THE EFFECT OF DIETARY RESTRICTION, ADRENALINE, HYDROCORTISONE AND SURGERY ON THE RATES OF DEATH OF ¹²⁵IUdR‐LABELLED, INTRAVENOUSLY INJECTED TUMOUR CELLS IN THE LUNGS OF MICE

Abstract

Summao'. Dietary restriction, adretiiiline. hydrocortisone or surgery reduced the rate at which pulmonarily arresied '-''IUdR-labelled murine lumour cells were lost within 7 h of intravenous (i.v.) injection. Mice that had been adrenalectomised 10 days previously showed a normal intrapiilmonary tumour cell loss rate wilh furiher surjjery reducing this rate to approximately half that observed in normal mice thai had been subjected to surgery. Thus, although it is likely that adrenal hormones play an important role in decreasing the rate of early intrapulmonary tumour cell loss, additional factors must be implicated.Mice subject to dietary restriction, adrenaline, hydrocortisone or surgery had reduced levels of in viirn growth inhibitor(s) In their sera. Despite this, individual surgically treated animals showed no correlation between serum in vitro growth inhibitor levels and rate of loss of i.v. injected tumour cells from the lungs. Furthermore, [he 24 h pre-incubation of tumour cells in inhibitor-rich serum did not influence the subsequent loss rate of such cells following i.v. injection into mice.Electron microscopic studies indicated that dietary restriction, adrenaline and surgery reduced the rale of intravascular tumour cell death. The decreased tumour cell death rate in mice receiving these treatments could not be related, however, to any consistent morphological change in the pulmonary vasculaturc.The decreased rate of intravascular lumour cell death in treated mice was followed by an increased number of lung tumours with only one of the tumour lines studied, indicating that the intravascular death rate need not be a major determinant of pulmonary tumour incidence.

The role of natural killer cells in the intravascular death of intravenously injected murine tumour cells

“…As the pulmonary loss of radioactivity within 24h of i.v. injection has been clearly shown to be a consequence of the intravascular death of arrested tumour cells (Bishop & Donald, 1979;Talmadge et al, 1980;Bishop et al, 1982), it was concluded in the above studies that the intravascular death of i.v. injected tumour cells was at least in part due to NK cell-mediated killing of the tumour cells.…”

“…Furthermore, the rate of intravascular tumour cell death following i.v. injection has been shown to be influenced by a wide variety of host treatments (Bishop et al, 1982). It is possible that multiple host factors, perhaps including NK cells to a minor extent, may be involved in the intravascular death of i.v.…”

“…The number of tumour cells undergoing coagulative necrosis did not significantly increase on incubation with spleen cells although it observed that with time some apoptotic bodies underwent secondary disintegration with membrane disruption. pulmonarily arrested tumour cells was carried out as previously described (Bishop & Donald, 1979;Bishop et al, 1982). The majority of intrapulmonarily arrested mastocytoma cells observed 4-7 h after i.v.…”

“…Previously we have shown that the mechanism of the intravascular death of tumour cells within 8 h following i.v. injection was coagulative necrosis (Bishop & Donald, 1979;Bishop et al, 1982) Spleen cell preparations were isolated from inbred syngeneic DBA/2 mice that had not previously been exposed to the tumour. As NK cell activity has been shown to be stimulated by agents that induce interferon production, such as polyinosinic-polycytidylic acid (poly I: C) (Gidlund et al, 1968;Djeu et al, 1979;Hanna, 1980), a poly I:C solution of 1.Omgml-P was prepared in PBS.…”