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.
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