total of seven days, a 
new cathodic membrane is seen (ar­
row) at the opposite side of the inter­
mediate fat zone. (e) Photomicrograph 
shows to the right dense, "modified 
cathodic" and to the left dense "modi· 
fled anodic" fibrous tissue after 70 
coulombs. Note fibroblasts only in the 
left "anodic'" part of rhe membrane 
(van Gieson stain). a ov oc 
around the edge of the fibrous membrane in Fig. XVI: 35 b. The fat cells are small and somewhat 
shrunken around the edge of the membrane. Another 
detail of interest in Fig. XVI: 35a, b is a presence of 
some small intracellular "bushes" situated in the tissue 
at a certain distance (0.2-0.3 mm) from the fibrous 
membrane along its anodic side in (a) and around its 
edge in (b). The small "bushes" contain birefringent 
materia.! but do not stain for calcium ions with Alizarin 
(b). We will return to this problem in SectionS , which 
deals with experimenta l production of microcalcifica ­
tions. In fully dtveltiped cathodic fibrous tissue from breast 
fat, the mesh-like structures are thickened and present 
crevices witb irregular, birefringent borderlines. Such 
fibrous tissue never shows fibroblasts (Fig. XVI: 36a). Fully developed anodic fibrous tissue from breast fat b 
10V 
31C c ov 
31C d 
10V 
70C 
shows a compact, homogeneous tissue of irregular, 
delicate, birefringent fibres. Fibroblasts may be com· 
pletel:y absent in large parts of the tissue or are present 
in local c<>nglomerations or are sparsely scattered in 
the tissue (Fig. XVI: 36 b, same slide preparation as 
Fig. XVI: 36a). The effect of reversal of polarity on membrane for­
matioon is shown in Fig. XVI: 37. Human breast fat 
with some glandular tissue was used. Its radiographic 
appearance before application of current is shown in 
Fig. XVI: 37 a. Ten volt electrode potential was ap­
plied. After 31 coulombs an intermed iate fat zo.ne is 
seen and some gas formation at the electrode surfaces 
(Fig. XVI: 37 b). The electrodes were then moved 
closer together for removal of the gas pockets and to 
improve electrode contact (Fig. XVI: 37 c). A thin 
membrane-like structure is also seen at the previously 
BCEC in cancer of the breast 239 cathodic side of the fat zone (arrow). Ten volts were 
then applied with reversed polarity. After an addition 
of 39 coulombs, a new membrane-like structure can be 
seen at the new cathodic side of the fat zone (Fig. XVI: 37 tf). One membrane structure was therefore 
obtained on each side of the fat zone of the specimen. Each of these membranes appeared as mixed anodic 
and cathodic types of fibrous tissue, as seen in Fig. XVI: 37 e (from the upper membrane of Fig. XVI: 37 tf). This membrane shows to the right, ca· 
thodic fibrous tissue with irregular crevices and no 
cellular elements. To the left, anodic fibrous tissue 
shows a group of fibroblasts and small, atrophic fat 
cells, without cytoplasmic reticulum. Knowledge about development of fibrous tissues 
remains in many respects incomplete. Even the origin 
of fibroblasts is not known with certainty. They are 
thought to derive from proliferation of local connective 
tissue, metaplasia of "wandering cells" or even from 
metaplasia of endothelial cells of the capillaries. Ross 
and Benditt (81) have claimed that fibroblasts may 
develop from a multipotential cell of haematogenous 
origin. Little is known of the factors which induce and 
stimulate fibroblast production in wound healing. It is 
claimed that substances liberated at the development 
of necrosis may possibly induce fibroblast prolifera­
tion. From the present experiments it is already evident 
that the flow of current over a "dead" piece of tissue 
may lead to new structural formations as fibrous tis­
sue. Ordinarily, we look upon such developments as 
reactions of a living tissue. It is further remarkable 
that two different kinds of fibrous tissue develop from 
the same material and that "fibroblasts" appear in the 
anodjc but not in the cathodjc fibrous tissue. Further­
more, the "fibroblasts" in the anodjc, fibrous tissue 
may be completely absent in large parts of this tissue. In other parts they are densely packed or sparsely 
scattered. These observations must raise the possibility that fibro­
blasts may not be necessary for the production of fibrous 
tissue. A search of the literature has yielded no conclu­
sive proof that fibrous tissue is produced only by 
fibroblasts. Fibroblasts are thought to produce poly­
peptide precursors of collagen in their cytoplasm in asso­
ciation with membrane-bound ribosomes (81). Confu· 
sion still remains regarding the cytological steps be· 
tween the intracellular synthesis of collagen precursors 
and the appearance of extracellular collagen fibrils. This question becomes even more timely in attempts 
to explain the experimental results here presented. Mechanisms associated with production of fibrous tis­
sue have long been known to be complex. We will 
therefore offer only a preliminary view toward explain­
ing the experimenta l results. It seems highly improbable that fibroblast-like cells 
240 BCEC in cancer of the breast present only in the vicinity of the anode should have 
the capacity to produce large amounts of "cathodjc 
fibrous tissue" far away (about 2-3 em) from their 
location in an isolated specimen of fat tissue. The 
quantity of cathodjc fibrous tissue also increased to­
ward the cathodic electrode. The quantity of "anodic 
fibrous tissue" increased toward the anodjc electrode. The fibroblast-like cells also appeared in groups with 
relatively small amounts of anodjc fibrous tissue be­
tween the cells in certain regions. In other anodic 
regions large amounts of anodjc fibrous tissue between 
the cells in certain regions. In other anodic regions 
large amounts of anodic fibrous tissue were present 
without any fibroblast-like cells. It is possible to explain the experimental results if 
we assume that an intracellular and extracellular pre­
cursor for cathodjc and anodic fibrous tissue were al­
ready present when the electrophoretic process was 
started. Under the influence of direct current the pre­
cursor of fibrous tissue then transformed into cathodic 
and anodjc fibrosis. The formation of specific cathodic 
and anodjc fibrous tissues is preliminarily explained as 
a result of cathodjc alkalinity and anodjc acidity during 
the electrically induced transformation of the precur­
sor material. The experimental results lead in this view 
to the logical conclusion that the precursor(s ) for ca­
thodic and anodic fibrous tissues must have been al· 
ready produced by normal cells. A similar process also 
appears to occur adjacent to endothelial cells, which in 
their basement lamina contain fibrous structures. The exposure of cells to direct current can lead to 
considerable cellular transformatio ns (Chapter XIV). The development of fibroblasts may therefore be ex­
plained as a result of such electrogenic transformation 
of cells. The experimental results suggest further that 
the presence of fibroblasts in fibrous tissue does not 
necessarily prove that these cells are the only cellular 
clement to which can be attributed the ability to pro­
duce precursor material of fibrous tissue. The experi­
ments also indicate that fibrous tissue devtlops from 
intracellula r and extracellular precursor material under the 
influence of direct current. The productio n of scar tissue in healing processes is 
still poorly understood. For increased understanding 
of these processes in the future, it will be necessary to 
consider the role of spontaneous, endogeno us direct 
currents in tissue over BCEC channels. N. Closed circuit production 
of anodic tissue channels 
Anodic and cathodic channels can also be produced in 
fat tissue by passing electric current over a tissue Fig. XVI: 38. In vitro pro· 
duction of anodic channels 
in huiTIJin breast fat (10 V, 
30 coulombs , 17 days). (a) Overview of newly devel· 
oped anodic fibrous strand. Same experimenl as shown 
in Fig. XVI: 30. Anode to 
the right. In the fibrous tis­
sue, "islands" of cells a.re 
seen (right part of Fig.) as 
well as dark Hrods" (arrow). (b) Magnified view of 
groups of cells, some of 
which form a central lumen. The Hislands" of cells arc 
surrounded by circular fi. brcs and fibroblasts. (c) Lcnthwise section of a 
rodli.ke collection of cells 
partly forming a primitive 
lumen. (tf) Fully developed 
channel, lined with epith· 
elial cells in the same speci­
men (see further Figs. XVI: 39,40 and text). (a-c) Haematoxylin-eosin , 
(tf) van Gieson stain. ':i! •. c { ·"­' 
sample. The possibility of producing anodic channels 
is presented in this section and cathodic channels in 
Section 0. A discussion on possibilities of producing 
vascular channels follows in Section P. 
The photomicrographs of Fig. XVI: 38a show ex-'"<!" ~ 
0.1mm • . perimenta lly produced anodic fibrous tissue in breast 
fat (10 V, 30 coulombs ). The anode had been posi· 
tioned to the right (same specimen as shown in Fig. XVI: 30c). In the right part of the specimen (close to 
the anode) some dark structures are seen as rounded 
BCEC in cancer of the breast 241 -• 
~ 
d 
..... 
' "" --r 
"islands" or groups of material. To !he left are rod­
like dark structures (arrow). Purther analyses of !he 
"islands" (Fig. XVI: 38b) show collections of cells, 
some of wb.ich form a ring wilh a light centre. They 
are surrounded by circularly arranged fibrous tissue 
containing "fibroblasts". The dense groupings of cells 
represent cross-sections of "rods" and the ring-shaped 
242 BCEC in cancer of the breast sovm Fig. XV/:39. In vitro pro-
duction of anodic channels 
in human breast fat (tO V, 
30 coulombs, 17 days). (a) Structural arrangements 
of cells of the ductal channel 
shown in Fig. XVI: 38d. (b) Cells of epithelial type 
fonn ring-like struc-rurcs 
tending to form a lumen. (c) Several "islands" of epi-
thelia! cells, interpreted as 
anodic 1'rods'' surrounded 
by circularly arranged fi. brous tissue. (t/J Lengthwise 
SOJJm section of"rod" of epithelial 
type of cells (see funher Fig. XVI:40). groups of cells cross-sections of primitive channels. A 
lengthwise sectioned, tortuous, partly opc:n "rod" is 
shown in Fig. XVI: 38c. A channel structure with a 
well-developed lumen is shown in Fig. XVI: 38d. Some details of these structures are further illustrated 
in Fig. XVI: 39. Thus, the arrangement of the epithe­
lial cells of the partly well-developed channel is shown Fig. XV/:4Q. In vitro pro­
duction of anodic channels 
in human fat tissue (10 V, 
30 coulombs, 17 days). (a) "Rods" develop in the 
same direction as the fi. brous structures. (b) They 
arc: $0lid and consi~t of 
cells of the same type as 
shown in Fig. XVI: 39c, d. 
They are surrounded by fi. brous tissue containing 
"fibroblasts". (c) Certain 
parts of such "rods" ap-
pear as if they are forming 
a lumen (van Gieson 
stain). in Fig. XVI: 39a. Circular arrangement of epithelial 
cells forming a lumen is shown in Fig. XVI: 39 b, 
while circular arrangement of fibrous material around 
collections of cells is shown in Fig. XVI: 39c. A detail 
of a lengthwise sectioned "rod,. is shown in Fig. XVI: 39d. It contains an epithelial type of cells. We are now approaching an important problem: 
were the groups of cells in the fibrous tissue already 
present before the electrophoretic treatments, or do 
they represent newly formed structures? More obser­
vations are evidently necessary before we can discuss 
this question. A fibrous anodic strand with several well-deve loped, 
19-824586 NtKdnu:riim dark rod-like structures is shown in Fig. XVI: 40a. The "rods" are oriented in the same direction as the 
fibrotic strand. They are only encountered in anodic, 
never in cathodic fibrosis. As seen in Fig. XVI: 40b, 
tbese "rods" consist of cellular elements . ln the centre 
they are rounded like the cells shown in Fig. XVI: 39c, 
d. Some "cells" have the appearance of fibroblasts 
and are preferably located outside the rounded "cells". Certain portions of such "rods" show initial develop­
ment of lumina of channels (Fig. XVI: 40c). Figs. XVI: 38-40 were aU obtained from the anodic part, 
close to the electrode, of the specimen shown in Fig. XVI: 30. This sequence illustrates the development of 
BCEC in cancer of the breast 243 . _ 
b 
-~! • 
. ':' J ,... 
cha.nnels which look very much like adenotic forma­
tion of primit.ivc galacrophores in breast tissue. We 
will soon return to these problems. It is, however, 
necessary first to describe some other anodic struc­
tures which were produced with a slightly modified 
technique. Human fat tissue was first treated with 20 V, 30 
coulombs for 3 days. The current was then reversed 
(20 V, 8 coulombs, 7 days). In the now anodic side of 
the specimen (fig. XVI: 41) structures were obtained 
consisting of delicately arranged rows of fibroblast-like 
cells, surrounded by dense anodic fibrous tissue. Fig. XVI: 41 a shows an overview of such a structure, 
which evidently tends to form a channel. The magni­
fied view of Fig. XVI: 41 b shows no rounded, epithe­
lial type of cells, as in the previously described anodic 
channel. Cross-sections of well-developed structures 
forming lumina and containing fibroblast-like cells in 
244 BCEC in cancer of the breast .. 
50pm Fig. XV/:41. In vitro pro­
duction of anodic channels 
in human breast fat by re­
versal of flow of current. Initial dose: 20 V, 30 cou­
lombs during 3 days. There­
after the current was re­
versed: 20 V, 8 coulombs, 7 
days. (a) Overview of a 
primitive channel in fibrous 
rissue in the newly anodic 
side of the specimen. Cellu· 
lar elements tend to arrange 
forming a rube. (b) This 
structure contains cells 
which look like fibroblasts. No cells of epithelial type 
are present (haematoxytin · 
eosin stain). their walls are shown in Fig. XVI:42a, b. The dense 
anodic type of newly formed anodic fibrous tissue 
surrounds these structures. These new channels ap­
pear to be clearly different from the channels which 
look like primitive galactophores. Perhaps these thin­
walled channels with fibroblast-like cells represent ear­
ly stages of vascular channels. In order to establish whether similar anodic struc­
tures can be produced by direct current in fat of a 
tissue other than breast, fresh abdomiiUll subcutaneous 
fat was obtained during surgery on three otherwise 
normal patientS with inguinal hernias. These tissues 
were treated like the samples of breast fat tissue. Ten 
volts were applied between the platinum elec~rodes to 
the specimens (2-3 em long) of abdominal fat tissue 
for two to five weeks. As in the breast fat studies, the 
initial current of a few rnA decreased rapidly to a few 
microamperes during the following hours. Still, / /-,; 
/...:• I . . / ,, / /I 
' <' 
' 
f ... 
b ; / / 
~ " Fig. XV/:42. ln vitro pro· 
duction of anodic chan· /' 
nels. (a, b)Cross·sectioned ~, 
channels, interpreted to 
contain the same type of 
cells in their walls as the ... ~ tubular structures of Fig. ~{ XVI:41. Tubular channels ( 7 
of this type could possibly ,~ 
rcpr~m the anodic phase "· of early development of I 
vessels (hacmatoxylin-e<>· If. sin stain). changes in the radiograph ic appearance could be seen 
during the following weeks. It rrught be mentioned in 
this connection that fat tissue undergoing electro· 
phoretic treatment even for weeks shows no signs 
of bacterial decomposition , which otherwise takes 
place after a few days in untreated specimens. Developed anodic fibrous tissue strands of abdonU· 
nal fat were found to contain scattered fibroblasc -like 
cells (Fig. XVI: 43 a) or centrally located groups of 
cells in the fibrous tissue (Fig. XVI: 43 b, c). Rod-like 
structures could also be identified but of another ap­
pearance than in breast fat. Thus, in Fig. XVI: 44a a 
small Structure is seen to the left, showing a central 
dark, irregular line (arrows). To the right in Fig. a, a 
"channel" is seen with an open lumen (X) and fibro· / , 
blast-like cells in the wall, which in turn is surrounded 
by some fibrous material. Fig. XVI: 44 b shows an· 
other "channel" without fibroblasts, surrounded by 
thick bluish-stained fibrous material (haematoxylin · 
eosin). This channel was found in the rrud-part of the 
specimen. A "channel" structure from the cathodic 
part of the same specimen is seen in Fig. XVI: 44c. This channel shows only a wall of fibrous tissue whh· 
out any cellular elements or differently stainable lay· 
ers. We are now almost ready to discuss the possibility 
that the structures described are induced by the cur· 
rent applied to the tissue specimens. For the moment, 
some of the indications pointing toward this possibility 
will be summarized. The objection that the structures 
BCEC in cancer of the breast 245 _f 
•• 
/ ' .' \ . . , 
' d· ..) .· / \ 
. o:i'mm ..:' ,_ 
p 
"''' r 
.a~ ·-
:~~ ' 
·~~ 
-~ ) • 
·~ (" 
·'" ' ·'l 
' ' ( b 
f 
·. 
' 246 BCEC in cancer of the breast 1 
\ 
.l 
[ 
,..J 
I '• ·-•• • Fig. XV/:43. In vitro production of anodic fibrosis in hu­
man abdominalfat tissue. 10 V, 1-2 microamperes for 30 
days produced anodic fibrous tissue strands with (a) scat· 
tered fibroblasts, (b) collections of fibroblasts along a new fi. bre, (c) fibroblas!s located centrally in the fibrous t.issue 
(haematoxylin-eosi n stain). See also Fig. XVI: 44. 
described after treatment of fat tissue samples might 
have been present before the treatments is evidently 
not valid for the development of anodic and cathodic 
fibrosis. The anodic and cathodic fibrous tissues arc 
histologically of distincly different appearan ces. These 
tissues are furthermore radiographically different and 
developed clearly during the electrophoretic treat· 
ments, as seen in serial radiographs. The rod-like, 
tubular and suggested vascular structures in the fibrot­
ic material, on the other hand, have a spatial distribu­
tion and size which make it difficult or impossible to 
detect them by radiographic techniques. Different evi­
dence indicates, however, that the structures de· 
scribed may be newly formed. (a) The rod-like and 
tubular structures, lined by cells, were not found in no 
specimens of untreated fat from the same breast tissue. (b) The tubular structures with an appearance similar 
to that of primitive galactophores have been found 
only in the treated samples in connection with newly 
developed fibrous material and (c) have been found 
only in anodic fibrous tissue. (d) When they are seen 
in lengthwise sections, they are oriented in the same 
way as the fibrous strands. (e) "Channels" of only 
fibrous material, containing fibroblast -like cells, have 
been encounte red only in anodic parts of electrophore· 
tically treated breast fat and abdominal fat. (f) "Epi· 
thelial cells" of primitive "galactophores " are encoun­
tered only in anodic fibrous tissue. The possibility that direct current may induce modi· 
fications of tissues and cells can not be excluded, on 
Fig. XV/:44. In vitro production of"channels" by electro· 
phoretic u-earment of human abdomina l fat tissue. Same tis· 
sue sample as in Fig. XVI: 43. (a) Rod-like structure (ar­
rows) in anodic fibrous tissue adjacent to a structure incer­
pretcd as a cross-sectioned channel with a well developed lu­
men (X). The "channel" has cells in its wall and is surround­
ed by circularly arran ~red fibres. (b) "Channels" from the 
mid-part of the same specimen show no fibroblasts in the 
dark (bluish) stained wall, which is surrounded by a thick 
layer of fibrous tissue. {c) HChannel" from the cathodic part 
of the same specimen. No fibroblasts or particularly stain­
able layers are seen in the wall {haematoxylin-eosin stain). the basis of the data thus far. If this possibility is 
correct and if we were also able to follow a preferential 
pathway for current through the tissue from the anodic 
to the cathodic side of the specimen, then we should 
be able to observe a gradual change in the modifica­
tions of the tissue. This observation will shortly be 
undertaken, but first we must try to identify cathodic 
structures which may correspond to the anodic struc­
tures described. 0. Closed circuit production 
of cathodic tissue channels 
In the cathodic field in electrophoresis of breast fat 
tis~ue, many of the cellular elements successively dis­
appear. Instead, fibrous tissue develops which does 
not contain fibroblasts. Other structural transform•· 
tions can, however, also be recognized. In order to 
demonstrate the relative differences between anodic 
and cathodic transformation of fat tissue, the cathodic 
changes will, as far as possible, be demonstrated in the 
same material as was used for demonstration of the 
anodic changes. The gradual development of cathodic atrophy of fat 
cells, reticular structuring of their cytoplasm and for­
mation of cathodic fibrosis were described in Section 
M (Fig. XVI: 33). Many cells in the anodic fibrous 
tis~ue were also described to form iroups surrounded 
by fibrous enclosures (Figs. XVI: 38, 39). These an­
odic grups can be compared with strange-appea ring 
groupings of "cells" in cathodic tissue (Fig. XVI:45). The survey in Fig. XVI: 45 a shows multiple cross­
sectioned and one lengthwise sectioned grouping of 
"cells" in cathodic fibrosis. The enlarged view in Fig. XVI: 45 b shows small circularly arranged fat "cells" 
inside a fibrotic enclosure around each group of"cells". The individual "cells", which represent new structural 
elements, each show a central, condensed material like 
a cellular nucleus. Each group of "cells" contains in its 
centre an "extracellular " collection of material, which 
looks like a local accumulation of fibrous tissue (X) 
and which extends as radiating structures between the 
"cells" to the circular fibrous sheet surrounding each 
group of "cells". Between the groups of "cells" <Fig. XVI:45b ) are also seen large "cells", some of which 
look empty. Some have the appearance of the grouped 
HceJls" and contain a "nucleus". An enlarged view of a 
lengthwise sectioned "core" is shown in Fig. XVI: 45 c. The groups of "cells" of this type may 
disappear gradually (Fig. XVI: 46a). Another line of 
transformation of small "cells" contains blue staining 
of their cytoplasm with haematoxylin-eosin (Fig. XVI:46b ). The development of cathodic channels by disap-
BCEC in cancer of the breast 247 Fig. XV/:45. In vitro production of cathodic channels in hu· 
man breast fat (10 V, 30 coulombs , 17 day1). (a) Overview of 
newly formed cathodic fibrosis, containing collections of 
transforming fat cells. (b) "Cells" of neoplastic appear•nce 
are arranged in groups inside a fibrous enclosure. The 
"cells" contain dark material in the centre. The middle of 
pearance of transformed fat "cells" is illustrated in 
Fig. XVI:47. The central location of a "core" of small 
transforming fat cells in a new-formed, cathodic fi. 248 BCEC in cancer of the breast each grou.p contains a possibly fibrous material (X) with ra· 
diatin.g structures whkh extend to 1he fibrous enclosure. The groups are assumed to represent cross-sectioned "cores" 
of transforming fat cells. (c) Lengthwise section of a "core" 
of fat cells (haematoxylin-eosin stain). brous stnnd is seen in Fig. XVI: 47 a. Its right part 
shows the formation of a primitive lumen. Fig. XVI: 47 b shows the small cells containing "nuclei" Fig.XV/:46 . Two lines of 
development of transformed 
cathodic fat "cells". (a) The 
small cells with a central 
dark "nucleus" may gradu­
ally dissolve, leaving a lu· 
men surrounded by a fi. brous wall without fibro· 
blasts. (b) Some of !he small 
uceUs" forming groups con­
rain bluish (dark) cytoplasm 
(haemaroxyHn-eosin stain). and disappearing cellular waUs. A newly formed ca· 
thodic channel is seen in Fig. XVI: 47 c, d. This chan· 
nel does not contain any cells in its "walls" or in the 
surrounding fibrous tissue. The waU of the channel 
takes relatively more blue stain with haematoxylin · 
eosin than does !he surrounding fibrous tissue. The 
inner surface of the channel is lined with a birefringent 
sheet (arrows, Fig. XVI: 47 d). Other structural developments leading to channels 
in the cathodic fat tissue have also been observed. These will be described in connection with a discus· 
sion on the possible role of flow of current over BCEC 
pathways in angiogenesis, Section Q. We will now 
continue to analyse the critical question of whether the 
structural modifications in the anodic and cathodic fields have developed under the influence of the ap· 
plied current or if they were presem in the fat tissue 
specimens before treatment. P. Transformation of tissue 
and cells across the 
intermediate zone between 
anode and cathode 
We have now described some structural characteristics 
of "pure" anodic and cathodic breast fat tissue in Sec· 
BCEC in cancer of the breast 249 a -· 
b 
d ,..._ 
Fig. XV! : 47. l.n vitro production of CBthodic channels in hu­
man breast (10 V, 30 coulombs, 17 days). (a) Overview of fi. brous strand with central "core .. of atrophying fat cells form· 
ing a channel. (b) Magnified view shows a!rophic fat cells 
with cen1rally located dark material. The lysing of the walls 
of many of these cells is e'-ident. (c) Well developed cathodic 
250 BCEC in cancer of the breast / -< o.3mni 
channel in fibrous tissue. No cells of any kind are present. The walls of the channel are more blue-stained than sur­
rounding fibrous tissue. (d) The inner surface of the wall is 
lined with a birefringent thin structure (arrows) (haematoxy · 
lin-eosin stain). Fig. XV/:48. The transition between cathodic "cores"(left) 
and anodic "-rods" (right) in the intermediate zone between 
the cathodic and anodic fields of electrophoretically treated 
humJin bre.~st fat (10 V, 30 coulombs, 17 days). (a) Overview 
of the intermediate zone. Two transitions between cores and 
rods are indicated by asterisks. (b) Enla.rged exrension of the 
zone in the cathodic direction (left of a) (see also Fig. XVI: 45a). (c) Enlarged extensin of the zone in the anodic direc· 
tion (right of a)(see also Fig. XVI: 40c). The cathodic core 
contains light cells with multiple dots (a, b) and the anodic 
rod contains dark small cells (a, b, c). The.e cells develop 
gradually into larger round or cubical cells of epithelial type 
outlining a lumen(<, to the right) (hacmatoxylin -cosin stain). BCEC in cancer of the breast 25 I lions N and 0. The appearances of these structures 
differ considerab ly from each other. If they are the 
result of the currem applied over each specimen, a 
continuous ttansition between the structural changes 
should be present in an intermediate zone be!Ween 
"pure" anodic and cathodic transformat ions. Anodic 
"rods" and cathodic "cores" extend along newly 
formed anodic and cathodic fibrous strands. "Rods" 
and "cores" should then have some connections in the 
fibrous tissue. A serach of serial sections was therefore 
undertaken to find the ttansition between "rods" and 
"cores, in an intermediate zone between anodic and 
cathodic tissue. This task proved not easy. A look at 
the direction of newly formed fibrous tissue (e.g., Fig. XVI: 30) shows that it develops as curved or crooked 
extensions, which should correspond to preferential 
pathways for current be!Ween the electrodes. There­
fore the intermediate zone for a specific pathway of 
current can not be found positioned in a predictable 
plane through the specimen. Different lengths of pref­
erential pathways for current through the specimen 
and variations of conductivity should lead to different 
gradients of flow of current. Hence intermediate zones 
of transition be!Ween cathodic "cores" and anodic 
"rods" should appear in different sites in the tissues. An overview of an intermediate zone between ca­
thodic "cores" and anodic "rods" is shown in Fig. XVI: 48 a. After staining with haematoxylin-eosin , the 
anodic fibres showed dominating birefringence and 
the cathodic fibres a bluish colour under polarized 
light and a red filter. This difference facilitated recog­
nition of the intermediate zone, which appeared to be 
irregularly extended. Already from Fig. XVI: 48, 
which represents a microphotograph taken under ordi­
nary light, it may be evident that a cathodic "core" to 
the left continues into an anodic "rod" to the right 
(upper part of Fig. a). The left part of Fig. a is seen as 
an enlarged cathodic extension in Fig. b, and the right 
pan of Fig. a as an enlarged anodic extension in Fig. c. 
In the upper pan of Fig. b, ttansforming cathodic fat 
"cells" are seen. In the lower part of Fig. b another 
transition is seen between a cathodic "core" and an 
anodic rod. More in the cathodic direction the cathodic 
"cells" appeared as shown in Fig. XVI: 45 a. Finally, 
in Fig. XVI: 48c, a gradual change of the anodic 
"rods" is seen as rather clearly visible cells of epithelial 
type which start to outline a lumen to the right. The 
continuation of this channel in the anodic direction 
was earlier shown in Fig. XVI: 40c. The appearance of 
cathodic and anodic "cells" in the intermediate zone 
gives the impression of a gradual change of their ap­
pearance. The cathodic "cells" in this zone show mul­
tiple small dots in their "cytoplasm". Deeper in the 
cathodic field the "cells" contain one single structure 
which looks like a cellular nucleus (to the left in Fig. XVI: 46a). The "cells" also appear in structured 
252 BCEC in cancer of the breast groups. The anodic "cells" in the intermediate zone 
appear spindle-shaped and stain dark-blue with hae­
matoxylin-eosin. Deeper in the anodic field they be­
come rounded or cubical, they increase in size and 
develop an epithelial a_ppearance before they form tu­
bular ducts (Figs. XVI: 38 c, 40). At this point we may conclude that the easily de­
tectable new formations of cathodic and anodic fibrosis 
are not the only structural changes which take place in 
a fat specimen under the influence of applied direct 
current. Very easily recognizable modifications of 
suuctures and cells are also obtained, which look like 
cellular and structural differentiation. The most com­
plex sttuctural components are also obtained relatively 
close to the two electrodes as cathodic and anodic 
groupings of newly formed complex structures. It is 
rather remarkable that these can be produced even in a 
piece of "dead" tissue. Electric inducticn of stru<tural 
modifications of cells and tissue is therefore pcssible. Cor­
responding spcnraneous transformations in tissue should 
evidently also be pcssibJe {)'t)tr activated BCEC systems. Given this background , we will next discuss the possi­
bility of formation of new vessels over activated BCEC 
systems. Q. Discussion on closed 
circuit development of vessels 
The presentation of the material in Sections N, 0 and 
P indicates that different channels may develop in a 
tissue when exposed to weak direct current over a 
relatively long time, i.e., 2-5 weeks. Some of these 
channels were interpreted tentatively as possible early 
stages in the development of vessels in breast fat tissue 
(Figs. XVI: 41, 42) and in normal subcutaneou s ab­
dominal fat (Figs. XVI: 43, 44). These assumptions 
were made merely because blood and lymph vessels 
are the only remaining channels we would expect to 
develop in these tissu.es. A tentative explanation for 
early development of galactoph ores in breast fat was 
presented in the previous Sections N, 0 and P. A 
different approach will now be illustrated to identify, 
if possible, newly formed vessels after electrophoretic 
tteattnent of abdominal and breast fat tissue. Newly formed vessels are common in granulation 
tissue and often around malignant tumours. In Figs. XVI: 49 and 52, comparisons will be made between 
endogenously developed pathological vessels and ves­
sel-like structures from elecuophoreticall y ueated ab­
dominal and mammary fat tissue. Thus, a thick-walled 
cathodic channel of multiple round ceUs and a central, 
narrow lumen is shown in Fig. XVI: 49a, b. This d 
Fig. XV/:49. Comparison betwee.n eJectrophorerk, in vir.ro 
production of cathodic tissue channel in human abdomina J 
fat and spontaneously developed pathological ''essel around a 
carcinoma of the lung. (a) Overview of cathodic fibrous 
strand in human abdominal fat containing a partly open, 
centrally located, narrow channel. (b)Thechanncl is lined with birefringent fibres and a thick layer of organized cells. (c) Overview of pathological vessel in the lung adjacent tO a 
carcinoma. (tf) The cellular components in the wall of the 
vessel appear similar to the newly formed structure seen in 
Figs. a, b (haematOxylin -eosin stain). BCEC in cancer of the breast 253 / .-
/ / .. \ 
structure was obtained after electrophoretic treatment 
of normal subcutaneous abdominal human fat (10 V, 
about 20 coulombs, 4 weeks). In Fig. XVI: 49 c, d, 
microphotographs are shown from a spontaneous ly 
developed pathological vessel adjacent to a pulmonary 
carcinoma. This vessel also has a thick wall but a well 
developed lumen. The magnified view shows cellular 
elements which have an appearance similar to the 
cellular elements of the newly formed structure in the 
abdominal fat specimen. The variability of newly 
formed structures from normal abdominal fat treated 
electrophoretically is, however, rather wide. Thus, the 
structures shown in Fig. XVI: 50 a are interpreted as 
early stages of development of the structures shown 
in Fig. XVI: 49a, b. The structures shown in Fig. XVI: 50 b represents, on the other hand, a presumably 
later phase of development. These examples (Figs. XVI: 49a, b and 50a, b) were aU obtained from the 
cathodic field and tlle same slide preparation (haema­
toxylin-eosin ). 254 BCEC in cancer of the breast Fig. XVI: SO. Development 
of cathodic "channels" by 
electrophore-tic rre.atment of 
normal human subcutane· 
ous abdominal fat tissue. (a) Suggested "earl)"' stages 
of development of the type 
of structure which is shown 
in Fig. XVI: 49a, b. (b) Channel-like structure 
with well developed lumen. Light cellular structures in 
the thick wall of the "chan· 
nel'' contain duk, point-like 
"nuclei", like those which 
develop in cathodic fat (see 
Fig. XVI: 48a, b). Same 
slide preparation as Fig. XVI: 49a, b (haematoxylin­
eosin stain). Suuctures sintilar to those shown in Figs. XVI: 49, 
50 also developed after treatment of breast fat. Thus, 
Fig. XVI: 51 a, b, c illustrates structures obtained 
from the cathodic field of an electrophoretically treat­
ed specimen from human breast fat. In the o\·erview 
(a) one small and one large circular structure are seen. Both contain fibrous elements and "cells" in their 
walls similar to the appearance shown in newly devel­
oped structures in cathodic abdominal fat (Figs. XVI: 49a, b and 50 a, b). The enlarged view (Fig. XVI: 51 b) shows that the large channel contains fibres 
of different directions, indicating a tendency toward 
structural differentiation. Fig. XVI: 51 c shows that 
the small structure does not have a fully developed 
lumen. One line of possible development of vascular chan­
nels was suggested in the description of atrophy of 
breast fat cells (Fig. XVI: 47) and in abdominal fat 
(Fig. XVI: 44). The complete Jack of cellular elements 
in these channels indicate that they represent only one Fig. XVI: 51. Development 
of cathodic "channels" by 
electrophoreti c treatment of 
human breast fat tissue (10 
V, approximately 26 cou­
lombs, 7 days). (a) Over­
view of rwo circular struc­
tures interpreted as cross­
sectioned "channels". The 
lumen of the smaller chan­
nel has not yet fully opened 
(arrows). (b, c) The walls of 
both structures show fibres 
in different directions and 
small cells with light "cyto­
plasm". The appearance of 
the walls of the large struc· 
ture gives an impress-jon of 
an ongoing differentiation <If 
layers (haematoxylin-eosi n 
stain). a 
stage in the development of channels. Some channels 
formed by atrophy of fat cells do have, however, an 
appearance which is rather similar to that of pathologi ­
cal vessels around breast carcinomas. In Fig. XVI: 52 a, a cathodic channel is seen in breast fat after 
electrophoretic treatinem ( 10 V, appr. 26 coulombs, 7 
days). Fig. XVI: 52 b shows a pathological vessel in a 
fibrotic strand adjacent to a mammary carcinoma. Each specimen shows cathodic transformation in the 
fat cells, some of which also showed reticulation in 
their cytoplnsm. The material presented in this section is intended 
only as a stepping stone for a preliminary discussion of 
the possibility that BCEC mechanisms might be in­
volved in the development of vascular channels. Recent work on tumour angiogenesis has been con-I 
!~;t· 
~r 
f·'.~m 
centrated on the assumed production of what has 
been called a tumour-angiogenetic factor (TAF), mito­
genic to capillary endothelium and thought to stimu­
late the formation of vessels (35, 36, 37, 58). Thus, 
new tumour capillaries have been elicited after a tu· 
mour is enclosed in a Millipore filter chamber (45) and 
the chamber implanted in a cheek pouch of a hamster. Such studies have led to the assumption that the in­
duction of capillary growth was caused by a diiTusable 
substance named the tumour-angiogenetic factor. This 
anticipated foetor hns not been characterized chemical­
ly. It has been· extracted from tumours and placental 
tissue (37). That the development of vessels is essential 
for growth of solid neoplasms has long been known. Vascularization of tumours takes place only by capil­
lary proliferation. Neoplastic vessels of a tumour are 
BCEC in cancer of the breast 255 thought to be unique in that the neoplasms usuaUy do 
not contain '. :veins" and "arteries" but a rich network 
of capillaries bounded only by an endothelial epitheli­
um. This type of capillary growth is, however, not 
unique to neoplasms ; it also occurs in granulation 
tissue (45). The mechanism that induces the growth of 
tumour vessels and granulation vessels is, however, 
considered as unknown ( 4 S). Many factors and mechanisms seem likely to be 
involved in these events. The existence or nonexis­
tence of a T AF need not necessaril y exclude the possi­
ble existence of an electrogenic component, which has 
been simulated in the present experiments by leading 
direct current over "dead" tissue in an electrophoretic 
chamber. Th.e metabolism or degrading processes of a 
tumour may produce electric polarization of the tu­
mour againsr its surroundings and hence induce an 
electric current over a BCEC. More specificaUy , such 
circuits may be represented by VICC (vascular-inter­
stitial closed circuits) for development of vessels. A 
spontaneou s current over such connections should be 
able to induce an outgrowth of new vessels. When a primitive vessel is subjected to spontaneous 
fluctuations of polarity of the driving electromot ive 
force caused by, e.g., a necrotizing process in the 
tumour, the vessel may eventuaUy develop further into 
a mixed an()dic and cathodic vessel, as a result of 
bidirectional flow of current. The development of a 
complete vessel should funher require, e.g., the modi­
fying influence of blood and the mechanics of circula­
tion. New primitive channels can be expected to grow 
at sites of preferential conductivity through capillary 
membranes and in preferential pathways for current in 
the interst:itial tissue. In future anempts to improve 
256 BCEC in cancer of the breast Fig. XVI: 52. Comparison 
between electrophoretic in 
vitro production of a cathod­
ic tissue channel in human 
breast fan and a spontane · 
ously developed pathological 
vessel around a mammary 
carcinoma. (a) Cathodic fi. brous strand in breast fat 
contains :fat cells, which 
seem to disappear , leaving a 
lumen. (b) Pathological ves­
sel in a fibrous strand 
around a breast carcinoma. Both cblOilllels (a and b) 
seem to develop by atrophy 
of fat ce!ns, leaving a fibrous 
channel (haematoxylin-cosin 
stain). vascularity in tissue, it may prove useful to consider 
this new view of angiogenesis. From this discussion it 
also appears evident that a mechanism for outgrowth 
of ductal channels and induction of neoplasia can be 
derived as a BCEC effect over ductal-interstitial closed 
circuits.
631928626-Biologically-Closed-Electric-Ci-Bjorn-Nordenstrom-pdf.txt
Summarize the following text section accurately and concisely. Maintain specific details and numerical information, and use anti-repetition mechanisms:

        Skin 
Retracting fibrous material 
Hydropic"B"-zone 
+''Retraction oedema" 
strUctures extending to the cutis will retract the skin and en­
hance the accumulation of elcctroosmotically transported 
warer in the skin. Thc "circular. structure (lower right) cur­
responds internally 10 the external "skin thickening". Re· 
traction forces of the radiating structures in this region are 
counterbalanced by retraction forces of the normal tissue dis· 
tal to the Hcircular" structure. The thickness of the Hc-irc-u­
lar" structure is the same as that of the "skin [hickening ", 
funher suggesting their common pathoge. nesis as hydropic 
"8" zones. straight (Fig. XVI: 27 b). One's lim impression may 
be that the underlying fibres represent artefacts of 
preparation. This explanation, however, is highly un· 
likely because identical appearances of undulating 
structures are seen irrespective of the direction of 
cutting the specimen. This observation was experi· 
mentally ch<-cked as follows; 
Tissue surrounding a scirrhous breast cancer was 
excised and divided into four pieces. Two pieces (a+b) 
were placed in saline solution and frozen. The remain· 
ing two pieces (<+d) were kept in a dry place in a 
refrigerator overnight in order to become slightly de· 
hydrated. Frozen sections were. then prepared of the 
four pieces. Pieces a+c were cut as closely as possible 
BCEC in cancer of the breast 229 Fig. XVI: 28. Dehydration shrinks hydrophilic components 
of fibrotic tissue between nonhydrophilic, birefringem colla­
gen fibres. Histclogic frozen sections (haematoxylin~in, 
a-<i, same magnification ). ArroWll indicate directions of cut­
ting. (a, b) Two specimens of fibrous tissue from a breast 
230 BCEC in cancer of the breast Pig. XVI: 27. Variable ap­
pearances of fibrous strands 
radiating from a scirrhous 
carcinoma of the breast (his­
tologic sections, haematoxy­
lin-eosin). (a) Undulating 
course of panly birefringen< 
fibres. (b) Straight course of 
fibres in another part of the 
same specimen. The undu· 
lating fibrous sttuctures are 
not necessarily artefacts of 
preparation. Identical ap­
pearances can be obtained 
regardless of the direction of 
culling the specimen (see 
further Fig. XV. : 28). cancer after soaking in saline solution overnight. The colla· 
gen fibres are straight, regardless of the di. recrjon of cuttinr. (c, d) Corresponding fibrous tissue after overnight dehydra­
tion of the mate. rial. The collagen fibres undulate, regardless 
of the direction of cutting. Fig. XV/:29. "Skin tltick­
eningJ' near a mammary 
carcinoma (40-year-old 
woman, I. J. in Table 
XVI: 3). Mammogram, 
mAstectomy specimen. (a) a 
The tumour is surrounded b 
by fibrous radiating struc­
tures and poo. sibly an u A" 
zone with some circular 
structures. (b) The same 
specimen. Radiograp h of 
the skin, which is tltick­
ened to the right and be­
low the retracted nipple 
but is of normal tltickness 
to the left. along the extensions of the fibrous radiating material, 
pieces b+d perpendicular to the extensions. The sec­
tions were mounted and stained.
The purpose of this experiment was to investigate the hydration and shrinkage of the hygroscopic fibrous material, which is not possible in the normal tissue.
What is the purpose of the experiment where human breast fat tissue was divided into four pieces and treated with saline solution and then frozen?
The explanation is that the hygroscopic material shrinks, leading to the formation of undulating structures.
What is the explanation for the undulating course of the birefringent collagenous material in the dehydrated specimen?
The conclusion is that the "skin thickening" is caused by local dehydration, which leads to the accumulation of water in the skin.
What is the conclusion drawn from the analysis of the fat and water content of "skin thickening" in breast cancer?
The result is the production of anodic and cathodic fibrous tissue, which resembles scar tissue and contains fibroblast-like cells.
What is the result of the experiment where platinum electrodes were used to produce membranes in human breast fat tissue?
The author suggests that fibroblasts may not be the only source of precursor material for fibrous tissue, and that electrogenic components may also play a role in its production.
What is the author's stance on the role of fibroblasts in the production of fibrous tissue?