the permeability of the blood vessels in and around grafted jensen

THE PERMEABILITY OF THE BLOOD VESSELS IN AND
AROUND GRAFTED JENSEN RAT SARCOMA
HAROLD BURBOWB, C.B.E.,F.R.U.S.
(From the Beseatoh Institute or The Cancer Hospital (Free), London)
A single dose of isamine blue was injected into the peritoneal
cavity in 192 young rats bearing grafted tumours of the Jensen
sarcoma in the right flank. The amounts of dye given varied from
0.5 to 1 C.C. of a 1 per cent solution, in accordance with each animal’s weight. Some of these rats prior to the injections had been
treated by exposure of their tumours to x-rays; others were untreated.
Of the 192 tumours, 117 grew, 72 underwent complete retrogression, and 3 rats died before a final result could be recorded.
Within twenty-four or forty-eight hours after its introduction into
the abdomen, the dye was found usually to have stained the tumour,
as seen in the intact animal, a pronounced blue. Such localkation
occurred in 171 of the total number. I n every instance in which a
tumour was shown by the chart book to be growing when the dye
was administered, staining of the tumour followed (Table I).
TABLEI: Loodimation of Dge after Intrapmitoned dddnktration (n Rats
with Flunk Turnouts o/ the J m e n Sarooma
4
Btate of tumour
when dye injectad
ffrowing
Btationary
Receding
-
D?e
Dyenot
Total
loealised loealised
number in tumour intumour
164
154
0
8
8
0
9
21
30
Tumours
grew
113
4
0
Tumours Rat died before
retroanal result
greased wascertain
39
2
3
1
30
0
On the other hand, if the tumour was undergoing retrogression
when the dye was introduced into the peritoneal cavity, there was
apt to be no localisation of dye in its neighbourhood. There were
30 animals which received injections of dye at a time when their
tumours were receding and in 21 of them no localisation of dye was
visible. I n all of these 30 animals the tumours eventually disappeared.
In a few instances when the dye was injected the tumours were
recorded as stationary in size. Among 8 such “stationary” tumours, 2 stained poorly and both of these retrogressed completely.
Of the remaining 6 in which the dye became well localised, 4 grew
to a fatal termination, one retrogressed, and in the remaining case
the rat died before a final result could be recorded for the tumour.
383
384
HAROLD BUBLtOWS
Of the 30 tumours which were receding when the isamine blue
was given, 17 had received a single dose of x-rays from six to ten
days previously, and 13 were untreated. Among the 81 receding
tumours which failed to show any localisation of dye, 12 had been
irradiated and 9 were untreated (Table 11).
TABLE11: Tumrourr B60sding whm
me
Number
Previoualy irradiated
Untreated
17
13
(ow
Infsoted into dbdorntm
Dye locrrllsed
in tnmour
5
4
Dye not localieed
in tnmonr
12
0
D~scussxoa
These experiments appear to show that the endothelium of the
blood vessels in the immediate neighbourhood of a Jensen rat sarcoma is exceptionally permeable and that in the absence of such increased permeability the tumour will not prosper. No assertion i R
made that the increased endothelial permeability must be regarded
as a cause of the continued growth of the tumours: possibly it is
merely an associated condition. It may be that in a growing tumour of this kind the newly formed blood vessels oontain cellular
elements in which differentiation has not become completed merely
through lack of time, and that the lessened capillary continence can
be attributed to immaturity. Or it may be that the vaacular
stroma in these tumours fails to undergo perfect 'differentiation
owing in some way to its proximity to neoplastic cells. Similar
suggestions have been made elsewhere by the writer (1). But
whatever the correct explanation.may be, the facts brought forward above carry implications which seem to render them interesting enough for publication.
SUMMABY
1. Isamine blue, after intraperitoneal administration, became
segregated in and around growing flank tumours of Jensen rat
sarooma.
2. Such segregation of dye did not occur in 21 out of 30 tumours
which were undergoing retrogression.
3. It is suggested that the increased permeability of the vascular endothelium thus demonstrated in and around growing tumours
may be attributed to imperfect cellular differentiation due either
to immnturity or to association with malignant cells.
REBQLWPCE
1. B m w 8 , HABOLD:
Some Faotore in the Loocrlisiltion of Disease in the Body,
London, BsilliBre, Tindell and CoxJ1992.