Single cell suspensions of two allogeneic tumours (W-256 and Y-P388) injected intravenously produced macrocolonies in the lungs of rats. Colony forming efficiency (CFE, the number of colonies produced by each viable cell injected) was low in 6-week or older rats but was markedly increased by 1000-1500 rad local thoracic irradiation (LTI) given 7-14 days before the tumour cell injection, or by antilymphocytic serum (ALS) but not by sublethal whole body irradiation (WBI). Similarly, LTI increased the incidence of pulmonary metastases produced by a solid tumour growing in the leg muscle. Stimulation of CFE by LTI was a strictly local phenomenon and not due to effects of irradiation on thymus, spleen or other tissues of the rat. LTI failed to increase CFE in immunized rats. It is concluded that (1) LTI stimulates clonogenic growth of tumour cells arrested in the lungs, by causing inflammatory reactions accompanied by regenerative cellular proliferation of lung tissue, which increases the “plating” efficiency of tumour cells, (2) the increase in CFE in lungs is not due to suppression of immunity to tumour growth by LTI.
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A proportion of W-256 tumour cells injected intravenously into a tail vein of the rat are diverted into venous plexuses en route to the lungs; here tumour cells remain trapped, proliferate and form invasive solid tumours in the pelvis and hindquarters, which cause paraplegia, metastases and death. Also, cells trapped in veins produce tumour nodules distributed along the length of the tail; this effect in markedly enhanced by temporarily arresting the outflow of blood from the tail for a few seconds only immediately after cells are injected. Continous monitoring of the radioactive signal over the lungs after W-256 cells labelled with 125IUDR were injected showed that massaging the tail or intravenously injecting isotonic saline into the tail dislodged cells trapped in veins. In heparinized rats, tail trapping was markedly reduced, although not entirely abolished, and venous trapping in vertebral and pravertebral regions was decreased. The anatomical distribution of growth of the trapped cells in rats closely resembled metastases involving dissemination via the "vertebral venous system" produced by certain cancers in man. Labelled tumour cells trapped in the lungs of untreated mature rats commenced dying rapidly in situ wiht 1-2 h after injection; the majority had disappeared within 24 h, and less than 1% of the injected tumour cells survived to form lung colonies. Experimental evidence is presented which indicates that the lungs play a vital role in rapidly eliminating a high proportion of blood-borne cancer cells in the adult individual.
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